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Biophys Chem

Silico analysis of interaction between full-length SARS-CoV2 S protein with human Ace2 receptor: Modelling, docking, MD simulation.

Many key residues, which mediate the interaction between SARS-CoV2 spike glycoprotein (S protein) and human ACE2 receptor, have been reviewed using the SARS-CoV2 S spike protein with human ACE2 complex. The initial SARS-CoV2 S protein and ACE2 protein complex structure is formed by RBD structure of SARS-CoV2 S protein and ACE2 protein. However, the cryo-EM structure study targeting SARS-Cov S protein with human ACE2 complex has shown that there exist different binding conformations during the binding process facing ACE2 protein. It suggests the interaction between SARS-CoV2 S spike protein complex might have different binding conformations, which request full-length of SARS-CoV2 S protein complex in the structure-functional analysis. In this study, we built a full-length SARS-CoV2 S protein with human ACE2 complex by computational methods. Residues K31, H34, E35 in ACE2 protein were showed both in our full-length model and RBD structure model, which recognized as critical residues in previous studies. Surprisingly, ACE2 residues E564, R559, N556 were only found participating in the interaction of our full-length model, which suggested the full-length model has bigger binding interface. This finding was further supported by the interaction network of full-length model and RBD model. Meanwhile, the method bias was taken into consideration. Eventually, the MM-PBSA results showed the full-length model had a stronger binding free energy (almost 5-fold) than the RBD structure model of SARS-CoV2 S spike protein complex. In computational level, we present a stronger binding model containing a full-length structure of SARS-CoV2 S protein with ACE2 complex.

ace2;md;mm-pbsa;sars-cov2;spike protein

Journal Article

Rui, Li;Haonan, Li;Wanyi, Chen

10.1016/j.bpc.2020.106472

[Title]: Silico analysis of interaction between full-length SARS-CoV2 S protein with human Ace2 receptor: Modelling, docking, MD simulation. [Abstract]: Many key residues, which mediate the interaction between SARS-CoV2 spike glycoprotein (S protein) and human ACE2 receptor, have been reviewed using the SARS-CoV2 S spike protein with human ACE2 complex. The initial SARS-CoV2 S protein and ACE2 protein complex structure is formed by RBD structure of SARS-CoV2 S protein and ACE2 protein. However, the cryo-EM structure study targeting SARS-Cov S protein with human ACE2 complex has shown that there exist different binding conformations during the binding process facing ACE2 protein. It suggests the interaction between SARS-CoV2 S spike protein complex might have different binding conformations, which request full-length of SARS-CoV2 S protein complex in the structure-functional analysis. In this study, we built a full-length SARS-CoV2 S protein with human ACE2 complex by computational methods. Residues K31, H34, E35 in ACE2 protein were showed both in our full-length model and RBD structure model, which recognized as critical residues in previous studies. Surprisingly, ACE2 residues E564, R559, N556 were only found participating in the interaction of our full-length model, which suggested the full-length model has bigger binding interface. This finding was further supported by the interaction network of full-length model and RBD model. Meanwhile, the method bias was taken into consideration. Eventually, the MM-PBSA results showed the full-length model had a stronger binding free energy (almost 5-fold) than the RBD structure model of SARS-CoV2 S spike protein complex. In computational level, we present a stronger binding model containing a full-length structure of SARS-CoV2 S protein with ACE2 complex. [Keywords]: ace2;md;mm-pbsa;sars-cov2;spike protein

Int J Clin Pharm

Clinical characteristics and drug therapies in patients with the common-type coronavirus disease 2019 in Hunan, China.

Background Clinical characteristics of patients with the coronavirus disease 2019 (COVID-19) may present differently within and outside the epicenter of Wuhan, China. More clinical investigations are needed. Objective The study was aimed to describe the clinical characteristics, laboratory parameters, and therapeutic methods of COVID-19 patients in Hunan, China. Setting The First Hospital of Changsha, First People's Hospital of Huaihua, and the Central Hospital of Loudi, Hunan province, China. Methods This was a retrospective multi-center case-series analysis. Patients with confirmed COVID-19 diagnosis hospitalized at the study centers from January 17 to February 10, 2020, were included. The following data were obtained from electronic medical records: demographics, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings, computer tomography scans, and treatment measures. Main outcome measure Epidemiological, clinical, laboratory, and radiological characteristics and treatments. Results A total of 54 patients were included (51 had the common-type COVID-19, three had the severe-type), the median age was 41, and 52% of them were men. The median time from the first symptoms to hospital admission was seven days. Among patients with the common-type COVID-19, the median length of stay was nine days, and 21 days among patients with severe COVID-19. The most common symptoms at the onset of illness were fever (74.5%), cough (56.9%), and fatigue (43.1%) among patients in the common-type group. Fourteen patients (37.8%) had a reduced WBC count, 23 (62.2%) had reduced eosinophil ratio, and 21 (56.76%) had decreased eosinophil count. The most common patterns on chest-computed tomography were ground-glass opacity (52.2%) and patchy bilateral shadowing (73.9%). Pharmacotherapy included recombinant human interferon alpha2b, lopinavir/ritonavir, novaferon, antibiotics, systematic corticosteroids and traditional Chinese medicine prescription. The outcome of treatment indicated that in patients with the common-type COVID-19, interferon-alpha2b, but not novaferon, had some benefits, antibiotics treatment was not needed, and corticosteroids should be used cautiously. Conclusion As of February 10, 2020, the symptoms of COVID-19 patients in Hunan province were relatively mild comparing to patients in Wuhan, the epicenter. We observed some treatment benefits with interferon-alpha2b and corticosteroid therapies but not with novaferon and antibiotic treatment in our study population.

covid-19;clinical characteristics;infection;pharmacotherapy

Journal Article;Multicenter Study

Huang, Qiong;Deng, Xuanyu;Li, Yongzhong;Sun, Xuexiong;Chen, Qiong;Xie, Mingxuan;Liu, Shao;Qu, Hui;Liu, Shouxian;Wang, Ling;He, Gefei;Gong, Zhicheng

10.1007/s11096-020-01031-2

[Title]: Clinical characteristics and drug therapies in patients with the common-type coronavirus disease 2019 in Hunan, China. [Abstract]: Background Clinical characteristics of patients with the coronavirus disease 2019 (COVID-19) may present differently within and outside the epicenter of Wuhan, China. More clinical investigations are needed. Objective The study was aimed to describe the clinical characteristics, laboratory parameters, and therapeutic methods of COVID-19 patients in Hunan, China. Setting The First Hospital of Changsha, First People's Hospital of Huaihua, and the Central Hospital of Loudi, Hunan province, China. Methods This was a retrospective multi-center case-series analysis. Patients with confirmed COVID-19 diagnosis hospitalized at the study centers from January 17 to February 10, 2020, were included. The following data were obtained from electronic medical records: demographics, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings, computer tomography scans, and treatment measures. Main outcome measure Epidemiological, clinical, laboratory, and radiological characteristics and treatments. Results A total of 54 patients were included (51 had the common-type COVID-19, three had the severe-type), the median age was 41, and 52% of them were men. The median time from the first symptoms to hospital admission was seven days. Among patients with the common-type COVID-19, the median length of stay was nine days, and 21 days among patients with severe COVID-19. The most common symptoms at the onset of illness were fever (74.5%), cough (56.9%), and fatigue (43.1%) among patients in the common-type group. Fourteen patients (37.8%) had a reduced WBC count, 23 (62.2%) had reduced eosinophil ratio, and 21 (56.76%) had decreased eosinophil count. The most common patterns on chest-computed tomography were ground-glass opacity (52.2%) and patchy bilateral shadowing (73.9%). Pharmacotherapy included recombinant human interferon alpha2b, lopinavir/ritonavir, novaferon, antibiotics, systematic corticosteroids and traditional Chinese medicine prescription. The outcome of treatment indicated that in patients with the common-type COVID-19, interferon-alpha2b, but not novaferon, had some benefits, antibiotics treatment was not needed, and corticosteroids should be used cautiously. Conclusion As of February 10, 2020, the symptoms of COVID-19 patients in Hunan province were relatively mild comparing to patients in Wuhan, the epicenter. We observed some treatment benefits with interferon-alpha2b and corticosteroid therapies but not with novaferon and antibiotic treatment in our study population. [Keywords]: covid-19;clinical characteristics;infection;pharmacotherapy

Int J Gynaecol Obstet

Clinical characteristics, prognostic factors, and maternal and neonatal outcomes of SARS-CoV-2 infection among hospitalized pregnant women: A systematic review.

BACKGROUND: Pregnant women represent a potentially high-risk population in the COVID-19 pandemic. OBJECTIVE: To summarize clinical characteristics and outcomes among pregnant women hospitalized with COVID-19. SEARCH STRATEGY: Relevant databases were searched up until May 29, 2020. SELECTION CRITERIA: Case series/reports of hospitalized pregnant women with laboratory-confirmed COVID-19. DATA COLLECTION AND ANALYSIS: PRISMA guidelines were followed. Methodologic quality was assessed via NIH assessment tools. MAIN RESULTS: Overall, 63 observational studies of 637 women (84.6% in third trimester) with laboratory-confirmed SARS-CoV-2 infection were included. Most (76.5%) women experienced mild disease. Maternal fatality, stillbirth, and neonatal fatality rates were 1.6%, 1.4%, and 1.0%, respectively. Older age, obesity, diabetes mellitus, and raised serum D-dimer and interleukin-6 were predictive of poor outcomes. Overall, 33.7% of live births were preterm, of which half were iatrogenic among women with mild COVID-19 and no complications. Most women underwent cesarean despite lacking a clear indication. Eight (2.0%) neonates had positive nasopharyngeal swabs after delivery and developed chest infection within 48 hours. CONCLUSIONS: Advanced gestation, maternal age, obesity, diabetes mellitus, and a combination of elevated D-dimer and interleukin-6 levels are predictive of poor pregnancy outcomes in COVID-19. The rate of iatrogenic preterm birth and cesarean delivery is high; vertical transmission may be possible but has not been proved.

covid-19;intrauterine fetal demise;maternal morbidity;maternal mortality;miscarriage;neonatal morbidity;neonatal mortality;preterm birth

Journal Article;Systematic Review

Turan, Ozlem;Hakim, Amir;Dashraath, Pradip;Jeslyn, Wong Jing Lin;Wright, Alison;Abdul-Kadir, Rezan

10.1002/ijgo.13329

[Title]: Clinical characteristics, prognostic factors, and maternal and neonatal outcomes of SARS-CoV-2 infection among hospitalized pregnant women: A systematic review. [Abstract]: BACKGROUND: Pregnant women represent a potentially high-risk population in the COVID-19 pandemic. OBJECTIVE: To summarize clinical characteristics and outcomes among pregnant women hospitalized with COVID-19. SEARCH STRATEGY: Relevant databases were searched up until May 29, 2020. SELECTION CRITERIA: Case series/reports of hospitalized pregnant women with laboratory-confirmed COVID-19. DATA COLLECTION AND ANALYSIS: PRISMA guidelines were followed. Methodologic quality was assessed via NIH assessment tools. MAIN RESULTS: Overall, 63 observational studies of 637 women (84.6% in third trimester) with laboratory-confirmed SARS-CoV-2 infection were included. Most (76.5%) women experienced mild disease. Maternal fatality, stillbirth, and neonatal fatality rates were 1.6%, 1.4%, and 1.0%, respectively. Older age, obesity, diabetes mellitus, and raised serum D-dimer and interleukin-6 were predictive of poor outcomes. Overall, 33.7% of live births were preterm, of which half were iatrogenic among women with mild COVID-19 and no complications. Most women underwent cesarean despite lacking a clear indication. Eight (2.0%) neonates had positive nasopharyngeal swabs after delivery and developed chest infection within 48 hours. CONCLUSIONS: Advanced gestation, maternal age, obesity, diabetes mellitus, and a combination of elevated D-dimer and interleukin-6 levels are predictive of poor pregnancy outcomes in COVID-19. The rate of iatrogenic preterm birth and cesarean delivery is high; vertical transmission may be possible but has not been proved. [Keywords]: covid-19;intrauterine fetal demise;maternal morbidity;maternal mortality;miscarriage;neonatal morbidity;neonatal mortality;preterm birth

Otolaryngol Head Neck Surg

Misconceptions About Negative Pressure Rooms and Their Impact Aboard USNS Comfort in New York City.

The outbreak of novel coronavirus disease 2019 (COVID-19) has had a momentous impact on the field of otolaryngology due to the high number of aerosol-generating procedures involving the upper aerodigestive tract. These procedures bear significant risk to the provider and clinical environment due to the possibility of viral aerosolization. While significant attention has been appropriately paid to personal protective equipment during this pandemic, an understanding of industrial hygiene is also necessary for the safe delivery of health care to mitigate the risk of exposure to other patients and health care workers. We provide a review of air ventilation practices and their role in reducing pathogen spread. In addition, we share our experiences with effectively treating COVID-19-positive patients aboard the USNS Comfort through proper environment control measures.

covid-19;sars cov-2;aerosol-generating procedure;air changes per hour;air handling;environmental control;environmental safety;high-risk aerosol;industrial hygiene;negative pressure room;otolaryngology;respiratory protection

Journal Article

Hill, Christopher J;Capra, Gregory G;McDonald, Thomas P;Santiago, Gabriel F;Radabaugh, J Paul

10.1177/0194599820938016

[Title]: Misconceptions About Negative Pressure Rooms and Their Impact Aboard USNS Comfort in New York City. [Abstract]: The outbreak of novel coronavirus disease 2019 (COVID-19) has had a momentous impact on the field of otolaryngology due to the high number of aerosol-generating procedures involving the upper aerodigestive tract. These procedures bear significant risk to the provider and clinical environment due to the possibility of viral aerosolization. While significant attention has been appropriately paid to personal protective equipment during this pandemic, an understanding of industrial hygiene is also necessary for the safe delivery of health care to mitigate the risk of exposure to other patients and health care workers. We provide a review of air ventilation practices and their role in reducing pathogen spread. In addition, we share our experiences with effectively treating COVID-19-positive patients aboard the USNS Comfort through proper environment control measures. [Keywords]: covid-19;sars cov-2;aerosol-generating procedure;air changes per hour;air handling;environmental control;environmental safety;high-risk aerosol;industrial hygiene;negative pressure room;otolaryngology;respiratory protection

Adv Simul (Lond)

The use of simulation to prepare and improve responses to infectious disease outbreaks like COVID-19: practical tips and resources from Norway, Denmark, and the UK.

In this paper, we describe the potential of simulation to improve hospital responses to the COVID-19 crisis. We provide tools which can be used to analyse the current needs of the situation, explain how simulation can help to improve responses to the crisis, what the key issues are with integrating simulation into organisations, and what to focus on when conducting simulations. We provide an overview of helpful resources and a collection of scenarios and support for centre-based and in situ simulations.

Journal Article

Dieckmann, Peter;Torgeirsen, Kjetil;Qvindesland, Sigrun Anna;Thomas, Libby;Bushell, Verity;Langli Ersdal, Hege

10.1186/s41077-020-00121-5

[Title]: The use of simulation to prepare and improve responses to infectious disease outbreaks like COVID-19: practical tips and resources from Norway, Denmark, and the UK. [Abstract]: In this paper, we describe the potential of simulation to improve hospital responses to the COVID-19 crisis. We provide tools which can be used to analyse the current needs of the situation, explain how simulation can help to improve responses to the crisis, what the key issues are with integrating simulation into organisations, and what to focus on when conducting simulations. We provide an overview of helpful resources and a collection of scenarios and support for centre-based and in situ simulations. [Keywords]:

FASEB J

SARS-CoV-2 and the possible connection to ERs, ACE2, and RAGE: Focus on susceptibility factors.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has provoked major stresses on the health-care systems of several countries, and caused the death of more than a quarter of a million people globally, mainly in the elderly population with preexisting pathologies. Previous studies with coronavirus (SARS-CoV) point to gender differences in infection and disease progression with increased susceptibility in male patients, indicating that estrogens may be associated with physiological protection against the coronavirus. Therefore, the objectives of this work are threefold. First, we aim to summarize the SARS-CoV-2 infection pathway and the roles both the virus and patient play in COVID-19 (Coronavirus disease 2019) progression, clinical symptomatology, and mortality. Second, we detail the effect estrogen has on viral infection and host infection response, including its role in both the regulation of key viral receptor expression and the mediation of inflammatory activity. Finally, we describe how ERs (estrogen receptors) and RAGE (receptor for advanced glycation end-products) play a critical role in metabolic pathways, which we envisage could maintain a close interplay with SARS-CoV and COVID-19 mortality rates, despite a current lack of research directly determining how. Taken together, we present the current state of the field regarding SARS-CoV-2 research and illuminate where research is needed to better define the role both estrogen and metabolic comorbidities have in the COVID-19 disease state, which can be key in screening potential therapeutic options as the search for effective treatments continue.

ace2;covid-19;rage;estrogen

Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't;Review

Stilhano, Roberta Sessa;Costa, Angelica Jardim;Nishino, Michelle Sayuri;Shams, Shahin;Bartolomeo, Cynthia Silva;Breithaupt-Faloppa, Ana Cristina;Silva, Eduardo Alexandre;Ramirez, Ana Lopez;Prado, Carla Maximo;Ureshino, Rodrigo Portes

10.1096/fj.202001394RR

[Title]: SARS-CoV-2 and the possible connection to ERs, ACE2, and RAGE: Focus on susceptibility factors. [Abstract]: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has provoked major stresses on the health-care systems of several countries, and caused the death of more than a quarter of a million people globally, mainly in the elderly population with preexisting pathologies. Previous studies with coronavirus (SARS-CoV) point to gender differences in infection and disease progression with increased susceptibility in male patients, indicating that estrogens may be associated with physiological protection against the coronavirus. Therefore, the objectives of this work are threefold. First, we aim to summarize the SARS-CoV-2 infection pathway and the roles both the virus and patient play in COVID-19 (Coronavirus disease 2019) progression, clinical symptomatology, and mortality. Second, we detail the effect estrogen has on viral infection and host infection response, including its role in both the regulation of key viral receptor expression and the mediation of inflammatory activity. Finally, we describe how ERs (estrogen receptors) and RAGE (receptor for advanced glycation end-products) play a critical role in metabolic pathways, which we envisage could maintain a close interplay with SARS-CoV and COVID-19 mortality rates, despite a current lack of research directly determining how. Taken together, we present the current state of the field regarding SARS-CoV-2 research and illuminate where research is needed to better define the role both estrogen and metabolic comorbidities have in the COVID-19 disease state, which can be key in screening potential therapeutic options as the search for effective treatments continue. [Keywords]: ace2;covid-19;rage;estrogen

ACS Pharmacol Transl Sci

Potential Therapeutic Agents and Associated Bioassay Data for COVID-19 and Related Human Coronavirus Infections.

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has led to several million confirmed cases and hundreds of thousands of deaths worldwide. To support the ongoing research and development of COVID-19 therapeutics, this report provides an overview of protein targets and corresponding potential drug candidates with bioassay and structure-activity relationship data found in the scientific literature and patents for COVID-19 or related virus infections. Highlighted are several sets of small molecules and biologics that act on specific targets, including 3CLpro, PLpro, RdRp, S-protein-ACE2 interaction, helicase/NTPase, TMPRSS2, and furin, which are involved in the viral life cycle or in other aspects of the disease pathophysiology. We hope this report will be valuable to the ongoing drug repurposing efforts and the discovery of new therapeutics with the potential for treating COVID-19.

Journal Article;Review

Zhou, Qiongqiong Angela;Kato-Weinstein, Junko;Li, Yingzhu;Deng, Yi;Granet, Roger;Garner, Linda;Liu, Cynthia;Polshakov, Dmitrii;Gessner, Chris;Watkins, Steven

10.1021/acsptsci.0c00074

[Title]: Potential Therapeutic Agents and Associated Bioassay Data for COVID-19 and Related Human Coronavirus Infections. [Abstract]: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has led to several million confirmed cases and hundreds of thousands of deaths worldwide. To support the ongoing research and development of COVID-19 therapeutics, this report provides an overview of protein targets and corresponding potential drug candidates with bioassay and structure-activity relationship data found in the scientific literature and patents for COVID-19 or related virus infections. Highlighted are several sets of small molecules and biologics that act on specific targets, including 3CLpro, PLpro, RdRp, S-protein-ACE2 interaction, helicase/NTPase, TMPRSS2, and furin, which are involved in the viral life cycle or in other aspects of the disease pathophysiology. We hope this report will be valuable to the ongoing drug repurposing efforts and the discovery of new therapeutics with the potential for treating COVID-19. [Keywords]:

J Orthop

Triaging Spine Surgery and Treatment during the COVID-19 Pandemic.

Objective: To utilize evidence-based medicine to help determine guidelines for spinal surgery during the Covid-19 era. Methods: A literature review was performed of peer-reviewed articles focused on indications for common procedures in spine surgery. Based on these indications, we sub-categorized these procedures into elective, urgent and emergent categories. Case examples provided. Results: Indications for spinal surgery were reviewed based on current literature and categorized. This manuscript presents a decision-making algorithm to help provide a guideline for determining the appropriateness of proceeding with spinal surgery during this COVID-19 time period. Conclusions: Spinal surgery during the COVID-19 pandemic is an intricate challenging decision-making process, involving clinical, sociologic and economic factors.

covid-19;coronavirus;infectious disease;pandemic;spinal surgery;spine

Journal Article;Review

Rizkalla, James M;Hotchkiss, William;Clavenna, Andrew;Dossett, Andrew;Syed, Ishaq Y

10.1016/j.jor.2020.06.015

[Title]: Triaging Spine Surgery and Treatment during the COVID-19 Pandemic. [Abstract]: Objective: To utilize evidence-based medicine to help determine guidelines for spinal surgery during the Covid-19 era. Methods: A literature review was performed of peer-reviewed articles focused on indications for common procedures in spine surgery. Based on these indications, we sub-categorized these procedures into elective, urgent and emergent categories. Case examples provided. Results: Indications for spinal surgery were reviewed based on current literature and categorized. This manuscript presents a decision-making algorithm to help provide a guideline for determining the appropriateness of proceeding with spinal surgery during this COVID-19 time period. Conclusions: Spinal surgery during the COVID-19 pandemic is an intricate challenging decision-making process, involving clinical, sociologic and economic factors. [Keywords]: covid-19;coronavirus;infectious disease;pandemic;spinal surgery;spine

Research (Wash D C)

Combating the Coronavirus Pandemic: Early Detection, Medical Treatment, and a Concerted Effort by the Global Community.

The World Health Organization (WHO) has declared the outbreak of 2019 novel coronavirus, known as 2019-nCoV, a pandemic, as the coronavirus has now infected over 2.6 million people globally and caused more than 185,000 fatalities as of April 23, 2020. Coronavirus disease 2019 (COVID-19) causes a respiratory illness with symptoms such as dry cough, fever, sudden loss of smell, and, in more severe cases, difficulty breathing. To date, there is no specific vaccine or treatment proven effective against this viral disease. Early and accurate diagnosis of COVID-19 is thus critical to curbing its spread and improving health outcomes. Reverse transcription-polymerase chain reaction (RT-PCR) is commonly used to detect the presence of COVID-19. Other techniques, such as recombinase polymerase amplification (RPA), loop-mediated isothermal amplification (LAMP), clustered regularly interspaced short palindromic repeats (CRISPR), and microfluidics, have allowed better disease diagnosis. Here, as part of the effort to expand screening capacity, we review advances and challenges in the rapid detection of COVID-19 by targeting nucleic acids, antigens, or antibodies. We also summarize potential treatments and vaccines against COVID-19 and discuss ongoing clinical trials of interventions to reduce viral progression.

Journal Article;Review

Luo, Zichao;Ang, Melgious Jin Yan;Chan, Siew Yin;Yi, Zhigao;Goh, Yi Yiing;Yan, Shuangqian;Tao, Jun;Liu, Kai;Li, Xiaosong;Zhang, Hongjie;Huang, Wei;Liu, Xiaogang

10.34133/2020/6925296

[Title]: Combating the Coronavirus Pandemic: Early Detection, Medical Treatment, and a Concerted Effort by the Global Community. [Abstract]: The World Health Organization (WHO) has declared the outbreak of 2019 novel coronavirus, known as 2019-nCoV, a pandemic, as the coronavirus has now infected over 2.6 million people globally and caused more than 185,000 fatalities as of April 23, 2020. Coronavirus disease 2019 (COVID-19) causes a respiratory illness with symptoms such as dry cough, fever, sudden loss of smell, and, in more severe cases, difficulty breathing. To date, there is no specific vaccine or treatment proven effective against this viral disease. Early and accurate diagnosis of COVID-19 is thus critical to curbing its spread and improving health outcomes. Reverse transcription-polymerase chain reaction (RT-PCR) is commonly used to detect the presence of COVID-19. Other techniques, such as recombinase polymerase amplification (RPA), loop-mediated isothermal amplification (LAMP), clustered regularly interspaced short palindromic repeats (CRISPR), and microfluidics, have allowed better disease diagnosis. Here, as part of the effort to expand screening capacity, we review advances and challenges in the rapid detection of COVID-19 by targeting nucleic acids, antigens, or antibodies. We also summarize potential treatments and vaccines against COVID-19 and discuss ongoing clinical trials of interventions to reduce viral progression. [Keywords]:

Am J Pathol

Immunopathology of Hyperinflammation in COVID-19.

The rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has resulted in an unprecedented public health crisis worldwide. Recent studies indicate that a hyperinflammatory syndrome induced by SARS-CoV-2 contributes to disease severity and mortality in COVID-19. In this review, an overview of the pathophysiology underlying the hyperinflammatory syndrome in severe COVID-19 is provided. The current evidence suggests that the hyperinflammatory syndrome results from a dysregulated host innate immune response. The gross and microscopic pathologic findings as well as the alterations in the cytokine milieu, macrophages/monocytes, natural killer cells, T cells, and neutrophils in severe COVID-19 are summarized. The data highlighted include the potential therapeutic approaches undergoing investigation to modulate the immune response and abrogate lung injury in severe COVID-19.

Journal Article;Review

Gustine, Joshua N;Jones, Dennis

10.1016/j.ajpath.2020.08.009

[Title]: Immunopathology of Hyperinflammation in COVID-19. [Abstract]: The rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has resulted in an unprecedented public health crisis worldwide. Recent studies indicate that a hyperinflammatory syndrome induced by SARS-CoV-2 contributes to disease severity and mortality in COVID-19. In this review, an overview of the pathophysiology underlying the hyperinflammatory syndrome in severe COVID-19 is provided. The current evidence suggests that the hyperinflammatory syndrome results from a dysregulated host innate immune response. The gross and microscopic pathologic findings as well as the alterations in the cytokine milieu, macrophages/monocytes, natural killer cells, T cells, and neutrophils in severe COVID-19 are summarized. The data highlighted include the potential therapeutic approaches undergoing investigation to modulate the immune response and abrogate lung injury in severe COVID-19. [Keywords]:

BMJ Glob Health

Thinking differently: lessons learned by international public health specialists while supporting the Integrated Disease Surveillance and Response system in Pakistan.

Internationally supported activities to build public health capacity and improve compliance with International Health Regulations (2005) so that countries are better able to 'prevent, protect against, control and provide a public health response to the international spread of disease' have had a positive impact in recent years. However, despite the proliferation of technical guidance, tools and roadmaps, as the recent COVID-19 emergency demonstrates, a significant challenge still remains. The unique and complex environment within countries is increasingly being recognised as a factor which needs greater consideration if system strengthening activities are to be successful.This paper reflects on the learning from and charts out the journey of the authors' in their efforts to support the Pakistan government to improve compliance with International Health Regulations, specifically through strengthening its Integrated Disease Surveillance and Response (IDSR) system.To effect change, public health technical specialists bring their grounded technical and scientific expertise along with their softer public health skills of, among other things, relationship building and multisector working. In the authors' experience, the importance of taking time throughout to build and maintain strong trusted relationships and peer-to-peer support has been the key to the successes experienced. The nature of this relationship and ongoing reflexive dialogue enabled the co-construction of the reality of the background environment, which, in turn, led to more realistic visioning of the desired system for IDSR, and therefore more appropriate bespoke technical support to be given, leading to the design and initial implementation of a country owned system developed with sustainability in mind.

diseases;disorders;health systems;infections;injuries;public health

Journal Article

Wilson, Anne;Cartwright, Christopher

10.1136/bmjgh-2020-003593

[Title]: Thinking differently: lessons learned by international public health specialists while supporting the Integrated Disease Surveillance and Response system in Pakistan. [Abstract]: Internationally supported activities to build public health capacity and improve compliance with International Health Regulations (2005) so that countries are better able to 'prevent, protect against, control and provide a public health response to the international spread of disease' have had a positive impact in recent years. However, despite the proliferation of technical guidance, tools and roadmaps, as the recent COVID-19 emergency demonstrates, a significant challenge still remains. The unique and complex environment within countries is increasingly being recognised as a factor which needs greater consideration if system strengthening activities are to be successful.This paper reflects on the learning from and charts out the journey of the authors' in their efforts to support the Pakistan government to improve compliance with International Health Regulations, specifically through strengthening its Integrated Disease Surveillance and Response (IDSR) system.To effect change, public health technical specialists bring their grounded technical and scientific expertise along with their softer public health skills of, among other things, relationship building and multisector working. In the authors' experience, the importance of taking time throughout to build and maintain strong trusted relationships and peer-to-peer support has been the key to the successes experienced. The nature of this relationship and ongoing reflexive dialogue enabled the co-construction of the reality of the background environment, which, in turn, led to more realistic visioning of the desired system for IDSR, and therefore more appropriate bespoke technical support to be given, leading to the design and initial implementation of a country owned system developed with sustainability in mind. [Keywords]: diseases;disorders;health systems;infections;injuries;public health

Am Fam Physician

Acute Respiratory Distress Syndrome: Diagnosis and Management.

Acute respiratory distress syndrome (ARDS) is noncardiogenic pulmonary edema that manifests as rapidly progressive dyspnea, tachypnea, and hypoxemia. Diagnostic criteria include onset within one week of a known insult or new or worsening respiratory symptoms, profound hypoxemia, bilateral pulmonary opacities on radiography, and inability to explain respiratory failure by cardiac failure or fluid overload. ARDS is thought to occur when a pulmonary or extrapulmonary insult causes the release of inflammatory mediators, promoting inflammatory cell accumulation in the alveoli and microcirculation of the lung. Inflammatory cells damage the vascular endothelium and alveolar epithelium, leading to pulmonary edema, hyaline membrane formation, decreased lung compliance, and decreased gas exchange. Most cases are associated with pneumonia or sepsis. ARDS is responsible for one in 10 admissions to intensive care units and one in four mechanical ventilations. In-hospital mortality for patients with severe ARDS ranges from 46% to 60%. ARDS often must be differentiated from pneumonia and congestive heart failure, which typically has signs of fluid overload. Treatment of ARDS is supportive and includes mechanical ventilation, prophylaxis for stress ulcers and venous thromboembolism, nutritional support, and treatment of the underlying injury. Low tidal volume and high positive end-expiratory pressure improve outcomes. Prone positioning is recommended for some moderate and all severe cases. As patients with ARDS improve and the underlying illness resolves, a spontaneous breathing trial is indicated to assess eligibility for ventilator weaning. Patients who survive ARDS are at risk of diminished functional capacity, mental illness, and decreased quality of life; ongoing care by a primary care physician is beneficial for these patients.

Journal Article;Review

Saguil, Aaron;Fargo, Matthew V

[Title]: Acute Respiratory Distress Syndrome: Diagnosis and Management. [Abstract]: Acute respiratory distress syndrome (ARDS) is noncardiogenic pulmonary edema that manifests as rapidly progressive dyspnea, tachypnea, and hypoxemia. Diagnostic criteria include onset within one week of a known insult or new or worsening respiratory symptoms, profound hypoxemia, bilateral pulmonary opacities on radiography, and inability to explain respiratory failure by cardiac failure or fluid overload. ARDS is thought to occur when a pulmonary or extrapulmonary insult causes the release of inflammatory mediators, promoting inflammatory cell accumulation in the alveoli and microcirculation of the lung. Inflammatory cells damage the vascular endothelium and alveolar epithelium, leading to pulmonary edema, hyaline membrane formation, decreased lung compliance, and decreased gas exchange. Most cases are associated with pneumonia or sepsis. ARDS is responsible for one in 10 admissions to intensive care units and one in four mechanical ventilations. In-hospital mortality for patients with severe ARDS ranges from 46% to 60%. ARDS often must be differentiated from pneumonia and congestive heart failure, which typically has signs of fluid overload. Treatment of ARDS is supportive and includes mechanical ventilation, prophylaxis for stress ulcers and venous thromboembolism, nutritional support, and treatment of the underlying injury. Low tidal volume and high positive end-expiratory pressure improve outcomes. Prone positioning is recommended for some moderate and all severe cases. As patients with ARDS improve and the underlying illness resolves, a spontaneous breathing trial is indicated to assess eligibility for ventilator weaning. Patients who survive ARDS are at risk of diminished functional capacity, mental illness, and decreased quality of life; ongoing care by a primary care physician is beneficial for these patients. [Keywords]:

Vaccine

Ensemble forecast modeling for the design of COVID-19 vaccine efficacy trials.

To rapidly evaluate the safety and efficacy of COVID-19 vaccine candidates, prioritizing vaccine trial sites in areas with high expected disease incidence can speed endpoint accrual and shorten trial duration. Mathematical and statistical forecast models can inform the process of site selection, integrating available data sources and facilitating comparisons across locations. We recommend the use of ensemble forecast modeling - combining projections from independent modeling groups - to guide investigators identifying suitable sites for COVID-19 vaccine efficacy trials. We describe an appropriate structure for this process, including minimum requirements, suggested output, and a user-friendly tool for displaying results. Importantly, we advise that this process be repeated regularly throughout the trial, to inform decisions about enrolling new participants at existing sites with waning incidence versus adding entirely new sites. These types of data-driven models can support the implementation of flexible efficacy trials tailored to the outbreak setting.

efficacy trial;ensemble modeling;forecast model;trial planning

Journal Article;Research Support, N.I.H., Extramural

Dean, Natalie E;Pastore Y Piontti, Ana;Madewell, Zachary J;Cummings, Derek A T;Hitchings, Matthew D T;Joshi, Keya;Kahn, Rebecca;Vespignani, Alessandro;Halloran, M Elizabeth;Longini, Ira M Jr

10.1016/j.vaccine.2020.09.031

[Title]: Ensemble forecast modeling for the design of COVID-19 vaccine efficacy trials. [Abstract]: To rapidly evaluate the safety and efficacy of COVID-19 vaccine candidates, prioritizing vaccine trial sites in areas with high expected disease incidence can speed endpoint accrual and shorten trial duration. Mathematical and statistical forecast models can inform the process of site selection, integrating available data sources and facilitating comparisons across locations. We recommend the use of ensemble forecast modeling - combining projections from independent modeling groups - to guide investigators identifying suitable sites for COVID-19 vaccine efficacy trials. We describe an appropriate structure for this process, including minimum requirements, suggested output, and a user-friendly tool for displaying results. Importantly, we advise that this process be repeated regularly throughout the trial, to inform decisions about enrolling new participants at existing sites with waning incidence versus adding entirely new sites. These types of data-driven models can support the implementation of flexible efficacy trials tailored to the outbreak setting. [Keywords]: efficacy trial;ensemble modeling;forecast model;trial planning

Mayo Clin Proc Innov Qual Outcomes

A Narrative Review of Emerging Therapeutics for COVID-19.

The novel severe acute respiratory syndrome coronavirus 2, the causal agent of coronavirus disease 2019 (COVID-19), quickly spread around the world, resulting in the most aggressive pandemic experienced in more than 100 years. Research on targeted therapies and vaccines has been initiated on an unprecedented scale and speed but will take months and even years to come to fruition. Meanwhile, the efficacy of emerging therapeutics for use in treating COVID-19 is feverishly being investigated to identify the best available treatment options for dealing with the current wave of disease. This review of publications with a "treatment" tag through June 29, 2020 in the National Library of Medicine's LitCovid literature hub, provides frontline clinicians with a pragmatic summary of the current state of the rapidly evolving evidence supporting emerging candidate therapeutics for COVID-19. Two main categories of pharmaceutical therapeutics are showing promise: those with antiviral activity directly addressing infection and those that counteract the inflammatory cytokine storm induced by severe disease. Preliminary results suggest that other approaches such as convalescent plasma therapy and lung radiation therapy may have some efficacy. The current clinical evidence for potential treatments is preliminary-often small retrospective series or early results of randomized trials-and the science is evolving rapidly. The long-term results from large, well-designed randomized controlled trials will provide definitive evidence for therapeutic effectiveness and are likely months away. The trial landscape for promising therapies is described.

covid-19, coronavirus disease 2019;cpt, convalescent plasma therapy;cq, chloroquine;ec50, half-maximal effective concentration;hcq, hydroxychloroquine;icu, intensive care unit;il-6, interleukin 6;jak, janus kinase;lpv/rtv, lopinavir/ritonavir;mers, middle east respiratory syndrome;rct, randomized controlled trial;sars, severe acute respiratory syndrome;sars-cov-2, severe acute respiratory syndrome coronavirus 2;who, world health organization

Journal Article;Review

Willis, Van C;Arriaga, Yull;Weeraratne, Dilhan;Reyes, Fredy;Jackson, Gretchen P

10.1016/j.mayocpiqo.2020.07.004

[Title]: A Narrative Review of Emerging Therapeutics for COVID-19. [Abstract]: The novel severe acute respiratory syndrome coronavirus 2, the causal agent of coronavirus disease 2019 (COVID-19), quickly spread around the world, resulting in the most aggressive pandemic experienced in more than 100 years. Research on targeted therapies and vaccines has been initiated on an unprecedented scale and speed but will take months and even years to come to fruition. Meanwhile, the efficacy of emerging therapeutics for use in treating COVID-19 is feverishly being investigated to identify the best available treatment options for dealing with the current wave of disease. This review of publications with a "treatment" tag through June 29, 2020 in the National Library of Medicine's LitCovid literature hub, provides frontline clinicians with a pragmatic summary of the current state of the rapidly evolving evidence supporting emerging candidate therapeutics for COVID-19. Two main categories of pharmaceutical therapeutics are showing promise: those with antiviral activity directly addressing infection and those that counteract the inflammatory cytokine storm induced by severe disease. Preliminary results suggest that other approaches such as convalescent plasma therapy and lung radiation therapy may have some efficacy. The current clinical evidence for potential treatments is preliminary-often small retrospective series or early results of randomized trials-and the science is evolving rapidly. The long-term results from large, well-designed randomized controlled trials will provide definitive evidence for therapeutic effectiveness and are likely months away. The trial landscape for promising therapies is described. [Keywords]: covid-19, coronavirus disease 2019;cpt, convalescent plasma therapy;cq, chloroquine;ec50, half-maximal effective concentration;hcq, hydroxychloroquine;icu, intensive care unit;il-6, interleukin 6;jak, janus kinase;lpv/rtv, lopinavir/ritonavir;mers, middle east respiratory syndrome;rct, randomized controlled trial;sars, severe acute respiratory syndrome;sars-cov-2, severe acute respiratory syndrome coronavirus 2;who, world health organization

Thorac Cancer

Surgical care of thoracic malignancies during the COVID-19 pandemic in Mexico: An expert consensus guideline from the Sociedad Mexicana de Oncologia (SMeO) and the Sociedad Mexicana de Cirujanos Toracicos Generales (SMCTG).

To date, the impact, timeline and duration of COVID-19 pandemic remains unknown and more than ever it is necessary to provide safe pathways for cancer patients. Multiple triage systems for nonemergent surgical procedures have been published, but potentially curative cancer procedures are essential surgery rather than elective surgery. In the present and future scenario of our country, thoracic oncology teams may have the difficult decision of weighing the utility of surgical intervention against the risk for inadvertent COVID-19 exposure for patients and medical staff. In consequence, traditional pathways of surgical care must be adjusted to reduce the risk of infection and the use of resources. It is recommended that all thoracic cancer patients should be offered treatment according to the accepted standard of care until shortage of services require a progressive reduction in surgical cases. Here, we present a consensus of recommendations discussed by a multidisciplinary panel of experts on thoracic oncology and based on the best available evidence, and hope it will provide a modifiable framework of guidance for local strategy planners in thoracic cancer care services in Mexico. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This article provides recommendations to guarantee the continuity of surgical care for thoracic oncology cases during COVID-19 pandemic, whilst maintaining the safety of patients and medical staff. WHAT THIS STUDY ADDS: This guideline is the result of an expert consensus on thoracic surgical oncology with recommendations adapted to medical, economic and social realities of Mexico.

covid-19;lung cancer;surgical oncology;thoracic oncology;thoracic surgery

Journal Article;Research Support, Non-U.S. Gov't

Corona-Cruz, Jose;Alba, Enrique Guzman-de;Iniguez-Garcia, Marco;Lopez-Saucedo, Raul;Olivares-Torres, Carlos;Rodriguez-Cid, Jeronimo;Salazar-Otaola, Gustavo;Martinez-Said, Hector;Flores, Raja M;Arrieta, Oscar

10.1111/1759-7714.13546

[Title]: Surgical care of thoracic malignancies during the COVID-19 pandemic in Mexico: An expert consensus guideline from the Sociedad Mexicana de Oncologia (SMeO) and the Sociedad Mexicana de Cirujanos Toracicos Generales (SMCTG). [Abstract]: To date, the impact, timeline and duration of COVID-19 pandemic remains unknown and more than ever it is necessary to provide safe pathways for cancer patients. Multiple triage systems for nonemergent surgical procedures have been published, but potentially curative cancer procedures are essential surgery rather than elective surgery. In the present and future scenario of our country, thoracic oncology teams may have the difficult decision of weighing the utility of surgical intervention against the risk for inadvertent COVID-19 exposure for patients and medical staff. In consequence, traditional pathways of surgical care must be adjusted to reduce the risk of infection and the use of resources. It is recommended that all thoracic cancer patients should be offered treatment according to the accepted standard of care until shortage of services require a progressive reduction in surgical cases. Here, we present a consensus of recommendations discussed by a multidisciplinary panel of experts on thoracic oncology and based on the best available evidence, and hope it will provide a modifiable framework of guidance for local strategy planners in thoracic cancer care services in Mexico. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This article provides recommendations to guarantee the continuity of surgical care for thoracic oncology cases during COVID-19 pandemic, whilst maintaining the safety of patients and medical staff. WHAT THIS STUDY ADDS: This guideline is the result of an expert consensus on thoracic surgical oncology with recommendations adapted to medical, economic and social realities of Mexico. [Keywords]: covid-19;lung cancer;surgical oncology;thoracic oncology;thoracic surgery

Int J Environ Res Public Health

A Call for Action to Safely Deliver Oral Health Care during and Post COVID-19 Pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak started just a couple of months ago and it grew rapidly causing several deaths and morbidities. The mechanism behind the transmission of the virus is still not completely understood despite a multitude of new specific manuscripts being published daily. This article highlights the oral cavity as a possible viral transmission route into the body via the Angiotensin converting enzyme 2 receptor. It also provides guidelines for routine protective measures in the dental office while delivering oral health care.

angiotensin ii;coronavirus;mouth;pandemics;professional practice;quarantine

Journal Article

Farronato, Marco;Tadakamadla, Santosh K;Ali Quadri, Mir Faeq;Acharya, Shashidhar;Tadakamadla, Jyothi;Love, Robert M;Jamal, Mohamed;Mulder, Riaan;Maspero, Cinzia;Farronato, Davide;Ivanov, Alexander;Neefs, Dirk;Cagetti, Maria Grazia;de Vito, Danila;Gupta, Rishi J;Connelly, Stephen Thaddeus;Tartaglia, Gianluca M

10.3390/ijerph17186704

[Title]: A Call for Action to Safely Deliver Oral Health Care during and Post COVID-19 Pandemic. [Abstract]: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak started just a couple of months ago and it grew rapidly causing several deaths and morbidities. The mechanism behind the transmission of the virus is still not completely understood despite a multitude of new specific manuscripts being published daily. This article highlights the oral cavity as a possible viral transmission route into the body via the Angiotensin converting enzyme 2 receptor. It also provides guidelines for routine protective measures in the dental office while delivering oral health care. [Keywords]: angiotensin ii;coronavirus;mouth;pandemics;professional practice;quarantine

Int J Health Plann Manage

Coronavirus Disease 2019 (COVID-19): Potential implications for weak health systems and conflict zones in the Middle East and North Africa region.

This short communication recognizes the underbelly of weak and conflict-prone health systems in the Middle East and North Africa region in the wake of COVID-19 pandemic. The communication highlights how the lack of basic resources, absence of a well-functioning health system and the dearth of well-coordinated communication channels, can bode ill for the successful fight against COVID-19. The article elucidates COVID-19 potential health, social, and economic implications for such countries. The communication cautions that if COVID-19 is left to incubate and makes a home in weak systems, it will have a much better chance of mutating and coming back to infect many people globally. The communication calls on the international institutions in collaboration with developed nations to be prepared to probe up health systems in weak and conflict-prone health systems with much-needed resources in order to nip COVID-19 in the bud.

covid-19;covid-19 implications;who mena region;weak health systems;conflict zones

Journal Article

Da'ar, Omar B;Haji, Mohamed;Jradi, Hoda

10.1002/hpm.2982

[Title]: Coronavirus Disease 2019 (COVID-19): Potential implications for weak health systems and conflict zones in the Middle East and North Africa region. [Abstract]: This short communication recognizes the underbelly of weak and conflict-prone health systems in the Middle East and North Africa region in the wake of COVID-19 pandemic. The communication highlights how the lack of basic resources, absence of a well-functioning health system and the dearth of well-coordinated communication channels, can bode ill for the successful fight against COVID-19. The article elucidates COVID-19 potential health, social, and economic implications for such countries. The communication cautions that if COVID-19 is left to incubate and makes a home in weak systems, it will have a much better chance of mutating and coming back to infect many people globally. The communication calls on the international institutions in collaboration with developed nations to be prepared to probe up health systems in weak and conflict-prone health systems with much-needed resources in order to nip COVID-19 in the bud. [Keywords]: covid-19;covid-19 implications;who mena region;weak health systems;conflict zones

J Med Internet Res

App-Based Tracking of Self-Reported COVID-19 Symptoms: Analysis of Questionnaire Data.

BACKGROUND: COVID-19 is an infectious disease characterized by various clinical presentations. Knowledge of possible symptoms and their distribution allows for the early identification of infected patients. OBJECTIVE: To determine the distribution pattern of COVID-19 symptoms as well as possible unreported symptoms, we created an app-based self-reporting tool. METHODS: The COVID-19 Symptom Tracker is an app-based daily self-reporting tool. Between April 8 and May 15, 2020, a total of 22,327 individuals installed this app on their mobile device. An initial questionnaire asked for demographic information (age, gender, postal code) and past medical history comprising relevant chronic diseases. The participants were reminded daily to report whether they were experiencing any symptoms and if they had been tested for SARS-CoV-2 infection. Participants who sought health care services were asked additional questions regarding diagnostics and treatment. Participation was open to all adults (>/=18 years). The study was completely anonymous. RESULTS: In total, 11,829 (52.98%) participants completed the symptom questionnaire at least once. Of these, 291 (2.46%) participants stated that they had undergone an RT-PCR (reverse transcription-polymerase chain reaction) test for SARS-CoV-2; 65 (0.55%) reported a positive test result and 226 (1.91%) a negative one. The mean number of reported symptoms among untested participants was 0.81 (SD 1.85). Participants with a positive test result had, on average, 5.63 symptoms (SD 2.82). The most significant risk factors were diabetes (odds ratio [OR] 8.95, 95% CI 3.30-22.37) and chronic heart disease (OR 2.85, 95% CI 1.43-5.69). We identified chills, fever, loss of smell, nausea and vomiting, and shortness of breath as the top five strongest predictors for a COVID-19 infection. The odds ratio for loss of smell was 3.13 (95% CI 1.76-5.58). Nausea and vomiting (OR 2.84, 95% CI 1.61-5.00) had been reported as an uncommon symptom previously; however, our data suggest a significant predictive value. CONCLUSIONS: Self-reported symptom tracking helps to identify novel symptoms of COVID-19 and to estimate the predictive value of certain symptoms. This aids in the development of reliable screening tools. Clinical screening with a high pretest probability allows for the rapid identification of infections and the cost-effective use of testing resources. Based on our results, we suggest that loss of smell and taste be considered cardinal symptoms; we also stress that diabetes is a risk factor for a highly symptomatic course of COVID-19 infection.

covid-19;app;digital tool;distribution;screening;self-reporting;surveillance;symptom;tracking

Journal Article;Research Support, Non-U.S. Gov't

Zens, Martin;Brammertz, Arne;Herpich, Juliane;Sudkamp, Norbert;Hinterseer, Martin

10.2196/21956

[Title]: App-Based Tracking of Self-Reported COVID-19 Symptoms: Analysis of Questionnaire Data. [Abstract]: BACKGROUND: COVID-19 is an infectious disease characterized by various clinical presentations. Knowledge of possible symptoms and their distribution allows for the early identification of infected patients. OBJECTIVE: To determine the distribution pattern of COVID-19 symptoms as well as possible unreported symptoms, we created an app-based self-reporting tool. METHODS: The COVID-19 Symptom Tracker is an app-based daily self-reporting tool. Between April 8 and May 15, 2020, a total of 22,327 individuals installed this app on their mobile device. An initial questionnaire asked for demographic information (age, gender, postal code) and past medical history comprising relevant chronic diseases. The participants were reminded daily to report whether they were experiencing any symptoms and if they had been tested for SARS-CoV-2 infection. Participants who sought health care services were asked additional questions regarding diagnostics and treatment. Participation was open to all adults (>/=18 years). The study was completely anonymous. RESULTS: In total, 11,829 (52.98%) participants completed the symptom questionnaire at least once. Of these, 291 (2.46%) participants stated that they had undergone an RT-PCR (reverse transcription-polymerase chain reaction) test for SARS-CoV-2; 65 (0.55%) reported a positive test result and 226 (1.91%) a negative one. The mean number of reported symptoms among untested participants was 0.81 (SD 1.85). Participants with a positive test result had, on average, 5.63 symptoms (SD 2.82). The most significant risk factors were diabetes (odds ratio [OR] 8.95, 95% CI 3.30-22.37) and chronic heart disease (OR 2.85, 95% CI 1.43-5.69). We identified chills, fever, loss of smell, nausea and vomiting, and shortness of breath as the top five strongest predictors for a COVID-19 infection. The odds ratio for loss of smell was 3.13 (95% CI 1.76-5.58). Nausea and vomiting (OR 2.84, 95% CI 1.61-5.00) had been reported as an uncommon symptom previously; however, our data suggest a significant predictive value. CONCLUSIONS: Self-reported symptom tracking helps to identify novel symptoms of COVID-19 and to estimate the predictive value of certain symptoms. This aids in the development of reliable screening tools. Clinical screening with a high pretest probability allows for the rapid identification of infections and the cost-effective use of testing resources. Based on our results, we suggest that loss of smell and taste be considered cardinal symptoms; we also stress that diabetes is a risk factor for a highly symptomatic course of COVID-19 infection. [Keywords]: covid-19;app;digital tool;distribution;screening;self-reporting;surveillance;symptom;tracking

Med Hypotheses

N-acetycysteine: A potential therapeutic agent in COVID-19 infection.

COVID-19 is an overwhelming pandemic which has shattered the whole world. Lung injury being the main clinical manifestation, it is likely to cause COPD (chronic obstructive pulmonary disease) and ARDS (acute respiratory distress syndrome). The possible cause behind this might be redox imbalance due to viral infection. Elevation in Glutathione (GSH) levels by administration of its promolecule might be effective. N-acetylcysteine is one such drug with potency to scavenge Reactive Oxygen Species, least side effects, and an effective precursor of glutathione. Consequently we hypothesize that N-acetylcysteine along with the conventional treatment may be treated as a potential therapeutic solution in cases of COVID-19 patients.

covid-19;glutathione;n-acetylcysteine;oxidative stress

Letter

Jaiswal, N;Bhatnagar, M;Shah, H

10.1016/j.mehy.2020.110133

[Title]: N-acetycysteine: A potential therapeutic agent in COVID-19 infection. [Abstract]: COVID-19 is an overwhelming pandemic which has shattered the whole world. Lung injury being the main clinical manifestation, it is likely to cause COPD (chronic obstructive pulmonary disease) and ARDS (acute respiratory distress syndrome). The possible cause behind this might be redox imbalance due to viral infection. Elevation in Glutathione (GSH) levels by administration of its promolecule might be effective. N-acetylcysteine is one such drug with potency to scavenge Reactive Oxygen Species, least side effects, and an effective precursor of glutathione. Consequently we hypothesize that N-acetylcysteine along with the conventional treatment may be treated as a potential therapeutic solution in cases of COVID-19 patients. [Keywords]: covid-19;glutathione;n-acetylcysteine;oxidative stress

Pathogens

Cellular Metabolic Profiling of CrFK Cells Infected with Feline Infectious Peritonitis Virus Using Phenotype Microarrays.

Feline infectious peritonitis (FIP) is a fatal feline immune-mediated disease caused by feline infectious peritonitis virus (FIPV). Little is known about the biological pathways associated in FIP pathogenesis. This is the first study aiming to determine the phenotypic characteristics on the cellular level in relation to specific metabolic pathways of importance to FIP pathogenesis. METHODS: The internalization of type II FIPV WSU 79-1146 in Crandell-Rees Feline Kidney (CrFK) cells was visualized using a fluorescence microscope, and optimization prior to phenotype microarray (PM) study was performed. Then, four types of Biolog Phenotype MicroArray plates (PM-M1 to PM-M4) precoated with different carbon and nitrogen sources were used to determine the metabolic profiles in FIPV-infected cells. RESULTS: The utilization of palatinose was significantly low in FIPV-infected cells; however, there were significant increases in utilizing melibionic acid, L-glutamine, L-glutamic acid and alanyl-glutamine (Ala-Gln) compared to non-infected cells. CONCLUSION: This study has provided the first insights into the metabolic profiling of a feline coronavirus infection in vitro using PMs and deduced that glutamine metabolism is one of the essential metabolic pathways for FIPV infection and replication. Further studies are necessary to develop strategies to target the glutamine metabolic pathway in FIPV infection.

crfk cells;cellular metabolism;feline infectious peritonitis virus;glutamine;metabolic profiling;phenotype microarray

Journal Article

Ng, Shing Wei;Selvarajah, Gayathri Thevi;Cheah, Yoke Kqueen;Mustaffa Kamal, Farina;Omar, Abdul Rahman

10.3390/pathogens9050412

[Title]: Cellular Metabolic Profiling of CrFK Cells Infected with Feline Infectious Peritonitis Virus Using Phenotype Microarrays. [Abstract]: Feline infectious peritonitis (FIP) is a fatal feline immune-mediated disease caused by feline infectious peritonitis virus (FIPV). Little is known about the biological pathways associated in FIP pathogenesis. This is the first study aiming to determine the phenotypic characteristics on the cellular level in relation to specific metabolic pathways of importance to FIP pathogenesis. METHODS: The internalization of type II FIPV WSU 79-1146 in Crandell-Rees Feline Kidney (CrFK) cells was visualized using a fluorescence microscope, and optimization prior to phenotype microarray (PM) study was performed. Then, four types of Biolog Phenotype MicroArray plates (PM-M1 to PM-M4) precoated with different carbon and nitrogen sources were used to determine the metabolic profiles in FIPV-infected cells. RESULTS: The utilization of palatinose was significantly low in FIPV-infected cells; however, there were significant increases in utilizing melibionic acid, L-glutamine, L-glutamic acid and alanyl-glutamine (Ala-Gln) compared to non-infected cells. CONCLUSION: This study has provided the first insights into the metabolic profiling of a feline coronavirus infection in vitro using PMs and deduced that glutamine metabolism is one of the essential metabolic pathways for FIPV infection and replication. Further studies are necessary to develop strategies to target the glutamine metabolic pathway in FIPV infection. [Keywords]: crfk cells;cellular metabolism;feline infectious peritonitis virus;glutamine;metabolic profiling;phenotype microarray

J Pediatr Surg

Allocation of resources and development of guidelines for extracorporeal membrane oxygenation (ECMO): Experience from a pediatric center in the epicenter of the COVID-19 pandemic.

The rapid spread of coronavirus disease 2019 (COVID-19) has exceeded the standard capacity of many hospital systems and led to an unprecedented scarcity of resources, including the already limited resource of extracorporeal membrane oxygenation (ECMO). With the large amount of critically ill patients and the highly contagious nature of the virus, significant consideration of ECMO candidacy is crucial for both appropriate allocation of resources as well as ensuring protection of health care personnel. As a leading pediatric ECMO program in the epicenter of the pandemic, we established new protocols and guidelines in order to continue caring for our pediatric patients while accepting adult patients to lessen the burden of our hospital system which was above capacity. This article describes our changes in consultation, cannulation, and daily care of COVID-19 positive patients requiring ECMO as well as discusses strategies for ensuring safety of our ECMO healthcare personnel and optimal allocation of resources. LEVEL OF EVIDENCE: Level V.

acute respiratory distress syndrome (ards);covid-19;extracorporeal membrane oxygenation (ecmo);pandemic;sars-cov-2

Journal Article;Review

Gerall, Claire;Cheung, Eva W;Klein-Cloud, Rafael;Kreines, Erica;Brewer, Michael;Middlesworth, William

10.1016/j.jpedsurg.2020.08.015

[Title]: Allocation of resources and development of guidelines for extracorporeal membrane oxygenation (ECMO): Experience from a pediatric center in the epicenter of the COVID-19 pandemic. [Abstract]: The rapid spread of coronavirus disease 2019 (COVID-19) has exceeded the standard capacity of many hospital systems and led to an unprecedented scarcity of resources, including the already limited resource of extracorporeal membrane oxygenation (ECMO). With the large amount of critically ill patients and the highly contagious nature of the virus, significant consideration of ECMO candidacy is crucial for both appropriate allocation of resources as well as ensuring protection of health care personnel. As a leading pediatric ECMO program in the epicenter of the pandemic, we established new protocols and guidelines in order to continue caring for our pediatric patients while accepting adult patients to lessen the burden of our hospital system which was above capacity. This article describes our changes in consultation, cannulation, and daily care of COVID-19 positive patients requiring ECMO as well as discusses strategies for ensuring safety of our ECMO healthcare personnel and optimal allocation of resources. LEVEL OF EVIDENCE: Level V. [Keywords]: acute respiratory distress syndrome (ards);covid-19;extracorporeal membrane oxygenation (ecmo);pandemic;sars-cov-2

Ned Tijdschr Geneeskd

[Hydroxychloroquine and chloroquine for COVID-19: no evidence of effectiveness].

On 3 March 2020, the document 'Drug treatment options for patients with COVID-19 (infections with SARS-CoV-2)' was published on the website of the Dutch Working Party on Antibiotic Policy (StichtingWerkgroepAntibioticabeleid, SWAB). Based on a 7-step analysis of the literature, hydroxychloroquine (HCQ) and chloroquine (CQ) were initially included in the SWAB document as possible drug treatments for hospitalised adult COVID-19 patients. However, recent weeks have seen the publication of the results of various studies into the effectiveness of treatment with HCQ and CQ in patients with COVID-19. On the basis of these results, we conclude that there is insufficient evidence to consider HCQ and CQ as meaningful treatment options in patients with COVID-19. Clinically relevant QTc prolongation occurs in at least 1 in 10 COVID-19 patients treated with HCQ or HQ.

Journal Article

Vollaard, A;Gieling, E M;van der Linden, P D;Sinha, B;de Boer, M G J

[Title]: [Hydroxychloroquine and chloroquine for COVID-19: no evidence of effectiveness]. [Abstract]: On 3 March 2020, the document 'Drug treatment options for patients with COVID-19 (infections with SARS-CoV-2)' was published on the website of the Dutch Working Party on Antibiotic Policy (StichtingWerkgroepAntibioticabeleid, SWAB). Based on a 7-step analysis of the literature, hydroxychloroquine (HCQ) and chloroquine (CQ) were initially included in the SWAB document as possible drug treatments for hospitalised adult COVID-19 patients. However, recent weeks have seen the publication of the results of various studies into the effectiveness of treatment with HCQ and CQ in patients with COVID-19. On the basis of these results, we conclude that there is insufficient evidence to consider HCQ and CQ as meaningful treatment options in patients with COVID-19. Clinically relevant QTc prolongation occurs in at least 1 in 10 COVID-19 patients treated with HCQ or HQ. [Keywords]:

Rev Recent Clin Trials

COVID-19 and Pneumolysis Simulating Extreme High-altitude Exposure with Altered Oxygen Transport Physiology; Multiple Diseases, and Scarce Need of Ventilators: Andean Condor's-eye-view.

BACKGROUND: Critical hypoxia in this COVID-19 pandemic results in high mortality and economic loss worldwide. Initially, this disease' pathophysiology was poorly understood and interpreted as a SARS (Severe Acute Respiratory Syndrome) pneumonia. The severe atypical lung CAT scan images alerted all countries, including the poorest, to purchase lacking sophisticated ventilators. However, 88% of the patients on ventilators lost their lives. It was suggested that COVID-19 could be similar to a High-Altitude Pulmonary Edema (HAPE). New observations and pathological findings are gradually clarifying the disease. METHODS: As high-altitude medicine and hypoxia physiology specialists from the highlands, we perform a perspective analysis of hypoxic diseases treated at high altitude and compare them to Covid-19. Oxygen transport physiology, SARSCov-2 characteristics, and its transmission, lung imaging in COVID-19, and HAPE, as well as the causes of clinical signs and symptoms, are discussed. RESULTS: High-altitude oxygen transport physiology has been systematically ignored. COVID-19 signs and symptoms indicate a progressive and irreversible failure in the oxygen transport system, secondary to pneumolysis produced by SARS-Cov-2's alveolar-capillary membrane "attack". HAPE's pulmonary compromise is treatable and reversible. COVID-19 is associated with several diseases, with different individual outcomes, in different countries, and at different altitudes.

epo;hape;open circuit earth space suits.;polyerythrocythemia;sars-cov-2;tolerance to hypoxia

Comparative Study;Journal Article;Review

Zubieta-Calleja, Gustavo R;Zubieta-DeUrioste, Natalia;Venkatesh, Thuppil;Das, Kusal;Soliz, Jorge

10.2174/1574887115666200925141108

[Title]: COVID-19 and Pneumolysis Simulating Extreme High-altitude Exposure with Altered Oxygen Transport Physiology; Multiple Diseases, and Scarce Need of Ventilators: Andean Condor's-eye-view. [Abstract]: BACKGROUND: Critical hypoxia in this COVID-19 pandemic results in high mortality and economic loss worldwide. Initially, this disease' pathophysiology was poorly understood and interpreted as a SARS (Severe Acute Respiratory Syndrome) pneumonia. The severe atypical lung CAT scan images alerted all countries, including the poorest, to purchase lacking sophisticated ventilators. However, 88% of the patients on ventilators lost their lives. It was suggested that COVID-19 could be similar to a High-Altitude Pulmonary Edema (HAPE). New observations and pathological findings are gradually clarifying the disease. METHODS: As high-altitude medicine and hypoxia physiology specialists from the highlands, we perform a perspective analysis of hypoxic diseases treated at high altitude and compare them to Covid-19. Oxygen transport physiology, SARSCov-2 characteristics, and its transmission, lung imaging in COVID-19, and HAPE, as well as the causes of clinical signs and symptoms, are discussed. RESULTS: High-altitude oxygen transport physiology has been systematically ignored. COVID-19 signs and symptoms indicate a progressive and irreversible failure in the oxygen transport system, secondary to pneumolysis produced by SARS-Cov-2's alveolar-capillary membrane "attack". HAPE's pulmonary compromise is treatable and reversible. COVID-19 is associated with several diseases, with different individual outcomes, in different countries, and at different altitudes. [Keywords]: epo;hape;open circuit earth space suits.;polyerythrocythemia;sars-cov-2;tolerance to hypoxia

Aliment Pharmacol Ther

Systematic review with meta-analysis: SARS-CoV-2 stool testing and the potential for faecal-oral transmission.

BACKGROUND: Since the start of the COVID-19 pandemic, there have been many scientific reports regarding gastrointestinal manifestations. Several reports indicate the possibility of viral shedding via faeces and the possibility of faecal-oral transmission. AIMS: To critically assess the clinical relevance of testing stool samples and anal swabs and provide an overview of the potential faecal-oral transmission of SARS-CoV-2. METHODS: A systematic literature search with MeSH terms was performed, scrutinising the Embase database, Google scholar, MEDLINE database through PubMed and The Cochrane Library, including articles from December 2019 until July 7 2020. Data were subsequently analysed with descriptive statistics. RESULTS: Ninety-five studies were included in the qualitative analysis. 934/2149 (43%) patients tested positive for SARS-CoV-2 in stool samples or anal swabs, with positive test results up to 70 days after symptom onset. A meta-analysis executed with studies of at least 10 patients revealed a pooled positive proportion of 51.8% (95% CI 43.8 - 59.7%). Positive faecal samples of 282/443 patients (64%) remained positive for SARS-CoV-2 for a mean of 12.5 days, up to 33 days maximum, after respiratory samples became negative for SARS-CoV-2. Viable SARS-CoV-2 was found in 6/17 (35%) patients in whom this was specifically investigated. CONCLUSIONS: Viral shedding of SARS-CoV-2 in stool samples occurs in a substantial proportion of patients, making faecal-oral transmission plausible. Furthermore, detection in stool samples or anal swabs can persist long after negative respiratory testing. Therefore, stool sample or anal swab testing should be (re)considered in relation to decisions for isolating or discharging a patient.

covid-19;coronavirus;sars-cov-2;anal swab;faecal-oral transmission;stool test

Journal Article;Meta-Analysis;Systematic Review

van Doorn, Amarylle S;Meijer, Berrie;Frampton, Chris M A;Barclay, Murray L;de Boer, Nanne K H

10.1111/apt.16036

[Title]: Systematic review with meta-analysis: SARS-CoV-2 stool testing and the potential for faecal-oral transmission. [Abstract]: BACKGROUND: Since the start of the COVID-19 pandemic, there have been many scientific reports regarding gastrointestinal manifestations. Several reports indicate the possibility of viral shedding via faeces and the possibility of faecal-oral transmission. AIMS: To critically assess the clinical relevance of testing stool samples and anal swabs and provide an overview of the potential faecal-oral transmission of SARS-CoV-2. METHODS: A systematic literature search with MeSH terms was performed, scrutinising the Embase database, Google scholar, MEDLINE database through PubMed and The Cochrane Library, including articles from December 2019 until July 7 2020. Data were subsequently analysed with descriptive statistics. RESULTS: Ninety-five studies were included in the qualitative analysis. 934/2149 (43%) patients tested positive for SARS-CoV-2 in stool samples or anal swabs, with positive test results up to 70 days after symptom onset. A meta-analysis executed with studies of at least 10 patients revealed a pooled positive proportion of 51.8% (95% CI 43.8 - 59.7%). Positive faecal samples of 282/443 patients (64%) remained positive for SARS-CoV-2 for a mean of 12.5 days, up to 33 days maximum, after respiratory samples became negative for SARS-CoV-2. Viable SARS-CoV-2 was found in 6/17 (35%) patients in whom this was specifically investigated. CONCLUSIONS: Viral shedding of SARS-CoV-2 in stool samples occurs in a substantial proportion of patients, making faecal-oral transmission plausible. Furthermore, detection in stool samples or anal swabs can persist long after negative respiratory testing. Therefore, stool sample or anal swab testing should be (re)considered in relation to decisions for isolating or discharging a patient. [Keywords]: covid-19;coronavirus;sars-cov-2;anal swab;faecal-oral transmission;stool test

Cureus

Searching an Effective Therapy for the Coronavirus Pandemic: Do We See Light at the End of the Tunnel?

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). First reported at the end of December 2019 as a cause for clusters of pneumonia cases in Wuhan city in China, the rapid spread of this condition was declared a pandemic on March 11, 2020, by the World Health Organization (WHO). Apart from the mortality and morbidity associated with COVID-19, the massive social and financial havoc inflicted by this pandemic has left the entire world pondering if medical science can innovate and curtail the ongoing damage due to SARS-CoV-2. Recent findings of an open-label study that investigated the use of hydroxychloroquine and azithromycin in COVID-19 patients in Marseille, France, has garnered some optimism in scientific quarters and the general public alike in terms of finding a treatment regimen to control the rampant rise of COVID-19. We will discuss the potential off-label therapy and studies as it pertains to COVID-19.

azithromycin;coronavirus disease;hydroxychloroquine;sars-cov-2 (severe acute respiratory syndrome coronavirus -2)

Journal Article;Review

Sharma, Munish;Surani, Salim

10.7759/cureus.7415

[Title]: Searching an Effective Therapy for the Coronavirus Pandemic: Do We See Light at the End of the Tunnel? [Abstract]: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). First reported at the end of December 2019 as a cause for clusters of pneumonia cases in Wuhan city in China, the rapid spread of this condition was declared a pandemic on March 11, 2020, by the World Health Organization (WHO). Apart from the mortality and morbidity associated with COVID-19, the massive social and financial havoc inflicted by this pandemic has left the entire world pondering if medical science can innovate and curtail the ongoing damage due to SARS-CoV-2. Recent findings of an open-label study that investigated the use of hydroxychloroquine and azithromycin in COVID-19 patients in Marseille, France, has garnered some optimism in scientific quarters and the general public alike in terms of finding a treatment regimen to control the rampant rise of COVID-19. We will discuss the potential off-label therapy and studies as it pertains to COVID-19. [Keywords]: azithromycin;coronavirus disease;hydroxychloroquine;sars-cov-2 (severe acute respiratory syndrome coronavirus -2)

J Orthop

Orthopaedic Walk-In Clinics: A model to lessen the burden on Emergency Departments during the COVID-19 pandemic.

Objective: Operating duties for orthopaedic surgeons decreased during the COVID-19 pandemic, while Emergency Department (ED) cases surged. Orthopaedic Walk-In Clinics (OWICs) were implemented to manage urgent musculoskeletal cases. Methods: OWICs, organized in three days, were staffed by one orthopaedic surgeon, one triage person, three medical assistants, and a physician assistant/nurse practitioner. Results: Musculoskeletal non-emergency ED referrals decreased by 40.6% (p < 0.001) after initiation of the OWICs, allowing optimal use of resources to address the COVID-19 surge. Conclusion: This paper describes the OWIC model and its preliminary impact. The OWICs could serve as a template for other orthopaedic departments during the pandemic.

Journal Article

MacKechnie, Madeline C;Nadeau, Molly;Deering, Ericka;Thaller, John;MacKechnie, Michael A

10.1016/j.jor.2020.05.014

[Title]: Orthopaedic Walk-In Clinics: A model to lessen the burden on Emergency Departments during the COVID-19 pandemic. [Abstract]: Objective: Operating duties for orthopaedic surgeons decreased during the COVID-19 pandemic, while Emergency Department (ED) cases surged. Orthopaedic Walk-In Clinics (OWICs) were implemented to manage urgent musculoskeletal cases. Methods: OWICs, organized in three days, were staffed by one orthopaedic surgeon, one triage person, three medical assistants, and a physician assistant/nurse practitioner. Results: Musculoskeletal non-emergency ED referrals decreased by 40.6% (p < 0.001) after initiation of the OWICs, allowing optimal use of resources to address the COVID-19 surge. Conclusion: This paper describes the OWIC model and its preliminary impact. The OWICs could serve as a template for other orthopaedic departments during the pandemic. [Keywords]:

Diabetes Metab Syndr

Neuroinvasive potential of a primary respiratory pathogen SARS- CoV2: Summarizing the evidences.

BACKROUND AND AIMS: After the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the last two decades, the world is facing its new challenge in SARS-CoV-2 pandemic with unfathomable global responses. The characteristic clinical symptoms for Coronavirus (COVID-19) affected patients are high fever, dry-cough, dyspnoea, lethal pneumonia whereas some patients also show additional neurological signs such as headache, nausea, vomiting etc. The accumulative evidences suggest that SARS-CoV-2 is not only confined within the respiratory tract but may also invade the central nervous system (CNS) and peripheral nervous system (PNS) inducing some fatal neurological diseases. Here, we analyze the phylogenetic perspective of SARS-CoV-2 with other strains of beta-Coronaviridae from a standpoint of neurological spectrum disorders. METHODOLOGY: A Pubmed/Medline, NIH Lit Covid, Cochrane library and some open data bases (BioRxiv, MedRxiv,preprint.org and others) search were carried out by using keywords relevant to our topic of discussion. The extracted literatures are scrutinized by the authors. RESULTS: 58 literatures including original articles, case reports and case series were selected by the authors to analyze the differential distribution of neurological impairments in COVID-19 positive patients along with angiotensin-converting enzyme-2 (ACE2) expression dynamics in neuronal and non-neuronal tissue in CNS and PNS with neuroinvasive potential of SARS-CoV2. CONCLUSION: We discuss the need for modulations in clinical approach from a neurological point of view, as a measure towards reducing disease transmission, morbidity and mortality in SARS-CoV2 positive patients.

ace2;cns;covid-19;coronavirus;neurological disorders;pns;phylogenetic perspective;sars-cov2

Journal Article;Review

Lahiri, Durjoy;Mondal, Ritwick;Deb, Shramana;Bandyopadhyay, Deebya;Shome, Gourav;Sarkar, Sukanya;Biswas, Subhas C

10.1016/j.dsx.2020.06.062

[Title]: Neuroinvasive potential of a primary respiratory pathogen SARS- CoV2: Summarizing the evidences. [Abstract]: BACKROUND AND AIMS: After the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the last two decades, the world is facing its new challenge in SARS-CoV-2 pandemic with unfathomable global responses. The characteristic clinical symptoms for Coronavirus (COVID-19) affected patients are high fever, dry-cough, dyspnoea, lethal pneumonia whereas some patients also show additional neurological signs such as headache, nausea, vomiting etc. The accumulative evidences suggest that SARS-CoV-2 is not only confined within the respiratory tract but may also invade the central nervous system (CNS) and peripheral nervous system (PNS) inducing some fatal neurological diseases. Here, we analyze the phylogenetic perspective of SARS-CoV-2 with other strains of beta-Coronaviridae from a standpoint of neurological spectrum disorders. METHODOLOGY: A Pubmed/Medline, NIH Lit Covid, Cochrane library and some open data bases (BioRxiv, MedRxiv,preprint.org and others) search were carried out by using keywords relevant to our topic of discussion. The extracted literatures are scrutinized by the authors. RESULTS: 58 literatures including original articles, case reports and case series were selected by the authors to analyze the differential distribution of neurological impairments in COVID-19 positive patients along with angiotensin-converting enzyme-2 (ACE2) expression dynamics in neuronal and non-neuronal tissue in CNS and PNS with neuroinvasive potential of SARS-CoV2. CONCLUSION: We discuss the need for modulations in clinical approach from a neurological point of view, as a measure towards reducing disease transmission, morbidity and mortality in SARS-CoV2 positive patients. [Keywords]: ace2;cns;covid-19;coronavirus;neurological disorders;pns;phylogenetic perspective;sars-cov2

TH Open

COVID-19 and Cold Agglutinin Hemolytic Anemia.

Novel coronavirus disease 2019 (COVID-19) has spread throughout the world and has infected close to 4 million people. It commonly presents with fever, cough, and fatigue. Due to the high inflammatory response, it is suggested that the coagulation cascade is enhanced causing thrombotic events for many patients. We describe a patient with clinical features of cerebrovascular accident, as well as documented blood clots in bilateral upper extremities. Labs revealed the presence of cold agglutinin hemolytic anemia. The association between cold agglutinin autoimmune hemolytic anemia and thrombotic events in COVID-19 patients has not been well investigated. The patient unfortunately passed away within 48 hours after admission. This case stresses the importance of considering a full workup to diagnose autoimmune hemolytic anemia (AIHA) in COVID-19 patients with thromboses and possible implications for management.

autoantibodies;thrombosis;viral infection

Case Reports

Maslov, Diana V;Simenson, Victoria;Jain, Suma;Badari, Ambuga

10.1055/s-0040-1715791

[Title]: COVID-19 and Cold Agglutinin Hemolytic Anemia. [Abstract]: Novel coronavirus disease 2019 (COVID-19) has spread throughout the world and has infected close to 4 million people. It commonly presents with fever, cough, and fatigue. Due to the high inflammatory response, it is suggested that the coagulation cascade is enhanced causing thrombotic events for many patients. We describe a patient with clinical features of cerebrovascular accident, as well as documented blood clots in bilateral upper extremities. Labs revealed the presence of cold agglutinin hemolytic anemia. The association between cold agglutinin autoimmune hemolytic anemia and thrombotic events in COVID-19 patients has not been well investigated. The patient unfortunately passed away within 48 hours after admission. This case stresses the importance of considering a full workup to diagnose autoimmune hemolytic anemia (AIHA) in COVID-19 patients with thromboses and possible implications for management. [Keywords]: autoantibodies;thrombosis;viral infection

J Am Geriatr Soc

State Actions and Shortages of Personal Protective Equipment and Staff in U.S. Nursing Homes.

BACKGROUND: It is crucial that nursing homes have adequate personal protective equipment (PPE) and staff to protect residents and staff from COVID-19. Some states have taken actions to mitigate shortages of PPE and staffing in nursing homes, including creating dedicated long-term care (LTC) teams and supporting staffing capacity. OBJECTIVE: To examine whether state actions and nursing home characteristics are associated with shortages of PPE and staffing. DESIGN AND SETTING: Facility-level data, released July 31, 2020, from the Nursing Home COVID-19 Public File, were combined with data from other sources. Our sample was the 13,445 facilities with information about PPE and staffing shortages for each of the 5 weeks between the week ending June 21, 2020, and the week ending July 19, 2020. Associations between facility characteristics and shortages were examined using descriptive statistics and logistic regression models. MEASUREMENTS: Outcome variables were whether or not a facility lacked a 1-week supply of PPE ("PPE shortage") and whether or not a facility had a staffing shortage during 1 or more weeks over the 5-week study period. RESULTS: Over the 5-week study period, 27.6% of facilities reported 1 or more weeks of PPE shortage, 30.2% of facilities reported at least 1 week of staffing shortage, and 46.5% of facilities lacked PPE and/or staff. Facilities located in states in the Northeast PPE Consortium or with LTC teams were modestly less likely to have had a PPE shortage, and facilities located in states that implemented processes to match job seekers with LTC facilities were marginally significantly less likely to have had a staffing shortage. CONCLUSION: Given that nearly half of U.S. nursing homes recently faced a shortage of PPE and/or staff, and that state budget deficits may limit further state actions, ongoing federal assistance with PPE and staffing of nursing homes is needed.

covid-19;nursing homes;personal protective equipment;staffing

Journal Article

Gibson, Diane M;Greene, Jessica

10.1111/jgs.16883

[Title]: State Actions and Shortages of Personal Protective Equipment and Staff in U.S. Nursing Homes. [Abstract]: BACKGROUND: It is crucial that nursing homes have adequate personal protective equipment (PPE) and staff to protect residents and staff from COVID-19. Some states have taken actions to mitigate shortages of PPE and staffing in nursing homes, including creating dedicated long-term care (LTC) teams and supporting staffing capacity. OBJECTIVE: To examine whether state actions and nursing home characteristics are associated with shortages of PPE and staffing. DESIGN AND SETTING: Facility-level data, released July 31, 2020, from the Nursing Home COVID-19 Public File, were combined with data from other sources. Our sample was the 13,445 facilities with information about PPE and staffing shortages for each of the 5 weeks between the week ending June 21, 2020, and the week ending July 19, 2020. Associations between facility characteristics and shortages were examined using descriptive statistics and logistic regression models. MEASUREMENTS: Outcome variables were whether or not a facility lacked a 1-week supply of PPE ("PPE shortage") and whether or not a facility had a staffing shortage during 1 or more weeks over the 5-week study period. RESULTS: Over the 5-week study period, 27.6% of facilities reported 1 or more weeks of PPE shortage, 30.2% of facilities reported at least 1 week of staffing shortage, and 46.5% of facilities lacked PPE and/or staff. Facilities located in states in the Northeast PPE Consortium or with LTC teams were modestly less likely to have had a PPE shortage, and facilities located in states that implemented processes to match job seekers with LTC facilities were marginally significantly less likely to have had a staffing shortage. CONCLUSION: Given that nearly half of U.S. nursing homes recently faced a shortage of PPE and/or staff, and that state budget deficits may limit further state actions, ongoing federal assistance with PPE and staffing of nursing homes is needed. [Keywords]: covid-19;nursing homes;personal protective equipment;staffing

FASEB J

Genetic gateways to COVID-19 infection: Implications for risk, severity, and outcomes.

The dynamics, such as transmission, spatial epidemiology, and clinical course of Coronavirus Disease-2019 (COVID-19) have emerged as the most intriguing features and remain incompletely understood. The genetic landscape of an individual in particular, and a population in general seems to play a pivotal role in shaping the above COVID-19 dynamics. Considering the implications of host genes in the entry and replication of SARS-CoV-2 and in mounting the host immune response, it appears that multiple genes might be crucially involved in the above processes. Herein, we propose three potentially important genetic gateways to COVID-19 infection; these could explain at least in part the discrepancies of its spread, severity, and mortality. The variations within Angiotensin-converting enzyme 2 (ACE2) gene might constitute the first genetic gateway, influencing the spatial transmission dynamics of COVID-19. The Human Leukocyte Antigen locus, a master regulator of immunity against infection seems to be crucial in influencing susceptibility and severity of COVID-19 and can be the second genetic gateway. The genes regulating Toll-like receptor and complement pathways and subsequently cytokine storm induced exaggerated inflammatory pathways seem to underlie the severity of COVID-19, and such genes might represent the third genetic gateway. Host-pathogen interaction is a complex event and some additional genes might also contribute to the dynamics of COVID-19. Overall, these three genetic gateways proposed here might be the critical host determinants governing the risk, severity, and outcome of COVID-19. Genetic variations within these gateways could be key in influencing geographical discrepancies of COVID-19.

ace;covid-19;hla;sars-cov-2;cytokine storm;genetics;immunity

Journal Article;Review

Debnath, Monojit;Banerjee, Moinak;Berk, Michael

10.1096/fj.202001115R

[Title]: Genetic gateways to COVID-19 infection: Implications for risk, severity, and outcomes. [Abstract]: The dynamics, such as transmission, spatial epidemiology, and clinical course of Coronavirus Disease-2019 (COVID-19) have emerged as the most intriguing features and remain incompletely understood. The genetic landscape of an individual in particular, and a population in general seems to play a pivotal role in shaping the above COVID-19 dynamics. Considering the implications of host genes in the entry and replication of SARS-CoV-2 and in mounting the host immune response, it appears that multiple genes might be crucially involved in the above processes. Herein, we propose three potentially important genetic gateways to COVID-19 infection; these could explain at least in part the discrepancies of its spread, severity, and mortality. The variations within Angiotensin-converting enzyme 2 (ACE2) gene might constitute the first genetic gateway, influencing the spatial transmission dynamics of COVID-19. The Human Leukocyte Antigen locus, a master regulator of immunity against infection seems to be crucial in influencing susceptibility and severity of COVID-19 and can be the second genetic gateway. The genes regulating Toll-like receptor and complement pathways and subsequently cytokine storm induced exaggerated inflammatory pathways seem to underlie the severity of COVID-19, and such genes might represent the third genetic gateway. Host-pathogen interaction is a complex event and some additional genes might also contribute to the dynamics of COVID-19. Overall, these three genetic gateways proposed here might be the critical host determinants governing the risk, severity, and outcome of COVID-19. Genetic variations within these gateways could be key in influencing geographical discrepancies of COVID-19. [Keywords]: ace;covid-19;hla;sars-cov-2;cytokine storm;genetics;immunity

Acta Med Indones

Prevention of Ventricular Arrhythmia and Sudden Cardiac Death in COVID-19 Patients.

Since the first case was reported at the end of 2019, COVID-19 has spread throughout the world and has become a pandemic. The high transmission rate of the virus has made it a threat to public health globally. Viral infections may trigger acute coronary syndromes, arrhythmias, and exacerbation of heart failure, due to a combination of effects including significant systemic inflammatory responses and localized vascular inflammation at the arterial plaque level. Indonesian clinical practice guideline stated that (hydroxy)chloroquine alone or in combination with azithromycin may be used to treat for COVID-19. However, chloroquine, hydroxychloroquine, and azithromycin all prolong the QT interval, raising concerns about the risk of arrhythmic death from individual or concurrent use of these medications. To date, there is still no vaccine or specific antiviral treatment for COVID-19. Therefore, prevention of infection in people with cardiovascular risk and mitigation of the adverse effects of treatment is necessary.

qt;arrhythmia;azithromycin;covid-19;hydroxychlorine

Journal Article;Review

Yamin, Muhammad;Demili, Amanda Ulfah

[Title]: Prevention of Ventricular Arrhythmia and Sudden Cardiac Death in COVID-19 Patients. [Abstract]: Since the first case was reported at the end of 2019, COVID-19 has spread throughout the world and has become a pandemic. The high transmission rate of the virus has made it a threat to public health globally. Viral infections may trigger acute coronary syndromes, arrhythmias, and exacerbation of heart failure, due to a combination of effects including significant systemic inflammatory responses and localized vascular inflammation at the arterial plaque level. Indonesian clinical practice guideline stated that (hydroxy)chloroquine alone or in combination with azithromycin may be used to treat for COVID-19. However, chloroquine, hydroxychloroquine, and azithromycin all prolong the QT interval, raising concerns about the risk of arrhythmic death from individual or concurrent use of these medications. To date, there is still no vaccine or specific antiviral treatment for COVID-19. Therefore, prevention of infection in people with cardiovascular risk and mitigation of the adverse effects of treatment is necessary. [Keywords]: qt;arrhythmia;azithromycin;covid-19;hydroxychlorine

Emerg Microbes Infect

A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses.

World Health Organization has declared the ongoing outbreak of coronavirus disease 2019 (COVID-19) a Public Health Emergency of International Concern. The virus was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. Human infection with SARS-CoV-2 leads to a wide range of clinical manifestations ranging from asymptomatic, mild, moderate to severe. The severe cases present with pneumonia, which can progress to acute respiratory distress syndrome. The outbreak provides an opportunity for real-time tracking of an animal coronavirus that has just crossed species barrier to infect humans. The outcome of SARS-CoV-2 infection is largely determined by virus-host interaction. Here, we review the discovery, zoonotic origin, animal hosts, transmissibility and pathogenicity of SARS-CoV-2 in relation to its interplay with host antiviral defense. A comparison with SARS-CoV, Middle East respiratory syndrome coronavirus, community-acquired human coronaviruses and other pathogenic viruses including human immunodeficiency viruses is made. We summarize current understanding of the induction of a proinflammatory cytokine storm by other highly pathogenic human coronaviruses, their adaptation to humans and their usurpation of the cell death programmes. Important questions concerning the interaction between SARS-CoV-2 and host antiviral defence, including asymptomatic and presymptomatic virus shedding, are also discussed.

2019 novel coronavirus;covid-19;coronavirus;sars-cov;sars-cov-2;host antiviral response;type i interferon

Journal Article;Review

Fung, Sin-Yee;Yuen, Kit-San;Ye, Zi-Wei;Chan, Chi-Ping;Jin, Dong-Yan

10.1080/22221751.2020.1736644

[Title]: A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses. [Abstract]: World Health Organization has declared the ongoing outbreak of coronavirus disease 2019 (COVID-19) a Public Health Emergency of International Concern. The virus was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. Human infection with SARS-CoV-2 leads to a wide range of clinical manifestations ranging from asymptomatic, mild, moderate to severe. The severe cases present with pneumonia, which can progress to acute respiratory distress syndrome. The outbreak provides an opportunity for real-time tracking of an animal coronavirus that has just crossed species barrier to infect humans. The outcome of SARS-CoV-2 infection is largely determined by virus-host interaction. Here, we review the discovery, zoonotic origin, animal hosts, transmissibility and pathogenicity of SARS-CoV-2 in relation to its interplay with host antiviral defense. A comparison with SARS-CoV, Middle East respiratory syndrome coronavirus, community-acquired human coronaviruses and other pathogenic viruses including human immunodeficiency viruses is made. We summarize current understanding of the induction of a proinflammatory cytokine storm by other highly pathogenic human coronaviruses, their adaptation to humans and their usurpation of the cell death programmes. Important questions concerning the interaction between SARS-CoV-2 and host antiviral defence, including asymptomatic and presymptomatic virus shedding, are also discussed. [Keywords]: 2019 novel coronavirus;covid-19;coronavirus;sars-cov;sars-cov-2;host antiviral response;type i interferon

Eur Arch Otorhinolaryngol

Delays in surgery for cholesteatoma due to COVID-19: is there an impact on rates of recidivism and major complications?

PURPOSE: To evaluate the relationship between the waiting time for surgery, and cholesteatoma recidivism rates and major complications. The secondary aims were to identify any other prognostic factors for cholesteatoma recidivism. METHODS: A retrospective single-centre study of 312 patients who underwent cholesteatoma surgery under the care of a single-surgeon, between 2004 and 2018, was performed. Waiting times for surgery were categorised into </= 90 days, 91-180 days, 181-270 days and > 271 days. The outcome measures were cholesteatoma recidivism and major complications (facial nerve palsy or intracranial complications). RESULTS: The mean age was 36.1 years +/- 21.5 with 242 adults (77.6%) and 70 children (22.4%). The mean waiting time for surgery was 126.2 days (4.1 months) +/- 96.0 days and the overall rate of recidivism was 11.2% (35/312 patients). No instances of facial nerve palsy or intracranial complications were identified. Rates of recidivism by waiting time for surgery were: 15.3% for 118 patients who waited </= 90 days, 9.7% for 134 patients who waited 91-180 days, 6.7% for 30 patients who waited 181-270 days and 4.3% for 23 patients who waited > 271 days. There was no significant difference amongst the different waiting time groups for rates of recidivism (p = 0.266). CONCLUSION: Increased waiting times for cholesteatoma surgery do not appear to be associated with increased rates of recidivism or major complications. Clinical judgement will always be required for complicated disease or patients with additional risk factors. The other prognostic factors for recidivism identified in this study were age (< 15 years) and congenital cholesteatoma.

cholesteatoma;mastoid;recidivism;recurrence;time factors

Journal Article

Hussain, Mohammed Hassan;Mair, Manish;Mahmood, Sara;Sakagiannis, Georgios;Rojoa, Djamila M;Raheman, Firas J;Irvine, Esmee;Rea, Peter

10.1007/s00405-020-06416-7

[Title]: Delays in surgery for cholesteatoma due to COVID-19: is there an impact on rates of recidivism and major complications? [Abstract]: PURPOSE: To evaluate the relationship between the waiting time for surgery, and cholesteatoma recidivism rates and major complications. The secondary aims were to identify any other prognostic factors for cholesteatoma recidivism. METHODS: A retrospective single-centre study of 312 patients who underwent cholesteatoma surgery under the care of a single-surgeon, between 2004 and 2018, was performed. Waiting times for surgery were categorised into </= 90 days, 91-180 days, 181-270 days and > 271 days. The outcome measures were cholesteatoma recidivism and major complications (facial nerve palsy or intracranial complications). RESULTS: The mean age was 36.1 years +/- 21.5 with 242 adults (77.6%) and 70 children (22.4%). The mean waiting time for surgery was 126.2 days (4.1 months) +/- 96.0 days and the overall rate of recidivism was 11.2% (35/312 patients). No instances of facial nerve palsy or intracranial complications were identified. Rates of recidivism by waiting time for surgery were: 15.3% for 118 patients who waited </= 90 days, 9.7% for 134 patients who waited 91-180 days, 6.7% for 30 patients who waited 181-270 days and 4.3% for 23 patients who waited > 271 days. There was no significant difference amongst the different waiting time groups for rates of recidivism (p = 0.266). CONCLUSION: Increased waiting times for cholesteatoma surgery do not appear to be associated with increased rates of recidivism or major complications. Clinical judgement will always be required for complicated disease or patients with additional risk factors. The other prognostic factors for recidivism identified in this study were age (< 15 years) and congenital cholesteatoma. [Keywords]: cholesteatoma;mastoid;recidivism;recurrence;time factors

Curr Protein Pept Sci

Fusion protein targeted antiviral peptides: fragment based drug design (FBDD) guided rational design of dipeptides against SARS-CoV-2.

Infectious diseases caused by viruses become a serious public health issue in the recent past, including current pandemic situation of COVID-19. Enveloped viruses are most commonly known to cause emerging and recurring infectious diseases. Viral and cell membrane fusion is the major key event in case of enveloped viruses that required for their entry into the cell. Viral fusion proteins are playing important role in fusion process and in infection establishment. Because of this, fusion process targeting antivirals become an interest to fight against viral diseases caused by enveloped virus. Lower respiratory tract infections casing viruses like influenza, respiratory syncytial virus (RSV) and severe acute respiratory syndrome corona virus (SARS-CoV) are examples of such enveloped viruses that are at top in public health issues. Here, we summarized the viral fusion protein targeted antiviral peptides along with their mechanism and specific design to combat viral fusion process. The pandemic COVID-19, severe respiratory syndrome disease is outbreak worldwide. There are no definitive drugs yet but few are in on-going trial. Here, an approach of fragment based drug design (FBDD) methodology was used to identify the broad spectrum agent target to the conserved region of fusion protein of SARS CoV-2. Three dipeptides (DL, LQ and ID) were chosen from the library and designed by the systematic combination along with their possible modifications of amino acids to the target sites. Designed peptides were docked with targeted fusion protein after energy minimization. Results show strong and significant binding affinity (DL = -60.1 kcal/mol; LQ = -62.8 kcal/mol; ID= -71.5 kcal/mol) during interaction. Any one of the active peptides from the developed libraries may help to block competitively the target sites to successfully control COVID-19.

viral infections;antiviral peptides;enveloped viruses;fusion protein

Journal Article

Manna, Sounik;Chowdhury, Trinath;Baindara, Piyush;Mandal, Santi M

10.2174/1389203721666200908164641

[Title]: Fusion protein targeted antiviral peptides: fragment based drug design (FBDD) guided rational design of dipeptides against SARS-CoV-2. [Abstract]: Infectious diseases caused by viruses become a serious public health issue in the recent past, including current pandemic situation of COVID-19. Enveloped viruses are most commonly known to cause emerging and recurring infectious diseases. Viral and cell membrane fusion is the major key event in case of enveloped viruses that required for their entry into the cell. Viral fusion proteins are playing important role in fusion process and in infection establishment. Because of this, fusion process targeting antivirals become an interest to fight against viral diseases caused by enveloped virus. Lower respiratory tract infections casing viruses like influenza, respiratory syncytial virus (RSV) and severe acute respiratory syndrome corona virus (SARS-CoV) are examples of such enveloped viruses that are at top in public health issues. Here, we summarized the viral fusion protein targeted antiviral peptides along with their mechanism and specific design to combat viral fusion process. The pandemic COVID-19, severe respiratory syndrome disease is outbreak worldwide. There are no definitive drugs yet but few are in on-going trial. Here, an approach of fragment based drug design (FBDD) methodology was used to identify the broad spectrum agent target to the conserved region of fusion protein of SARS CoV-2. Three dipeptides (DL, LQ and ID) were chosen from the library and designed by the systematic combination along with their possible modifications of amino acids to the target sites. Designed peptides were docked with targeted fusion protein after energy minimization. Results show strong and significant binding affinity (DL = -60.1 kcal/mol; LQ = -62.8 kcal/mol; ID= -71.5 kcal/mol) during interaction. Any one of the active peptides from the developed libraries may help to block competitively the target sites to successfully control COVID-19. [Keywords]: viral infections;antiviral peptides;enveloped viruses;fusion protein

J Cell Commun Signal

Repurposing calcium channel blockers as antiviral drugs.

The current pandemic caused by the SARS-CoV-2 has claimed over a half a million lives within a very short span of time. A therapeutic drug which could prevent the entry and propagation of the virus is the need of the hour. Several lines of evidence collected from experimental studies older than three decades have pointed out the fact that inhibiting calcium entry into cells can affect vital steps in the lifecycle of viruses. Hence, calcium channel blockers may be considered as an effective measure in the containment of the viruses. This commentary throws light two scientific papers although with divergent facts converging at a point by suggesting a promising treatment option for CoVID-19 (Fang et al. Lancet Respir Med 8:e21, 2020; Straus et al. J Virol 94:e00426, 2020).

ccb;calcium channels;calcium homeostasis;sars;verapamil;virus

Journal Article

Jayaseelan, Vijayashree Priyadharsini;Paramasivam, Arumugam

10.1007/s12079-020-00579-y

[Title]: Repurposing calcium channel blockers as antiviral drugs. [Abstract]: The current pandemic caused by the SARS-CoV-2 has claimed over a half a million lives within a very short span of time. A therapeutic drug which could prevent the entry and propagation of the virus is the need of the hour. Several lines of evidence collected from experimental studies older than three decades have pointed out the fact that inhibiting calcium entry into cells can affect vital steps in the lifecycle of viruses. Hence, calcium channel blockers may be considered as an effective measure in the containment of the viruses. This commentary throws light two scientific papers although with divergent facts converging at a point by suggesting a promising treatment option for CoVID-19 (Fang et al. Lancet Respir Med 8:e21, 2020; Straus et al. J Virol 94:e00426, 2020). [Keywords]: ccb;calcium channels;calcium homeostasis;sars;verapamil;virus

Health Informatics J

Intermittent demand forecasting for medical consumables with short life cycle using a dynamic neural network during the COVID-19 epidemic.

Accurate demand forecasting is always critical to supply chain management. However, many uncertain factors in the market make this issue a huge challenge. Especially during the current COVID-19 outbreak, the shortage of certain types of medical consumables has become a global problem. The intermittent demand forecast of medical consumables with a short life cycle brings some new challenges, such as the demand occurring randomly in many time periods with zero demand. In this research, a seasonal adjustment method is introduced to deal with seasonal influences, and a dynamic neural network model with optimized model selection procedure and an appropriate model selection criterion are introduced as the main forecasting models. In addition, in order to reduce the impact of zero demand, it adds some input nodes to the neural network by preprocessing the original input data. Lastly, a modified error measurement method is proposed for performance evaluation. Experimental results show that the proposed forecasting framework is superior to other intermittent demand models.

accuracy measurement;dynamic neural network;intermittent demand forecasting;optimized model selection;short life cycle

Journal Article;Research Support, Non-U.S. Gov't

Liu, Peipei

10.1177/1460458220954730

[Title]: Intermittent demand forecasting for medical consumables with short life cycle using a dynamic neural network during the COVID-19 epidemic. [Abstract]: Accurate demand forecasting is always critical to supply chain management. However, many uncertain factors in the market make this issue a huge challenge. Especially during the current COVID-19 outbreak, the shortage of certain types of medical consumables has become a global problem. The intermittent demand forecast of medical consumables with a short life cycle brings some new challenges, such as the demand occurring randomly in many time periods with zero demand. In this research, a seasonal adjustment method is introduced to deal with seasonal influences, and a dynamic neural network model with optimized model selection procedure and an appropriate model selection criterion are introduced as the main forecasting models. In addition, in order to reduce the impact of zero demand, it adds some input nodes to the neural network by preprocessing the original input data. Lastly, a modified error measurement method is proposed for performance evaluation. Experimental results show that the proposed forecasting framework is superior to other intermittent demand models. [Keywords]: accuracy measurement;dynamic neural network;intermittent demand forecasting;optimized model selection;short life cycle

Viruses

Impact of Microbiota: A Paradigm for Evolving Herd Immunity against Viral Diseases.

Herd immunity is the most critical and essential prophylactic intervention that delivers protection against infectious diseases at both the individual and community level. This process of natural vaccination is immensely pertinent to the current context of a pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection around the globe. The conventional idea of herd immunity is based on efficient transmission of pathogens and developing natural immunity within a population. This is entirely encouraging while fighting against any disease in pandemic circumstances. A spatial community is occupied by people having variable resistance capacity against a pathogen. Protection efficacy against once very common diseases like smallpox, poliovirus or measles has been possible only because of either natural vaccination through contagious infections or expanded immunization programs among communities. This has led to achieving herd immunity in some cohorts. The microbiome plays an essential role in developing the body's immune cells for the emerging competent vaccination process, ensuring herd immunity. Frequency of interaction among microbiota, metabolic nutrients and individual immunity preserve the degree of vaccine effectiveness against several pathogens. Microbiome symbiosis regulates pathogen transmissibility and the success of vaccination among different age groups. Imbalance of nutrients perturbs microbiota and abrogates immunity. Thus, a particular population can become vulnerable to the infection. Intestinal dysbiosis leads to environmental enteropathy (EE). As a consequence, the generation of herd immunity can either be delayed or not start in a particular cohort. Moreover, disparities of the protective response of many vaccines in developing countries outside of developed countries are due to inconsistencies of healthy microbiota among the individuals. We suggested that pan-India poliovirus vaccination program, capable of inducing herd immunity among communities for the last 30 years, may also influence the inception of natural course of heterologous immunity against SARS-CoV-2 infection. Nonetheless, this anamnestic recall is somewhat counterintuitive, as antibody generation against original antigens of SARS-CoV-2 will be subdued due to original antigenic sin.

ee;sars-cov-2;herd immunity;heterologous immunity;microbiome;nutrition

Journal Article;Research Support, Non-U.S. Gov't;Review

Shelly, Asha;Gupta, Priya;Ahuja, Rahul;Srichandan, Sudeepa;Meena, Jairam;Majumdar, Tanmay

10.3390/v12101150

[Title]: Impact of Microbiota: A Paradigm for Evolving Herd Immunity against Viral Diseases. [Abstract]: Herd immunity is the most critical and essential prophylactic intervention that delivers protection against infectious diseases at both the individual and community level. This process of natural vaccination is immensely pertinent to the current context of a pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection around the globe. The conventional idea of herd immunity is based on efficient transmission of pathogens and developing natural immunity within a population. This is entirely encouraging while fighting against any disease in pandemic circumstances. A spatial community is occupied by people having variable resistance capacity against a pathogen. Protection efficacy against once very common diseases like smallpox, poliovirus or measles has been possible only because of either natural vaccination through contagious infections or expanded immunization programs among communities. This has led to achieving herd immunity in some cohorts. The microbiome plays an essential role in developing the body's immune cells for the emerging competent vaccination process, ensuring herd immunity. Frequency of interaction among microbiota, metabolic nutrients and individual immunity preserve the degree of vaccine effectiveness against several pathogens. Microbiome symbiosis regulates pathogen transmissibility and the success of vaccination among different age groups. Imbalance of nutrients perturbs microbiota and abrogates immunity. Thus, a particular population can become vulnerable to the infection. Intestinal dysbiosis leads to environmental enteropathy (EE). As a consequence, the generation of herd immunity can either be delayed or not start in a particular cohort. Moreover, disparities of the protective response of many vaccines in developing countries outside of developed countries are due to inconsistencies of healthy microbiota among the individuals. We suggested that pan-India poliovirus vaccination program, capable of inducing herd immunity among communities for the last 30 years, may also influence the inception of natural course of heterologous immunity against SARS-CoV-2 infection. Nonetheless, this anamnestic recall is somewhat counterintuitive, as antibody generation against original antigens of SARS-CoV-2 will be subdued due to original antigenic sin. [Keywords]: ee;sars-cov-2;herd immunity;heterologous immunity;microbiome;nutrition

JAMA Netw Open

Comparison of Clinical Features of COVID-19 vs Seasonal Influenza A and B in US Children.

Importance: Compared with seasonal influenza, the clinical features and epidemiologic characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus 2019 (COVID-19) in US children remain largely unknown. Objective: To describe the similarities and differences in clinical features between COVID-19 and seasonal influenza in US children. Design, Setting, and Participants: This retrospective cohort study included children who were diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15, 2020, and children diagnosed with seasonal influenza between October 1, 2019, and June 6, 2020, at Children's National Hospital in the District of Columbia. Exposures: COVID-19 or influenza A or B. Main Outcomes and Measures: Rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use and the association between underlying medical conditions, clinical symptoms, and COVID-19 vs seasonal influenza. Results: The study included 315 patients diagnosed with COVID-19 (164 [52%] male; median age, 8.3 years [range, 0.03-35.6 years]) and 1402 patients diagnosed with seasonal influenza (743 [53%] male; median age, 3.9 years [range, 0.04-40.4 years]). Patients with COVID-19 and those with seasonal influenza had a similar hospitalization rate (54 [17%] vs 291 [21%], P = .15), intensive care unit admission rate (18 [6%] vs 98 [7%], P = .42), and use of mechanical ventilators (10 [3%] vs 27 [2%], P = .17). More patients hospitalized with COVID-19 than with seasonal influenza reported fever (41 [76%] vs 159 [55%], P = .005), diarrhea or vomiting (14 [26%] vs 36 [12%], P = .01), headache (6 [11%] vs 9 [3%], P = .01), body ache or myalgia (12 [22%] vs 20 [7%], P = .001), and chest pain (6 [11%] vs 9 [3%], P = .01). Differences between patients hospitalized with COVID-19 vs influenza who reported cough (24 [48%] vs 90 [31%], P = .05) and shortness of breath (16 [30%] vs 59 [20%], P = .13) were not statistically significant. Conclusions and Relevance: In this cohort study of US children with COVID-19 or seasonal influenza, there was no difference in hospitalization rates, intensive care unit admission rates, and mechanical ventilator use between the 2 groups. More patients hospitalized with COVID-19 than with seasonal influenza reported clinical symptoms at the time of diagnosis.

Journal Article;Comment

Song, Xiaoyan;Delaney, Meghan;Shah, Rahul K;Campos, Joseph M;Wessel, David L;DeBiasi, Roberta L

10.1001/jamanetworkopen.2020.20495

[Title]: Comparison of Clinical Features of COVID-19 vs Seasonal Influenza A and B in US Children. [Abstract]: Importance: Compared with seasonal influenza, the clinical features and epidemiologic characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus 2019 (COVID-19) in US children remain largely unknown. Objective: To describe the similarities and differences in clinical features between COVID-19 and seasonal influenza in US children. Design, Setting, and Participants: This retrospective cohort study included children who were diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15, 2020, and children diagnosed with seasonal influenza between October 1, 2019, and June 6, 2020, at Children's National Hospital in the District of Columbia. Exposures: COVID-19 or influenza A or B. Main Outcomes and Measures: Rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use and the association between underlying medical conditions, clinical symptoms, and COVID-19 vs seasonal influenza. Results: The study included 315 patients diagnosed with COVID-19 (164 [52%] male; median age, 8.3 years [range, 0.03-35.6 years]) and 1402 patients diagnosed with seasonal influenza (743 [53%] male; median age, 3.9 years [range, 0.04-40.4 years]). Patients with COVID-19 and those with seasonal influenza had a similar hospitalization rate (54 [17%] vs 291 [21%], P = .15), intensive care unit admission rate (18 [6%] vs 98 [7%], P = .42), and use of mechanical ventilators (10 [3%] vs 27 [2%], P = .17). More patients hospitalized with COVID-19 than with seasonal influenza reported fever (41 [76%] vs 159 [55%], P = .005), diarrhea or vomiting (14 [26%] vs 36 [12%], P = .01), headache (6 [11%] vs 9 [3%], P = .01), body ache or myalgia (12 [22%] vs 20 [7%], P = .001), and chest pain (6 [11%] vs 9 [3%], P = .01). Differences between patients hospitalized with COVID-19 vs influenza who reported cough (24 [48%] vs 90 [31%], P = .05) and shortness of breath (16 [30%] vs 59 [20%], P = .13) were not statistically significant. Conclusions and Relevance: In this cohort study of US children with COVID-19 or seasonal influenza, there was no difference in hospitalization rates, intensive care unit admission rates, and mechanical ventilator use between the 2 groups. More patients hospitalized with COVID-19 than with seasonal influenza reported clinical symptoms at the time of diagnosis. [Keywords]:

Hum Resour Health

Maternal and newborn care during the COVID-19 pandemic in Kenya: re-contextualising the community midwifery model.

Peripartum deaths remain significantly high in low- and middle-income countries, including Kenya. The COVID-19 pandemic has disrupted essential services, which could lead to an increase in maternal and neonatal mortality and morbidity. Furthermore, the lockdowns, curfews, and increased risk for contracting COVID-19 may affect how women access health facilities. SARS-CoV-2 is a novel coronavirus that requires a community-centred response, not just hospital-based interventions. In this prolonged health crisis, pregnant women deserve a safe and humanised birth that prioritises the physical and emotional safety of the mother and the baby. There is an urgent need for innovative strategies to prevent the deterioration of maternal and child outcomes in an already strained health system. We propose strengthening community-based midwifery to avoid unnecessary movements, decrease the burden on hospitals, and minimise the risk of COVID-19 infection among women and their newborns.

africa;covid-19;community interventions;community health;coronavirus;kenya;lmic;maternal;midwifery;neonatal;pandemic;pregnant women

Journal Article;Review

Kimani, Rachel Wangari;Maina, Rose;Shumba, Constance;Shaibu, Sheila

10.1186/s12960-020-00518-3

[Title]: Maternal and newborn care during the COVID-19 pandemic in Kenya: re-contextualising the community midwifery model. [Abstract]: Peripartum deaths remain significantly high in low- and middle-income countries, including Kenya. The COVID-19 pandemic has disrupted essential services, which could lead to an increase in maternal and neonatal mortality and morbidity. Furthermore, the lockdowns, curfews, and increased risk for contracting COVID-19 may affect how women access health facilities. SARS-CoV-2 is a novel coronavirus that requires a community-centred response, not just hospital-based interventions. In this prolonged health crisis, pregnant women deserve a safe and humanised birth that prioritises the physical and emotional safety of the mother and the baby. There is an urgent need for innovative strategies to prevent the deterioration of maternal and child outcomes in an already strained health system. We propose strengthening community-based midwifery to avoid unnecessary movements, decrease the burden on hospitals, and minimise the risk of COVID-19 infection among women and their newborns. [Keywords]: africa;covid-19;community interventions;community health;coronavirus;kenya;lmic;maternal;midwifery;neonatal;pandemic;pregnant women

Blood

Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious respiratory virus that can lead to venous/arterial thrombosis, stroke, renal failure, myocardial infarction, thrombocytopenia, and other end-organ damage. Animal models demonstrating end-organ protection in C3-deficient mice and evidence of complement activation in humans have led to the hypothesis that SARS-CoV-2 triggers complement-mediated endothelial damage, but the mechanism is unclear. Here, we demonstrate that the SARS-CoV-2 spike protein (subunit 1 and 2), but not the N protein, directly activates the alternative pathway of complement (APC). Complement-dependent killing using the modified Ham test is blocked by either C5 or factor D inhibition. C3 fragments and C5b-9 are deposited on TF1PIGAnull target cells, and complement factor Bb is increased in the supernatant from spike protein-treated cells. C5 inhibition prevents the accumulation of C5b-9 on cells, but not C3c; however, factor D inhibition prevents both C3c and C5b-9 accumulation. Addition of factor H mitigates the complement attack. In conclusion, SARS-CoV-2 spike proteins convert nonactivator surfaces to activator surfaces by preventing the inactivation of the cell-surface APC convertase. APC activation may explain many of the clinical manifestations (microangiopathy, thrombocytopenia, renal injury, and thrombophilia) of COVID-19 that are also observed in other complement-driven diseases such as atypical hemolytic uremic syndrome and catastrophic antiphospholipid antibody syndrome. C5 inhibition prevents accumulation of C5b-9 in vitro but does not prevent upstream complement activation in response to SARS-CoV-2 spike proteins.

Journal Article;Research Support, N.I.H., Extramural

Yu, Jia;Yuan, Xuan;Chen, Hang;Chaturvedi, Shruti;Braunstein, Evan M;Brodsky, Robert A

10.1182/blood.2020008248

[Title]: Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition. [Abstract]: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious respiratory virus that can lead to venous/arterial thrombosis, stroke, renal failure, myocardial infarction, thrombocytopenia, and other end-organ damage. Animal models demonstrating end-organ protection in C3-deficient mice and evidence of complement activation in humans have led to the hypothesis that SARS-CoV-2 triggers complement-mediated endothelial damage, but the mechanism is unclear. Here, we demonstrate that the SARS-CoV-2 spike protein (subunit 1 and 2), but not the N protein, directly activates the alternative pathway of complement (APC). Complement-dependent killing using the modified Ham test is blocked by either C5 or factor D inhibition. C3 fragments and C5b-9 are deposited on TF1PIGAnull target cells, and complement factor Bb is increased in the supernatant from spike protein-treated cells. C5 inhibition prevents the accumulation of C5b-9 on cells, but not C3c; however, factor D inhibition prevents both C3c and C5b-9 accumulation. Addition of factor H mitigates the complement attack. In conclusion, SARS-CoV-2 spike proteins convert nonactivator surfaces to activator surfaces by preventing the inactivation of the cell-surface APC convertase. APC activation may explain many of the clinical manifestations (microangiopathy, thrombocytopenia, renal injury, and thrombophilia) of COVID-19 that are also observed in other complement-driven diseases such as atypical hemolytic uremic syndrome and catastrophic antiphospholipid antibody syndrome. C5 inhibition prevents accumulation of C5b-9 in vitro but does not prevent upstream complement activation in response to SARS-CoV-2 spike proteins. [Keywords]:

J Med Internet Res

Public Health in the Information Age: Recognizing the Infosphere as a Social Determinant of Health.

Since 2016, social media companies and news providers have come under pressure to tackle the spread of political mis- and disinformation (MDI) online. However, despite evidence that online health MDI (on the web, on social media, and within mobile apps) also has negative real-world effects, there has been a lack of comparable action by either online service providers or state-sponsored public health bodies. We argue that this is problematic and seek to answer three questions: why has so little been done to control the flow of, and exposure to, health MDI online; how might more robust action be justified; and what specific, newly justified actions are needed to curb the flow of, and exposure to, online health MDI? In answering these questions, we show that four ethical concerns-related to paternalism, autonomy, freedom of speech, and pluralism-are partly responsible for the lack of intervention. We then suggest that these concerns can be overcome by relying on four arguments: (1) education is necessary but insufficient to curb the circulation of health MDI, (2) there is precedent for state control of internet content in other domains, (3) network dynamics adversely affect the spread of accurate health information, and (4) justice is best served by protecting those susceptible to inaccurate health information. These arguments provide a strong case for classifying the quality of the infosphere as a social determinant of health, thus making its protection a public health responsibility. In addition, they offer a strong justification for working to overcome the ethical concerns associated with state-led intervention in the infosphere to protect public health.

covid-19;disinformation;infodemic;infodemiology;information ethics;infosphere;misinformation;public health;social determinants of health

Journal Article

Morley, Jessica;Cowls, Josh;Taddeo, Mariarosaria;Floridi, Luciano

10.2196/19311

[Title]: Public Health in the Information Age: Recognizing the Infosphere as a Social Determinant of Health. [Abstract]: Since 2016, social media companies and news providers have come under pressure to tackle the spread of political mis- and disinformation (MDI) online. However, despite evidence that online health MDI (on the web, on social media, and within mobile apps) also has negative real-world effects, there has been a lack of comparable action by either online service providers or state-sponsored public health bodies. We argue that this is problematic and seek to answer three questions: why has so little been done to control the flow of, and exposure to, health MDI online; how might more robust action be justified; and what specific, newly justified actions are needed to curb the flow of, and exposure to, online health MDI? In answering these questions, we show that four ethical concerns-related to paternalism, autonomy, freedom of speech, and pluralism-are partly responsible for the lack of intervention. We then suggest that these concerns can be overcome by relying on four arguments: (1) education is necessary but insufficient to curb the circulation of health MDI, (2) there is precedent for state control of internet content in other domains, (3) network dynamics adversely affect the spread of accurate health information, and (4) justice is best served by protecting those susceptible to inaccurate health information. These arguments provide a strong case for classifying the quality of the infosphere as a social determinant of health, thus making its protection a public health responsibility. In addition, they offer a strong justification for working to overcome the ethical concerns associated with state-led intervention in the infosphere to protect public health. [Keywords]: covid-19;disinformation;infodemic;infodemiology;information ethics;infosphere;misinformation;public health;social determinants of health

Age Ageing

COVID-19 in older people: a rapid clinical review.

INTRODUCTION: the COVID-19 pandemic poses a high risk to older people. The aim of this article is to provide a rapid overview of the COVID-19 literature, with a specific focus on older adults. We frame our findings within an overview of the disease and have also evaluated the inclusion of older people within forthcoming clinical trials. METHODS: we searched PubMed and bioRxiv/medRxiv to identify English language papers describing the testing, treatment and prognosis of COVID-19. PubMed and bioRxiv/medRxiv searches took place on 20 and 24 March 2020, respectively. RESULTS: screening of over 1,100 peer-reviewed and pre-print papers yielded n = 22 on COVID-19 testing, n = 15 on treatment and n = 13 on prognosis. Viral polymerase chain reaction (PCR) and serology are the mainstays of testing, but a positive diagnosis may be increasingly supported by radiological findings. The current evidence for the effectiveness of antiviral, corticosteroid and immunotherapies is inconclusive, although trial data are largely based on younger people. In addition to age, male gender and comorbidities, specific laboratory and radiology findings are important prognostic factors. Evidence suggests that social distancing policies could have important negative consequences, particularly if in place for an extended period. CONCLUSION: given the established association between increasing age and poor prognosis in COVID-19, we anticipate that this rapid review of the current and emergent evidence might form a basis on which future work can be established. Exclusion of older people, particularly those with comorbidities, from clinical trials is well recognised and is potentially being perpetuated in the field of current COVID-19 research.

covid-19;non-pharmaceutical interventions;older adults;pandemic;prognosis;virology

Journal Article;Review

Lithander, Fiona E;Neumann, Sandra;Tenison, Emma;Lloyd, Katherine;Welsh, Tomas J;Rodrigues, Jonathan C L;Higgins, Julian P T;Scourfield, Lily;Christensen, Hannah;Haunton, Victoria J;Henderson, Emily J

10.1093/ageing/afaa093

[Title]: COVID-19 in older people: a rapid clinical review. [Abstract]: INTRODUCTION: the COVID-19 pandemic poses a high risk to older people. The aim of this article is to provide a rapid overview of the COVID-19 literature, with a specific focus on older adults. We frame our findings within an overview of the disease and have also evaluated the inclusion of older people within forthcoming clinical trials. METHODS: we searched PubMed and bioRxiv/medRxiv to identify English language papers describing the testing, treatment and prognosis of COVID-19. PubMed and bioRxiv/medRxiv searches took place on 20 and 24 March 2020, respectively. RESULTS: screening of over 1,100 peer-reviewed and pre-print papers yielded n = 22 on COVID-19 testing, n = 15 on treatment and n = 13 on prognosis. Viral polymerase chain reaction (PCR) and serology are the mainstays of testing, but a positive diagnosis may be increasingly supported by radiological findings. The current evidence for the effectiveness of antiviral, corticosteroid and immunotherapies is inconclusive, although trial data are largely based on younger people. In addition to age, male gender and comorbidities, specific laboratory and radiology findings are important prognostic factors. Evidence suggests that social distancing policies could have important negative consequences, particularly if in place for an extended period. CONCLUSION: given the established association between increasing age and poor prognosis in COVID-19, we anticipate that this rapid review of the current and emergent evidence might form a basis on which future work can be established. Exclusion of older people, particularly those with comorbidities, from clinical trials is well recognised and is potentially being perpetuated in the field of current COVID-19 research. [Keywords]: covid-19;non-pharmaceutical interventions;older adults;pandemic;prognosis;virology

J Thromb Thrombolysis

Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2.

Severe coronavirus disease 2019 (COVID-19) is commonly complicated with coagulopathy, the difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 has not been analyzed. Coagulation results and clinical features of consecutive patients with severe pneumonia induced by SARS-CoV2 (COVID group) and non-SARS-CoV2 (non-COVID group) in Tongji hospital were retrospectively analyzed and compared. Whether patients with elevated D-dimer could benefit from anticoagulant treatment was evaluated. There were 449 COVID patients and 104 non-COVID patients enrolled into the study. The 28-day mortality in COVID group was approximately twofold of mortality in non-COVID group (29.8% vs. 15.4%, P = 0.003), COVID group were older (65.1 +/- 12.0 vs. 58.4 +/- 18.0, years, P < 0.001) and with higher platelet count (215 +/- 100 vs. 188 +/- 98, x10(9)/L, P = 0.015), comparing to non-COVID group. The 28-day mortality of heparin users were lower than nonusers In COVID group with D-dimer > 3.0 mug/mL (32.8% vs. 52.4%, P = 0.017). Patients with severe pneumonia induced by SARS-CoV2 had higher platelet count than those induced by non-SARS-CoV2, and only the former with markedly elevated D-dimer may benefit from anticoagulant treatment.

coagulopathy;coronavirus disease 2019;d-dimer;severe pneumonia

Journal Article

Yin, Shiyu;Huang, Ming;Li, Dengju;Tang, Ning

10.1007/s11239-020-02105-8

[Title]: Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2. [Abstract]: Severe coronavirus disease 2019 (COVID-19) is commonly complicated with coagulopathy, the difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 has not been analyzed. Coagulation results and clinical features of consecutive patients with severe pneumonia induced by SARS-CoV2 (COVID group) and non-SARS-CoV2 (non-COVID group) in Tongji hospital were retrospectively analyzed and compared. Whether patients with elevated D-dimer could benefit from anticoagulant treatment was evaluated. There were 449 COVID patients and 104 non-COVID patients enrolled into the study. The 28-day mortality in COVID group was approximately twofold of mortality in non-COVID group (29.8% vs. 15.4%, P = 0.003), COVID group were older (65.1 +/- 12.0 vs. 58.4 +/- 18.0, years, P < 0.001) and with higher platelet count (215 +/- 100 vs. 188 +/- 98, x10(9)/L, P = 0.015), comparing to non-COVID group. The 28-day mortality of heparin users were lower than nonusers In COVID group with D-dimer > 3.0 mug/mL (32.8% vs. 52.4%, P = 0.017). Patients with severe pneumonia induced by SARS-CoV2 had higher platelet count than those induced by non-SARS-CoV2, and only the former with markedly elevated D-dimer may benefit from anticoagulant treatment. [Keywords]: coagulopathy;coronavirus disease 2019;d-dimer;severe pneumonia

J Pediatr Urol

A survey and panel discussion of the effects of the COVID-19 pandemic on paediatric urological productivity, guideline adherence and provider stress.

INTRODUCTION: The COVID-19 pandemic has led to an unprecedented need to re-organise and re-align priorities for all surgical specialties. Despite the current declining numbers globally, the direct effects of the pandemic on institutional practices and on personal stress and coping mechanisms remains unknown. The aims of this study were to assess the effect of the pandemic on daily scheduling and work balances, its effects on stress, and to determine compliance with guidelines and to assess whether quarantining has led to other areas of increased productivity. METHODS: A trans-Atlantic convenience sample of paediatric urologists was created in which panellists (Zoom) discussed the direct effects of the COVID-19 pandemic on individual units, as well as creating a questionnaire using a mini-Delphi method to provide current semi-quantitative data regarding practice, and adherence levels to recently published risk stratification guidelines. They also filled out a Perceived Stress Scale (PSS) questionnaire to assess contemporary pandemic stress levels. RESULTS: There was an 86% response rate from paediatric urologists. The majority of respondents reported near complete disruption to planned operations (70%), and trainee education (70%). They were also worried about the effects of altered home-lives on productivity (</=90%), as well as a lack of personal protective equipment (57%). The baseline stress rate was measured at a very high level (PSS) during the pandemic. Adherence to recent operative guidelines for urgent cases was 100%. CONCLUSION: This study represents a panel discussion of a number of practical implications for paediatric urologists, and is one of the few papers to assess more pragmatic effects and combines opinions from both sides of the Atlantic. The impact of the pandemic has been very significant for paediatric urologists and includes a decrease in the number of patients seen and operated on, decreased salary, increased self-reported stress levels, substantially increased telemedicine usage, increased free time for various activities, and good compliance with guidelines and hospital management decisions.

covid-19;pss (perceived stress scale);pandemic;sars-cov-2;telemedicine;training

Journal Article;Multicenter Study

O'Kelly, Fardod;Sparks, Scott;Seideman, Casey;Gargollo, Patricio;Granberg, Candace;Ko, Joan;Malhotra, Neha;Hecht, Sarah;Swords, Kelly;Rowe, Courtney;Whittam, Ben;Spinoit, Anne-Francoise;Dudley, Anne;Ellison, Jonathan;Chu, David;Routh, Jonathan;Cannon, Glenn;Kokorowski, Paul;Koyle, Martin;Silay, Mesrur Selcuk

10.1016/j.jpurol.2020.06.024

[Title]: A survey and panel discussion of the effects of the COVID-19 pandemic on paediatric urological productivity, guideline adherence and provider stress. [Abstract]: INTRODUCTION: The COVID-19 pandemic has led to an unprecedented need to re-organise and re-align priorities for all surgical specialties. Despite the current declining numbers globally, the direct effects of the pandemic on institutional practices and on personal stress and coping mechanisms remains unknown. The aims of this study were to assess the effect of the pandemic on daily scheduling and work balances, its effects on stress, and to determine compliance with guidelines and to assess whether quarantining has led to other areas of increased productivity. METHODS: A trans-Atlantic convenience sample of paediatric urologists was created in which panellists (Zoom) discussed the direct effects of the COVID-19 pandemic on individual units, as well as creating a questionnaire using a mini-Delphi method to provide current semi-quantitative data regarding practice, and adherence levels to recently published risk stratification guidelines. They also filled out a Perceived Stress Scale (PSS) questionnaire to assess contemporary pandemic stress levels. RESULTS: There was an 86% response rate from paediatric urologists. The majority of respondents reported near complete disruption to planned operations (70%), and trainee education (70%). They were also worried about the effects of altered home-lives on productivity (</=90%), as well as a lack of personal protective equipment (57%). The baseline stress rate was measured at a very high level (PSS) during the pandemic. Adherence to recent operative guidelines for urgent cases was 100%. CONCLUSION: This study represents a panel discussion of a number of practical implications for paediatric urologists, and is one of the few papers to assess more pragmatic effects and combines opinions from both sides of the Atlantic. The impact of the pandemic has been very significant for paediatric urologists and includes a decrease in the number of patients seen and operated on, decreased salary, increased self-reported stress levels, substantially increased telemedicine usage, increased free time for various activities, and good compliance with guidelines and hospital management decisions. [Keywords]: covid-19;pss (perceived stress scale);pandemic;sars-cov-2;telemedicine;training

J Med Virol

COVID-19 in people living with HIV: Clinical implications of dynamics of the immune response to SARS-CoV-2.

Little evidence on coronavirus disease 2019 (COVID-19) in people living with HIV (PLWH) is currently available. We reported clinical and viroimmunological data of all HIV-positive patients admitted to our center with COVID-19 from March 1 to May 12, 2020. Overall, five patients were included: all were virologically-suppressed on antiretroviral therapy and CD4+ count was greater than 350 cell/mm(3) in all but two patients. Although all patients had evidence of pneumonia on admission, only one developed respiratory failure. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was never detected from nasopharyngeal swabs in two patients, whereas in the others, viral clearance occurred within a maximum of 43 days. Immunoglobulin G production was elicited in all patients and neutralizing antibodies in all but one patient. Specific-T-cell response developed in all patients but was stronger in those with the more severe presentations. Similarly, the highest level of proinflammatory cytokines was found in the only patient experiencing respiratory failure. Despite a mild presentation, patients with more pronounced immunosuppression showed high degrees of both cytokines production and immune activation. Our study did not find an increased risk and severity of COVID-19 in PLWH. Adaptative cellular immune response to SARS-CoV-2 appeared to correlate to disease severity. The mild clinical picture showed in advanced HIV patients, despite a significant T-cell activation and inflammatory profile, suggests a potential role of HIV-driven immunological dysregulation in avoiding immune-pathogenetic processes. However, other possible explanations, as a protective role of certain antiretroviral drugs, should be considered. Further larger studies are needed to better clarify the impact of HIV infection on COVID-19.

covid-19;hiv infection;sars-cov-2;immune response

Journal Article

Mondi, Annalisa;Cimini, Eleonora;Colavita, Francesca;Cicalini, Stefania;Pinnetti, Carmela;Matusali, Giulia;Casetti, Rita;Maeurer, Markus;Vergori, Alessandra;Mazzotta, Valentina;Gagliardini, Roberta;De Zottis, Federico;Schinina, Vincenzo;Girardi, Enrico;Puro, Vincenzo;Ippolito, Giuseppe;Vaia, Francesco;Capobianchi, Maria Rosaria;Castilletti, Concetta;Agrati, Chiara;Antinori, Andrea

10.1002/jmv.26556

[Title]: COVID-19 in people living with HIV: Clinical implications of dynamics of the immune response to SARS-CoV-2. [Abstract]: Little evidence on coronavirus disease 2019 (COVID-19) in people living with HIV (PLWH) is currently available. We reported clinical and viroimmunological data of all HIV-positive patients admitted to our center with COVID-19 from March 1 to May 12, 2020. Overall, five patients were included: all were virologically-suppressed on antiretroviral therapy and CD4+ count was greater than 350 cell/mm(3) in all but two patients. Although all patients had evidence of pneumonia on admission, only one developed respiratory failure. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was never detected from nasopharyngeal swabs in two patients, whereas in the others, viral clearance occurred within a maximum of 43 days. Immunoglobulin G production was elicited in all patients and neutralizing antibodies in all but one patient. Specific-T-cell response developed in all patients but was stronger in those with the more severe presentations. Similarly, the highest level of proinflammatory cytokines was found in the only patient experiencing respiratory failure. Despite a mild presentation, patients with more pronounced immunosuppression showed high degrees of both cytokines production and immune activation. Our study did not find an increased risk and severity of COVID-19 in PLWH. Adaptative cellular immune response to SARS-CoV-2 appeared to correlate to disease severity. The mild clinical picture showed in advanced HIV patients, despite a significant T-cell activation and inflammatory profile, suggests a potential role of HIV-driven immunological dysregulation in avoiding immune-pathogenetic processes. However, other possible explanations, as a protective role of certain antiretroviral drugs, should be considered. Further larger studies are needed to better clarify the impact of HIV infection on COVID-19. [Keywords]: covid-19;hiv infection;sars-cov-2;immune response

Nutr Metab Cardiovasc Dis

A close-up on COVID-19 and cardiovascular diseases.

AIMS: To analyze the potential mechanism of cardiovascular dysfunctions induced by Coronavirus Disease 2019 (COVID-19) and to evaluate more effective therapeutic pathways for patients with cardiovascular diseases. DATA SYNTHESIS: COVID-19 mainly invades the lungs, causing its serious damage. Studies found that COVID-19 induced the renin-angiotensin system imbalance, inflammatory storm, hypoxemia, stress response, and so on; all contributed to hypertension and serious myocardial damage in the process of virus pathogenesis, even increasing mortality in COVID-19 patients. CONCLUSION: In the process of management of COVID-19 infections, close attention should be paid on both lung and cardiovascular damage, especially on those with only symptoms of cardiovascular diseases. Early identification, timely and effective treatments, and maintenance of hemodynamics and electrophysiological stability are of great significance on effective treatment and long-term prognosis.

covid-19;cardiovascular disease;potential mechanism

Journal Article;Research Support, Non-U.S. Gov't;Review

Li, Gang;Hu, Rui;Gu, Xuefang

10.1016/j.numecd.2020.04.001

[Title]: A close-up on COVID-19 and cardiovascular diseases. [Abstract]: AIMS: To analyze the potential mechanism of cardiovascular dysfunctions induced by Coronavirus Disease 2019 (COVID-19) and to evaluate more effective therapeutic pathways for patients with cardiovascular diseases. DATA SYNTHESIS: COVID-19 mainly invades the lungs, causing its serious damage. Studies found that COVID-19 induced the renin-angiotensin system imbalance, inflammatory storm, hypoxemia, stress response, and so on; all contributed to hypertension and serious myocardial damage in the process of virus pathogenesis, even increasing mortality in COVID-19 patients. CONCLUSION: In the process of management of COVID-19 infections, close attention should be paid on both lung and cardiovascular damage, especially on those with only symptoms of cardiovascular diseases. Early identification, timely and effective treatments, and maintenance of hemodynamics and electrophysiological stability are of great significance on effective treatment and long-term prognosis. [Keywords]: covid-19;cardiovascular disease;potential mechanism

Int J Environ Res Public Health

New Ways of Working? A Rapid Exploration of Emerging Evidence Regarding the Care of Older People during COVID19.

Health and social care staff have had to quickly adapt, respond and improve teamwork, as a response to the COVID-19 pandemic. Our objective was to rapidly summarize the emerging evidence of new ways of working in the care of older people during this period. We conducted an exploration of the emerging evidence within the timeframe of 1 March 2020 to 11 May 2020. To capture a broad perspective, we undertook thematic analysis of Twitter data which was extracted through a broad search for new ways of working in health and social care. For a more in-depth focus on the health and social care of older people, we undertook a systematic scoping of newspapers using the Nexis UK database. We undertook a validation workshop with members of the interprofessional working group of the Irish National Integrated Care Programme for Older People, and with researchers. A total of 317 tweets were extracted related to six new ways of working. There was evidence of using telehealth to provide ongoing care to patients; interprofessional work; team meetings using online platforms; trust and collaboration within teams; as well as teams feeling empowered to change at a local level. 34 newspaper articles were extracted related to new ways of working in the care of older people, originating in England (n = 17), Wales (n = 6), Scotland (n = 6), Ireland (n = 4) and Germany (n = 1). Four main themes were captured that focused on role expansion, innovations in communication, environmental restructuring and enablement. The results of this exploration of emerging evidence show that health and social care teams can transform very rapidly. Much of the change was based on goodwill as a response to the pandemic. Further analysis of empirical evidence of changing practices should include the perspectives of older people and should capture the resources needed to sustain innovations, as well as evaluate gaps in service provision.

covid-19;health and social care;integrated care;new ways of working;older people;social media;teamwork

Journal Article

Ni She, Eidin;O'Donnell, Deirdre;O'Shea, Marie;Stokes, Diarmuid

10.3390/ijerph17186442

[Title]: New Ways of Working? A Rapid Exploration of Emerging Evidence Regarding the Care of Older People during COVID19. [Abstract]: Health and social care staff have had to quickly adapt, respond and improve teamwork, as a response to the COVID-19 pandemic. Our objective was to rapidly summarize the emerging evidence of new ways of working in the care of older people during this period. We conducted an exploration of the emerging evidence within the timeframe of 1 March 2020 to 11 May 2020. To capture a broad perspective, we undertook thematic analysis of Twitter data which was extracted through a broad search for new ways of working in health and social care. For a more in-depth focus on the health and social care of older people, we undertook a systematic scoping of newspapers using the Nexis UK database. We undertook a validation workshop with members of the interprofessional working group of the Irish National Integrated Care Programme for Older People, and with researchers. A total of 317 tweets were extracted related to six new ways of working. There was evidence of using telehealth to provide ongoing care to patients; interprofessional work; team meetings using online platforms; trust and collaboration within teams; as well as teams feeling empowered to change at a local level. 34 newspaper articles were extracted related to new ways of working in the care of older people, originating in England (n = 17), Wales (n = 6), Scotland (n = 6), Ireland (n = 4) and Germany (n = 1). Four main themes were captured that focused on role expansion, innovations in communication, environmental restructuring and enablement. The results of this exploration of emerging evidence show that health and social care teams can transform very rapidly. Much of the change was based on goodwill as a response to the pandemic. Further analysis of empirical evidence of changing practices should include the perspectives of older people and should capture the resources needed to sustain innovations, as well as evaluate gaps in service provision. [Keywords]: covid-19;health and social care;integrated care;new ways of working;older people;social media;teamwork

Eur J Clin Microbiol Infect Dis

Influenza and respiratory syncytial virus infections in the oldest-old continent.

SARS-CoV-2 dramatically revealed the sudden impact of respiratory viruses in our lives. Influenza and respiratory syncytial virus (RSV) infections are associated with high rates of morbidity, mortality, and an important burden on healthcare systems worldwide, especially in elderly patients. The aim of this study was to identify severity predictors in the oldest-old admitted with influenza and/or RSV infections. This is a multicenter, retrospective study of all oldest-old patients (>/= 85 years old) admitted for laboratory-confirmed influenza and/or RSV infection in three tertiary hospitals in Portugal, Italy, and Cyprus over two consecutive winter seasons. The outcomes included the following: pneumonia on infection presentation, use of non-invasive ventilation (NIV), and in-hospital death (IHD). The association with possible predictors, including clinical features and type of virus infection, was assessed using uni- and multivariable analyses. A total of 251 oldest-old patients were included in the study. Pneumonia was evident in 32.3% (n = 81). NIV was implemented in 8.8% (n = 22), and IHD occurred in 13.9% (n = 35). Multivariable analyses revealed that chronic obstructive pulmonary disease (COPD) or asthma was associated with pneumonia (OR 1.86; 95% CI 1.02-3.43; p = 0.045). COPD or asthma (OR 4.4; 95% CI 1.67-11.6; p = 0.003), RSV (OR 3.12; 95% CI 1.09-8.92; p = 0.023), and influenza B infections (OR 3.77; 95% CI 1.06-13.5; p = 0.041) were associated with NIV use, respectively, while chronic kidney disease was associated with IHD (OR 2.50; 95% CI 1.14-5.51; p = 0.023). Among the oldest-old, chronic organ failure, such as COPD or asthma, and CKD predicted pneumonia and IHD, respectively, beyond the importance of viral virulence itself. These findings could impact on public health policies, such as fostering influenza immunization campaigns, home-based care programs, and end-of-life care. Filling knowledge gaps is crucial to set priorities and advise on transition model of care that best fits the oldest-old.

geriatrics;influenza;oldest-old;pneumonia;respiratory syncytial virus

Journal Article;Multicenter Study

Boattini, Matteo;Almeida, Andre;Christaki, Eirini;Cruz, Lourenco;Antao, Diogo;Moreira, Maria Ines;Bianco, Gabriele;Iannaccone, Marco;Tsiolakkis, Georgios;Khattab, Elina;Kasapi, Diamanto;Charrier, Lorena;Tosatto, Valentina;Marques, Torcato Moreira;Cavallo, Rossana;Costa, Cristina

10.1007/s10096-020-03959-9

[Title]: Influenza and respiratory syncytial virus infections in the oldest-old continent. [Abstract]: SARS-CoV-2 dramatically revealed the sudden impact of respiratory viruses in our lives. Influenza and respiratory syncytial virus (RSV) infections are associated with high rates of morbidity, mortality, and an important burden on healthcare systems worldwide, especially in elderly patients. The aim of this study was to identify severity predictors in the oldest-old admitted with influenza and/or RSV infections. This is a multicenter, retrospective study of all oldest-old patients (>/= 85 years old) admitted for laboratory-confirmed influenza and/or RSV infection in three tertiary hospitals in Portugal, Italy, and Cyprus over two consecutive winter seasons. The outcomes included the following: pneumonia on infection presentation, use of non-invasive ventilation (NIV), and in-hospital death (IHD). The association with possible predictors, including clinical features and type of virus infection, was assessed using uni- and multivariable analyses. A total of 251 oldest-old patients were included in the study. Pneumonia was evident in 32.3% (n = 81). NIV was implemented in 8.8% (n = 22), and IHD occurred in 13.9% (n = 35). Multivariable analyses revealed that chronic obstructive pulmonary disease (COPD) or asthma was associated with pneumonia (OR 1.86; 95% CI 1.02-3.43; p = 0.045). COPD or asthma (OR 4.4; 95% CI 1.67-11.6; p = 0.003), RSV (OR 3.12; 95% CI 1.09-8.92; p = 0.023), and influenza B infections (OR 3.77; 95% CI 1.06-13.5; p = 0.041) were associated with NIV use, respectively, while chronic kidney disease was associated with IHD (OR 2.50; 95% CI 1.14-5.51; p = 0.023). Among the oldest-old, chronic organ failure, such as COPD or asthma, and CKD predicted pneumonia and IHD, respectively, beyond the importance of viral virulence itself. These findings could impact on public health policies, such as fostering influenza immunization campaigns, home-based care programs, and end-of-life care. Filling knowledge gaps is crucial to set priorities and advise on transition model of care that best fits the oldest-old. [Keywords]: geriatrics;influenza;oldest-old;pneumonia;respiratory syncytial virus

Cardiovasc Diagn Ther

Pulmonary vascular endothelial injury and acute pulmonary hypertension caused by COVID-19: the fundamental cause of refractory hypoxemia?

Coronavirus disease (COVID-19) is a severe infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that binds to the cells; angiotensin converting enzyme 2 (ACE2) receptor. In the first severe case of COVID-19 in Shenzhen city, we found that in addition to the typical clinical manifestations, our patient presented hemoptysis, refractory hypoxemia and pulmonary fibrosis-like changes on computed tomography (CT) involving alveoli and pulmonary interstitium in the early stage and acute pulmonary hypertension and right heart failure in the later stage, which were not completely justified by myocarditis, acute respiratory distress syndrome (ARDS), pulmonary fibrosis and high PEEP level. The lung compliance deterioration of this patient was not as serious as we expected, indicating classic ARDS was not existed. Simultaneously, the first autopsy report of COVID-19 in China showed normal-structured alveoli and massive thick excretion in the airway. Then, we speculated that the virus not only attacked alveolar epithelial cells, but also affected pulmonary vascular endothelial cells. Imbalance in the ACE2-RAAS- bradykinin axis and the cytokine storm could be an important mechanism leading to pathophysiological changes in pulmonary vascular and secondary refractory hypoxemia. Pulmonary vasculitis or capillaritis associated to immune damage and an inflammatory storm could exist in COVID-19 because of ground-glass opacities in the subpleural area, which are similar to connective tissue disease associated interstitial lung disease (CTD-ILD). Thus, this case elucidates new treatment measures for COVID-19.

ace2;coronavirus disease (covid-19);pulmonary hypertension;pulmonary vascular endothelium;refractory hypoxemia

Case Reports

Wang, Xinxin;Tu, Yunliang;Huang, Bin;Li, Yinfeng;Li, Yanyan;Zhang, Sheng;Lin, Yingxin;Huang, Lei;Zhang, Weixing;Luo, Hua

10.21037/cdt-20-429

[Title]: Pulmonary vascular endothelial injury and acute pulmonary hypertension caused by COVID-19: the fundamental cause of refractory hypoxemia? [Abstract]: Coronavirus disease (COVID-19) is a severe infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that binds to the cells; angiotensin converting enzyme 2 (ACE2) receptor. In the first severe case of COVID-19 in Shenzhen city, we found that in addition to the typical clinical manifestations, our patient presented hemoptysis, refractory hypoxemia and pulmonary fibrosis-like changes on computed tomography (CT) involving alveoli and pulmonary interstitium in the early stage and acute pulmonary hypertension and right heart failure in the later stage, which were not completely justified by myocarditis, acute respiratory distress syndrome (ARDS), pulmonary fibrosis and high PEEP level. The lung compliance deterioration of this patient was not as serious as we expected, indicating classic ARDS was not existed. Simultaneously, the first autopsy report of COVID-19 in China showed normal-structured alveoli and massive thick excretion in the airway. Then, we speculated that the virus not only attacked alveolar epithelial cells, but also affected pulmonary vascular endothelial cells. Imbalance in the ACE2-RAAS- bradykinin axis and the cytokine storm could be an important mechanism leading to pathophysiological changes in pulmonary vascular and secondary refractory hypoxemia. Pulmonary vasculitis or capillaritis associated to immune damage and an inflammatory storm could exist in COVID-19 because of ground-glass opacities in the subpleural area, which are similar to connective tissue disease associated interstitial lung disease (CTD-ILD). Thus, this case elucidates new treatment measures for COVID-19. [Keywords]: ace2;coronavirus disease (covid-19);pulmonary hypertension;pulmonary vascular endothelium;refractory hypoxemia

Curr Biol

On the evolutionary epidemiology of SARS-CoV-2.

There is no doubt that the novel coronavirus SARS-CoV-2 that causes COVID-19 is mutating and thus has the potential to adapt during the current pandemic. Whether this evolution will lead to changes in the transmission, the duration, or the severity of the disease is not clear. This has led to considerable scientific and media debate, from raising alarms about evolutionary change to dismissing it. Here we review what little is currently known about the evolution of SARS-CoV-2 and extend existing evolutionary theory to consider how selection might be acting upon the virus during the COVID-19 pandemic. Although there is currently no definitive evidence that SARS-CoV-2 is undergoing further adaptation, continued evidence-based analysis of evolutionary change is important so that public health measures can be adjusted in response to substantive changes in the infectivity or severity of COVID-19.

Journal Article;Research Support, Non-U.S. Gov't

Day, Troy;Gandon, Sylvain;Lion, Sebastien;Otto, Sarah P

10.1016/j.cub.2020.06.031

[Title]: On the evolutionary epidemiology of SARS-CoV-2. [Abstract]: There is no doubt that the novel coronavirus SARS-CoV-2 that causes COVID-19 is mutating and thus has the potential to adapt during the current pandemic. Whether this evolution will lead to changes in the transmission, the duration, or the severity of the disease is not clear. This has led to considerable scientific and media debate, from raising alarms about evolutionary change to dismissing it. Here we review what little is currently known about the evolution of SARS-CoV-2 and extend existing evolutionary theory to consider how selection might be acting upon the virus during the COVID-19 pandemic. Although there is currently no definitive evidence that SARS-CoV-2 is undergoing further adaptation, continued evidence-based analysis of evolutionary change is important so that public health measures can be adjusted in response to substantive changes in the infectivity or severity of COVID-19. [Keywords]:

J Transl Med

Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak.

BACKGROUND: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next 'Disease X'. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim((R))) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim((R)) creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-Upsilon, leading to development of an "anti-viral state", by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allo-specific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-Upsilon, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/CTL in circulation capable of responding to the next viral encounter. CONCLUSION: Allo-priming has potential to provide universal protection from viral disease and is a strategy to reverse immunosenescence and counter-regulate chronic inflammation (inflammaging). Allo-priming can be used as an adjuvant for anti-viral vaccines and as a counter-measure for unknown biological threats and bio-economic terrorism.

covid-19;cell therapy;immunosenescence;immunotherapy;inflammaging;vaccine

Journal Article

Har-Noy, Michael;Or, Reuven

10.1186/s12967-020-02363-3

[Title]: Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak. [Abstract]: BACKGROUND: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next 'Disease X'. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim((R))) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim((R)) creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-Upsilon, leading to development of an "anti-viral state", by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allo-specific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-Upsilon, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/CTL in circulation capable of responding to the next viral encounter. CONCLUSION: Allo-priming has potential to provide universal protection from viral disease and is a strategy to reverse immunosenescence and counter-regulate chronic inflammation (inflammaging). Allo-priming can be used as an adjuvant for anti-viral vaccines and as a counter-measure for unknown biological threats and bio-economic terrorism. [Keywords]: covid-19;cell therapy;immunosenescence;immunotherapy;inflammaging;vaccine

Front Med (Lausanne)

Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms: An Analysis of Seven Patients in China.

Objectives: Patients with novel coronavirus disease 2019 (COVID-19) can present with gastrointestinal symptoms as their initial symptoms or as the main manifestations during disease progression, but the clinical characteristics of these patients are still unknown. Methods: We identified COVID-19 patients who admitted to Xiangyang No. 1 People's Hospital and presented with gastrointestinal symptoms as their initial or main symptoms. Their medical records were reviewed by two independent clinical scientists. The epidemiological and clinical characteristics as well as the clinical outcomes were analyzed. Results: Among 142 confirmed COVID-19 cases, 7 (4.9%) of them presented with gastrointestinal symptoms. Three patients had gastrointestinal symptoms as the initial symptoms and chief complaints, and 4 patients as the main symptoms during disease progression. Six patients had symptoms of diarrhea (3-16 days), 7 with anorexia (7-22 days), 6 with upper abdominal discomfort (1-7 days), and 4 with nausea (1-7 days), 1 with heartburn lasting 2 days, and 2 with vomiting symptoms (1 day). The chest CT scan showed typical COVID-19 imaging features, and associated with the progression of the disease. During treatment, 2 patients died due to organ failure. Discussion: COVID-19 patients with gastrointestinal symptoms are relatively rare and might be misdiagnosed. The clinical features include watery stools, anorexia, and upper abdominal discomfort. These patients may have severe disease and be associated with a poor prognosis. The underlying mechanisms of SARS-CoV-2 related gastrointestinal symptoms need to clarify in future studies.

2019-ncov;covid-19;sars-cov-2;diarrhea;digestive tract;gastrointestinal symptom

Journal Article

Ai, Jin-Wei;Zi, Hao;Wang, Yong;Huang, Qiao;Wang, Na;Li, Lu-Yao;Pei, Bin;Ji, Jianguang;Zeng, Xian-Tao

10.3389/fmed.2020.00308

[Title]: Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms: An Analysis of Seven Patients in China. [Abstract]: Objectives: Patients with novel coronavirus disease 2019 (COVID-19) can present with gastrointestinal symptoms as their initial symptoms or as the main manifestations during disease progression, but the clinical characteristics of these patients are still unknown. Methods: We identified COVID-19 patients who admitted to Xiangyang No. 1 People's Hospital and presented with gastrointestinal symptoms as their initial or main symptoms. Their medical records were reviewed by two independent clinical scientists. The epidemiological and clinical characteristics as well as the clinical outcomes were analyzed. Results: Among 142 confirmed COVID-19 cases, 7 (4.9%) of them presented with gastrointestinal symptoms. Three patients had gastrointestinal symptoms as the initial symptoms and chief complaints, and 4 patients as the main symptoms during disease progression. Six patients had symptoms of diarrhea (3-16 days), 7 with anorexia (7-22 days), 6 with upper abdominal discomfort (1-7 days), and 4 with nausea (1-7 days), 1 with heartburn lasting 2 days, and 2 with vomiting symptoms (1 day). The chest CT scan showed typical COVID-19 imaging features, and associated with the progression of the disease. During treatment, 2 patients died due to organ failure. Discussion: COVID-19 patients with gastrointestinal symptoms are relatively rare and might be misdiagnosed. The clinical features include watery stools, anorexia, and upper abdominal discomfort. These patients may have severe disease and be associated with a poor prognosis. The underlying mechanisms of SARS-CoV-2 related gastrointestinal symptoms need to clarify in future studies. [Keywords]: 2019-ncov;covid-19;sars-cov-2;diarrhea;digestive tract;gastrointestinal symptom

Catheter Cardiovasc Interv

The experience of treating patients with acute myocardial infarction under the COVID-19 epidemic.

Worldwide Coronavirus Disease 2019 (COVID-19) epidemic makes the management of acute myocardial infarction (AMI) more complicated, effective treatment without further dissemination is thus quite challenging. Recently, we successfully treated three representative AMI cases, by sharing these detailed procedures, we summarized some important issues including patient screening, reperfusion strategy selecting, personnel/catheter lab protection principle, as well as operation tactics, which may lend precious experience on AMI treating during the ongoing COVID-19 pandemic situation.

covid-19;acute myocardial infarction;pandemic;percutaneous coronary intervention;personnel protection equipment

Case Reports;Journal Article

Xiao, Zhichao;Xu, Chang;Wang, Daowen;Zeng, Hesong

10.1002/ccd.28951

[Title]: The experience of treating patients with acute myocardial infarction under the COVID-19 epidemic. [Abstract]: Worldwide Coronavirus Disease 2019 (COVID-19) epidemic makes the management of acute myocardial infarction (AMI) more complicated, effective treatment without further dissemination is thus quite challenging. Recently, we successfully treated three representative AMI cases, by sharing these detailed procedures, we summarized some important issues including patient screening, reperfusion strategy selecting, personnel/catheter lab protection principle, as well as operation tactics, which may lend precious experience on AMI treating during the ongoing COVID-19 pandemic situation. [Keywords]: covid-19;acute myocardial infarction;pandemic;percutaneous coronary intervention;personnel protection equipment

Int J Audiol

Telehealth tinnitus therapy during the COVID-19 outbreak in the UK: uptake and related factors.

OBJECTIVE: The Audiology Department at the Royal Surrey County Hospital usually offers face-to-face audiologist-delivered cognitive behavioural therapy (CBT) for tinnitus rehabilitation. During COVID-19 lockdown, patients were offered telehealth CBT via video using a web-based platform. This study evaluated the proportion of patients who took up the offer of telehealth sessions and factors related to this. DESIGN: Retrospective service evaluation. STUDY SAMPLE: 113 consecutive patients whose care was interrupted by the lockdown. RESULTS: 80% of patients accepted telehealth. The main reasons for declining were not having access to a suitable device and the belief that telehealth appointments would not be useful. Compared to having no hearing loss in the better ear, having a mild or moderate hearing loss increased the chance of declining telehealth by factors of 3.5 (p = 0.04) and 14.9 (p = 0.038), respectively. High tinnitus annoyance as measured via the visual analogue scale increased the chance of declining telehealth appointments by a factor of 1.4 (p = 0.019). CONCLUSIONS: Although CBT via telehealth was acceptable to most patients, alternatives may be necessary for the 20% who declined. These tended to have worse hearing in their better ear and more annoying tinnitus.

tinnitus;audiology;covid-19;telehealth;video

Journal Article

Aazh, Hashir;Swanepoel, De Wet;Moore, Brian C J

10.1080/14992027.2020.1822553

[Title]: Telehealth tinnitus therapy during the COVID-19 outbreak in the UK: uptake and related factors. [Abstract]: OBJECTIVE: The Audiology Department at the Royal Surrey County Hospital usually offers face-to-face audiologist-delivered cognitive behavioural therapy (CBT) for tinnitus rehabilitation. During COVID-19 lockdown, patients were offered telehealth CBT via video using a web-based platform. This study evaluated the proportion of patients who took up the offer of telehealth sessions and factors related to this. DESIGN: Retrospective service evaluation. STUDY SAMPLE: 113 consecutive patients whose care was interrupted by the lockdown. RESULTS: 80% of patients accepted telehealth. The main reasons for declining were not having access to a suitable device and the belief that telehealth appointments would not be useful. Compared to having no hearing loss in the better ear, having a mild or moderate hearing loss increased the chance of declining telehealth by factors of 3.5 (p = 0.04) and 14.9 (p = 0.038), respectively. High tinnitus annoyance as measured via the visual analogue scale increased the chance of declining telehealth appointments by a factor of 1.4 (p = 0.019). CONCLUSIONS: Although CBT via telehealth was acceptable to most patients, alternatives may be necessary for the 20% who declined. These tended to have worse hearing in their better ear and more annoying tinnitus. [Keywords]: tinnitus;audiology;covid-19;telehealth;video

Inform Med Unlocked

Structure-based drug designing towards the identification of potential anti-viral for COVID-19 by targeting endoribonuclease NSP15.

The world is facing health and economic havoc due to the Corona Virus Disease-2019 (COVID-19) pandemic. Given the number of affected people and the mortality rate, the virus is undoubtedly a serious threat to humanity. By analogy with earlier reports about Severe Acute Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) - viruses, the novel Coronavirus' replication mechanism is likely well understood. The structure of an endoribonuclease (NSP15) of SARS-CoV-2 was reported recently. This enzyme is expected to play a crucial role in replication. In this work, attempts were made to identify inhibitors of this enzyme. To achieve the goal, high throughput in silico screening and molecular docking procedures were performed. From an Enamine database of a billion compounds, 3978 compounds with potential antiviral activity were selected for screening and induced fit docking that funneled down to eight compounds with good docking score and docking energy. Detailed analysis of non-covalent interactions at the active site and the apparent match of the molecule with the shape of the binding pocket were assessed. All the compounds show significant interactions for tight binding. Since all the compounds are synthetic with favorable drug-like properties, these may be considered for immediate optimization and downstream applications.

covid-19;coronavirus;endoribonuclease;nsp15 inhibitors

Journal Article

Krishnan, D Anantha;Sangeetha, G;Vajravijayan, S;Nandhagopal, N;Gunasekaran, K

10.1016/j.imu.2020.100392

[Title]: Structure-based drug designing towards the identification of potential anti-viral for COVID-19 by targeting endoribonuclease NSP15. [Abstract]: The world is facing health and economic havoc due to the Corona Virus Disease-2019 (COVID-19) pandemic. Given the number of affected people and the mortality rate, the virus is undoubtedly a serious threat to humanity. By analogy with earlier reports about Severe Acute Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) - viruses, the novel Coronavirus' replication mechanism is likely well understood. The structure of an endoribonuclease (NSP15) of SARS-CoV-2 was reported recently. This enzyme is expected to play a crucial role in replication. In this work, attempts were made to identify inhibitors of this enzyme. To achieve the goal, high throughput in silico screening and molecular docking procedures were performed. From an Enamine database of a billion compounds, 3978 compounds with potential antiviral activity were selected for screening and induced fit docking that funneled down to eight compounds with good docking score and docking energy. Detailed analysis of non-covalent interactions at the active site and the apparent match of the molecule with the shape of the binding pocket were assessed. All the compounds show significant interactions for tight binding. Since all the compounds are synthetic with favorable drug-like properties, these may be considered for immediate optimization and downstream applications. [Keywords]: covid-19;coronavirus;endoribonuclease;nsp15 inhibitors

Crit Care Resusc

ANZICS guiding principles for complex decision making during the COVID-19 pandemic.

The global 2019 coronavirus disease (COVID-19) pandemic has led to major challenges in clinical decision making when the demand for intensive care exceeds local capacity. In order to promote consistent, transparent, objective and ethical decision making, the Australian and New Zealand Intensive Care Society (ANZICS) formed a committee to urgently develop guidelines outlining key principles that should be utilised during the pandemic. This guidance is intended to support the practice of intensive care specialists during the COVID-19 pandemic and to promote the development of local admission policies that should be endorsed by health care organisations and relevant local authorities.

covid-19

Journal Article

Warrillow, Stephen;Austin, Danielle;Cheung, Winston;Close, Eliana;Holley, Anthony;Horgan, Ben;Jansen, Melanie;Joynt, Gavin;Lister, Paula;Moodie, Stewart;Nichol, Alistair;Nicholls, Mark;Peake, Sandra;Skowronski, George;Streat, Stephen;White, Ben;Willmott, Lindy

[Title]: ANZICS guiding principles for complex decision making during the COVID-19 pandemic. [Abstract]: The global 2019 coronavirus disease (COVID-19) pandemic has led to major challenges in clinical decision making when the demand for intensive care exceeds local capacity. In order to promote consistent, transparent, objective and ethical decision making, the Australian and New Zealand Intensive Care Society (ANZICS) formed a committee to urgently develop guidelines outlining key principles that should be utilised during the pandemic. This guidance is intended to support the practice of intensive care specialists during the COVID-19 pandemic and to promote the development of local admission policies that should be endorsed by health care organisations and relevant local authorities. [Keywords]: covid-19

Otolaryngol Head Neck Surg

Patients With Voice Prosthesis Rehabilitation During the COVID-19 Pandemic: Analyzing the Effectiveness of Remote Triage and Management.

OBJECTIVE: To describe a remote approach used with patients with voice prosthesis after laryngectomy during the COVID-19 pandemic and the resulting clinical outcomes in terms of voice prosthesis complications management, oncological monitoring, and psychophysical well-being. STUDY DESIGN: Prospective cohort study. SETTING: Otolaryngology Clinic of the University Polyclinic A. Gemelli, IRCCS Foundation. SUBJECTS AND METHODS: All patients with voice prosthesis who underwent laryngectomy followed by our institute were offered enrollment. Patients who agreed to participate were interviewed to inquire about the nature of the need and to plan a video call with the appropriate clinician. Before and 1 week after the clinician's call, patients were tested with the Hospital Anxiety and Depression Scale. Degrees of satisfaction were investigated with a visual analog scale. A comparison between those who accepted and refused telematic support was carried out to identify factors that influence patient interest in teleservice. RESULTS: Video call service allowed us to reach 37 (50.68%) of 73 patients. In 23 (62.16%) of 37 cases, the video call was sufficient to manage the problem. In the remaining 14 cases (37.83%), an outpatient visit was necessary. Participants who refused telematic support had a significantly shorter time interval from the last ear, nose, and throat visit than patients who accepted (57.95 vs 96.14 days, P = .03). Video-called patients showed significantly decreased levels of anxiety and depression (mean Hospital Anxiety and Depression Scale total score pre- vs post-video call: 13.97 vs. 10.23, P < .0001) and reported high levels of satisfaction about the service. CONCLUSION: Remote approach may be a viable support in the management of patients with voice prosthesis rehabilitation.

covid-19;management;total laryngectomy;voice prosthesis

Journal Article

Longobardi, Ylenia;Galli, Jacopo;D'Alatri, Lucia;Savoia, Vezio;Mari, Giorgia;Rigante, Mario;Passali, Giulio Cesare;Bussu, Francesco;Parrilla, Claudio

10.1177/0194599820948043

[Title]: Patients With Voice Prosthesis Rehabilitation During the COVID-19 Pandemic: Analyzing the Effectiveness of Remote Triage and Management. [Abstract]: OBJECTIVE: To describe a remote approach used with patients with voice prosthesis after laryngectomy during the COVID-19 pandemic and the resulting clinical outcomes in terms of voice prosthesis complications management, oncological monitoring, and psychophysical well-being. STUDY DESIGN: Prospective cohort study. SETTING: Otolaryngology Clinic of the University Polyclinic A. Gemelli, IRCCS Foundation. SUBJECTS AND METHODS: All patients with voice prosthesis who underwent laryngectomy followed by our institute were offered enrollment. Patients who agreed to participate were interviewed to inquire about the nature of the need and to plan a video call with the appropriate clinician. Before and 1 week after the clinician's call, patients were tested with the Hospital Anxiety and Depression Scale. Degrees of satisfaction were investigated with a visual analog scale. A comparison between those who accepted and refused telematic support was carried out to identify factors that influence patient interest in teleservice. RESULTS: Video call service allowed us to reach 37 (50.68%) of 73 patients. In 23 (62.16%) of 37 cases, the video call was sufficient to manage the problem. In the remaining 14 cases (37.83%), an outpatient visit was necessary. Participants who refused telematic support had a significantly shorter time interval from the last ear, nose, and throat visit than patients who accepted (57.95 vs 96.14 days, P = .03). Video-called patients showed significantly decreased levels of anxiety and depression (mean Hospital Anxiety and Depression Scale total score pre- vs post-video call: 13.97 vs. 10.23, P < .0001) and reported high levels of satisfaction about the service. CONCLUSION: Remote approach may be a viable support in the management of patients with voice prosthesis rehabilitation. [Keywords]: covid-19;management;total laryngectomy;voice prosthesis

Clin Gastroenterol Hepatol

Surveillance and Monitoring of Hepatocellular Carcinoma During the COVID-19 Pandemic.

The Coronavirus disease 2019 (COVID-19) pandemic is expected to have a long-lasting impact on the approach to care for patients at risk for and with hepatocellular carcinoma (HCC) due to the risks from potential exposure and resource reallocation. The goal of this document is to provide recommendations on HCC surveillance and monitoring, including strategies to limit unnecessary exposure while continuing to provide high-quality care for patients. Publications and guidelines pertaining to the management of HCC during COVID-19 were reviewed for recommendations related to surveillance and monitoring practices, and any available guidance was referenced to support the authors' recommendations when applicable. Existing HCC risk stratification models should be utilized to prioritize imaging resources to those patients at highest risk of incident HCC and recurrence following therapy though surveillance can likely continue as before in settings where COVID-19 prevalence is low and adequate protections are in place. Waitlisted patients who will benefit from urgent LT should be prioritized for surveillance whereas it would be reasonable to extend surveillance interval by a short period in HCC patients with lower risk tumor features and those more than 2 years since their last treatment. For patients eligible for systemic therapy, the treatment regimen should be dictated by the risk of COVID-19 associated with route of administration, monitoring and treatment of adverse events, within the context of relative treatment efficacy.

afp;alpha-fetoprotein;coronavirus;hcc;screening

Journal Article;Review

Mehta, Neil;Parikh, Neehar;Kelley, R Katie;Hameed, Bilal;Singal, Amit G

10.1016/j.cgh.2020.06.072

[Title]: Surveillance and Monitoring of Hepatocellular Carcinoma During the COVID-19 Pandemic. [Abstract]: The Coronavirus disease 2019 (COVID-19) pandemic is expected to have a long-lasting impact on the approach to care for patients at risk for and with hepatocellular carcinoma (HCC) due to the risks from potential exposure and resource reallocation. The goal of this document is to provide recommendations on HCC surveillance and monitoring, including strategies to limit unnecessary exposure while continuing to provide high-quality care for patients. Publications and guidelines pertaining to the management of HCC during COVID-19 were reviewed for recommendations related to surveillance and monitoring practices, and any available guidance was referenced to support the authors' recommendations when applicable. Existing HCC risk stratification models should be utilized to prioritize imaging resources to those patients at highest risk of incident HCC and recurrence following therapy though surveillance can likely continue as before in settings where COVID-19 prevalence is low and adequate protections are in place. Waitlisted patients who will benefit from urgent LT should be prioritized for surveillance whereas it would be reasonable to extend surveillance interval by a short period in HCC patients with lower risk tumor features and those more than 2 years since their last treatment. For patients eligible for systemic therapy, the treatment regimen should be dictated by the risk of COVID-19 associated with route of administration, monitoring and treatment of adverse events, within the context of relative treatment efficacy. [Keywords]: afp;alpha-fetoprotein;coronavirus;hcc;screening

Korean J Anesthesiol

Perioperative considerations for COVID-19 patients: lessons learned from the pandemic -a case series.

Background: As the coronavirus disease 2019 (COVID-19) pandemic spreads globally, hospitals are rushing to adapt their facilities, which were not designed to deal with infections adequately. Here, we present the management of a suspected COVID-19 patient. Case: A 66-year-old man with a recent travel history, infective symptoms, and chest X-ray was presented to our hospital. Considering his septic condition, we decided to perform an emergency surgery. The patient was given supplemental oxygen through a face mask and transported to an operating theatre on a plastic-covered trolley. An experienced anesthetist performed rapid sequence intubation using a video laryngoscope. Due to the initial presentation of respiratory distress, the patient remained intubated after surgery to avoid re-intubation. Precautions against droplet, contact, and airborne infection were instituted. Conclusions: Our objective was to facilitate surgical management of patients with known or suspected COVID-19 while minimizing the risk of nosocomial transmission to healthcare workers and other patients.

covid-19;communication;coronavirus;infection control;pandemics;perioperative care;perioperative period;personal protective equipment

Case Reports

Yek, Jia Lin Jacklyn;Kiew, Sheng Chuu Anne;Ngu, James Chi-Yong;Lim, Jimmy Guan Cheng

10.4097/kja.20182

[Title]: Perioperative considerations for COVID-19 patients: lessons learned from the pandemic -a case series. [Abstract]: Background: As the coronavirus disease 2019 (COVID-19) pandemic spreads globally, hospitals are rushing to adapt their facilities, which were not designed to deal with infections adequately. Here, we present the management of a suspected COVID-19 patient. Case: A 66-year-old man with a recent travel history, infective symptoms, and chest X-ray was presented to our hospital. Considering his septic condition, we decided to perform an emergency surgery. The patient was given supplemental oxygen through a face mask and transported to an operating theatre on a plastic-covered trolley. An experienced anesthetist performed rapid sequence intubation using a video laryngoscope. Due to the initial presentation of respiratory distress, the patient remained intubated after surgery to avoid re-intubation. Precautions against droplet, contact, and airborne infection were instituted. Conclusions: Our objective was to facilitate surgical management of patients with known or suspected COVID-19 while minimizing the risk of nosocomial transmission to healthcare workers and other patients. [Keywords]: covid-19;communication;coronavirus;infection control;pandemics;perioperative care;perioperative period;personal protective equipment

Diabetes Metab Syndr

A review of modern technologies for tackling COVID-19 pandemic.

OBJECTIVE: Science and technology sector constituting of data science, machine learning and artificial intelligence are contributing towards COVID-19. The aim of the present study is to discuss the various aspects of modern technology used to fight against COVID-19 crisis at different scales, including medical image processing, disease tracking, prediction outcomes, computational biology and medicines. METHODS: A progressive search of the database related to modern technology towards COVID-19 is made. Further, a brief review is done on the extracted information by assessing the various aspects of modern technologies for tackling COVID-19 pandemic. RESULTS: We provide a window of thoughts on review of the technology advances used to decrease and smother the substantial impact of the outburst. Though different studies relating to modern technology towards COVID-19 have come up, yet there are still constrained applications and contributions of technology in this fight. CONCLUSIONS: On-going progress in the modern technology has contributed in improving people's lives and hence there is a solid conviction that validated research plans including artificial intelligence will be of significant advantage in helping people to fight this infection.

artificial intelligence;covid-19;epidemic;machine learning

Journal Article;Review

Kumar, Aishwarya;Gupta, Puneet Kumar;Srivastava, Ankita

10.1016/j.dsx.2020.05.008

[Title]: A review of modern technologies for tackling COVID-19 pandemic. [Abstract]: OBJECTIVE: Science and technology sector constituting of data science, machine learning and artificial intelligence are contributing towards COVID-19. The aim of the present study is to discuss the various aspects of modern technology used to fight against COVID-19 crisis at different scales, including medical image processing, disease tracking, prediction outcomes, computational biology and medicines. METHODS: A progressive search of the database related to modern technology towards COVID-19 is made. Further, a brief review is done on the extracted information by assessing the various aspects of modern technologies for tackling COVID-19 pandemic. RESULTS: We provide a window of thoughts on review of the technology advances used to decrease and smother the substantial impact of the outburst. Though different studies relating to modern technology towards COVID-19 have come up, yet there are still constrained applications and contributions of technology in this fight. CONCLUSIONS: On-going progress in the modern technology has contributed in improving people's lives and hence there is a solid conviction that validated research plans including artificial intelligence will be of significant advantage in helping people to fight this infection. [Keywords]: artificial intelligence;covid-19;epidemic;machine learning

Int J Infect Dis

Increased Complement Receptor-3 levels in monocytes and granulocytes distinguish COVID-19 patients with pneumonia from those with mild symptoms.

BACKGROUND: The reasons why some patients with COVID-19 develop pneumonia and others do not are unclear. To better understand this, we used multiparameter flow cytometry to profile circulating leukocytes from non-immunocompromised adult patients with PCR-proven COVID-19 and specifically compared those with mild symptoms with those who had developed pneumonia. METHODS: Using clinically validated antibody panels we studied leukocytes from 29 patients with PCR-proven COVID-19. Ten were hypoxic requiring ventilatory support, eleven were febrile but otherwise well, and eight were convalescing having previously required ventilatory support. Additionally, we analysed patients who did not have COVID-19 but received ventilatory support for other reasons. We examined routine Full Blood Count (FBC) specimens that were surplus to routine diagnostic requirements; normal ranges were established in a historic group of healthy volunteers. FINDINGS: We observed striking and unexpected differences in cells of the innate immune system. Levels of CD11b and CD18, which together comprise Complement Receptor 3 (CR3), were increased in granulocytes and monocytes from hypoxic COVID-19 patients, but not in those with COVID-19 who remained well, or in those without COVID-19 but ventilated for other reasons. Granulocyte and monocyte numbers were unchanged, however Natural Killer (NK) cell numbers were two-fold higher than normal in COVID-19 patients who remained well. INTERPRETATION: CR3 is central to leukocyte activation and subsequent cytokine release in response to infection. It is also a fibrinogen receptor, and its over-expression in granulocytes and monocytes of patients with respiratory failure tables it as a candidate effector of both the thrombotic and inflammatory features of COVID-19 pneumonia, and both a biomarker of impending respiratory failure and potential therapeutic target. NK cells are innate immune cells that retain immunological memory. Rapid expansion of memory NK cells targeting common antigens shared with other Coronaviruses may explain why most patients with COVID-19 do not develop respiratory complications. Understanding the innate immune response to SARS-CoV-may uncover why most infected individuals experience mild symptoms, and inform a preventive approach to COVID-19 pneumonia in the future.

covid-19;complement receptor 3;flow cytometry;hypoxia;immunology and inflammation;therapeutics

Journal Article

Gupta, Rajeev;Gant, Vanya Alasdair;Williams, Bryan;Enver, Tariq

10.1016/j.ijid.2020.08.004

[Title]: Increased Complement Receptor-3 levels in monocytes and granulocytes distinguish COVID-19 patients with pneumonia from those with mild symptoms. [Abstract]: BACKGROUND: The reasons why some patients with COVID-19 develop pneumonia and others do not are unclear. To better understand this, we used multiparameter flow cytometry to profile circulating leukocytes from non-immunocompromised adult patients with PCR-proven COVID-19 and specifically compared those with mild symptoms with those who had developed pneumonia. METHODS: Using clinically validated antibody panels we studied leukocytes from 29 patients with PCR-proven COVID-19. Ten were hypoxic requiring ventilatory support, eleven were febrile but otherwise well, and eight were convalescing having previously required ventilatory support. Additionally, we analysed patients who did not have COVID-19 but received ventilatory support for other reasons. We examined routine Full Blood Count (FBC) specimens that were surplus to routine diagnostic requirements; normal ranges were established in a historic group of healthy volunteers. FINDINGS: We observed striking and unexpected differences in cells of the innate immune system. Levels of CD11b and CD18, which together comprise Complement Receptor 3 (CR3), were increased in granulocytes and monocytes from hypoxic COVID-19 patients, but not in those with COVID-19 who remained well, or in those without COVID-19 but ventilated for other reasons. Granulocyte and monocyte numbers were unchanged, however Natural Killer (NK) cell numbers were two-fold higher than normal in COVID-19 patients who remained well. INTERPRETATION: CR3 is central to leukocyte activation and subsequent cytokine release in response to infection. It is also a fibrinogen receptor, and its over-expression in granulocytes and monocytes of patients with respiratory failure tables it as a candidate effector of both the thrombotic and inflammatory features of COVID-19 pneumonia, and both a biomarker of impending respiratory failure and potential therapeutic target. NK cells are innate immune cells that retain immunological memory. Rapid expansion of memory NK cells targeting common antigens shared with other Coronaviruses may explain why most patients with COVID-19 do not develop respiratory complications. Understanding the innate immune response to SARS-CoV-may uncover why most infected individuals experience mild symptoms, and inform a preventive approach to COVID-19 pneumonia in the future. [Keywords]: covid-19;complement receptor 3;flow cytometry;hypoxia;immunology and inflammation;therapeutics

Cureus

COVID-19 Associated Coagulopathy in the Setting of Underlying Malignancy.

Coronavirus disease 2019 (COVID-19) associated coagulopathy is a well-recognized predictor for morbidity and mortality in COVID-19 patients. Both deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in COVID-19 patients. Nonetheless, there are no consensus guidelines on the use of therapeutic coagulation in this group of patients. We herein present a unique case of a confirmed COVID-19 patient with metastatic ovarian cancer who presented with DVT and PE despite being on therapeutic anticoagulation, highlighting the unpredictability of COVID-19 associated coagulopathy. This case study raises the awareness that the thrombophilic state in metastatic malignancies is potentially augmented by COVID-19. We also discuss the complexity of making anticoagulation treatment decision in COVID-19 patients in the absence of evidence-based guidelines.

covid-19 associated coagulopathy;deep venous thrombosis;metastatic ovarian cancer;pulmonary embolism

Case Reports

Lim, Su Lin;Chan, Kok Hoe;Slim, Jihad;Guron, Gunwant;Shaaban, Hamid S

10.7759/cureus.10095

[Title]: COVID-19 Associated Coagulopathy in the Setting of Underlying Malignancy. [Abstract]: Coronavirus disease 2019 (COVID-19) associated coagulopathy is a well-recognized predictor for morbidity and mortality in COVID-19 patients. Both deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in COVID-19 patients. Nonetheless, there are no consensus guidelines on the use of therapeutic coagulation in this group of patients. We herein present a unique case of a confirmed COVID-19 patient with metastatic ovarian cancer who presented with DVT and PE despite being on therapeutic anticoagulation, highlighting the unpredictability of COVID-19 associated coagulopathy. This case study raises the awareness that the thrombophilic state in metastatic malignancies is potentially augmented by COVID-19. We also discuss the complexity of making anticoagulation treatment decision in COVID-19 patients in the absence of evidence-based guidelines. [Keywords]: covid-19 associated coagulopathy;deep venous thrombosis;metastatic ovarian cancer;pulmonary embolism

Rev Assoc Med Bras (1992)

Gastrointestinal emergency care during the COVID-19 pandemic: rapid communication.

OBJECTIVE: Social distancing during the COVID-19 pandemic has been associated with a decrease in the search for medical care. High-risk patients have avoided hospital environments fearing infection. We hypothesize that there was also a decrease in the search for medical care related to gastrointestinal emergencies. The aim of this study is to evaluate the frequency of consultations for severe gastrointestinal emergencies during and before the months of the pandemic. METHODS: This was a transversal study. The inclusion criteria were cases of consultation in the emergency department for gastrointestinal diseases that required hospitalization, from January to April, from 2015 to 2020. The pediatric population (under age 12) was excluded. RESULTS: A total of 2,457 cases of cases was included. The number of emergency hospitalizations for gastrointestinal cases decreased during the first four months of 2020: 108, 112, 82, and 77, respectively. Comparing April of 2020 with previous years, there was a lower than expected number of cases during the social distancing period (P=0.002). CONCLUSION: This study reports a pronounced decrease in consultations for severe gastrointestinal emergencies during the pandemic. Governments and society should be aware that health crises do not halt the natural occurrence of noninfectious diseases; otherwise, an increase in mortality from these morbidities may arise.

Journal Article

Leite, Carine;Trindade, Eduardo Neubarth;Grillo, Leonardo Wagner;Trindade, Manoel Roberto Maciel

10.1590/1806-9282.66.9.1187

[Title]: Gastrointestinal emergency care during the COVID-19 pandemic: rapid communication. [Abstract]: OBJECTIVE: Social distancing during the COVID-19 pandemic has been associated with a decrease in the search for medical care. High-risk patients have avoided hospital environments fearing infection. We hypothesize that there was also a decrease in the search for medical care related to gastrointestinal emergencies. The aim of this study is to evaluate the frequency of consultations for severe gastrointestinal emergencies during and before the months of the pandemic. METHODS: This was a transversal study. The inclusion criteria were cases of consultation in the emergency department for gastrointestinal diseases that required hospitalization, from January to April, from 2015 to 2020. The pediatric population (under age 12) was excluded. RESULTS: A total of 2,457 cases of cases was included. The number of emergency hospitalizations for gastrointestinal cases decreased during the first four months of 2020: 108, 112, 82, and 77, respectively. Comparing April of 2020 with previous years, there was a lower than expected number of cases during the social distancing period (P=0.002). CONCLUSION: This study reports a pronounced decrease in consultations for severe gastrointestinal emergencies during the pandemic. Governments and society should be aware that health crises do not halt the natural occurrence of noninfectious diseases; otherwise, an increase in mortality from these morbidities may arise. [Keywords]:

Euro Surveill

Epidemiology of measles during the COVID-19 pandemic, a description of the surveillance data, 29 EU/EEA countries and the United Kingdom, January to May 2020.

The number of measles cases declined in European Union/European Economic Area countries and the United Kingdom in 2020. Reported cases to The European Centre for Disease Prevention and Control decreased from 710 to 54 between January and May. Epidemic intelligence screening observed a similar trend. Under-diagnoses and under-reporting during the coronavirus disease (COVID-19) pandemic should be ruled out before concluding reduced measles circulation is because of social distancing and any community control measures taken to control COVID-19.

covid-19;epidemics;measles;public health surveillance

Journal Article

Nicolay, Nathalie;Mirinaviciute, Grazina;Mollet, Thomas;Celentano, Lucia Pastore;Bacci, Sabrina

10.2807/1560-7917.ES.2020.25.31.2001390

[Title]: Epidemiology of measles during the COVID-19 pandemic, a description of the surveillance data, 29 EU/EEA countries and the United Kingdom, January to May 2020. [Abstract]: The number of measles cases declined in European Union/European Economic Area countries and the United Kingdom in 2020. Reported cases to The European Centre for Disease Prevention and Control decreased from 710 to 54 between January and May. Epidemic intelligence screening observed a similar trend. Under-diagnoses and under-reporting during the coronavirus disease (COVID-19) pandemic should be ruled out before concluding reduced measles circulation is because of social distancing and any community control measures taken to control COVID-19. [Keywords]: covid-19;epidemics;measles;public health surveillance

Br J Oral Maxillofac Surg

Coronavirus antibody positive tests and continued use of personal protective equipment throughout the pandemic.

The COVID-19 pandemic has thrust not only a novel virus onto the world, but new challenges resulting in novel approaches. Governments have reduced regulation in order to facilitate timely advances to combat the disease. Antibody testing has rapidly been deployed but it is creating challenges for staff and patients. Mask use has come to the forefront and human factor (HF) strategies must be examined to reduce risk associated with lack of engagement from both healthcare staff and patients. In this we explore these issues and suggest some solutions.

antibody tests;covid-19;coronavirus;personal protective equipment;pandemic

Journal Article

Herron, J B T;Dennis, J;Brennan, P A

10.1016/j.bjoms.2020.06.021

[Title]: Coronavirus antibody positive tests and continued use of personal protective equipment throughout the pandemic. [Abstract]: The COVID-19 pandemic has thrust not only a novel virus onto the world, but new challenges resulting in novel approaches. Governments have reduced regulation in order to facilitate timely advances to combat the disease. Antibody testing has rapidly been deployed but it is creating challenges for staff and patients. Mask use has come to the forefront and human factor (HF) strategies must be examined to reduce risk associated with lack of engagement from both healthcare staff and patients. In this we explore these issues and suggest some solutions. [Keywords]: antibody tests;covid-19;coronavirus;personal protective equipment;pandemic

Work

A review of studies on the COVID-19 epidemic crisis disease with a preventive approach.

BACKGROUND: COVID-19 is a highly contagious acute respiratory syndrome and has been declared a pandemic in more than 209 countries worldwide. At the time of writing, no preventive vaccine has been developed and tested in the community. This study was conducted to review studies aimed at preventing the spread of the coronavirus worldwide. METHODS: This study was a review of the evidence-based literature and was conducted by searching databases, including Google Scholar, PubMed, and ScienceDirect, until April 2020. The search was performed based on keywords including "coronavirus", "COVID-19", and "prevention". The list of references in the final studies has also been re-reviewed to find articles that might not have been obtained through the search. The guidelines published by trustworthy organizations such as the World Health Organization and Center for Disease Control have been used in this study. CONCLUSION: So far, no vaccine or definitive treatment for COVID-19 has been invented, and the disease has become a pandemic. Therefore, observation of hand hygiene, disinfection of high-touch surfaces, observation of social distance, and lack of presence in public places are recommended as preventive measures. Moreover, to control the situation and to reduce the incidence of the virus, some of the measures taken by the decision-making bodies and the guidelines of the deterrent institutions to strengthen telecommuting of employees and reduce the presence of people in the community and prevent unnecessary activities, are very important.

covid-19;pandemic;novel coronaviruses;prevention

Journal Article;Systematic Review

Arefi, Maryam Feiz;Poursadeqiyan, Mohsen

10.3233/WOR-203218

[Title]: A review of studies on the COVID-19 epidemic crisis disease with a preventive approach. [Abstract]: BACKGROUND: COVID-19 is a highly contagious acute respiratory syndrome and has been declared a pandemic in more than 209 countries worldwide. At the time of writing, no preventive vaccine has been developed and tested in the community. This study was conducted to review studies aimed at preventing the spread of the coronavirus worldwide. METHODS: This study was a review of the evidence-based literature and was conducted by searching databases, including Google Scholar, PubMed, and ScienceDirect, until April 2020. The search was performed based on keywords including "coronavirus", "COVID-19", and "prevention". The list of references in the final studies has also been re-reviewed to find articles that might not have been obtained through the search. The guidelines published by trustworthy organizations such as the World Health Organization and Center for Disease Control have been used in this study. CONCLUSION: So far, no vaccine or definitive treatment for COVID-19 has been invented, and the disease has become a pandemic. Therefore, observation of hand hygiene, disinfection of high-touch surfaces, observation of social distance, and lack of presence in public places are recommended as preventive measures. Moreover, to control the situation and to reduce the incidence of the virus, some of the measures taken by the decision-making bodies and the guidelines of the deterrent institutions to strengthen telecommuting of employees and reduce the presence of people in the community and prevent unnecessary activities, are very important. [Keywords]: covid-19;pandemic;novel coronaviruses;prevention

J Dent Educ

Are dental schools adequately preparing dental students to face outbreaks of infectious diseases such as COVID-19?

The recent 2019-novel coronavirus (2019-nCoV, also known as SARS-CoV-2) has caused >2,622,571 confirmed cases of coronavirus disease 2019 (COVID-19) in >185 countries, and >182,359 deaths globally. More than 9000 healthcare workers have also been infected by 2019-nCoV. Prior to the present pandemic of COVID-19, there have been multiple large-scale epidemics and pandemics of other viral respiratory infections, such as seasonal flu, Spanish flu (H1N1), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and others. Dental professionals are at an increased risk for contracting these viruses from dental patients, as dental practice involves face-to-face communication with the patients and frequent exposure to saliva, blood, and other body fluids. Dental education can play an important role in the training of dentists, helping them to adopt adequate knowledge and attitudes related to infection control measures. The current dental curriculum does not cover infection control adequately, especially from airborne pathogens. Infection control education needs to be included in the dental curriculum itself, and students should be trained adequately to protect them and prevent the infection from disseminating even before they see their first patient.

Editorial;Historical Article

Ghai, Suhani

10.1002/jdd.12174

[Title]: Are dental schools adequately preparing dental students to face outbreaks of infectious diseases such as COVID-19? [Abstract]: The recent 2019-novel coronavirus (2019-nCoV, also known as SARS-CoV-2) has caused >2,622,571 confirmed cases of coronavirus disease 2019 (COVID-19) in >185 countries, and >182,359 deaths globally. More than 9000 healthcare workers have also been infected by 2019-nCoV. Prior to the present pandemic of COVID-19, there have been multiple large-scale epidemics and pandemics of other viral respiratory infections, such as seasonal flu, Spanish flu (H1N1), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and others. Dental professionals are at an increased risk for contracting these viruses from dental patients, as dental practice involves face-to-face communication with the patients and frequent exposure to saliva, blood, and other body fluids. Dental education can play an important role in the training of dentists, helping them to adopt adequate knowledge and attitudes related to infection control measures. The current dental curriculum does not cover infection control adequately, especially from airborne pathogens. Infection control education needs to be included in the dental curriculum itself, and students should be trained adequately to protect them and prevent the infection from disseminating even before they see their first patient. [Keywords]:

J Epidemiol

Public Awareness, Individual Prevention Practice, and Psychological Effect at the Beginning of the COVID-19 Outbreak in China.

BACKGROUND: The COVID-19 has spread to more than 200 countries and territories. But less is known about the knowledge, protection behavior and anxiety regarding the outbreak among the general population. METHODS: A cross-sectional, population-based online survey was conducted in China and abroad from January 28 to February 1, 2020. Socio-demographic information was collected and knowledge scores, practice scores, anxiety scores and perceived risk were calculated. General linear model and binary logistic regression were used to identify possible associations. RESULTS: We included 9,764 individuals in this study, and 156 (1.6%) were from Hubei Province. The average knowledge score was 4.7 (standard deviation, 1.0) (scored on a 6-point scale); 96.1% maintained hand hygiene, and 90.3% of participants had varying levels of anxiety. People in Hubei Province were the most anxious, followed by those in Beijing and Shanghai. People who had experienced risk behaviors did not pay more attention to wearing masks and hand hygiene. CONCLUSIONS: The public had high awareness on knowledge of COVID-19 outbreak, and a high proportion of people practiced good hand hygiene behavior. Many people claimed anxiety, especially in heavily affected areas during pandemic, suggesting the importance of closing the gap between risk awareness and good practice and conduct psychological counseling to public and patients.

covid-19;awareness;prevention practice;psychology

Journal Article;Research Support, Non-U.S. Gov't

Han, Bingfeng;Zhao, Tianshuo;Liu, Bei;Liu, Hanyu;Zheng, Hui;Wan, Yongmei;Qiu, Jiayi;Zhuang, Hui;Cui, Fuqiang

10.2188/jea.JE20200148

[Title]: Public Awareness, Individual Prevention Practice, and Psychological Effect at the Beginning of the COVID-19 Outbreak in China. [Abstract]: BACKGROUND: The COVID-19 has spread to more than 200 countries and territories. But less is known about the knowledge, protection behavior and anxiety regarding the outbreak among the general population. METHODS: A cross-sectional, population-based online survey was conducted in China and abroad from January 28 to February 1, 2020. Socio-demographic information was collected and knowledge scores, practice scores, anxiety scores and perceived risk were calculated. General linear model and binary logistic regression were used to identify possible associations. RESULTS: We included 9,764 individuals in this study, and 156 (1.6%) were from Hubei Province. The average knowledge score was 4.7 (standard deviation, 1.0) (scored on a 6-point scale); 96.1% maintained hand hygiene, and 90.3% of participants had varying levels of anxiety. People in Hubei Province were the most anxious, followed by those in Beijing and Shanghai. People who had experienced risk behaviors did not pay more attention to wearing masks and hand hygiene. CONCLUSIONS: The public had high awareness on knowledge of COVID-19 outbreak, and a high proportion of people practiced good hand hygiene behavior. Many people claimed anxiety, especially in heavily affected areas during pandemic, suggesting the importance of closing the gap between risk awareness and good practice and conduct psychological counseling to public and patients. [Keywords]: covid-19;awareness;prevention practice;psychology

Pharmacol Res

Enhanced platelet inhibition treatment improves hypoxemia in patients with severe Covid-19 and hypercoagulability. A case control, proof of concept study.

Patients affected by severe coronavirus induced disease-2019 (Covid-19) often experience hypoxemia due to alveolar involvement and endothelial dysfunction, which leads to the formation of micro thrombi in the pulmonary capillary vessels. Both hypoxemia and a prothrombotic diathesis have been associated with more severe disease and increased risk of death. To date, specific indications to treat this condition are lacking. This was a single center, investigator initiated, compassionate use, proof of concept, case control, phase IIb study (NCT04368377) conducted in the Intermediate Respiratory Care Unit of L. Sacco University Hospital in Milano, Italy. Our objective was to explore the effects of the administration of anti-platelet therapy on arterial oxygenation and clinical outcomes in patients with severe Covid-19 with hypercoagulability. We enrolled five consecutive patients with laboratory confirmed SARS-CoV-2 infection, severe respiratory failure requiring helmet continuous positive airway pressure (CPAP), bilateral pulmonary infiltrates and a pro-thrombotic state identified as a D-dimer > 3 times the upper limit of normal. Five patients matched for age, D-dimer value and SOFA score formed the control group. Beyond standard of care, treated patients received 25 mug/Kg/body weight tirofiban as bolus infusion, followed by a continuous infusion of 0.15 mug/Kg/body weight per minute for 48 hours. Before tirofiban, patients received acetylsalicylic acid 250 mg infusion and oral clopidogrel 300 mg; both were continued at a dose of 75 mg daily for 30 days. Fondaparinux2.5 mg/day sub-cutaneous was given for the duration of the hospital stay. All controls were receiving prophylactic or therapeutic dose heparin, according to local standard operating procedures. Treated patients consistently experienced a mean (SD) reduction in A-a O2 gradient of -32.6 mmHg (61.9, P = 0.154), -52.4 mmHg (59.4, P = 0.016) and -151.1 mmHg (56.6, P = 0.011; P = 0.047 vs. controls) at 24, 48 hours and 7 days after treatment. PaO2/FiO2 ratio increased by 52 mmHg (50, P = 0.172), 64 mmHg (47, P = 0.040) and 112 mmHg (51, P = 0.036) after 24, 48 hours and 7 days, respectively. All patients but one were successfully weaned from CPAP after 3 days. This was not true for the control group. No major adverse events were observed. Antiplatelet therapy might be effective in improving the ventilation/perfusion ratio in Covid-19 patients with severe respiratory failure. The effects might be sustained by the prevention and interference on forming clots in lung capillary vessels and by modulating megakaryocytes' function and platelet adhesion. Randomized clinical trials are urgently needed to confirm these results.

antiplatelet;coagulation;coronavirus;covid-19;d-dimer;respiratory failure

Clinical Trial, Phase II;Controlled Clinical Trial;Journal Article

Viecca, Maurizio;Radovanovic, Dejan;Forleo, Giovanni Battista;Santus, Pierachille

10.1016/j.phrs.2020.104950

[Title]: Enhanced platelet inhibition treatment improves hypoxemia in patients with severe Covid-19 and hypercoagulability. A case control, proof of concept study. [Abstract]: Patients affected by severe coronavirus induced disease-2019 (Covid-19) often experience hypoxemia due to alveolar involvement and endothelial dysfunction, which leads to the formation of micro thrombi in the pulmonary capillary vessels. Both hypoxemia and a prothrombotic diathesis have been associated with more severe disease and increased risk of death. To date, specific indications to treat this condition are lacking. This was a single center, investigator initiated, compassionate use, proof of concept, case control, phase IIb study (NCT04368377) conducted in the Intermediate Respiratory Care Unit of L. Sacco University Hospital in Milano, Italy. Our objective was to explore the effects of the administration of anti-platelet therapy on arterial oxygenation and clinical outcomes in patients with severe Covid-19 with hypercoagulability. We enrolled five consecutive patients with laboratory confirmed SARS-CoV-2 infection, severe respiratory failure requiring helmet continuous positive airway pressure (CPAP), bilateral pulmonary infiltrates and a pro-thrombotic state identified as a D-dimer > 3 times the upper limit of normal. Five patients matched for age, D-dimer value and SOFA score formed the control group. Beyond standard of care, treated patients received 25 mug/Kg/body weight tirofiban as bolus infusion, followed by a continuous infusion of 0.15 mug/Kg/body weight per minute for 48 hours. Before tirofiban, patients received acetylsalicylic acid 250 mg infusion and oral clopidogrel 300 mg; both were continued at a dose of 75 mg daily for 30 days. Fondaparinux2.5 mg/day sub-cutaneous was given for the duration of the hospital stay. All controls were receiving prophylactic or therapeutic dose heparin, according to local standard operating procedures. Treated patients consistently experienced a mean (SD) reduction in A-a O2 gradient of -32.6 mmHg (61.9, P = 0.154), -52.4 mmHg (59.4, P = 0.016) and -151.1 mmHg (56.6, P = 0.011; P = 0.047 vs. controls) at 24, 48 hours and 7 days after treatment. PaO2/FiO2 ratio increased by 52 mmHg (50, P = 0.172), 64 mmHg (47, P = 0.040) and 112 mmHg (51, P = 0.036) after 24, 48 hours and 7 days, respectively. All patients but one were successfully weaned from CPAP after 3 days. This was not true for the control group. No major adverse events were observed. Antiplatelet therapy might be effective in improving the ventilation/perfusion ratio in Covid-19 patients with severe respiratory failure. The effects might be sustained by the prevention and interference on forming clots in lung capillary vessels and by modulating megakaryocytes' function and platelet adhesion. Randomized clinical trials are urgently needed to confirm these results. [Keywords]: antiplatelet;coagulation;coronavirus;covid-19;d-dimer;respiratory failure

Clin Infect Dis

Novel Coronavirus Disease 2019 (COVID-19) Pneumonia Progression Course in 17 Discharged Patients: Comparison of Clinical and Thin-Section Computed Tomography Features During Recovery.

BACKGROUND: Our objective was to retrospectively analyze the evolution of clinical features and thin-section computed tomography (CT) imaging of novel coronavirus disease 2019 (COVID-19) pneumonia in 17 discharged patients. METHODS: Serial thin-section CT scans of 17 discharged patients with COVID-19 were obtained during recovery. Longitudinal changes of clinical parameters and a CT pattern were documented in all patients during the 4 weeks after admission. A CT score was used to evaluate the extent of the disease. RESULTS: There were marked improvements of fever, lymphocyte counts, C-reactive proteins, and erythrocyte sedimentation rates within the first 2 weeks after admission. However, the mean CT score rapidly increased from the first to the third week, with a top score of 8.2 obtained in the second week. During the first week, the main CT pattern was ground-glass opacities (GGO; 76.5%). The frequency of GGO (52.9%) decreased in the second week. Consolidation and mixed patterns (47.0%) were noted in the second week. Thereafter, consolidations generally dissipated into GGO, and the frequency of GGO increased in the third week (76.5%) and fourth week (71.4%). Opacities were mainly located in the peripheral (76.5%) and subpleural (47.1%) zones of the lungs; they presented as focal (35.3%) or multifocal (29.4%) in the first week and became more diffuse in the second (47.1%) and third weeks (58.8%), then showed a reduced extent in fourth week (50%). CONCLUSIONS: The progression course of the CT pattern was later than the progression of the clinical parameters within the first 2 weeks after admission; however, there were synchronized improvements in both the clinical and radiologic features in the fourth week.

covid-19;computed tomography;novel coronavirus pneumonia;viral pneumonia

Journal Article

Han, Xiaoyu;Cao, Yukun;Jiang, Nanchuan;Chen, Yan;Alwalid, Osamah;Zhang, Xin;Gu, Jin;Dai, Meng;Liu, Jie;Zhu, Wanyue;Zheng, Chuansheng;Shi, Heshui

10.1093/cid/ciaa271

[Title]: Novel Coronavirus Disease 2019 (COVID-19) Pneumonia Progression Course in 17 Discharged Patients: Comparison of Clinical and Thin-Section Computed Tomography Features During Recovery. [Abstract]: BACKGROUND: Our objective was to retrospectively analyze the evolution of clinical features and thin-section computed tomography (CT) imaging of novel coronavirus disease 2019 (COVID-19) pneumonia in 17 discharged patients. METHODS: Serial thin-section CT scans of 17 discharged patients with COVID-19 were obtained during recovery. Longitudinal changes of clinical parameters and a CT pattern were documented in all patients during the 4 weeks after admission. A CT score was used to evaluate the extent of the disease. RESULTS: There were marked improvements of fever, lymphocyte counts, C-reactive proteins, and erythrocyte sedimentation rates within the first 2 weeks after admission. However, the mean CT score rapidly increased from the first to the third week, with a top score of 8.2 obtained in the second week. During the first week, the main CT pattern was ground-glass opacities (GGO; 76.5%). The frequency of GGO (52.9%) decreased in the second week. Consolidation and mixed patterns (47.0%) were noted in the second week. Thereafter, consolidations generally dissipated into GGO, and the frequency of GGO increased in the third week (76.5%) and fourth week (71.4%). Opacities were mainly located in the peripheral (76.5%) and subpleural (47.1%) zones of the lungs; they presented as focal (35.3%) or multifocal (29.4%) in the first week and became more diffuse in the second (47.1%) and third weeks (58.8%), then showed a reduced extent in fourth week (50%). CONCLUSIONS: The progression course of the CT pattern was later than the progression of the clinical parameters within the first 2 weeks after admission; however, there were synchronized improvements in both the clinical and radiologic features in the fourth week. [Keywords]: covid-19;computed tomography;novel coronavirus pneumonia;viral pneumonia

Medicine (Baltimore)

The adverse skin reactions of health care workers using personal protective equipment for COVID-19.

In December 2019, a new coronavirus was found in Wuhan, Hubei Province, China, and spread rapidly throughout the country, attracting global attention. On February 11, the World Health Organization (WHO) officially named the disease caused by 2019-nCoV coronavirus disease 2019 (COVID-19). With the increasing number of cases, health care workers (HCWs) from all over China volunteered to work in Hubei Province. Because of the strong infectivity of COVID-19, HCWs need to wear personal protective equipment (PPE), such as N95 masks, latex gloves, and protective clothing. Due to the long-term use of PPE, many adverse skin reactions may occur. Therefore, the purpose of this study is to explore the adverse skin reactions among HCWs using PPE.Questionnaires were used for the research; a quantitative study was carried out to determine the incidence of adverse skin reactions among HCWs using PPE.A total of 61 valid questionnaires were collected. The most common adverse skin reactions among HCWs wearing N95 masks were nasal bridge scarring (68.9%) and facial itching (27.9%). The most common adverse skin reactions among HCWs wearing latex gloves were dry skin (55.7%), itching (31.2%), and rash (23.0%). The most common adverse skin reactions among HCWs wearing protective clothing were dry skin (36.1%) and itching (34.4%).When most HCWs wear PPE for a long period of time, they will experience adverse skin reactions. The incidence of adverse skin reactions to the N95 mask was 95.1%, that to latex gloves was 88.5%, and that to protective clothing was 60.7%.

Journal Article

Hu, Kaihui;Fan, Jing;Li, Xueqin;Gou, Xin;Li, Xinyuan;Zhou, Xiang

10.1097/MD.0000000000020603

[Title]: The adverse skin reactions of health care workers using personal protective equipment for COVID-19. [Abstract]: In December 2019, a new coronavirus was found in Wuhan, Hubei Province, China, and spread rapidly throughout the country, attracting global attention. On February 11, the World Health Organization (WHO) officially named the disease caused by 2019-nCoV coronavirus disease 2019 (COVID-19). With the increasing number of cases, health care workers (HCWs) from all over China volunteered to work in Hubei Province. Because of the strong infectivity of COVID-19, HCWs need to wear personal protective equipment (PPE), such as N95 masks, latex gloves, and protective clothing. Due to the long-term use of PPE, many adverse skin reactions may occur. Therefore, the purpose of this study is to explore the adverse skin reactions among HCWs using PPE.Questionnaires were used for the research; a quantitative study was carried out to determine the incidence of adverse skin reactions among HCWs using PPE.A total of 61 valid questionnaires were collected. The most common adverse skin reactions among HCWs wearing N95 masks were nasal bridge scarring (68.9%) and facial itching (27.9%). The most common adverse skin reactions among HCWs wearing latex gloves were dry skin (55.7%), itching (31.2%), and rash (23.0%). The most common adverse skin reactions among HCWs wearing protective clothing were dry skin (36.1%) and itching (34.4%).When most HCWs wear PPE for a long period of time, they will experience adverse skin reactions. The incidence of adverse skin reactions to the N95 mask was 95.1%, that to latex gloves was 88.5%, and that to protective clothing was 60.7%. [Keywords]:

Bull Environ Contam Toxicol

The Impact of COVID-19 Partial Lockdown on Primary Pollutant Concentrations in the Atmosphere of Rio de Janeiro and Sao Paulo Megacities (Brazil).

As COVID-19 spread all over the world, most of the countries adopted some kind of restrictions to avoid the collapse of health systems. In Brazil, Sao Paulo and Rio the Janeiro, the two most populated cities in the country, were the first to determine social distancing. In this study, the impact of the social distancing measures on the concentrations of the three main primary air pollutants (PM10, NO2 and CO) was analyzed. CO levels showed the most significant reductions (up to 100%) since it is related to light-duty vehicular emissions. NO2 also showed reductions (9.1%-41.8%) while PM10 levels were only reduced in the 1st lockdown week. The decrease of pollutants was not directly proportional to the vehicular flux reduction, because it depends on other factors such as the transport of air masses from industrial and rural areas. The differences observed can be explained considering the fleet characteristics in the two cities and the response of the population to the social distancing recommendations.

atmospheric pollutants;brazil;covid-19;lockdown;social distancing

Journal Article

Siciliano, Bruno;Carvalho, Giovanna;da Silva, Cleyton Martins;Arbilla, Graciela

10.1007/s00128-020-02907-9

[Title]: The Impact of COVID-19 Partial Lockdown on Primary Pollutant Concentrations in the Atmosphere of Rio de Janeiro and Sao Paulo Megacities (Brazil). [Abstract]: As COVID-19 spread all over the world, most of the countries adopted some kind of restrictions to avoid the collapse of health systems. In Brazil, Sao Paulo and Rio the Janeiro, the two most populated cities in the country, were the first to determine social distancing. In this study, the impact of the social distancing measures on the concentrations of the three main primary air pollutants (PM10, NO2 and CO) was analyzed. CO levels showed the most significant reductions (up to 100%) since it is related to light-duty vehicular emissions. NO2 also showed reductions (9.1%-41.8%) while PM10 levels were only reduced in the 1st lockdown week. The decrease of pollutants was not directly proportional to the vehicular flux reduction, because it depends on other factors such as the transport of air masses from industrial and rural areas. The differences observed can be explained considering the fleet characteristics in the two cities and the response of the population to the social distancing recommendations. [Keywords]: atmospheric pollutants;brazil;covid-19;lockdown;social distancing

Otolaryngol Head Neck Surg

Olfactory and Gustatory Dysfunction as an Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study.

OBJECTIVE: To evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in coronavirus disease 2019 (COVID-19) patients. STUDY DESIGN: Multicenter case series. SETTING: Five tertiary care hospitals (3 in China, 1 in France, 1 in Germany). SUBJECTS AND METHODS: In total, 394 polymerase chain reaction (PCR)-confirmed COVID-19-positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and visual analog scale (VAS) were used to quantify olfactory and gustatory dysfunction, respectively. All subjects at 1 hospital (Shanghai) without subjective olfactory complaints underwent objective testing. RESULTS: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n = 239), German (n = 39), and French (n = 116) cohorts was 32%, 69%, and 49%, respectively. The median age of included subjects was 39 years, 92 of 161 (57%) were male, and 10 of 161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10 of 90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. Forty-three percent (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. CONCLUSIONS: Olfactory and/or gustatory disorders may represent early or isolated symptoms of severe acute respiratory syndrome coronavirus 2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

covid-19;covid-19 screening;sars-cov-2;anosmia;dysgeusia;gustatory dysfunction;olfactory dysfunction

Journal Article;Multicenter Study;Research Support, Non-U.S. Gov't

Qiu, Chenghao;Cui, Chong;Hautefort, Charlotte;Haehner, Antje;Zhao, Jun;Yao, Qi;Zeng, Hui;Nisenbaum, Eric J;Liu, Li;Zhao, Yu;Zhang, Di;Levine, Corinna G;Cejas, Ivette;Dai, Qi;Zeng, Mei;Herman, Philippe;Jourdaine, Clement;de With, Katja;Draf, Julia;Chen, Bing;Jayaweera, Dushyantha T;Denneny, James C 3rd;Casiano, Roy;Yu, Hongmeng;Eshraghi, Adrien A;Hummel, Thomas;Liu, Xuezhong;Shu, Yilai;Lu, Hongzhou

10.1177/0194599820934376

[Title]: Olfactory and Gustatory Dysfunction as an Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study. [Abstract]: OBJECTIVE: To evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in coronavirus disease 2019 (COVID-19) patients. STUDY DESIGN: Multicenter case series. SETTING: Five tertiary care hospitals (3 in China, 1 in France, 1 in Germany). SUBJECTS AND METHODS: In total, 394 polymerase chain reaction (PCR)-confirmed COVID-19-positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and visual analog scale (VAS) were used to quantify olfactory and gustatory dysfunction, respectively. All subjects at 1 hospital (Shanghai) without subjective olfactory complaints underwent objective testing. RESULTS: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n = 239), German (n = 39), and French (n = 116) cohorts was 32%, 69%, and 49%, respectively. The median age of included subjects was 39 years, 92 of 161 (57%) were male, and 10 of 161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10 of 90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. Forty-three percent (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. CONCLUSIONS: Olfactory and/or gustatory disorders may represent early or isolated symptoms of severe acute respiratory syndrome coronavirus 2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection. [Keywords]: covid-19;covid-19 screening;sars-cov-2;anosmia;dysgeusia;gustatory dysfunction;olfactory dysfunction

Jpn J Clin Oncol

When cancer encounters COVID-19 in China: what have we suffered, experienced and learned.

The outbreak of the coronavirus disease (COVID-19) occurred in Wuhan, China, in December 2019. As of 21 March 2020, this epidemic has spread to 179 countries with more than 200 000 confirmed cases and 8578 deaths. The outbreak has put enormous pressure on the medical establishment and even led to exhaustion of medical resources in the most affected areas. Other medical work has been significantly affected in the context of COVID-19 epidemic. In order to reduce or avoid cross-infection with COVID-19, many hospitals have taken measures to limit the number of outpatient visits and inpatients. For example, emergency surgery can only be guaranteed, and most other surgeries can be postponed. Patients with cancer are one of the groups most affected by the epidemic because of their systematic immunosuppressive state and requirement of frequent admission to hospital. Consequently, specific adjustments for their treatment need to be made to cope with this situation. Therefore, it is of significance to summarize the relevant experience of China in the prevention and control of COVID-19 infection and treatment of patients with cancer during the epidemic.

covid-19;sars-cov-2;cancer;diagnosis;treatment

Journal Article

Chen, Haiyang;Wu, Xuan;Wang, Wei;Wang, Qiming

10.1093/jjco/hyaa077

[Title]: When cancer encounters COVID-19 in China: what have we suffered, experienced and learned. [Abstract]: The outbreak of the coronavirus disease (COVID-19) occurred in Wuhan, China, in December 2019. As of 21 March 2020, this epidemic has spread to 179 countries with more than 200 000 confirmed cases and 8578 deaths. The outbreak has put enormous pressure on the medical establishment and even led to exhaustion of medical resources in the most affected areas. Other medical work has been significantly affected in the context of COVID-19 epidemic. In order to reduce or avoid cross-infection with COVID-19, many hospitals have taken measures to limit the number of outpatient visits and inpatients. For example, emergency surgery can only be guaranteed, and most other surgeries can be postponed. Patients with cancer are one of the groups most affected by the epidemic because of their systematic immunosuppressive state and requirement of frequent admission to hospital. Consequently, specific adjustments for their treatment need to be made to cope with this situation. Therefore, it is of significance to summarize the relevant experience of China in the prevention and control of COVID-19 infection and treatment of patients with cancer during the epidemic. [Keywords]: covid-19;sars-cov-2;cancer;diagnosis;treatment

J Med Internet Res

Digital Health Strategies to Fight COVID-19 Worldwide: Challenges, Recommendations, and a Call for Papers.

The coronavirus disease (COVID-19) pandemic has created an urgent need for coordinated mechanisms to respond to the outbreak across health sectors, and digital health solutions have been identified as promising approaches to address this challenge. This editorial discusses the current situation regarding digital health solutions to fight COVID-19 as well as the challenges and ethical hurdles to broad and long-term implementation of these solutions. To decrease the risk of infection, telemedicine has been used as a successful health care model in both emergency and primary care. Official communication plans should promote facile and diverse channels to inform people about the pandemic and to avoid rumors and reduce threats to public health. Social media platforms such as Twitter and Google Trends analyses are highly beneficial to model pandemic trends as well as to monitor the evolution of patients' symptoms or public reaction to the pandemic over time. However, acceptability of digital solutions may face challenges due to potential conflicts with users' cultural, moral, and religious backgrounds. Digital tools can provide collective public health benefits; however, they may be intrusive and can erode individual freedoms or leave vulnerable populations behind. The COVID-19 pandemic has demonstrated the strong potential of various digital health solutions that have been tested during the crisis. More concerted measures should be implemented to ensure that future digital health initiatives will have a greater impact on the epidemic and meet the most strategic needs to ease the life of people who are at the forefront of the crisis.

covid-19;communication;coronavirus;digital health;digital technology;ehealth;epidemiology;health care;infodemiology;public health;review;surveillance

Editorial

Fagherazzi, Guy;Goetzinger, Catherine;Rashid, Mohammed Ally;Aguayo, Gloria A;Huiart, Laetitia

10.2196/19284

[Title]: Digital Health Strategies to Fight COVID-19 Worldwide: Challenges, Recommendations, and a Call for Papers. [Abstract]: The coronavirus disease (COVID-19) pandemic has created an urgent need for coordinated mechanisms to respond to the outbreak across health sectors, and digital health solutions have been identified as promising approaches to address this challenge. This editorial discusses the current situation regarding digital health solutions to fight COVID-19 as well as the challenges and ethical hurdles to broad and long-term implementation of these solutions. To decrease the risk of infection, telemedicine has been used as a successful health care model in both emergency and primary care. Official communication plans should promote facile and diverse channels to inform people about the pandemic and to avoid rumors and reduce threats to public health. Social media platforms such as Twitter and Google Trends analyses are highly beneficial to model pandemic trends as well as to monitor the evolution of patients' symptoms or public reaction to the pandemic over time. However, acceptability of digital solutions may face challenges due to potential conflicts with users' cultural, moral, and religious backgrounds. Digital tools can provide collective public health benefits; however, they may be intrusive and can erode individual freedoms or leave vulnerable populations behind. The COVID-19 pandemic has demonstrated the strong potential of various digital health solutions that have been tested during the crisis. More concerted measures should be implemented to ensure that future digital health initiatives will have a greater impact on the epidemic and meet the most strategic needs to ease the life of people who are at the forefront of the crisis. [Keywords]: covid-19;communication;coronavirus;digital health;digital technology;ehealth;epidemiology;health care;infodemiology;public health;review;surveillance

BMJ

Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study.

OBJECTIVES: To describe a national cohort of pregnant women admitted to hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, identify factors associated with infection, and describe outcomes, including transmission of infection, for mothers and infants. DESIGN: Prospective national population based cohort study using the UK Obstetric Surveillance System (UKOSS). SETTING: All 194 obstetric units in the UK. PARTICIPANTS: 427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020. MAIN OUTCOME MEASURES: Incidence of maternal hospital admission and infant infection. Rates of maternal death, level 3 critical care unit admission, fetal loss, caesarean birth, preterm birth, stillbirth, early neonatal death, and neonatal unit admission. RESULTS: The estimated incidence of admission to hospital with confirmed SARS-CoV-2 infection in pregnancy was 4.9 (95% confidence interval 4.5 to 5.4) per 1000 maternities. 233 (56%) pregnant women admitted to hospital with SARS-CoV-2 infection in pregnancy were from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth. CONCLUSIONS: Most pregnant women admitted to hospital with SARS-CoV-2 infection were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes, and transmission of SARS-CoV-2 to infants was uncommon. The high proportion of women from black or minority ethnic groups admitted with infection needs urgent investigation and explanation. STUDY REGISTRATION: ISRCTN 40092247.

Journal Article

Knight, Marian;Bunch, Kathryn;Vousden, Nicola;Morris, Edward;Simpson, Nigel;Gale, Chris;O'Brien, Patrick;Quigley, Maria;Brocklehurst, Peter;Kurinczuk, Jennifer J

10.1136/bmj.m2107

[Title]: Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. [Abstract]: OBJECTIVES: To describe a national cohort of pregnant women admitted to hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, identify factors associated with infection, and describe outcomes, including transmission of infection, for mothers and infants. DESIGN: Prospective national population based cohort study using the UK Obstetric Surveillance System (UKOSS). SETTING: All 194 obstetric units in the UK. PARTICIPANTS: 427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020. MAIN OUTCOME MEASURES: Incidence of maternal hospital admission and infant infection. Rates of maternal death, level 3 critical care unit admission, fetal loss, caesarean birth, preterm birth, stillbirth, early neonatal death, and neonatal unit admission. RESULTS: The estimated incidence of admission to hospital with confirmed SARS-CoV-2 infection in pregnancy was 4.9 (95% confidence interval 4.5 to 5.4) per 1000 maternities. 233 (56%) pregnant women admitted to hospital with SARS-CoV-2 infection in pregnancy were from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth. CONCLUSIONS: Most pregnant women admitted to hospital with SARS-CoV-2 infection were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes, and transmission of SARS-CoV-2 to infants was uncommon. The high proportion of women from black or minority ethnic groups admitted with infection needs urgent investigation and explanation. STUDY REGISTRATION: ISRCTN 40092247. [Keywords]:

Eur J Obstet Gynecol Reprod Biol

Can a health care worker have sex in the time of COVID-19?

Covid-19 is not transmitted by sex but close proximity during the act could aide in spread of the disease. Health care workers by virtue of the nature of their work have higher chances of exposure to the virus and them indulging in sex needs risk reduction strategies.

covid-19;health care workers;sex

Letter

Naik, B Sadananda

10.1016/j.ejogrb.2020.07.059

[Title]: Can a health care worker have sex in the time of COVID-19? [Abstract]: Covid-19 is not transmitted by sex but close proximity during the act could aide in spread of the disease. Health care workers by virtue of the nature of their work have higher chances of exposure to the virus and them indulging in sex needs risk reduction strategies. [Keywords]: covid-19;health care workers;sex

Ther Adv Respir Dis

TNFalpha inhibitor may be effective for severe COVID-19: learning from toxic epidermal necrolysis.

Increased inflammatory cytokines [such as tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6)] are observed in COVID-19 patients, especially in the severe group. The phenomenon of a cytokine storm may be the central inducer of apoptosis of alveolar epithelial cells, which leads to rapid progression in severe group patients. Given the similarities of clinical features and pathogenesis between toxic epidermal necrolysis (TEN) and COVID-19, we hypothesize that the application of etanercept, an inhibitor of TNFalpha, could attenuate disease progression in severe group COVID-19 patients by suppressing systemic auto-inflammatory responses. The reviews of this paper are available via the supplemental material section.

covid-19;tnfalpha inhibitor;etanercept;toxic epidermal necrolysis

Journal Article;Review

Chen, Xue-Yan;Yan, Bing-Xi;Man, Xiao-Yong

10.1177/1753466620926800

[Title]: TNFalpha inhibitor may be effective for severe COVID-19: learning from toxic epidermal necrolysis. [Abstract]: Increased inflammatory cytokines [such as tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6)] are observed in COVID-19 patients, especially in the severe group. The phenomenon of a cytokine storm may be the central inducer of apoptosis of alveolar epithelial cells, which leads to rapid progression in severe group patients. Given the similarities of clinical features and pathogenesis between toxic epidermal necrolysis (TEN) and COVID-19, we hypothesize that the application of etanercept, an inhibitor of TNFalpha, could attenuate disease progression in severe group COVID-19 patients by suppressing systemic auto-inflammatory responses. The reviews of this paper are available via the supplemental material section. [Keywords]: covid-19;tnfalpha inhibitor;etanercept;toxic epidermal necrolysis

Integr Med Res

Efficacy and safety of herbal medicine (Lianhuaqingwen) for treating COVID-19: A systematic review and meta-analysis.

Background: Lianhuaqingwen (LH) has been proven effective for influenza. However, the promotion of LH for the treatment of patients with COVID-19 remains controversial. Therefore, our study aimed to assess the efficacy and safety of Lianhuaqingwen (LH) in treating patients with COVID-19 by a systematic review and meta-analysis. Methods: We conducted the literature search using six electronic databases from December 1, 2019, to June 2, 2020. Cochrane Risk of Bias tool was used to assess the quality of randomized controlled trials. Newcastle-Ottawa Scale was used to assess the quality of case control studies. Agency for Healthcare Research and Quality checklist was used to assess the quality of case series. All analyses were conducted by RevMan 5.3. For outcomes that could not be meta-analyzed were performed a descriptive analysis. Results: Eight studies with 924 patients were included. Three studies were RCTs, three were case control studies, and two were case series. The quality of the included studies was poor. Compared with patients treated by conventional treatment, patients treated by LH combined with conventional treatment have a higher overall effective rate (RR=1.16, 95%CIs: 1.04 approximately 1.30, P=0.01) and CT recovery rate (RR=1.21, 95%CIs: 1.02 approximately 1.43, P=0.03). Patients of LH groups have a lower incidence of diarrhea (5.6% vs.13.4%), and have statistically significant (P=0.026). But the rate of abnormal liver function in the combined medication group is higher than that in the single LH group. Conclusion: LH combined with conventional treatment seems to be more effective for patients with mild or ordinary COVID-19.

covid-19;herbal medicine;lianhuaqingwen;meta-analysis;systematic review

Journal Article;Review

Liu, Ming;Gao, Ya;Yuan, Yuan;Yang, Kelu;Shi, Shuzhen;Tian, Jinhui;Zhang, Junhua

10.1016/j.imr.2020.100644

[Title]: Efficacy and safety of herbal medicine (Lianhuaqingwen) for treating COVID-19: A systematic review and meta-analysis. [Abstract]: Background: Lianhuaqingwen (LH) has been proven effective for influenza. However, the promotion of LH for the treatment of patients with COVID-19 remains controversial. Therefore, our study aimed to assess the efficacy and safety of Lianhuaqingwen (LH) in treating patients with COVID-19 by a systematic review and meta-analysis. Methods: We conducted the literature search using six electronic databases from December 1, 2019, to June 2, 2020. Cochrane Risk of Bias tool was used to assess the quality of randomized controlled trials. Newcastle-Ottawa Scale was used to assess the quality of case control studies. Agency for Healthcare Research and Quality checklist was used to assess the quality of case series. All analyses were conducted by RevMan 5.3. For outcomes that could not be meta-analyzed were performed a descriptive analysis. Results: Eight studies with 924 patients were included. Three studies were RCTs, three were case control studies, and two were case series. The quality of the included studies was poor. Compared with patients treated by conventional treatment, patients treated by LH combined with conventional treatment have a higher overall effective rate (RR=1.16, 95%CIs: 1.04 approximately 1.30, P=0.01) and CT recovery rate (RR=1.21, 95%CIs: 1.02 approximately 1.43, P=0.03). Patients of LH groups have a lower incidence of diarrhea (5.6% vs.13.4%), and have statistically significant (P=0.026). But the rate of abnormal liver function in the combined medication group is higher than that in the single LH group. Conclusion: LH combined with conventional treatment seems to be more effective for patients with mild or ordinary COVID-19. [Keywords]: covid-19;herbal medicine;lianhuaqingwen;meta-analysis;systematic review

J Dent Res

Coronavirus Disease 2019 (COVID-19): Emerging and Future Challenges for Dental and Oral Medicine.

The epidemic of coronavirus disease 2019 (COVID-19), originating in Wuhan, China, has become a major public health challenge for not only China but also countries around the world. The World Health Organization announced that the outbreaks of the novel coronavirus have constituted a public health emergency of international concern. As of February 26, 2020, COVID-19 has been recognized in 34 countries, with a total of 80,239 laboratory-confirmed cases and 2,700 deaths. Infection control measures are necessary to prevent the virus from further spreading and to help control the epidemic situation. Due to the characteristics of dental settings, the risk of cross infection can be high between patients and dental practitioners. For dental practices and hospitals in areas that are (potentially) affected with COVID-19, strict and effective infection control protocols are urgently needed. This article, based on our experience and relevant guidelines and research, introduces essential knowledge about COVID-19 and nosocomial infection in dental settings and provides recommended management protocols for dental practitioners and students in (potentially) affected areas.

dental education;dental practice management;dental public health;infection control;transmission;virology

Journal Article;Research Support, Non-U.S. Gov't

Meng, L;Hua, F;Bian, Z

10.1177/0022034520914246

[Title]: Coronavirus Disease 2019 (COVID-19): Emerging and Future Challenges for Dental and Oral Medicine. [Abstract]: The epidemic of coronavirus disease 2019 (COVID-19), originating in Wuhan, China, has become a major public health challenge for not only China but also countries around the world. The World Health Organization announced that the outbreaks of the novel coronavirus have constituted a public health emergency of international concern. As of February 26, 2020, COVID-19 has been recognized in 34 countries, with a total of 80,239 laboratory-confirmed cases and 2,700 deaths. Infection control measures are necessary to prevent the virus from further spreading and to help control the epidemic situation. Due to the characteristics of dental settings, the risk of cross infection can be high between patients and dental practitioners. For dental practices and hospitals in areas that are (potentially) affected with COVID-19, strict and effective infection control protocols are urgently needed. This article, based on our experience and relevant guidelines and research, introduces essential knowledge about COVID-19 and nosocomial infection in dental settings and provides recommended management protocols for dental practitioners and students in (potentially) affected areas. [Keywords]: dental education;dental practice management;dental public health;infection control;transmission;virology

Clin Exp Allergy

UK consensus statement on the diagnosis of inducible laryngeal obstruction in light of the COVID-19 pandemic.

Prior to the COVID-19 pandemic, laryngoscopy was the mandatory gold standard for the accurate assessment and diagnosis of inducible laryngeal obstruction. However, upper airway endoscopy is considered an aerosol-generating procedure in professional guidelines, meaning routine procedures are highly challenging and the availability of laryngoscopy is reduced. In response, we have convened a multidisciplinary panel with broad experience in managing this disease and agreed a recommended strategy for presumptive diagnosis in patients who cannot have laryngoscopy performed due to pandemic restrictions. To maintain clinical standards whilst ensuring patient safety, we discuss the importance of triage, information gathering, symptom assessment and early review of response to treatment. The consensus recommendations will also be potentially relevant to other future situations where access to laryngoscopy is restricted, although we emphasize that this investigation remains the gold standard.

covid-19;inducible laryngeal obstruction;laryngoscopy

Journal Article

Haines, Jemma;Esposito, Karen;Slinger, Claire;Pargeter, Nicola;Murphy, Jennifer;Selby, Julia;Prior, Kathryn;Mansur, Adel;Vyas, Aashish;Stanton, Andrew E;Sabroe, Ian;Hull, James H;Fowler, Stephen J

10.1111/cea.13745

[Title]: UK consensus statement on the diagnosis of inducible laryngeal obstruction in light of the COVID-19 pandemic. [Abstract]: Prior to the COVID-19 pandemic, laryngoscopy was the mandatory gold standard for the accurate assessment and diagnosis of inducible laryngeal obstruction. However, upper airway endoscopy is considered an aerosol-generating procedure in professional guidelines, meaning routine procedures are highly challenging and the availability of laryngoscopy is reduced. In response, we have convened a multidisciplinary panel with broad experience in managing this disease and agreed a recommended strategy for presumptive diagnosis in patients who cannot have laryngoscopy performed due to pandemic restrictions. To maintain clinical standards whilst ensuring patient safety, we discuss the importance of triage, information gathering, symptom assessment and early review of response to treatment. The consensus recommendations will also be potentially relevant to other future situations where access to laryngoscopy is restricted, although we emphasize that this investigation remains the gold standard. [Keywords]: covid-19;inducible laryngeal obstruction;laryngoscopy

BMC Infect Dis

Potential implications of SARS-CoV-2 epidemic in Africa: where are we going from now?

The SARS-CoV-2, which emerged from East Asia in December 2019, has rapidly evolved into a global pandemic infecting close to 7 million people. The current uncertainties regarding its impact on Africa calls for critical monitoring of the evolution of the pandemic and correlation of factors that influence the burden of the disease. We herein discuss possible implications of SARS-CoV-2 on the African continent.

africa;covid-19;coronavirus;low-income countries;sars-cov-2

Editorial

Torti, Carlo;Mazzitelli, Maria;Trecarichi, Enrico Maria;Darius, Owachi

10.1186/s12879-020-05147-8

[Title]: Potential implications of SARS-CoV-2 epidemic in Africa: where are we going from now? [Abstract]: The SARS-CoV-2, which emerged from East Asia in December 2019, has rapidly evolved into a global pandemic infecting close to 7 million people. The current uncertainties regarding its impact on Africa calls for critical monitoring of the evolution of the pandemic and correlation of factors that influence the burden of the disease. We herein discuss possible implications of SARS-CoV-2 on the African continent. [Keywords]: africa;covid-19;coronavirus;low-income countries;sars-cov-2

Acad Radiol

Assessment of Small Pulmonary Blood Vessels in COVID-19 Patients Using HRCT.

RATIONALE AND OBJECTIVES: Mounting evidence supports the role of pulmonary hemodynamic alternations in the pathogenesis of COVID-19. Previous studies have demonstrated that changes in pulmonary blood volumes measured on computed tomography (CT) are associated with histopathological markers of pulmonary vascular pruning, suggesting that quantitative CT analysis may eventually be useful in the assessment pulmonary vascular dysfunction more broadly. MATERIALS AND METHODS: Building upon previous work, automated quantitative CT measures of small blood vessel volume and pulmonary vascular density were developed. Scans from 103 COVID-19 patients and 107 healthy volunteers were analyzed and their results compared, with comparisons made both on lobar and global levels. RESULTS: Compared to healthy volunteers, COVID-19 patients showed significant reduction in BV5 (pulmonary blood volume contained in blood vessels of <5 mm(2)) expressed as BV5/(total pulmonary blood volume; p < 0.0001), and significant increases in BV5-10 and BV 10 (pulmonary blood volumes contained in vessels between 5 and 10 mm(2) and above 10 mm(2), respectively, p < 0.0001). These changes were consistent across lobes. CONCLUSION: COVID-19 patients display striking anomalies in the distribution of blood volume within the pulmonary vascular tree, consistent with increased pulmonary vasculature resistance in the pulmonary vessels below the resolution of CT.

covid-19;pulmonary vascular disease;quantitative ct metrics

Journal Article;Research Support, Non-U.S. Gov't

Lins, Muriel;Vandevenne, Jan;Thillai, Muhunthan;Lavon, Ben R;Lanclus, Maarten;Bonte, Stijn;Godon, Rik;Kendall, Irvin;De Backer, Jan;De Backer, Wilfried

10.1016/j.acra.2020.07.019

[Title]: Assessment of Small Pulmonary Blood Vessels in COVID-19 Patients Using HRCT. [Abstract]: RATIONALE AND OBJECTIVES: Mounting evidence supports the role of pulmonary hemodynamic alternations in the pathogenesis of COVID-19. Previous studies have demonstrated that changes in pulmonary blood volumes measured on computed tomography (CT) are associated with histopathological markers of pulmonary vascular pruning, suggesting that quantitative CT analysis may eventually be useful in the assessment pulmonary vascular dysfunction more broadly. MATERIALS AND METHODS: Building upon previous work, automated quantitative CT measures of small blood vessel volume and pulmonary vascular density were developed. Scans from 103 COVID-19 patients and 107 healthy volunteers were analyzed and their results compared, with comparisons made both on lobar and global levels. RESULTS: Compared to healthy volunteers, COVID-19 patients showed significant reduction in BV5 (pulmonary blood volume contained in blood vessels of <5 mm(2)) expressed as BV5/(total pulmonary blood volume; p < 0.0001), and significant increases in BV5-10 and BV 10 (pulmonary blood volumes contained in vessels between 5 and 10 mm(2) and above 10 mm(2), respectively, p < 0.0001). These changes were consistent across lobes. CONCLUSION: COVID-19 patients display striking anomalies in the distribution of blood volume within the pulmonary vascular tree, consistent with increased pulmonary vasculature resistance in the pulmonary vessels below the resolution of CT. [Keywords]: covid-19;pulmonary vascular disease;quantitative ct metrics

Intern Emerg Med

Neither ACEIs nor ARBs are associated with respiratory distress or mortality in COVID-19 results of a prospective study on a hospital-based cohort.

Considerable concern has emerged for the potential harm in the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor inhibitors (ARBs) in COVID-19 patients, given that ACEIs and ARBs may increase the expression of ACE2 receptors that represent the way for coronavirus 2 to entry into the cell and cause severe acute respiratory syndrome. Assess the effect of ACEI/ARBs on outcome in COVID-19 patients. Hospital-based prospective study. A total of 431 patients consecutively presenting at the Emergency Department and found to be affected by COVID-19 were assessed. Relevant clinical and laboratory variables were recorded, focusing on the type of current anti hypertensive treatment. Outcome variables were NO, MILD, SEVERE respiratory distress (RD) operationally defined and DEATH. Hypertension was the single most frequent comorbidity (221/431 = 51%). Distribution of antihypertensive treatment was: ACEIs 77/221 (35%), ARBs 63/221 (28%), OTHER than ACEIs or ARBs 64/221 (29%). In 17/221 (8%) antihypertensive medication was unknown. The proportion of patients taking ACEIs, ARBs or OTHERs who developed MILD or SEVERE RD was 43/77 (56%), 33/53 (52%), 39/64 (61%) and 19/77 (25%), 16/63 (25%) and 16/64 (25%), respectively, with no statistical difference between groups. Despite producing a RR for SEVERE RD of 2.59 (95% CI 1.93-3.49), hypertension was no longer significant in a logistic regression analysis that identified age, CRP and creatinine as the sole independent predictors of SEVERE RD and DEATH. ACEIs and ARBs do not promote a more severe outcome of COVID-19. There is no reason why they should be withheld in affected patients.

angiotensin converting enzyme inhibitor;angiotensin receptor blocker;covid-19

Journal Article

Anzola, Gian Paolo;Bartolaminelli, Clara;Gregorini, Gina Alessandra;Coazzoli, Chiara;Gatti, Francesca;Mora, Alessandra;Charalampakis, Dimitrios;Palmigiano, Andrea;De Simone, Michele;Comini, Alice;Dellaglio, Erica;Cassetti, Salvatore;Chiesa, Maurizio;Spedini, Francesca;d'Ottavi, Patrizia;Savio, Maria Cristina

10.1007/s11739-020-02500-2

[Title]: Neither ACEIs nor ARBs are associated with respiratory distress or mortality in COVID-19 results of a prospective study on a hospital-based cohort. [Abstract]: Considerable concern has emerged for the potential harm in the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor inhibitors (ARBs) in COVID-19 patients, given that ACEIs and ARBs may increase the expression of ACE2 receptors that represent the way for coronavirus 2 to entry into the cell and cause severe acute respiratory syndrome. Assess the effect of ACEI/ARBs on outcome in COVID-19 patients. Hospital-based prospective study. A total of 431 patients consecutively presenting at the Emergency Department and found to be affected by COVID-19 were assessed. Relevant clinical and laboratory variables were recorded, focusing on the type of current anti hypertensive treatment. Outcome variables were NO, MILD, SEVERE respiratory distress (RD) operationally defined and DEATH. Hypertension was the single most frequent comorbidity (221/431 = 51%). Distribution of antihypertensive treatment was: ACEIs 77/221 (35%), ARBs 63/221 (28%), OTHER than ACEIs or ARBs 64/221 (29%). In 17/221 (8%) antihypertensive medication was unknown. The proportion of patients taking ACEIs, ARBs or OTHERs who developed MILD or SEVERE RD was 43/77 (56%), 33/53 (52%), 39/64 (61%) and 19/77 (25%), 16/63 (25%) and 16/64 (25%), respectively, with no statistical difference between groups. Despite producing a RR for SEVERE RD of 2.59 (95% CI 1.93-3.49), hypertension was no longer significant in a logistic regression analysis that identified age, CRP and creatinine as the sole independent predictors of SEVERE RD and DEATH. ACEIs and ARBs do not promote a more severe outcome of COVID-19. There is no reason why they should be withheld in affected patients. [Keywords]: angiotensin converting enzyme inhibitor;angiotensin receptor blocker;covid-19

JMIR Public Health Surveill

Statistical Issues and Lessons Learned From COVID-19 Clinical Trials With Lopinavir-Ritonavir and Remdesivir.

BACKGROUND: Recently, three randomized clinical trials on coronavirus disease (COVID-19) treatments were completed: one for lopinavir-ritonavir and two for remdesivir. One trial reported that remdesivir was superior to placebo in shortening the time to recovery, while the other two showed no benefit of the treatment under investigation. OBJECTIVE: The aim of this paper is to, from a statistical perspective, identify several key issues in the design and analysis of three COVID-19 trials and reanalyze the data from the cumulative incidence curves in the three trials using more appropriate statistical methods. METHODS: The lopinavir-ritonavir trial enrolled 39 additional patients due to insignificant results after the sample size reached the planned number, which led to inflation of the type I error rate. The remdesivir trial of Wang et al failed to reach the planned sample size due to a lack of eligible patients, and the bootstrap method was used to predict the quantity of clinical interest conditionally and unconditionally if the trial had continued to reach the originally planned sample size. Moreover, we used a terminal (or cure) rate model and a model-free metric known as the restricted mean survival time or the restricted mean time to improvement (RMTI) to analyze the reconstructed data. The remdesivir trial of Beigel et al reported the median recovery time of the remdesivir and placebo groups, and the rate ratio for recovery, while both quantities depend on a particular time point representing local information. We use the restricted mean time to recovery (RMTR) as a global and robust measure for efficacy. RESULTS: For the lopinavir-ritonavir trial, with the increase of sample size from 160 to 199, the type I error rate was inflated from 0.05 to 0.071. The difference of RMTIs between the two groups evaluated at day 28 was -1.67 days (95% CI -3.62 to 0.28; P=.09) in favor of lopinavir-ritonavir but not statistically significant. For the remdesivir trial of Wang et al, the difference of RMTIs at day 28 was -0.89 days (95% CI -2.84 to 1.06; P=.37). The planned sample size was 453, yet only 236 patients were enrolled. The conditional prediction shows that the hazard ratio estimates would reach statistical significance if the target sample size had been maintained. For the remdesivir trial of Beigel et al, the difference of RMTRs between the remdesivir and placebo groups at day 30 was -2.7 days (95% CI -4.0 to -1.2; P<.001), confirming the superiority of remdesivir. The difference in the recovery time at the 25th percentile (95% CI -3 to 0; P=.65) was insignificant, while the differences became more statistically significant at larger percentiles. CONCLUSIONS: Based on the statistical issues and lessons learned from the recent three clinical trials on COVID-19 treatments, we suggest more appropriate approaches for the design and analysis of ongoing and future COVID-19 trials.

covid-19;coronavirus;cure rate model;restricted mean survival time;sample size adjustment;terminal event;type i error rate

Journal Article;Research Support, Non-U.S. Gov't

Yin, Guosheng;Zhang, Chenyang;Jin, Huaqing

10.2196/19538

[Title]: Statistical Issues and Lessons Learned From COVID-19 Clinical Trials With Lopinavir-Ritonavir and Remdesivir. [Abstract]: BACKGROUND: Recently, three randomized clinical trials on coronavirus disease (COVID-19) treatments were completed: one for lopinavir-ritonavir and two for remdesivir. One trial reported that remdesivir was superior to placebo in shortening the time to recovery, while the other two showed no benefit of the treatment under investigation. OBJECTIVE: The aim of this paper is to, from a statistical perspective, identify several key issues in the design and analysis of three COVID-19 trials and reanalyze the data from the cumulative incidence curves in the three trials using more appropriate statistical methods. METHODS: The lopinavir-ritonavir trial enrolled 39 additional patients due to insignificant results after the sample size reached the planned number, which led to inflation of the type I error rate. The remdesivir trial of Wang et al failed to reach the planned sample size due to a lack of eligible patients, and the bootstrap method was used to predict the quantity of clinical interest conditionally and unconditionally if the trial had continued to reach the originally planned sample size. Moreover, we used a terminal (or cure) rate model and a model-free metric known as the restricted mean survival time or the restricted mean time to improvement (RMTI) to analyze the reconstructed data. The remdesivir trial of Beigel et al reported the median recovery time of the remdesivir and placebo groups, and the rate ratio for recovery, while both quantities depend on a particular time point representing local information. We use the restricted mean time to recovery (RMTR) as a global and robust measure for efficacy. RESULTS: For the lopinavir-ritonavir trial, with the increase of sample size from 160 to 199, the type I error rate was inflated from 0.05 to 0.071. The difference of RMTIs between the two groups evaluated at day 28 was -1.67 days (95% CI -3.62 to 0.28; P=.09) in favor of lopinavir-ritonavir but not statistically significant. For the remdesivir trial of Wang et al, the difference of RMTIs at day 28 was -0.89 days (95% CI -2.84 to 1.06; P=.37). The planned sample size was 453, yet only 236 patients were enrolled. The conditional prediction shows that the hazard ratio estimates would reach statistical significance if the target sample size had been maintained. For the remdesivir trial of Beigel et al, the difference of RMTRs between the remdesivir and placebo groups at day 30 was -2.7 days (95% CI -4.0 to -1.2; P<.001), confirming the superiority of remdesivir. The difference in the recovery time at the 25th percentile (95% CI -3 to 0; P=.65) was insignificant, while the differences became more statistically significant at larger percentiles. CONCLUSIONS: Based on the statistical issues and lessons learned from the recent three clinical trials on COVID-19 treatments, we suggest more appropriate approaches for the design and analysis of ongoing and future COVID-19 trials. [Keywords]: covid-19;coronavirus;cure rate model;restricted mean survival time;sample size adjustment;terminal event;type i error rate

Nefrologia

[Management of the SARS-CoV-2 (COVID-19) coronavirus epidemic in hemodialysis units].

The current outbreak of SARS-CoV-2 represents a special risk for renal patients due to their comorbidities and advanced age. The usual performance of hemodialysis treatments in collective rooms increases the risk. The specific information at this time in this regard is very limited. This manuscript includes a proposal for action to prevent infection in the Nephrology Services, and in particular in Hemodialysis Units, with the objective of early identification of patients who meet the definition of a suspected case of infection by SARS-CoV-2 and propose circuits and mechanisms to carry out hemodialysis treatments. They are recommendations in continuous review and can be modified if the epidemiological situation, the diagnostic and therapeutic options so require.

covid-19;coronavirus;hemodialysis;hemodialisis;sars-cov-2

Practice Guideline

Arenas, Maria Dolores;Villar, Judit;Gonzalez, Cristina;Cao, Higinio;Collado, Silvia;Crespo, Marta;Horcajada, Juan Pablo;Pascual, Julio

10.1016/j.nefro.2020.04.001

[Title]: [Management of the SARS-CoV-2 (COVID-19) coronavirus epidemic in hemodialysis units]. [Abstract]: The current outbreak of SARS-CoV-2 represents a special risk for renal patients due to their comorbidities and advanced age. The usual performance of hemodialysis treatments in collective rooms increases the risk. The specific information at this time in this regard is very limited. This manuscript includes a proposal for action to prevent infection in the Nephrology Services, and in particular in Hemodialysis Units, with the objective of early identification of patients who meet the definition of a suspected case of infection by SARS-CoV-2 and propose circuits and mechanisms to carry out hemodialysis treatments. They are recommendations in continuous review and can be modified if the epidemiological situation, the diagnostic and therapeutic options so require. [Keywords]: covid-19;coronavirus;hemodialysis;hemodialisis;sars-cov-2

Front Med (Lausanne)

Re-positive Cases of Nucleic Acid Tests in Discharged Patients With COVID-19: A Follow-Up Study.

Background: The frequent emergence of the re-positive patients with COVID-19 is a potential threat worldwide. This study aimed to describe data from admission to follow-up for patients with COVID-19 and analyze the possible causes for re-positive nucleic acid tests to provide more scientific basis for reducing the numbers of re-positive patients after discharge. Methods: We retrospectively recorded 15 patients with COVID-19 admitted to the Xianyang Central Hospital, China. The baseline, exposure histories, clinical syndromes, laboratory characteristics, nucleic acid, and follow-up tests were analyzed, and the radiological characteristics of re-positive patient at different periods were compared. Results: Eight (53.33%) patients had the history of travel to Wuhan, four (26.67%) patients had close contact with confirmed patients, and one (6.67%) patient had close contact with suspected patients. After treatment, all patients had two consecutively negative nucleic acid tests and were discharged from hospital. All patients were followed up for more than 14 days, and the average time from discharge to the first follow-up was 14.67 +/- 3.31 days (from 9 to 22 days). Most patients showed no clinical symptoms and negative nucleic acid tests, while one patient had an itchy throat, her CT scan showed a light density shadow in the right lower lobe of the lung, and the nucleic acid was once again positive. The second follow-up of the other 14 patients (except the re-positive one) was conducted 20.80 +/- 7.78 days (from 13 to 30 days) after discharge, and all of them had negative nucleic acid tests. The positive patient was immediately readmitted and received a new round of treatment. Her family members and colleagues remained healthy until now. Conclusions: The quality of nucleic acid testing reagents should be enhanced, and the training of nucleic acid sampling operators should be strengthened to reduce the false-negative results in the nucleic acid of SARS-CoV-2; the clinical specimens of throat and nasopharynx swabs can be collected at the same time; IgM- and IgG-specific antibodies of SARS-CoV-2 should be carried out for discharged patients; the radiological characteristics should be evaluated strictly; and the discharge standard can be specified according to the baseline and severity of disease of patients.

covid-19;sars-cov-2;discharge;follow-up;re-positive

Journal Article

Qiao, Xi-Min;Xu, Xiao-Feng;Zi, Hao;Liu, Guo-Xiong;Li, Bing-Hui;Du, Xiang;Tian, Zhi-Hai;Liu, Xiao-Ying;Luo, Li-Sha;Wang, Xiao

10.3389/fmed.2020.00349

[Title]: Re-positive Cases of Nucleic Acid Tests in Discharged Patients With COVID-19: A Follow-Up Study. [Abstract]: Background: The frequent emergence of the re-positive patients with COVID-19 is a potential threat worldwide. This study aimed to describe data from admission to follow-up for patients with COVID-19 and analyze the possible causes for re-positive nucleic acid tests to provide more scientific basis for reducing the numbers of re-positive patients after discharge. Methods: We retrospectively recorded 15 patients with COVID-19 admitted to the Xianyang Central Hospital, China. The baseline, exposure histories, clinical syndromes, laboratory characteristics, nucleic acid, and follow-up tests were analyzed, and the radiological characteristics of re-positive patient at different periods were compared. Results: Eight (53.33%) patients had the history of travel to Wuhan, four (26.67%) patients had close contact with confirmed patients, and one (6.67%) patient had close contact with suspected patients. After treatment, all patients had two consecutively negative nucleic acid tests and were discharged from hospital. All patients were followed up for more than 14 days, and the average time from discharge to the first follow-up was 14.67 +/- 3.31 days (from 9 to 22 days). Most patients showed no clinical symptoms and negative nucleic acid tests, while one patient had an itchy throat, her CT scan showed a light density shadow in the right lower lobe of the lung, and the nucleic acid was once again positive. The second follow-up of the other 14 patients (except the re-positive one) was conducted 20.80 +/- 7.78 days (from 13 to 30 days) after discharge, and all of them had negative nucleic acid tests. The positive patient was immediately readmitted and received a new round of treatment. Her family members and colleagues remained healthy until now. Conclusions: The quality of nucleic acid testing reagents should be enhanced, and the training of nucleic acid sampling operators should be strengthened to reduce the false-negative results in the nucleic acid of SARS-CoV-2; the clinical specimens of throat and nasopharynx swabs can be collected at the same time; IgM- and IgG-specific antibodies of SARS-CoV-2 should be carried out for discharged patients; the radiological characteristics should be evaluated strictly; and the discharge standard can be specified according to the baseline and severity of disease of patients. [Keywords]: covid-19;sars-cov-2;discharge;follow-up;re-positive

Front Microbiol

Food Safety During and After the Era of COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020 due to its rapid and extensive spread among many countries through its very contagious nature and its high mortality among the elderly and infirm. Recently, data on the survival of SARS-CoV-2 on contact surfaces has been reported, but there is none on the survival of COVID-19 on food surfaces and packages. The potential survival and transmission of SARS-CoV-2 on/via food and packages are discussed based on data available for other respiratory viruses such as SARS-CoV and MERS-CoV. However, studies are needed to explore its transmission via food and survival on food packaging materials. The implementation of food safety management systems such as Hazard Analysis and Critical Control Points (HACCP), and Good Manufacturing Practices (GMP) are important to reduce the risk of COVID-19 infection. Cleaning, sanitation, good hygienic practices, and active packaging are also needed from farm to fork.

covid-19;sars-cov-2;active packaging;coronavirus;food package;food safety;sanitation;transmission

Journal Article

Olaimat, Amin N;Shahbaz, Hafiz M;Fatima, Nayab;Munir, Sadia;Holley, Richard A

10.3389/fmicb.2020.01854

[Title]: Food Safety During and After the Era of COVID-19 Pandemic. [Abstract]: The coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020 due to its rapid and extensive spread among many countries through its very contagious nature and its high mortality among the elderly and infirm. Recently, data on the survival of SARS-CoV-2 on contact surfaces has been reported, but there is none on the survival of COVID-19 on food surfaces and packages. The potential survival and transmission of SARS-CoV-2 on/via food and packages are discussed based on data available for other respiratory viruses such as SARS-CoV and MERS-CoV. However, studies are needed to explore its transmission via food and survival on food packaging materials. The implementation of food safety management systems such as Hazard Analysis and Critical Control Points (HACCP), and Good Manufacturing Practices (GMP) are important to reduce the risk of COVID-19 infection. Cleaning, sanitation, good hygienic practices, and active packaging are also needed from farm to fork. [Keywords]: covid-19;sars-cov-2;active packaging;coronavirus;food package;food safety;sanitation;transmission

Adv Ther

Baseline Demographics and Clinical Characteristics Among 3471 US Patients Hospitalized with COVID-19 and Pulmonary Involvement: A Retrospective Study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can present as a range of symptoms, from mild to critical; lower pulmonary involvement, including pneumonia, is often associated with severe and critical cases. Understanding the baseline characteristics of patients hospitalized with COVID-19 illness is essential for effectively targeting clinical care and allocating resources. This study aimed to describe baseline demographics and clinical characteristics of US patients hospitalized with COVID-19 and pulmonary involvement. METHODS: US patients with COVID-19 and pulmonary involvement during an inpatient admission from December 1, 2019, to May 20, 2020, were identified using the IBM Explorys((R)) electronic health records database. Baseline (up to 12 months prior to first COVID-19 hospitalization) demographics and clinical characteristics and preadmission (14 days to 1 day prior to admission) pulmonary diagnoses were assessed. Patients were stratified by sex, age, race, and geographic region. RESULTS: Overall, 3471 US patients hospitalized with COVID-19 and pulmonary involvement were included. The mean (SD) age was 63.5 (16.3) years; 51.2% of patients were female, 55.0% African American, 81.6% from the South, and 16.8% from the Midwest. The most common comorbidities included hypertension (27.7%), diabetes (17.3%), hyperlipidemia (16.3%), and obesity (9.7%). Cough (27.3%) and dyspnea (15.2%) were the most common preadmission pulmonary symptoms. African American patients were younger (mean [SD], 62.5 [15.4] vs. 67.8 [6.2]) with higher mean (SD) body mass index (33.66 [9.46] vs. 30.42 [7.86]) and prevalence of diabetes (19.8% vs. 16.7%) and lower prevalence of chronic obstructive pulmonary disease (5.6% vs. 8.2%) and smoking/tobacco use (28.1% vs. 37.2%) than White patients. CONCLUSIONS: Among US patients primarily from the South and Midwest hospitalized with COVID-19 and pulmonary involvement, the most common comorbidities were hypertension, diabetes, hyperlipidemia, and obesity. Differences observed between African American and White patients should be considered in the context of the complex factors underlying racial disparities in COVID-19.

baseline characteristics;covid-19;coronavirus;demographics;hospitalized;infectious disease;pulmonary involvement

Journal Article;Research Support, Non-U.S. Gov't

Best, Jennie H;Mohan, Shalini V;Kong, Amanda M;Patel, Krish;Pagel, John M;Ivanov, Boris;Brawley, Otis W;Jariwala-Parikh, Krutika;Zazzali, James L;Pauk, John

10.1007/s12325-020-01510-y

[Title]: Baseline Demographics and Clinical Characteristics Among 3471 US Patients Hospitalized with COVID-19 and Pulmonary Involvement: A Retrospective Study. [Abstract]: INTRODUCTION: Coronavirus disease 2019 (COVID-19) can present as a range of symptoms, from mild to critical; lower pulmonary involvement, including pneumonia, is often associated with severe and critical cases. Understanding the baseline characteristics of patients hospitalized with COVID-19 illness is essential for effectively targeting clinical care and allocating resources. This study aimed to describe baseline demographics and clinical characteristics of US patients hospitalized with COVID-19 and pulmonary involvement. METHODS: US patients with COVID-19 and pulmonary involvement during an inpatient admission from December 1, 2019, to May 20, 2020, were identified using the IBM Explorys((R)) electronic health records database. Baseline (up to 12 months prior to first COVID-19 hospitalization) demographics and clinical characteristics and preadmission (14 days to 1 day prior to admission) pulmonary diagnoses were assessed. Patients were stratified by sex, age, race, and geographic region. RESULTS: Overall, 3471 US patients hospitalized with COVID-19 and pulmonary involvement were included. The mean (SD) age was 63.5 (16.3) years; 51.2% of patients were female, 55.0% African American, 81.6% from the South, and 16.8% from the Midwest. The most common comorbidities included hypertension (27.7%), diabetes (17.3%), hyperlipidemia (16.3%), and obesity (9.7%). Cough (27.3%) and dyspnea (15.2%) were the most common preadmission pulmonary symptoms. African American patients were younger (mean [SD], 62.5 [15.4] vs. 67.8 [6.2]) with higher mean (SD) body mass index (33.66 [9.46] vs. 30.42 [7.86]) and prevalence of diabetes (19.8% vs. 16.7%) and lower prevalence of chronic obstructive pulmonary disease (5.6% vs. 8.2%) and smoking/tobacco use (28.1% vs. 37.2%) than White patients. CONCLUSIONS: Among US patients primarily from the South and Midwest hospitalized with COVID-19 and pulmonary involvement, the most common comorbidities were hypertension, diabetes, hyperlipidemia, and obesity. Differences observed between African American and White patients should be considered in the context of the complex factors underlying racial disparities in COVID-19. [Keywords]: baseline characteristics;covid-19;coronavirus;demographics;hospitalized;infectious disease;pulmonary involvement

Eur Radiol

Coronavirus disease 2019: initial chest CT findings.

OBJECTIVES: To systematically analyze CT findings during the early and progressive stages of natural course of coronavirus disease 2019 and also to explore possible changes in pulmonary parenchymal abnormalities during these two stages. METHODS: We retrospectively reviewed the initial chest CT data of 62 confirmed coronavirus disease 2019 patients (34 men, 28 women; age range 20-91 years old) who did not receive any antiviral treatment between January 21 and February 4, 2020, in Chongqing, China. Patients were assigned to the early-stage group (onset of symptoms within 4 days) or progressive-stage group (onset of symptoms within 4-7 days) for analysis. CT characteristics and the distribution, size, and CT score of pulmonary parenchymal abnormalities were assessed. RESULTS: In our study, the major characteristic of coronavirus disease 2019 was ground-glass opacity (61.3%), followed by ground-glass opacity with consolidation (35.5%), rounded opacities (25.8%), a crazy-paving pattern (25.8%), and an air bronchogram (22.6%). No patient presented cavitation, a reticular pattern, or bronchial wall thickening. The CT scores of the progressive-stage group were significantly greater than those of the early-stage group (p = 0.004). CONCLUSIONS: Multiple ground-glass opacities with consolidations in the periphery of the lungs were the primary CT characteristic of coronavirus disease 2019. CT score can be used to evaluate the severity of the disease. If these typical alterations are found, then the differential diagnosis of coronavirus disease 2019 must be considered. KEY POINTS: * Multiple GGOs with consolidations in the periphery of the lungs were the primary CT characteristic of COVID-19. * The halo sign may be a special CT feature in the early-stage COVID-19 patients. * Significantly increased CT score may indicate the aggravation of COVID-19 in the progressive stage.

covid-19;coronavirus;pneumonia;sars-cov-2;spiral ct scan

Journal Article

Zhou, Zhiming;Guo, Dajing;Li, Chuanming;Fang, Zheng;Chen, Linli;Yang, Ran;Li, Xiang;Zeng, Wenbing

10.1007/s00330-020-06816-7

[Title]: Coronavirus disease 2019: initial chest CT findings. [Abstract]: OBJECTIVES: To systematically analyze CT findings during the early and progressive stages of natural course of coronavirus disease 2019 and also to explore possible changes in pulmonary parenchymal abnormalities during these two stages. METHODS: We retrospectively reviewed the initial chest CT data of 62 confirmed coronavirus disease 2019 patients (34 men, 28 women; age range 20-91 years old) who did not receive any antiviral treatment between January 21 and February 4, 2020, in Chongqing, China. Patients were assigned to the early-stage group (onset of symptoms within 4 days) or progressive-stage group (onset of symptoms within 4-7 days) for analysis. CT characteristics and the distribution, size, and CT score of pulmonary parenchymal abnormalities were assessed. RESULTS: In our study, the major characteristic of coronavirus disease 2019 was ground-glass opacity (61.3%), followed by ground-glass opacity with consolidation (35.5%), rounded opacities (25.8%), a crazy-paving pattern (25.8%), and an air bronchogram (22.6%). No patient presented cavitation, a reticular pattern, or bronchial wall thickening. The CT scores of the progressive-stage group were significantly greater than those of the early-stage group (p = 0.004). CONCLUSIONS: Multiple ground-glass opacities with consolidations in the periphery of the lungs were the primary CT characteristic of coronavirus disease 2019. CT score can be used to evaluate the severity of the disease. If these typical alterations are found, then the differential diagnosis of coronavirus disease 2019 must be considered. KEY POINTS: * Multiple GGOs with consolidations in the periphery of the lungs were the primary CT characteristic of COVID-19. * The halo sign may be a special CT feature in the early-stage COVID-19 patients. * Significantly increased CT score may indicate the aggravation of COVID-19 in the progressive stage. [Keywords]: covid-19;coronavirus;pneumonia;sars-cov-2;spiral ct scan

Rev Bras Enferm

Prevention and control measures for neonatal COVID-19 infection: a scoping review.

OBJECTIVE: to identify with the literature the measures to prevent and control neonatal infection by COVID-19. METHODS: a scope review carried out by searching for studies in databases and institutional health websites. The final sample was 25 articles. RESULTS: among the main measures are the use of masks by suspected or infected people in contact with healthy newborns, hand hygiene before and after each care and feeding as well as the tools used for milking. It is indispensable to use personal protective equipment by health professionals in neonatology services to maintain a private room for infected newborns or to use physical barriers. Early diagnosis and timely case management is essential to reduce virus transmissibility. CONCLUSIONS: the research contributed to elucidate health and nursing actions in preventing and controlling neonatal infection by COVID-19.

Journal Article;Systematic Review

Freitas, Bruna Hinnah Borges Martins de;Alves, Mayrene Dias de Sousa Moreira;Gaiva, Maria Aparecida Munhoz

10.1590/0034-7167-2020-0467

[Title]: Prevention and control measures for neonatal COVID-19 infection: a scoping review. [Abstract]: OBJECTIVE: to identify with the literature the measures to prevent and control neonatal infection by COVID-19. METHODS: a scope review carried out by searching for studies in databases and institutional health websites. The final sample was 25 articles. RESULTS: among the main measures are the use of masks by suspected or infected people in contact with healthy newborns, hand hygiene before and after each care and feeding as well as the tools used for milking. It is indispensable to use personal protective equipment by health professionals in neonatology services to maintain a private room for infected newborns or to use physical barriers. Early diagnosis and timely case management is essential to reduce virus transmissibility. CONCLUSIONS: the research contributed to elucidate health and nursing actions in preventing and controlling neonatal infection by COVID-19. [Keywords]:

New Microbes New Infect

The current situation of COVID-19 in Sudan.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global public health concern with rapid growth in the number of patients with significant mortality rates. The first case in Sudan was reported on 13 March 2020, and up to 3 July 2020 there are 9894 confirmed cases and 616 deaths. The case fatality rate was 6.23%. There is variation in case fatality rate (CFR), which in some cities (like Khartoum) was low (3.8%), but in others (like North Darfur) it was very high (31.7%). The government of Sudan has implemented preventive measures during the current coronavirus disease pandemic, such as partial lockdown, contact monitoring, risk communication, social distance, quarantine and isolation to prevent the spread of SARS-CoV-2. However, there are new community cases every day; this could be as a result of the weak application of these measures by the government, and the lack of commitment of people to these measures. The number of COVID-19 cases is currently decreasing in Sudan, but we are expected to see an increase in numbers of cases as a result of the massive demonstrations that occurred in Sudan recently, and as a result of the expected reopening and restoration of normal life. The government must increase testing facilities, and maintain social distancing and necessary precautions to limit the spread of infection after life returns to normal.

covid-19;sars-cov-2;sudan;current scenario;testing facilities

Journal Article

Altayb, H N;Altayeb, N M E;Hamadalnil, Y;Elsayid, M;Mahmoud, N E

10.1016/j.nmni.2020.100746

[Title]: The current situation of COVID-19 in Sudan. [Abstract]: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global public health concern with rapid growth in the number of patients with significant mortality rates. The first case in Sudan was reported on 13 March 2020, and up to 3 July 2020 there are 9894 confirmed cases and 616 deaths. The case fatality rate was 6.23%. There is variation in case fatality rate (CFR), which in some cities (like Khartoum) was low (3.8%), but in others (like North Darfur) it was very high (31.7%). The government of Sudan has implemented preventive measures during the current coronavirus disease pandemic, such as partial lockdown, contact monitoring, risk communication, social distance, quarantine and isolation to prevent the spread of SARS-CoV-2. However, there are new community cases every day; this could be as a result of the weak application of these measures by the government, and the lack of commitment of people to these measures. The number of COVID-19 cases is currently decreasing in Sudan, but we are expected to see an increase in numbers of cases as a result of the massive demonstrations that occurred in Sudan recently, and as a result of the expected reopening and restoration of normal life. The government must increase testing facilities, and maintain social distancing and necessary precautions to limit the spread of infection after life returns to normal. [Keywords]: covid-19;sars-cov-2;sudan;current scenario;testing facilities

JCI Insight

High levels of SARS-CoV-2-specific T cells with restricted functionality in severe courses of COVID-19.

BACKGROUNDPatients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2-specific immunity correlate with disease severity.METHODSIn this study, SARS-CoV-2-specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2-specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-gamma, IL-2, and TNF-alpha) and markers for activation, proliferation, and functional anergy. SARS-CoV-2-specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls.RESULTSDespite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2-specific T cells as compared with convalescent individuals. SARS-CoV-2-specific CD4+ T cells dominated over CD8+ T cells and closely correlated with the number of plasmablasts and SARS-CoV-2-specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2-specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4+ and CD8+ T cells in general.CONCLUSIONGiven the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung.FUNDINGThe study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung.

covid-19;cellular immune response;immunoglobulins;t cells

Journal Article;Research Support, Non-U.S. Gov't

Schub, David;Klemis, Verena;Schneitler, Sophie;Mihm, Janine;Lepper, Philipp M;Wilkens, Heinrike;Bals, Robert;Eichler, Hermann;Gartner, Barbara C;Becker, Soren L;Sester, Urban;Sester, Martina;Schmidt, Tina

10.1172/jci.insight.142167

[Title]: High levels of SARS-CoV-2-specific T cells with restricted functionality in severe courses of COVID-19. [Abstract]: BACKGROUNDPatients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2-specific immunity correlate with disease severity.METHODSIn this study, SARS-CoV-2-specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2-specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-gamma, IL-2, and TNF-alpha) and markers for activation, proliferation, and functional anergy. SARS-CoV-2-specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls.RESULTSDespite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2-specific T cells as compared with convalescent individuals. SARS-CoV-2-specific CD4+ T cells dominated over CD8+ T cells and closely correlated with the number of plasmablasts and SARS-CoV-2-specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2-specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4+ and CD8+ T cells in general.CONCLUSIONGiven the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung.FUNDINGThe study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung. [Keywords]: covid-19;cellular immune response;immunoglobulins;t cells

Sci Total Environ

Can we predict the occurrence of COVID-19 cases? Considerations using a simple model of growth.

This study aimed to present a simple model to follow the evolution of the COVID-19 (CV-19) pandemic in different countries. The cumulative distribution function (CDF) and its first derivative were employed for this task. The simulations showed that it is almost impossible to predict based on the initial CV-19 cases (1st 2nd or 3rd weeks) how the pandemic will evolve. However, the results presented here revealed that this approach can be used as an alternative for the exponential growth model, traditionally employed as a prediction model, and serve as a valuable tool for investigating how protective measures are changing the evolution of the pandemic.

coronavirus;cumulative distribution function;pandemic;sars-cov-2

Journal Article

Cassaro, Fabio A M;Pires, Luiz F

10.1016/j.scitotenv.2020.138834

[Title]: Can we predict the occurrence of COVID-19 cases? Considerations using a simple model of growth. [Abstract]: This study aimed to present a simple model to follow the evolution of the COVID-19 (CV-19) pandemic in different countries. The cumulative distribution function (CDF) and its first derivative were employed for this task. The simulations showed that it is almost impossible to predict based on the initial CV-19 cases (1st 2nd or 3rd weeks) how the pandemic will evolve. However, the results presented here revealed that this approach can be used as an alternative for the exponential growth model, traditionally employed as a prediction model, and serve as a valuable tool for investigating how protective measures are changing the evolution of the pandemic. [Keywords]: coronavirus;cumulative distribution function;pandemic;sars-cov-2

Eur J Clin Microbiol Infect Dis

Evaluations of the serological test in the diagnosis of 2019 novel coronavirus (SARS-CoV-2) infections during the COVID-19 outbreak.

We developed a chemiluminescence immunoassay method based on the recombinant nucleocapsid antigen and assessed its performance for the clinical diagnosis of severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infections by detecting SARS-CoV-2-specific IgM and IgG antibodies in patients. Full-length recombinant nucleocapsid antigen and tosyl magnetic beads were used to develop the chemiluminescence immunoassay approach. Plasmas from 29 healthy cohorts, 51 tuberculosis patients, and 79 confirmed SARS-CoV-2 patients were employed to evaluate the chemiluminescence immunoassay method performance for the clinical diagnosis of SARS-CoV-2 infections. A commercial ELISA kit (Darui Biotech, China) using the same nucleocapsid antigen was used for the in-parallel comparison with our chemiluminescence immunoassay method. The IgM and IgG manner of testing in the chemiluminescence immunoassay method showed a sensitivity and specificity of 60.76% (95% CI 49.1 to 71.6) and 92.25% (95% CI 83.4 to 97.2) and 82.28% (95% CI 72.1 to 90.0) and 97.5% (95% CI 91.3 to 99.7), respectively. Higher sensitivity and specificity were observed in the chemiluminescence immunoassay method compared with the Darui Biotech ELISA kit. The developed high sensitivity and specificity chemiluminescence immunoassay IgG testing method combined with the RT-PCR approach can improve the clinical diagnosis for SARS-CoV-2 infections and thus contribute to the control of COVID-19 expansion.

chemiluminescence immunoassay;igm and igg;sars-cov-2;serological testing

Journal Article

Lin, Dachuan;Liu, Lei;Zhang, Mingxia;Hu, Yunlong;Yang, Qianting;Guo, Jiubiao;Dai, Youchao;Xu, Yuzhong;Cai, Yi;Chen, Xinchun;Huang, Kaisong;Zhang, Zheng

10.1007/s10096-020-03978-6

[Title]: Evaluations of the serological test in the diagnosis of 2019 novel coronavirus (SARS-CoV-2) infections during the COVID-19 outbreak. [Abstract]: We developed a chemiluminescence immunoassay method based on the recombinant nucleocapsid antigen and assessed its performance for the clinical diagnosis of severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infections by detecting SARS-CoV-2-specific IgM and IgG antibodies in patients. Full-length recombinant nucleocapsid antigen and tosyl magnetic beads were used to develop the chemiluminescence immunoassay approach. Plasmas from 29 healthy cohorts, 51 tuberculosis patients, and 79 confirmed SARS-CoV-2 patients were employed to evaluate the chemiluminescence immunoassay method performance for the clinical diagnosis of SARS-CoV-2 infections. A commercial ELISA kit (Darui Biotech, China) using the same nucleocapsid antigen was used for the in-parallel comparison with our chemiluminescence immunoassay method. The IgM and IgG manner of testing in the chemiluminescence immunoassay method showed a sensitivity and specificity of 60.76% (95% CI 49.1 to 71.6) and 92.25% (95% CI 83.4 to 97.2) and 82.28% (95% CI 72.1 to 90.0) and 97.5% (95% CI 91.3 to 99.7), respectively. Higher sensitivity and specificity were observed in the chemiluminescence immunoassay method compared with the Darui Biotech ELISA kit. The developed high sensitivity and specificity chemiluminescence immunoassay IgG testing method combined with the RT-PCR approach can improve the clinical diagnosis for SARS-CoV-2 infections and thus contribute to the control of COVID-19 expansion. [Keywords]: chemiluminescence immunoassay;igm and igg;sars-cov-2;serological testing

BMJ Open Respir Res

Is continuous positive airway pressure (CPAP) a new standard of care for type 1 respiratory failure in COVID-19 patients? A retrospective observational study of a dedicated COVID-19 CPAP service.

The aim of this case series is to describe and evaluate our experience of continuous positive airway pressure (CPAP) to treat type 1 respiratory failure in patients with COVID-19. CPAP was delivered in negative pressure rooms in the newly repurposed infectious disease unit. We report a cohort of 24 patients with type 1 respiratory failure and COVID-19 admitted to the Royal Liverpool Hospital between 1 April and 30 April 2020. Overall, our results were positive; we were able to safely administer CPAP outside the walls of a critical care or high dependency unit environment and over half of patients (58%) avoided mechanical ventilation and a total of 19 out of 24 (79%) have survived and been discharged from our care.

non invasive ventilation;respiratory infection

Journal Article;Observational Study

Nightingale, Rebecca;Nwosu, Nneka;Kutubudin, Farheen;Fletcher, Tom;Lewis, Joe;Frost, Frederick;Haigh, Kathryn;Robinson, Ryan;Kumar, Ayesha;Jones, Gareth;Brown, Deborah;Abouyannis, Michael;Beadsworth, Mike;Hampshire, Peter;Aston, Stephen;Gautam, Manish;Burhan, Hassan

10.1136/bmjresp-2020-000639

[Title]: Is continuous positive airway pressure (CPAP) a new standard of care for type 1 respiratory failure in COVID-19 patients? A retrospective observational study of a dedicated COVID-19 CPAP service. [Abstract]: The aim of this case series is to describe and evaluate our experience of continuous positive airway pressure (CPAP) to treat type 1 respiratory failure in patients with COVID-19. CPAP was delivered in negative pressure rooms in the newly repurposed infectious disease unit. We report a cohort of 24 patients with type 1 respiratory failure and COVID-19 admitted to the Royal Liverpool Hospital between 1 April and 30 April 2020. Overall, our results were positive; we were able to safely administer CPAP outside the walls of a critical care or high dependency unit environment and over half of patients (58%) avoided mechanical ventilation and a total of 19 out of 24 (79%) have survived and been discharged from our care. [Keywords]: non invasive ventilation;respiratory infection

Nat Med

A serological assay to detect SARS-CoV-2 seroconversion in humans.

Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.

Journal Article;Observational Study;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't

Amanat, Fatima;Stadlbauer, Daniel;Strohmeier, Shirin;Nguyen, Thi H O;Chromikova, Veronika;McMahon, Meagan;Jiang, Kaijun;Arunkumar, Guha Asthagiri;Jurczyszak, Denise;Polanco, Jose;Bermudez-Gonzalez, Maria;Kleiner, Giulio;Aydillo, Teresa;Miorin, Lisa;Fierer, Daniel S;Lugo, Luz Amarilis;Kojic, Erna Milunka;Stoever, Jonathan;Liu, Sean T H;Cunningham-Rundles, Charlotte;Felgner, Philip L;Moran, Thomas;Garcia-Sastre, Adolfo;Caplivski, Daniel;Cheng, Allen C;Kedzierska, Katherine;Vapalahti, Olli;Hepojoki, Jussi M;Simon, Viviana;Krammer, Florian

10.1038/s41591-020-0913-5

[Title]: A serological assay to detect SARS-CoV-2 seroconversion in humans. [Abstract]: Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection. [Keywords]:

Dermatol Ther

Hidden threat lurking behind the alcohol sanitizers in COVID-19 outbreak.

The ongoing COVID-19 pandemic has made various challenges for communications all over the world. Nowadays hand hygiene practices with alcohol sanitizers are an unavoidable reality for many people, which cause skin dryness and flaking. The current short communication has been explained about monitoring the quality control of alcohol concentrations and hand rub formulation, which needs more attention and should consider meticulous in this crisis.

covid-19;alcohol concentrations;hand dermatitis

Journal Article;Review

Emami, Amir;Javanmardi, Fatemeh;Keshavarzi, Abdolkhalegh;Pirbonyeh, Neda

10.1111/dth.13627

[Title]: Hidden threat lurking behind the alcohol sanitizers in COVID-19 outbreak. [Abstract]: The ongoing COVID-19 pandemic has made various challenges for communications all over the world. Nowadays hand hygiene practices with alcohol sanitizers are an unavoidable reality for many people, which cause skin dryness and flaking. The current short communication has been explained about monitoring the quality control of alcohol concentrations and hand rub formulation, which needs more attention and should consider meticulous in this crisis. [Keywords]: covid-19;alcohol concentrations;hand dermatitis

Antioxid Redox Signal

Is Albumin Predictor of Mortality in COVID-19?

Coronavirus 2019 (COVID-19) is a pandemic associated with a high risk of mortality. Human serum albumin (HSA) is an acute phase reactant with antioxidant property; however, its behavior and impact on survival in COVID-19 patients have never been studied so far. Among 319 COVID-19 patients followed up for a median of 19 days, 64 died. Compared with survivors, nonsurvivors had more prevalence of intensive care unit (ICU) admission, chronic obstructive pulmonary disease (COPD), heart failure, elevated levels of D-dimer, high-sensitivity C reactive protein (hs-CRP) and troponins, and lower values of albumin. At the Cox regression analysis, albumin (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.23-0.63, p < 0.001) and age (HR: 1.03, 95% CI: 1.01-1.06, p = 0.001) were independently associated with mortality, irrespective of adjustment for gender, ICU admission, heart failure, COPD, and hs-CRP levels. Our observation leads to the hypothesis that HSA analysis may be used to identify patients at higher risk of death in COVID-19 patients.

covid-19;albumin;mortality

Journal Article

Violi, Francesco;Cangemi, Roberto;Romiti, Giulio Francesco;Ceccarelli, Giancarlo;Oliva, Alessandra;Alessandri, Francesco;Pirro, Matteo;Pignatelli, Pasquale;Lichtner, Miriam;Carraro, Anna;Cipollone, Francesco;D'Ardes, Damiano;Pugliese, Francesco;Mastroianni, Claudio Maria

10.1089/ars.2020.8142

[Title]: Is Albumin Predictor of Mortality in COVID-19? [Abstract]: Coronavirus 2019 (COVID-19) is a pandemic associated with a high risk of mortality. Human serum albumin (HSA) is an acute phase reactant with antioxidant property; however, its behavior and impact on survival in COVID-19 patients have never been studied so far. Among 319 COVID-19 patients followed up for a median of 19 days, 64 died. Compared with survivors, nonsurvivors had more prevalence of intensive care unit (ICU) admission, chronic obstructive pulmonary disease (COPD), heart failure, elevated levels of D-dimer, high-sensitivity C reactive protein (hs-CRP) and troponins, and lower values of albumin. At the Cox regression analysis, albumin (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.23-0.63, p < 0.001) and age (HR: 1.03, 95% CI: 1.01-1.06, p = 0.001) were independently associated with mortality, irrespective of adjustment for gender, ICU admission, heart failure, COPD, and hs-CRP levels. Our observation leads to the hypothesis that HSA analysis may be used to identify patients at higher risk of death in COVID-19 patients. [Keywords]: covid-19;albumin;mortality

Cureus

Regional Anesthesia Practices in Turkey During the COVID-19 Pandemic.

Introduction The aim of the survey was to investigate the changes, methods, and preferences in regional anesthesia (RA) applications during the COVID-19 pandemic in Turkey. Methods The questionnaire prepared on surveymonkey.com was sent to anesthesiology and reanimation specialists by e-mail. Results A total of 126 physicians participated in the study. Forty-two point sixty-two percent (42.62%) of the participants reported an increase in RA practices in their clinical anesthesia applications, whereas 57.38% did not state any change. Neuraxial anesthesia was determined to be the most preferred RA application, with a rate of 74%. The distribution of peripheral nerve blocks (PNBs) showed that upper extremity blocks were used at a rate of 64.9%, lower extremity blocks at 30.38%, and trunk blocks at 15%. Investigation of neurostimulator (NS) and/or ultrasound (US) use with PNB showed that 44% of the participants used only US while 50% used both US and NS. Conclusion Neuraxial blocks play an important role in RA applications. PNB comprise one-quarter of RA applications during the pandemic. The importance of ultrasound has gradually increased in RA applications worldwide, as well as in Turkey, during the pandemic.

covid-19;peripheral nerve blocks;regional anaesthesia;survey research;ultrasound-guided

Journal Article

Cesur, Sevim;Aksu, Can;Kus, Alparslan

10.7759/cureus.10135

[Title]: Regional Anesthesia Practices in Turkey During the COVID-19 Pandemic. [Abstract]: Introduction The aim of the survey was to investigate the changes, methods, and preferences in regional anesthesia (RA) applications during the COVID-19 pandemic in Turkey. Methods The questionnaire prepared on surveymonkey.com was sent to anesthesiology and reanimation specialists by e-mail. Results A total of 126 physicians participated in the study. Forty-two point sixty-two percent (42.62%) of the participants reported an increase in RA practices in their clinical anesthesia applications, whereas 57.38% did not state any change. Neuraxial anesthesia was determined to be the most preferred RA application, with a rate of 74%. The distribution of peripheral nerve blocks (PNBs) showed that upper extremity blocks were used at a rate of 64.9%, lower extremity blocks at 30.38%, and trunk blocks at 15%. Investigation of neurostimulator (NS) and/or ultrasound (US) use with PNB showed that 44% of the participants used only US while 50% used both US and NS. Conclusion Neuraxial blocks play an important role in RA applications. PNB comprise one-quarter of RA applications during the pandemic. The importance of ultrasound has gradually increased in RA applications worldwide, as well as in Turkey, during the pandemic. [Keywords]: covid-19;peripheral nerve blocks;regional anaesthesia;survey research;ultrasound-guided