Many of the risk factors for developing severe coronavirus disease 2019 (COVID-19) are also risk factors for eye diseases such as age-related macular degeneration (AMD). During the past decades,... Show moreMany of the risk factors for developing severe coronavirus disease 2019 (COVID-19) are also risk factors for eye diseases such as age-related macular degeneration (AMD). During the past decades, macro-phages and the complement pathway (as a part of the innate immune system) have been identified as important contributors to the development of AMD, and we suggest that these mechanisms are of similar importance for the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Based on the experience with AMD, we discuss how behavioral factors such as diet, smoking and higher body mass index, as well as genetic determinants such as the complement and immune pathway genes may lead to the overactive inflammatory phenotypes seen in some patients with COVID-19, and may in part explain the heterogeneity of disease manifestations and outcomes. Based on this experience, we discuss potential genetic research projects and elaborate on preventive and treatment approaches related to COVID-19. Show less
During the coronavirus (COVID-19) pandemic, governments implemented travel restrictions and self-isolation, decreasing mobility for most individuals, but also permitted repatriation and ‘essential’... Show moreDuring the coronavirus (COVID-19) pandemic, governments implemented travel restrictions and self-isolation, decreasing mobility for most individuals, but also permitted repatriation and ‘essential’ work, increasing mobility for others. How has the governance of human mobility from March to August 2020 affected the concepts of borders and citizenship? Drawing on evidence from countries in the European Union and South America—regions with more fluid intraregional mobility pre-pandemic—we compare states’ reactions to evaluate moving borders and citizenship. We find fluctuating internal borders and external borders pushing further into other territories. By differentiating between people and essential work, governments deteriorated the rule of law since the frequently changed measures undermined individuals’ ability to predict mobility and income. Migrants were additionally affected because of legal statuses of being a resident national, emigrant, dual national, temporary or permanent immigrant, or having an irregular status. Short-term policy reactions may lead to long-term consequences; we foresee exceptions and control mechanisms under expanded Leviathan-style approaches could continue to affect individual mobility in and between countries. Show less
Eldercare professionals engaged in precarious work in the Netherlands faced shortages in personal protective equipment (PPE), testing, and staffing during the COVID-19 pandemic. This qualitative... Show moreEldercare professionals engaged in precarious work in the Netherlands faced shortages in personal protective equipment (PPE), testing, and staffing during the COVID-19 pandemic. This qualitative study of the health, financial situations, and paid and unpaid caring responsibilities of freelance eldercare workers illustrates how labor market inequalities have been (re)produced and exacerbated during the pandemic. Freelancers were pushed toward the margins of the labor market, working risky shifts and compromising their own interests, while unprotected by organizations, social security, or political efforts. Consequently, these workers were stretched to limits where they could no longer attend to their own health or to their paid and unpaid care responsibilities. The study places these empirical findings within Nancy Fraser and Rahel Jaeggi's theoretical work on capitalism, illustrating how eldercare workers found themselves at the center of boundary struggles during the pandemic. Show less
Like many Western European countries, Belgium and the Netherlands have been strongly hit by COVID-19. Almost simultaneously, the virus spread, caused a relatively high number of infections and... Show moreLike many Western European countries, Belgium and the Netherlands have been strongly hit by COVID-19. Almost simultaneously, the virus spread, caused a relatively high number of infections and severe lockdown measures were imposed; however, at the same time, the crisis management response has been sufficiently different to justify a systematic comparative analysis. We start with the premise that decisions made on the basis of incomplete information show the true nature of governments’ response to a crisis, which is conditioned by legacies arising from the past and organizational cultures, existing and new governance structures, and strategies used by specific actors. We show that the difference in crisis management echoes the countries’ different types of consociationalism, though also that Belgian federalism and Dutch decentralism impeded a truly coherent response. The cost of coordinating different government levels made a uniform approach difficult too. Actor strategies attempting to exploit the crisis seem to have influenced the response the least but did have an impact on perceptions of the response. Show less
Al-Mansoori, R.; Arjomand, B.; Larik, J.; Petcu, C.; Ponzio, R.; Siddique, M.; Torrez, P. 2020
The Doha Forum Report 2020 examines the leadership deficit in multilateral cooperation toward both the coronavirus pandemic and other existing and emerging global challenges, including runaway... Show moreThe Doha Forum Report 2020 examines the leadership deficit in multilateral cooperation toward both the coronavirus pandemic and other existing and emerging global challenges, including runaway climate change, rising political violence, menacing cyber-attacks, and growing inequality within and between countries. It finds that present international efforts are too often fragmented, delayed, ad hoc, and under-resourced, while pointing to promising new public-private partnerships to spur innovation through new technologies and to promote decent job and wealth creation opportunities. The report also recommends a roadmap for a durable, green, and broad-based global recovery and institutional revitalization, culminating in a 2023 World Summit on Inclusive Global Governance. With the recent news on the expected arrival of one or more effective vaccines, the road to recovery must chart a bold new course and avoid a return to the “old normal” of unsustainable practices. Show less
Introduction: No studies have reported mental health symptom comparisons prior to and during COVID-19 in vulnerable medical populations.Objective: To compare anxiety and depression symptoms among... Show moreIntroduction: No studies have reported mental health symptom comparisons prior to and during COVID-19 in vulnerable medical populations.Objective: To compare anxiety and depression symptoms among people with a pre-existing medical condition and factors associated with changes.Methods: Pre-COVID-19 Scleroderma Patient-centered Intervention Network Cohort data were linked to COVID-19 data from April 2020. Multiple linear and logistic regression were used to assess factors associated with continuous change and >= 1 minimal clinically important difference (MCID) change for anxiety (PROMIS Anxiety 4a v1.0; MCID = 4.0) and depression (Patient Health Questionnaire-8; MCID = 3.0) symptoms, controlling for pre-COVID-19 levels.Results: Mean anxiety symptoms increased 4.9 points (95% confidence interval [CI] 4.0 to 5.7). Depression symptom change was negligible (0.3 points; 95% CI-0.7 to 0.2). Compared to France (N = 159), adjusted anxiety symptom change scores were significantly higher in the United Kingdom (N = 50; 3.3 points, 95% CI 0.9 to 5.6), United States (N = 128; 2.5 points, 95% CI 0.7 to 4.2), and Canada (N = 98; 1.9 points, 95% CI 0.1 to 3.8). Odds of >= 1 MCID increase were 2.6 for the United Kingdom (95% CI 1.2 to 5.7) but not significant for the United States (1.6, 95% CI 0.9 to 2.9) or Canada (1.4, 95% CI 0.7 to 2.5). Older age and adequate financial resources were associated with less continuous anxiety increase. Employment and shorter time since diagnosis were associated with lower odds of a >= 1 MCID increase.Conclusions: Anxiety symptoms, but not depression symptoms, increased dramatically during COVID-19 among people with a pre-existing medical condition. Show less
Linschoten, M.; Peters, S.; Smeden, M. van; Jewbali, L.S.; Schaap, J.; Siebelink, H.M.; ... ; CAPACITY-COVID Collaborative Conso 2020
Aims:To determine the frequency and pattern of cardiac complications in patients hospitalised with coronavirus disease (COVID-19).Methods and results:CAPACITY-COVID is an international patient... Show moreAims:To determine the frequency and pattern of cardiac complications in patients hospitalised with coronavirus disease (COVID-19).Methods and results:CAPACITY-COVID is an international patient registry established to determine the role of cardiovascular disease in the COVID-19 pandemic. In this registry, data generated during routine clinical practice are collected in a standardised manner for patients with a (highly suspected) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring hospitalisation. For the current analysis, consecutive patients with laboratory confirmed COVID-19 registered between 28 March and 3 July 2020 were included. Patients were followed for the occurrence of cardiac complications and pulmonary embolism from admission to discharge. In total, 3011 patients were included, of which 1890 (62.8%) were men. The median age was 67 years (interquartile range 56-76); 937 (31.0%) patients had a history of cardiac disease, with pre-existent coronary artery disease being most common (n=463, 15.4%). During hospitalisation, 595 (19.8%) patients died, including 16 patients (2.7%) with cardiac causes. Cardiac complications were diagnosed in 349 (11.6%) patients, with atrial fibrillation (n=142, 4.7%) being most common. The incidence of other cardiac complications was 1.8% for heart failure (n=55), 0.5% for acute coronary syndrome (n=15), 0.5% for ventricular arrhythmia (n=14), 0.1% for bacterial endocarditis (n=4) and myocarditis (n=3), respectively, and 0.03% for pericarditis (n=1). Pulmonary embolism was diagnosed in 198 (6.6%) patients.Conclusion:This large study among 3011 hospitalised patients with COVID-19 shows that the incidence of cardiac complications during hospital admission is low, despite a frequent history of cardiovascular disease. Long-term cardiac outcomes and the role of pre-existing cardiovascular disease in COVID-19 outcome warrants further investigation. Show less
Background: COVID-19 is a global challenge to healthcare. Obesity is common in patients with COVID-19 and seems to aggravate disease prognosis. In this review we explore the link between obesity,... Show moreBackground: COVID-19 is a global challenge to healthcare. Obesity is common in patients with COVID-19 and seems to aggravate disease prognosis. In this review we explore the link between obesity, chronic disease, lifestyle factors and the immune system, and propose societal interventions to enhance global immunity.Search Strategy and Selection Criteria: We performed three literature searches using the keywords (1) coronavirus AND comorbidities, (2) comorbidities AND immune system, and (3) lifestyle factors AND immune system. Results were screened for relevance by the main author and a total of 215 articles were thoroughly analyzed.Results: The relationship between obesity and unfavorable COVID-19 prognosis is discussed in light of the impact of chronic disease and lifestyle on the immune system. Several modifiable lifestyle factors render us susceptible to viral infections. In this context, we make a case for fostering a healthy lifestyle on a global scale.Conclusions: Obesity, additional chronic disease and an unhealthy lifestyle interactively impair immune function and increase the risk of severe infectious disease. In adverse metabolic and endocrine conditions, the immune system is geared toward inflammation. Collective effort is needed to ameliorate modifiable risk factors for obesity and chronic disease on a global scale and increase resistance to viruses like SARS-CoV-2. Show less
Ong, D.S.Y.; Claas, E.C.J.; Breijer, S.; Vaessen, N. 2020
Background: Due to the emergence of the coronavirus disease 2019 (COVID-19) pandemic there is an urgent need for rapid and accurate testing on the severe acute respiratory syndrome coronavirus 2 ... Show moreBackground: Due to the emergence of the coronavirus disease 2019 (COVID-19) pandemic there is an urgent need for rapid and accurate testing on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Objectives: The aim of this study was to assess the diagnostic performance of the GeneFinderTMCOVID-19 Plus RealAmp Kit on the ELITe InGenius sample-to-result platform, which is a commercial nucleic acid amplification test (NAT) targeting genes of SARS-CoV-2.Study design: Patients were eligible between March 18 and May 27, 2020, when they had respiratory symptoms that were suspected for COVID-19. The InGenius platform was compared to routine in-house NAT that was validated according to the national reference.Results: Of 128 randomly selected patients, 58 (45 %) tested positive and 55 (43 %) tested negative in both platforms. Sensitivity of the InGenius platform was 100 % (95 % confidence interval 94-100). In the remaining 15 (12 %) cases E and RdRp genes were not detected in both platforms but the nucleoprotein (N) gene was tested positive by the InGenius platform. All solitary N gene positive cases were confirmed by a N-gene specific in-house validated NAT, and most of these patients could also be considered positive based on other recently available COVID-19 positive respiratory samples or highly suspected radiological findings.Conclusion: The InGenius platform for SARS-CoV-2 detection has excellent sensitivity, is easy to use and provides fast results. The inclusion of the N gene as a third gene target may further increase sensitivity for the diagnosis of COVID-19 in comparison to the national reference method. Show less
Background: The COVID-19 pandemic has markedly affected renal transplant care. During this time of social distancing, limited in-person visits, and uncertainty, patients and donors are relying more... Show moreBackground: The COVID-19 pandemic has markedly affected renal transplant care. During this time of social distancing, limited in-person visits, and uncertainty, patients and donors are relying more than ever on telemedicine and web-based information. Several factors can influence patients' understanding of web-based information, such as delivery modes (instruction, interaction, and assessment) and social-epistemological dimensions (choices in interactive knowledge building).Objective: The aim of this study was to systemically evaluate the content, delivery modes, and social-epistemological dimensions of web-based information on COVID-19 and renal transplantation at time of the pandemic.Methods: Multiple keyword combinations were used to retrieve websites on COVID-19 and renal transplantation using the search engines Google.com and Google.nl. From 14 different websites, 30 webpages were examined to determine their organizational sources, topics, delivery modes, and social-epistemological dimensions.Results: The variety of topics and delivery modes was limited. A total of 13 different delivery modes were encountered, of which 8 (62%) were instructional and 5 (38%) were interactional; no assessment delivery modes were observed. No website offered all available delivery modes. The majority of delivery modes (8/13, 62%) focused on individual and passive learning, whereas group learning and active construction of knowledge were rarely encountered.Conclusions: By taking interactive knowledge transfer into account, the educational quality of eHealth for transplant care could increase, especially in times of crisis when rapid knowledge transfer is needed. Show less
BackgroundTo evaluate the association between crowding and transmission of viral respiratory infectious diseases, we investigated the change in transmission patterns of influenza and COVID-19... Show moreBackgroundTo evaluate the association between crowding and transmission of viral respiratory infectious diseases, we investigated the change in transmission patterns of influenza and COVID-19 before and after a mass gathering event (i.e., carnival) in the Netherlands.MethodsInformation on individual hospitalizations related to the 2017/2018 influenza epidemic were accessed from Statistics Netherlands. The influenza cases were stratified between non-carnival and carnival regions. Distributions of influenza cases were plotted with time and compared between regions. A similar investigation in the early outbreak of COVID-19 was also conducted using open data from the Dutch National Institute for Public Health and the Environment.ResultsBaseline characteristics between non-carnival and carnival regions were broadly similar. There were 13,836 influenza-related hospitalizations in the 2017/2018 influenza epidemic, and carnival fell about 1week before the peak of these hospitalizations. The distributions of new influenza-related hospitalizations per 100,000 inhabitants with time between regions followed the same pattern with a surge of new cases in the carnival region about 1week after carnival, which did not occur in the non-carnival region. The increase of new cases for COVID-19 in the carnival region exceeded that in the non-carnival region about 1week after the first case was reported, but these results warrant caution as for COVID-19 there were no cases reported before the carnival and social measures were introduced shortly after carnival.ConclusionIn this study, a mass gathering event (carnival) was associated with aggravating the spread of viral respiratory infectious diseases. Show less
Introduction: The SARS-CoV-2 pandemic of 2020 is a prime example of the omnipresent threat of emerging viruses that can infect humans. A protocol for the identification of novel coronaviruses by... Show moreIntroduction: The SARS-CoV-2 pandemic of 2020 is a prime example of the omnipresent threat of emerging viruses that can infect humans. A protocol for the identification of novel coronaviruses by viral metagenomic sequencing in diagnostic laboratories may contribute to pandemic preparedness.Aim: The aim of this study is to validate a metagenomic virus discovery protocol as a tool for coronavirus pandemic preparedness.Methods: The performance of a viral metagenomic protocol in a clinical setting for the identification of novel coronaviruses was tested using clinical samples containing SARS-CoV-2, SARS-CoV, and MERS-CoV, in combination with databases generated to contain only viruses of before the discovery dates of these coronaviruses, to mimic virus discovery.Results: Classification of NGS reads using Centrifuge and Genome Detective resulted in assignment of the reads to the closest relatives of the emerging coronaviruses. Low nucleotide and amino acid identity (81% and 84%, respectively, for SARS-CoV-2) in combination with up to 98% genome coverage were indicative for a related, novel coronavirus. Capture probes targeting vertebrate viruses, designed in 2015, enhanced both sequencing depth and coverage of the SARS-CoV-2 genome, the latter increasing from 71% to 98%.Conclusion: The model used for simulation of virus discovery enabled validation of the metagenomic sequencing protocol. The metagenomic protocol with virus probes designed before the pandemic, can assist the detection and identification of novel coronaviruses directly in clinical samples. Show less
The continued absence of viable vaccines, limited diagnostic tools, insufficient protocol for isolation period, and weak health care system in developing countries with Nigeria inclusive heightens... Show moreThe continued absence of viable vaccines, limited diagnostic tools, insufficient protocol for isolation period, and weak health care system in developing countries with Nigeria inclusive heightens the tension trailing the arrival of Novel SARS-CoV-2 that was officially declared a global health emergency by World Health Organization (WHO) in January 2020. In this context, this study assesses the adequacy and potency of treatment for pneumonia associated with the Novel SARS-CoV-2. Counting from 27th February 2020, exponential rise in cases of SARS-CoV-2 has been recorded in Nigeria. Despite limited data on person-to-person transmission or nosocomial transmission, we report the epidemiological features of a familial cluster of 4 positive cases to SARS-CoV-2 in Nasarawa State, North Central Nigeria. This cluster presented with an unexplained pneumonia after having contact with a family member who died after manifesting symptoms of Novel SARS-CoV-2; the test came outpositive after his demise. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 nucleic acid were performed using nasopharyngeal swabs (Novel Coronavirus PCR Fluorescence Diagnostic Kit, BioGerm Medical Biotechnology at the Nigeria Centre for Disease Control (NCDC) in Abuja. Nigeria. From March 10, 2020, we enrolled a family of four patients out of a family of 10 who were positive to novel coronavirus. Four family members (aged 36-43 years) all presented with fever, upper or lower respiratory tract symptoms, or diarrhea, or a combination of these 3-6 days after exposure. These conditions continued to manifest at the Federal Medical Center, Keffi in Nasarawa State, 3-7 days after symptom onset. Their nasopharyngeal or throat swabs of these 10 family members were taken and four returned positive to coronavirus, while six tested negative. The epidemiological evidence from our study on familial cluster analysis reveals possible transmission of Novel SARS-CoV-2 during the incubation period. Study outcomes underscore the importance of probing contact history of potentially infected individuals, for prompt identification to preventing further spread. Show less
Despite significant efforts, the COVID-19 pandemic has put enormous pressure on health care systems around the world, threatening the quality of patient care. Telemonitoring offers the opportunity... Show moreDespite significant efforts, the COVID-19 pandemic has put enormous pressure on health care systems around the world, threatening the quality of patient care. Telemonitoring offers the opportunity to carefully monitor patients with a confirmed or suspected case of COVID-19 from home and allows for the timely identification of worsening symptoms. Additionally, it may decrease the number of hospital visits and admissions, thereby reducing the use of scarce resources, optimizing health care capacity, and minimizing the risk of viral transmission. In this paper, we present a COVID-19 telemonitoring care pathway developed at a tertiary care hospital in the Netherlands, which combined the monitoring of vital parameters with video consultations for adequate clinical assessment. Additionally, we report a series of medical, scientific, organizational, and ethical recommendations that may be used as a guide for the design and implementation of telemonitoring pathways for COVID-19 and other diseases worldwide. Show less
Deprest, J.; Choolani, M.; Chervenak, F.; Farmer, D.; Lagrou, K.; Lopriore, E.; ... ; Ryan, G. 2020
The COVID-19 pandemic has stressed patients and healthcare givers alike and challenged our practice of antenatal care, including fetal diagnosis and therapy. This document aims to review relevant... Show moreThe COVID-19 pandemic has stressed patients and healthcare givers alike and challenged our practice of antenatal care, including fetal diagnosis and therapy. This document aims to review relevant recent information to allow us to optimize prenatal care delivery. We discuss potential modifications to obstetric management and fetal procedures in SARS-CoV2-negative and SARS-CoV2-positive patients with fetal anomalies or disorders. Most fetal therapies are time sensitive and cannot be delayed. If personnel and resources are available, we should continue to offer procedures of proven benefit, acknowledging any fetal and maternal risks, including those to health care workers. There is, to date, minimal, unconfirmed evidence of spontaneous vertical transmission, though it may theoretically be increased with some procedures. Knowing a mother's preoperative SARS-CoV-2 status would enable us to avoid or defer certain procedures while she is contagious and to protect health care workers appropriately. Some fetal conditions may alternatively be managed neonatally. Counseling regarding fetal interventions which have a possibility of additional intra- or postoperative morbidity must be performed in the context of local resource availability. Procedures of unproven benefit should not be offered. We encourage participation in registries and trials that may help us to understand the impact of COVID-19 on pregnant women, their fetuses, and neonates. Show less
The COVID-19 pandemic has disproportionately affected care home residents internationally, with 19-72% of COVID-19 deaths occurring in care homes. COVID-19 presents atypically in care home... Show moreThe COVID-19 pandemic has disproportionately affected care home residents internationally, with 19-72% of COVID-19 deaths occurring in care homes. COVID-19 presents atypically in care home residents and up to 56% of residents may test positive whilst pre-symptomatic. In this article, we provide a commentary on challenges and dilemmas identified in the response to COVID-19 for care homes and their residents. We highlight the low sensitivity of polymerase chain reaction testing and the difficulties this poses for blanket screening and isolation of residents. We discuss quarantine of residents and the potential harms associated with this. Personal protective equipment supply for care homes during the pandemic has been suboptimal and we suggest that better integration of procurement and supply is required. Advance care planning has been challenged by the pandemic and there is a need to for healthcare staff to provide support to care homes with this. Finally, we discuss measures to implement augmented care in care homes, including treatment with oxygen and subcutaneous fluids, and the frameworks which will be required if these are to be sustainable. All of these challenges must be met by healthcare, social care and government agencies if care home residents and staff are to be physically and psychologically supported during this time of crisis for care homes. Show less
The global pandemic caused by severe acute respiratory syndrome coronavirus 2 has upended surgical practice. In an effort to preserve resources, mitigate risk, and maintain health system capacity,... Show moreThe global pandemic caused by severe acute respiratory syndrome coronavirus 2 has upended surgical practice. In an effort to preserve resources, mitigate risk, and maintain health system capacity, nonurgent surgeries have been deferred in many jurisdictions, with urgent procedures facing increasing wait times and unpredictability given potential future surges. Shared decision making, a process that integrates patient values and preferences with the scientific expertise of clinicians, may be of particular benefit during these unprecedented times. Aligning patient choices with their values, reducing unnecessary health care use, and promoting consistency between providers are now more critical than ever before. We review important aspects of shared decision making and provide guidance for its perioperative application during the coronavirus disease 2019 pandemic. Show less
Dam, L.F. van; Kroft, L.J.M.; Wal, L.I. van der; Cannegieter, S.C.; Eikenboom, J.; Jonge, E. de; ... ; Klok, F.A. 2020
Introduction: COVID-19 infections are associated with a high prevalence of venous thromboembolism, particularly pulmonary embolism (PE). It is suggested that COVID-19 associated PE represents in... Show moreIntroduction: COVID-19 infections are associated with a high prevalence of venous thromboembolism, particularly pulmonary embolism (PE). It is suggested that COVID-19 associated PE represents in situ immunothrombosis rather than venous thromboembolism, although the origin of thrombotic lesions in COVID-19 patients remains largely unknown.Methods: In this study, we assessed the clinical and computed tomography (CT) characteristics of PE in 23 consecutive patients with COVID-19 pneumonia and compared these to those of 100 consecutive control patients diagnosed with acute PE before the COVID-19 outbreak. Specifically, RV/LV diameter ratio, pulmonary artery trunk diameter and total thrombus load (according to Qanadli score) were measured and compared.Results: We observed that all thrombotic lesions in COVID-19 patients were found to be in lung parenchyma affected by COVID-19. Also, the thrombus load was lower in COVID-19 patients (Qanadli score -8%, 95% confidence interval [95%CI] -16 to -0.36%) as was the prevalence of the most proximal PE in the main/lobar pulmonary artery (17% versus 47%; -30%, 95%CI -44% to -8.2). Moreover, the mean RV/LV ratio (mean difference -0.23, 95%CI -0.39 to -0.07) and the prevalence of RV/LV ratio > 1.0 (prevalence difference -23%, 95%CI -41 to -0.86%) were lower in the COVID-19 patients.Conclusion: Our findings therefore suggest that the phenotype of COVID-19 associated PE indeed differs from PE in patients without COVID-19, fuelling the discussion on its pathophysiology. Show less
The SARS-CoV-2 coronavirus encodes an essential papain-like protease domain as part of its non-structural protein (nsp)-3, namely SARS2 PLpro, that cleaves the viral polyprotein, but also removes... Show moreThe SARS-CoV-2 coronavirus encodes an essential papain-like protease domain as part of its non-structural protein (nsp)-3, namely SARS2 PLpro, that cleaves the viral polyprotein, but also removes ubiquitin-like ISG15 protein modifications as well as, with lower activity, Lys48-linked polyubiquitin. Structures of PLpro bound to ubiquitin and ISG15 reveal that the S1 ubiquitin-binding site is responsible for high ISG15 activity, while the S2 binding site provides Lys48 chain specificity and cleavage efficiency. To identify PLpro inhibitors in a repurposing approach, screening of 3,727 unique approved drugs and clinical compounds against SARS2 PLpro identified no compounds that inhibited PLpro consistently or that could be validated in counterscreens. More promisingly, non-covalent small molecule SARS PLpro inhibitors also target SARS2 PLpro, prevent self-processing of nsp3 in cells and display high potency and excellent antiviral activity in a SARS-CoV-2 infection model. Show less
Background Best practice for prevention, diagnosis, and management of venous thromboembolism (VTE) in patients with coronavirus disease 2019 (COVID-19) is unknown due to limited published data in... Show moreBackground Best practice for prevention, diagnosis, and management of venous thromboembolism (VTE) in patients with coronavirus disease 2019 (COVID-19) is unknown due to limited published data in this population. Objectives We aimed to assess current global practice and experience in management of COVID-19-associated coagulopathy to identify information to guide prospective and randomized studies. Methods Physicians were queried about their current approach to prophylaxis, diagnosis, and treatment of VTE in patients with COVID-19 using an online survey tool distributed through multiple international organizations between April 10 and 14, 2020. Results Five hundred fifteen physicians from 41 countries responded. The majority of respondents (78%) recommended prophylactic anticoagulation for all hospitalized patients with COVID-19, with most recommending use of low-molecular-weight heparin or unfractionated heparin. Significant practice variation was found regarding the need for dose escalation of anticoagulation outside the setting of confirmed or suspected VTE. Respondents reported the use of bedside testing when unable to perform standard diagnostic imaging for diagnosis of VTE. Two hundred ninety-one respondents reported observing thrombotic complications in their patients, with 64% noting that the complication was pulmonary embolism. Of the 44% of respondents who estimated incidence of thrombosis in patients with COVID-19 in their hospital, estimates ranged widely from 1% to 50%. One hundred seventy-four respondents noted bleeding complications (34% minor bleeding, 14% clinically relevant nonmajor bleeding, and 12% major bleeding). Conclusion Well-designed epidemiologic studies are urgently needed to understand the incidence and risk factors of VTE and bleeding complications in patients with COVID-19. Randomized clinical trials addressing use of anticoagulation are also needed. Show less
