title: Identification of IgG antibody response to SARS-CoV-2 spike protein and its receptor binding domain does not predict rapid recovery from COVID-19

text: Diagnostic testing and evaluation of patient immunity against the novel severe acute respiratory syndrome (SARS) corona virus that emerged last year (SARS-CoV-2) are essential for health and economic crisis recovery of the world. It is suggested that potential acquired immunity against SARS-CoV-2 from prior exposure may be determined by detecting the presence of circulating IgG antibodies against viral antigens, such as the spike glycoprotein and its receptor binding domain (RBD). Testing our asymptomatic population for evidence of COVID-19 immunity would also offer valuable epidemiologic data to aid health care policies and health care management. Currently, there are over 100 antibody tests that are being used around the world without approval from the FDA or similar regulatory bodies, and they are mostly for rapid and qualitative assessment, with different degrees of error rates. ELISA-based testing for sensitive and rigorous quantitative assessment of SARS-CoV-2 antibodies can potentially offer mechanistic insights into the COVID-19 disease and aid communities uniquely challenged by limited financial resources and access to commercial testing products. Employing recombinant SARS-CoV-2 RBD and spike protein generated in the laboratory, we devised a quantitative ELISA for the detection of circulating serum antibodies. Serum from twenty SARS-CoV-2 RT-PCR confirmed COVID-19 hospitalized patients were used to detect circulating IgG titers against SARS-CoV-2 spike protein and RBD. Quantitative detection of IgG antibodies to the spike glycoprotein or the RBD in patient samples was not always associated with faster recovery, compared to patients with borderline antibody response to the RBD. One patient who did not develop antibodies to the RBD completely recovered from COVID-19. In surveying 99 healthy donor samples (procured between 2017-February 2020), we detected RBD antibodies in one donor from February 2020 collection with three others exhibiting antibodies to the spike protein but not the RBD. Collectively, our study suggests that more rigorous and quantitative analysis, employing large scale sample sets, is required to determine whether antibodies to SARS-CoV-2 spike protein or RBD is associated with protection from COVID-19 disease. It is also conceivable that humoral response to SARS-CoV-2 spike protein or RBD works in association with adaptive T cell response to determine clinical sequela and severity of COVID-19 disease.


title: Delivering oxygen-enriched CPAP respiratory support using a non-invasive ventilation device

text: Here we report an investigation to adapt existing non-invasive ventilators (NIV) capable of delivering CPAP for use with oxygen to deliver enriched ventilation of 40%+ FiO2. Our intention is to maximise use of existing resources available to HCPs, as NIV and sleep apnoea (CPAP) machines are widely available, to deliver therapeutic benefit and potentially avoid the need for positive pressure ventilation during the COVID-19 pandemic.


title: The distress of Iranian adults during the Covid-19 pandemic - More distressed than the Chinese and with different predictors

text: Background Early papers on the mental health of the public during the Covid-19 pandemic surveyed participants from China. Outside of China, Iran has emerged as one of the most affected countries with a high death count and rate. The paper presents the first empirical evidence from Iranian adults during the Covid-19 pandemic on their level of distress and its predictors. Methods On March 25-28, 2020, a dire time for Covid-19 in Iran, we surveyed 1058 adults from all 30 provinces in Iran using the Covid-19 Peritraumatic Distress Index (CPDI). Findings The distress level of Iranian adults (mean: 34.54; s.d.: 14.92) was significantly higher (mean difference: 10.9; t=22.7; p<0.0001; 95% CI: 10.0 to 11.8) than that of Chinese adults (mean: 23.65; s.d.: 5.45) as reported in a prior study with the same measure of Covid-19 Peritraumatic Distress Index (CPDI). We also found the predictors of distress in Iran vary from those in China. Interpretation Our findings that the predictors of distress in Iran vary from those in China suggest the need to study the predictors of mental health in individual countries during the Covid-19 pandemic to effectively identify and screen for those more susceptible to mental health issues. Keywords: Coronavirus; 2019-nCoV; Distress; Mental health; Psychiatric screening; Identifiers of mental issues in Covid-19 pandemic; Iran; Early evidence


title: Years of life lost due to the psychosocial consequences of COVID19 mitigation strategies based on Swiss data

text: Background: The pandemic caused by COVID-19 has forced governments to implement strict social mitigation strategies to reduce the acute morbidity and mortality from acute infections. These strategies however carry a significant risk for mental health which can lead to increased short-term and long-term mortality, which is currently not included in modelling the impact of the pandemic. Methods: We used years of life lost (YLL) as the main outcome measure as applied to Switzerland as an exemplar. We focused on suicide, depression, alcohol use disorder, childhood physical abuse and social isolation as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We also estimated a minimum duration of mitigation of 3 months based on current public health plans. Results: The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by a subpopulation of 2.1 percent of the population, the average of whom suffer an average 9.79 YLL. Conclusions: The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, model like the one presented here highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.


title: Exploring active ingredients and function mechanism of Chaihu Guizhi Ganjiang Decoction against coronavirus disease 2019 based on molecular docking technology/ 基于分子对接柴胡桂枝干姜汤干预初期寒湿郁肺型新型冠状病毒肺炎的活性成分及功效作用机制探讨

text: Objective: To predict the efficacy components and key targets of Chaihu Guizhi Ganjiang Decoction (CGGD) in the intervention of novel coronavirus pneumonia in the cold-dampness obstructing lungs in early stage, and clarify its mechanism. Methods: The novel coronavirus pneumonia TCM stage, clinical manifestations and the function of CGGD were analyzed by literature mining and clinical reports. TCMSP database was used to screen potential active components and related targets in CGGD. PubMed database was used to screen pneumonia, cough and fever related targets. With the help of Cytoscape software, a “drug-disease-target” visual network diagram and protein interaction network were constructed, and GO and pathway enrichment analysis of key targets was performed through the STRING database. The active ingredients were molecularly docked with SARS-CoV-2 3CL hydrolase protein and ACE2 by AutoDock Vina. Results: The analysis of the relationship between prescriptions and syndromes showed that CGGD could play warm-yang scattered cold, resolve dampness, clear stagnation and heat, and open up membrane’s power to intervene in early cold-dampness lung type COVID-19. Through screening, the therapeutic effects of CGGD were mainly in 156 chemical components acting on 159 related targets. The core 27 genes predicted and analyzed included EGFR, TP53, YWHAZ, HSP90AB1, PIK3R1, GRB2, etc. GO and pathway analysis showed that CGGD was mainly involved in biological processes such as cell regulation and immune system related pathways to play a therapeutic role. The 10 core components were molecularly docked, saikosaponin A, saikosaponin D, and peroxyergosterol in CGGD had good affinity with 3CL hydrolase protein and ACE2. Conclusion: Using network pharmacology and molecular docking technology to predict that CGGD can be used for the treatment of novel coronavirus pneumonia with symptom of cold-dampness obstructing lungs in early stage, potential antiviral ingredients contained in prescription of CGGD, can play a therapeutic role in the treatment of new type of coronavirus pneumonia in the early stage by regulating the immune system. It explains the characteristics of “multi-component-multi-target-multi-disease” of Chinese materia medica, and provides theoretical basis for clinical rational use of medicines.


title: Estimating the number of SARS-CoV-2 infections in the United States

text: We apply a model developed by The COVID-19 Response Team [S. Flaxman, S. Mishra, A. Gandy, et al., ''Estimating the number of infections and the impact of non- pharmaceutical interventions on COVID-19 in 11 European countries,'' tech. rep., Imperial College London, 2020.] to estimate the total number of SARS-CoV-2 infections in the United States. Across the United States we estimate as of April 18, 2020 the fraction of the population infected was 4.6% [3.6%, 5.8%], 21 times the portion of the population with a positive test result. Excluding New York state, which we estimate accounts for over half of infections in the United States, we estimate an infection rate of 2.3% [2.1%, 2.8%]. We include the timing of each state's implementation of interventions including encouraging social distancing, closing schools, banning public events, and a lockdown / stay-at-home order. We assume fatalities are reported correctly and infer the number and timing of infections based on the infection fatality rate measured in populations that were tested universally for SARS-CoV-2. Underreporting of deaths would drive our estimates to be too low. Reporting of deaths on the wrong day could drive errors in either direction. This model does not include effects of herd immunity; in states where the estimated infection rate is very high - namely, New York - our estimates may be too high.


title: Air Pollution Increases Influenza Hospitalizations

text: Seasonal influenza is a recurring health burden shared widely across the globe. We study whether air quality affects the occurrence of severe influenza cases that require inpatient hospitalization. Using longitudinal information on local air quality and hospital admissions across the United States, we find that poor air quality increases the incidence of significant influenza hospital admissions. Effects diminish in years with greater influenza vaccine effectiveness. Apart from increasing vaccination rates, improving air quality may help reduce the spread and severity of influenza.


title: Beyond R0: Heterogeneity in secondary infections and probabilistic epidemic forecasting

text: The basic reproductive number --- R0 --- is one of the most common and most commonly misapplied numbers in public health. Although often used to compare outbreaks and forecast pandemic risk, this single number belies the complexity that two different pathogens can exhibit, even when they have the same R0. Here, we show how to predict outbreak size using estimates of the distribution of secondary infections, leveraging both its average R0 and the underlying heterogeneity. To do so, we reformulate and extend a classic result from random network theory~\cite{Newman2001} that relies on contact tracing data to simultaneously determine the first moment (R0) and the higher moments (representing the heterogeneity) in the distribution of secondary infections. Further, we show the different ways in which this framework can be implemented in the data-scarce reality of emerging pathogens. Lastly, we demonstrate that without data on the heterogeneity in secondary infections for emerging infectious diseases like COVID-19, the uncertainty in outbreak size ranges dramatically. %, in the case of COVID-19 from 10-70\% of susceptible individuals. Taken together, our work highlights the critical need for contact tracing during emerging infectious disease outbreaks and the need to look beyond R0 when predicting epidemic size.


title: Renin-angiotensin-aldosterone system inhibitors and COVID-19 infection or hospitalization: a cohort study

text: There are plausible mechanisms by which angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of COVID-19 infection or affect disease severity. To examine the association between these medications and COVID-19 infection or hospitalization, we conducted a retrospective cohort study within a US integrated healthcare system. Among people aged [≥]18 years enrolled in the health plan for at least 4 months as of 2/29/2020, current ACEI and ARB use was identified from pharmacy data, and the estimated daily dose was calculated and standardized across medications. COVID-19 infections were identified through 6/14/2020 from laboratory and hospitalization data. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals. Among 322,044 individuals, 720 developed COVID-19 infection. Among people using ACEI/ARBs, 183/56,105 developed COVID-19 (3.3 per 1000 individuals) compared with 537/265,939 without ACEI/ARB use (2.0 per 1000), yielding an adjusted OR of 0.94 (95% CI 0.75-1.16). For use of < 1 defined daily dose vs. nonuse, the adjusted OR for infection was 0.89 (95% CI 0.62-1.26); for 1 to < 2 defined daily doses, 0.97 (95% CI 0.71-1.31); and for [≥]2 defined daily doses, 0.94 (95% CI 0.72-1.23). The OR was similar for ACEIs and ARBs and in subgroups by age and sex. 29% of people with COVID-19 infection were hospitalized; the adjusted OR for hospitalization in relation to ACEI/ARB use was 0.92 (95% CI 0.54-1.57), and there was no association with dose. These findings support current recommendations that individuals on these medications continue their use.


docid: pgrrurrc

title: Renal carcinoma is associated with increased risk of coronavirus infections

text: The current pandemic COVID-19 has affected most severely to the people with old age, or with comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, COPD, and cancers. Cancer patients are twice more likely to contract the disease because of the malignancy or treatment-related immunosuppression; hence identification of the vulnerable population among these patients is essential. It is speculated that along with ACE2, other auxiliary proteins (DPP4, ANPEP, ENPEP, TMPRSS2) might facilitate the entry of coronaviruses in the host cells. We took a bioinformatics approach to analyze the gene and protein expression data of these coronavirus receptors in human normal and cancer tissues of multiple organs. Here, we demonstrated an extensive RNA and protein expression profiling analysis of these receptors across solid tumors and normal tissues. We found that among all, renal tumor and normal tissues exhibited increased levels of ACE2, DPP4, ANPEP, and ENPEP. Our results revealed that TMPRSS2 may not be the co-receptor for coronavirus in renal carcinoma patients. The receptors’ expression levels were variable in different tumor stage, molecular and immune subtypes of renal carcinoma. In clear cell renal cell carcinomas, coronavirus receptors were associated with high immune infiltration, markers of immunosuppression, and T cell exhaustion. Our study indicates that CoV receptors may play an important role in modulating the immune infiltrate and hence cellular immunity in renal carcinoma. As our current knowledge of pathogenic mechanisms will improve, it may help us in designing focused therapeutic approaches.


title: Transmission and epidemiological characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected Pneumonia (COVID-19): preliminary evidence obtained in comparison with 2003-SARS

text: Objectives: Latest epidemic data of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected Pneumonia (COVID-19) was collected and a detailed statistical analysis was carried out to make comparison with 2003-SARS in order to provide scientific reference for the prevention and control of COVID-19. Methods: The information of COVID-19 and 2003-SARS from websites of NHCPRC and the World Health Organization was collected, and then the transmission dynamics of the two kinds of infectious diseases were analyzed. The information of 853 confirmed COVID-19 patients obtained from the website of health committees of 18 provinces. A descriptive epidemiological analysis method was employed to carefully analyze the epidemic characteristics. Subsequently, the COVID-19 epidemic data in Wuhan and other inland regions of China was analyzed separately and compared. A multivariate function model was constructed based on the confirmed COVID-19 case data. Results: The growth rate of new cases and deaths of COVID-19 were significantly faster than those of 2003-SARS. The number of confirmed cases in Wuhan and other inland areas both showed increasing trends. 853 confirmed COVID-19 cases aged 1 months to 94 years and the average age was (45.05 ± 17.22) years. The gender ratio (M: F) was 1.12: 1. Conclusions: The fatality rate of COVID-19 is lower than that of 2003-SARS and the cure rate is higher. The age of COVID-19 patients is mainly concentrated in the 30-50 years old (60.61%). The harm of the first-generation COVID-19 patients is higher than that of secondary cases.


docid: hrhmtyfl

title: SARS-CoV-2 sample-to-answer nucleic acid testing in a tertiary care emergency department: evaluation and utility

text: Rapid sample-to-answer tests for detection of SARS-CoV-2 are emerging and data on their relative performance is urgently needed. We evaluated the analytical performance of two rapid nucleic acid tests, Cepheid Xpert(R) Xpress SARS-CoV-2 and Mobidiag Novodiag(R) Covid-19, in comparison to a combination reference of three large-scale PCR tests. Moreover, utility of the Novodiag(R) test in tertiary care emergency departments was assessed. In the preliminary evaluation, analysis of 90 respiratory samples resulted in 100% specificity and sensitivity for Xpert(R), whereas analysis of 107 samples resulted in 93.4% sensitivity and 100% specificity for Novodiag(R). Rapid SARS-CoV-2 testing with Novodiag(R) was made available for four tertiary care emergency departments in Helsinki, Finland between 18 and 31 May, coinciding with a rapidly declining epidemic phase. Altogether 361 respiratory specimens, together with relevant clinical data, were analyzed with Novodiag(R) and reference tests: 355/361 of the specimens were negative with both methods, and 1/361 was positive in Novodiag(R) and negative by the reference method. Of the 5 remaining specimens, two were negative with Novodiag(R), but positive with the reference method with late Ct values. On average, a test result using Novodiag(R) was available nearly 8 hours earlier than that obtained with the large-scale PCR tests. While the performance of novel sample-to-answer PCR tests need to be carefully evaluated, they may provide timely and reliable results in detection of SARS-CoV-2 and thus facilitate patient management including effective cohorting.


docid: jubwcobb

title: Efficacy and Safety of Antibiotic Agents in Children with COVID-19: A Rapid Review

text: Background: The aim of this review was to evaluate the efficacy and safety of antibiotic agents in children with COVID-19, as well as to introduce the present situation of antibiotics use and bacterial coinfections in COVID-19 patients. Methods: We searched Cochrane library, Medline, Embase, Web of Science, CBM, Wanfang Data and CNKI from their inception to March 31, 2020. In addition, we searched related studies on COVID-19 published before March 31, 2020 through Google Scholar. We evaluated the risk of bias of included studies, and synthesized the results using a qualitative synthesis. Results: Six studies met our inclusion criteria. Five studies on SARS showed an overall risk of death of 7.2% to 20.0%. One study of SARS patients who used macrolides, quinolones or beta lactamases showed that the mean duration of hospital stay was 14.2, 13.8 and 16.2 days, respectively, and their average duration of fever was 14.3, 14.0 and 16.2 days, respectively. One cohort study on MERS indicated that macrolide therapy was not associated with a significant reduction in 90-day mortality (adjusted odds ratio [OR] 0.84, 95% confidence interval [CI] 0.47-1.51, P = 0.56) and improvement in MERS-CoV RNA clearance (adjusted hazard ratio [HR] 0.88, 95% CI 0.47, -1.64], P = 0.68). According to the findings of 33 studies, the proportion of antibiotics use ranged from 19.4% to 100.0% in children and 13.2% to 100.0% in adults, despite the lack of etiological evidence. The most commonly used antibiotics in adults were quinolones, cephalosporins and macrolides and in children meropenem and linezolid. Conclusions: The benefits of antibiotic agents for adults with SARS or MERS were questionable in the absence of bacterial coinfections. There is no evidence to support the use of antibiotic agents for children with COVID-19 in the absence of bacterial coinfection.


title: Twitter and Census Data Analytics to Explore Socioeconomic Factors for Post-COVID-19 Reopening Sentiment

text: Investigating and classifying sentiments of social media users (e.g., positive, negative) towards an item, situation, and system are very popular among the researchers. However, they rarely discuss the underlying socioeconomic factor associations for such sentiments. This study attempts to explore the factors associated with positive and negative sentiments of the people about reopening the economy, in the United States (US) amidst the COVID-19 global crisis. It takes into consideration the situational uncertainties (i.e., changes in work and travel pattern due to lockdown policies), economic downturn and associated trauma, and emotional factors such as depression. To understand the sentiment of the people about the reopening economy, Twitter data was collected, representing the 51 states including Washington DC of the US. State-wide socioeconomic characteristics of the people (e.g., education, income, family size, and employment status), built environment data (e.g., population density), and the number of COVID-19 related cases were collected and integrated with Twitter data to perform the analysis. A binary logit model was used to identify the factors that influence people toward a positive or negative sentiment. The results from the logit model demonstrate that family households, people with low education levels, people in the labor force, low-income people, and people with higher house rent are more interested in reopening the economy. In contrast, households with a high number of members and high income are less interested to reopen the economy. The accuracy of the model is good (i.e., the model can correctly classify 56.18% of the sentiments). The Pearson chi2 test indicates that overall this model has high goodness-of-fit. This study provides a clear indication to the policymakers where to allocate resources and what policy options they can undertake to improve the socioeconomic situations of the people and mitigate the impacts of pandemics in the current situation and as well as in the future.


title: ACE2 interaction networks in COVID-19: a physiological framework for prediction of outcome in patients with cardiovascular risk factors

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019; COVID-19) is associated with adverse outcome in patients with cardiovascular disease (CVD). Aim To characterize the interaction between SARS-CoV-2 and Angiotensin Converting Enzyme 2 (ACE2) functional networks with focus on CVD. Methods Using bioinformatic tools, network medicine approaches and publicly available datasets, we investigated ACE2 tissue expression and described ACE2 interaction network which could be affected by SARS-CoV-2 infection. We identified top ACE2 interactors, including miRNAs which are shared regulators between the ACE2, virus-infection related proteins and heart interaction networks, using lung and nervous system networks as a reference. We also identified main SARS-CoV-2 risk groups and performed drug predictions for them. Results We found the same range of ACE2 expression confidence in respiratory and cardiovascular systems (averaging 4.48 and 4.64, respectively). Analysing the complete ACE2 interaction network, we identified 11 genes (ACE2, DPP4, ANPEP, CCL2, TFRC, MEP1A, ADAM17, FABP2, NPC1, CLEC4M, TMPRSS2) associated with virus-infection related processes. Previously described genes associated with cardiovascular risk factors DPP4, CCL2 and ANPEP were extensively connected with top regulators of ACE2 network, including ACE, INS and KNG1. Enrichment analysis revealed several disease phenotypes associated with interaction networks of ACE2, heart tissue, and virus-infection related protein, with the strongest associations with the following diseases (in decreasing rank order): obesity, hypertensive disease, non-insulin dependent diabetes mellitus, congestive heart failure, and coronary artery disease. We described for the first time microRNAs-miR (miR-302c-5p, miR-1305, miR-587, miR-26b-5p, and mir-27a-3p), which were common regulators of the three networks: ACE2, heart tissue and virus-infection related proteins. Conclusion Our study provides novel information regarding the complexity of signaling pathways affected by SARS-CoV-2 and proposes predictive tools as miR towards personalized diagnosis and therapy in COVID-19. Additionally, our study provides a list of miRNAs with biomarker potential in prediction of adverse outcome in patients with COVID-19 and CVD.


title: Clinical features and outcomes of inpatients with neurological disease and COVID-19

text: Objective: To report the clinical and laboratory characteristics, as well as treatment and clinical outcomes of patients admitted for neurological diseases with COVID-19 in a Neuro-COVID unit compared to patients without COVID-19. Methods: In this retrospective, single centre cohort study, we included all adult inpatients with confirmed COVID-19, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records. Results: 173 patients were included in this study, of whom 56 resulted positive for COVID-19 and 117 resulted negative for COVID-19. Patients with COVID-19 were older, had a different distribution regarding admission diagnoses, including cerebrovascular disorders, and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (all p<0.05). In-hospital mortality rates and incident delirium were significantly higher in the COVID-19 group (all p<0.05). COVID-19 and non-COVID patients with stroke had similar baseline characteristics but patients with COVID-19 had higher modified Rankin scale scores at discharge (p<0.0001), with a significantly lower number of patients with a good outcome (p<0.0001). Multivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (odds ratio 4.47, 95% CI 1.21-16.5; p=0.025), lower platelet count (0.98, 0.97-0.99; p=0.005) and higher lactate dehydrogenase (1.01, 1.00-1.03; p=0.009) on admission. Conclusions: COVID-19 patients admitted with neurological disease, including stroke, have a significantly higher in-hospital mortality, incident delirium and higher disability than patients without COVID-19.


title: UV Sterilization of Personal Protective Equipment with Idle Laboratory Biosafety Cabinets During the Covid-19 Pandemic

text: Personal protective equipment (PPE), including surgical masks and N95 respirators, is crucially important to the safety of both patients and medical personnel, particularly in the event of infectious pandemics. As the incidence of Coronavirus Disease (COVID-19) is increasing exponentially in the United States and worldwide, healthcare provider demand for these necessities is currently outpacing supply. As such, strategies to safely expand the lifespan of the supply of medical equipment are critically important. In the recent days, weeks, and months, in the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve Personal Protective Equipment, including sterilization after use. Some hospitals have already begun using UV-C light to sterilize N95 respirators, but many lack the space or equipment to implement existing protocols. In this study, we outline a procedure by which N95 respirators may be sterilized using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories. The primary obstacle to this approach is the possibility the UV radiation levels vary within BSCs. To account for this potential variation in dosing across the base of the BSC, we tested the UV-C radiation in two randomly chosen idle BSCs in our research institute and observed a maximum ratio between the minimum and maximum recorded intensities within a given BSC to be 1.98. Based on these values, we calculated that an N95 mask placed within a BSC with a manufacturer reported fluence of 100 W/cm^2 should be effectively sanitized for reuse after approximately 15-20 minutes per side. Our results provide support to healthcare organizations looking for alternative methods to extend their reserves of PPE. It is our hope that with an easily implemented strategy, as we have presented here, idle BSCs can be utilized to alleviate the PPE shortage by providing a way to sterilize PPE to allow safe daily re-use. This should be tested on a larger scale, and confirmed in a virology laboratory before adoption, though we contend that in extremis, this method would be preferred compared to re-use without sterilization.


title: The reproduction number R for COVID-19 in England: Why hasn't ''lockdown'' been more effective?

text: The reproduction number R, the average number of people that a single individual with a contagious disease infects, is central to understanding the dynamics of the COVID-19 epidemic. Values greater than one correspond to increasing rates of infection, and values less than one indicate that control measures are being effective. Here, we summarise how changes in the behaviour of individuals alter the value of R. We also use matrix models that correctly recreate distributions of times that individuals spend incubating the disease and being infective to demonstrate the accuracy of a simple approximation to estimate R directly from time series of case numbers, hospital admissions or deaths. The largest uncertainty is that the generation time of the infection is not precisely known, but this challenge also affects most of the more complex methods of calculating R. We use this approximation to examine changes in R in response to the introduction of lockdown restrictions in England. This suggests that there was a substantial reduction in R before large scale compulsory restrictions on economic and social activity were imposed on 23rd March 2020. From mid-April to mid-June decline of the epidemic at national and regional level has been relatively slow, despite these restrictions (R values clustered around 0.81). However, these estimates of R are consistent with the relatively high average numbers of close contacts reported by confirmed cases combined with directly measured attack rates via close interactions. This implies that a significant portion of transmission is occurring in workplaces; overcrowded housing or through close contacts that are not currently lawful, routes on which nationwide lockdown will have limited impact.


title: Scarce COVID-19 Testing Capabilities at Urgent Care Centers in States with Greatest Disease Burden

text: As of March 22, 2020, the number of confirmed COVID-19 cases in the U.S. has reached nearly 30,000. While rapid and accessible diagnosis is paramount to monitoring and reducing the spread of disease, COVID-19 testing capabilities across the U.S. remain constrained. For many individuals, urgent care centers (UCCs) may offer the most accessible avenue to be tested. Through a phone survey, we describe the COVID-19 testing capabilities at UCCs and provide a snapshot highlighting the limited COVID-19 testing capabilities at UCCs in states with the greatest disease burden.


title: Predictions of COVID-19 dynamics in the UK: short-term forecasting and analysis of potential exit strategies

text: Background: Efforts to suppress transmission of SARS-CoV-2 in the UK have seen non-pharmaceutical interventions being invoked. The most severe measures to date include all restaurants, pubs and cafes being ordered to close on 20th March, followed by a "stay at home" order on the 23rd March and the closure of all non-essential retail outlets for an indefinite period. Government agencies are presently analysing how best to develop an exit strategy from these measures and to determine how the epidemic may progress once measures are lifted. Mathematical models are currently providing short and long term forecasts regarding the future course of the COVID-19 outbreak in the UK to support evidence-based policymaking. Methods: We present a deterministic, age-structured transmission model that uses real-time data on confirmed cases requiring hospital care and mortality to provide up-to-date predictions on epidemic spread in ten regions of the UK. We simulated a suite of scenarios to assess the impact of differing approaches to relaxing social distancing measures from 7th May 2020, on the estimated number of patients requiring inpatient and critical care treatment, and deaths. With regard to future epidemic outcomes, we investigated the impact of reducing compliance, ongoing shielding of elder age groups, reapplying stringent social distancing measures using region based triggers and the role of asymptomatic transmission. Findings: We find that significant relaxation of social distancing measures on 7th May can lead to a rapid resurgence of COVID-19 disease and the health system being quickly overwhelmed by a sizeable, second epidemic wave. In all considered age-shielding based strategies, we projected serious demand on critical care resources during the course of the pandemic. The reintroduction and release of strict measures on a regional basis, based on ICU bed occupancy, results in a long epidemic tail, until the second half of 2021, but ensures that the health service is protected by reintroducing social distancing measures for all individuals in a region when required. Conclusions: Our work supports the decision to apply stringent non-pharmaceutical measures in March 2020 to suppress the epidemic. We provide strong evidence to support the need for a cautious, measured approach to relaxation of lockdown measures, to protect the most vulnerable members of society and support the health service through subduing demand on hospital beds, in particular bed occupancy in intensive care units.


title: Social Stress Alters Immune Response and Results in Higher Viral Load During Acute SIV Infection in a Pigtailed Macaque Model of HIV

text: While social distancing is a key response to viral pandemics, social stress has been implicated in adverse health outcomes. A comprehensive understanding of the direct physiologic effects of social stress on viral pathophysiology is needed. To determine the effect of social stress on HIV pathogenesis during acute viral infection without sociobehavioral confounders inherent in human cohorts, we compared commonly measured parameters of HIV progression between singly and socially housed SIV-infected pigtailed macaques (Macaca nemestrina). Singly housed macaques demonstrated lower CD4/CD8 ratios, greater CD4 T cell declines and greater T cell activation compared to socially housed macaques during acute SIV infection. Singly housed macaques furthermore had higher viral loads in the plasma and cerebrospinal fluid throughout acute infection. These data demonstrate that social stress directly impacts the pathogenesis of acute lentiviral infection and imply that social stress has a direct effect on the pathogenesis of HIV and potentially other viral infections. One Sentence Summary Social stress impacts the pathogenesis of acute HIV infection, leading to immune system dysregulation and higher viral load.


title: COVID-19 and emergency eLearning: Consequences of the securitization of higher education for post-pandemic pedagogy

text: The COVID-19 pandemic quickly led to the closure of universities and colleges around the world, in hopes that public health officials’ advice of social distancing could help to flatten the infection curve and reduce total fatalities from the disease. Drawing on Copenhagen school securitization theory and analyzing 25 declarations of emergency eLearning at American universities, I argue that in addition to COVID-19 being framed as a general threat, face-to-face schooling was also presented as a threat through these policies. A review of securitization theory—with particular attention to the question of advocacy and the relationship of desecuritization to emancipation—grounds the investigation theoretically. I argue that securitization theory is an important tool for educators not only for observing (and understanding) the phenomenon of emergency eLearning, but also for advocating the desecuritization of schooling after the COVID-19 crisis passes.


docid: tcnpskpy

title: The experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of Chongqing, China

text: BACKGROUND: The outbreak of a novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) is currently ongoing in China. Most of the critically ill patients received high-flow nasal cannula (HFNC) oxygen therapy. However, the experience of HFNC in this population is lacking. METHODS: We retrospectively screened 318 confirmed patients with NCIP in two hospitals of Chongqing, China, from January 1st to March 4th, 2020. Among them, 27 (8.4%) patients experienced severe acute respiratory failure including 17 patients (63%) treated with HFNC as first-line therapy, 9 patients (33%) treated with noninvasive ventilation (NIV) and one patient (4%) treated with invasive ventilation. HFNC failure was defined by the need of NIV or intubation as rescue therapy. RESULTS: Of the 17 HFNC patients, 7 (41%) experienced HFNC failure. The HFNC failure rate was 0% (0/6) in patients with PaO(2)/FiO(2) > 200 mm Hg vs. 63% (7/11) in those with PaO(2)/FiO(2) ≤ 200 mm Hg (p = 0.04). Compared with baseline data, the respiratory rate significantly decreased after 1–2 h of HFNC in successful group [median 26 (IQR: 25–29) vs. 23 (22–25), p = 0.03]. However, it did not in the unsuccessful group. After initiation of NIV as rescue therapy among the 7 patients with HFNC failure, PaO(2)/FiO(2) significantly improved after 1–2 h of NIV [median 172 (150–208) mmHg vs. 114 (IQR: 79–130) under HFNC, p = 0.04]. However, two out of seven (29%) patients with NIV as rescue therapy ultimately received intubation. Among the 27 patients with severe acute respiratory failure, four patients were eventually intubated (15%). CONCLUSIONS: Our study indicated that HFNC was the most common ventilation support for patients with NCIP. Patients with lower PaO(2)/FiO(2) were more likely to experience HFNC failure.


title: Times of uncertainty

text: Epidemiological modelling informs government responses to the COVID-19 pandemic, but confusion abounds about the models What can physicists do to help?


title: A Fully Automatic Deep Learning System for COVID-19 Diagnostic and Prognostic Analysis

text: Coronavirus disease 2019 (COVID-19) has spread globally, and medical resources become insufficient in many regions. Fast diagnosis of COVID-19, and finding high-risk patients with worse prognosis for early prevention and medical resources optimization is important. Here, we proposed a fully automatic deep learning system for COVID-19 diagnostic and prognostic analysis by routinely used computed tomography. We retrospectively collected 5372 patients with computed tomography images from 7 cities or provinces. Firstly, 4106 patients with computed tomography images and gene information were used to pre-train the DL system, making it learn lung features. Afterwards, 1266 patients (924 with COVID-19, and 471 had follow-up for 5+ days; 342 with other pneumonia) from 6 cities or provinces were enrolled to train and externally validate the performance of the deep learning system. In the 4 external validation sets, the deep learning system achieved good performance in identifying COVID-19 from other pneumonia (AUC=0.87 and 0.88) and viral pneumonia (AUC=0.86). Moreover, the deep learning system succeeded to stratify patients into high-risk and low-risk groups whose hospital-stay time have significant difference (p=0.013 and 0.014). Without human-assistance, the deep learning system automatically focused on abnormal areas that showed consistent characteristics with reported radiological findings. Deep learning provides a convenient tool for fast screening COVID-19 and finding potential high-risk patients, which may be helpful for medical resource optimization and early prevention before patients show severe symptoms.


title: ReScan, a Multiplex Diagnostic Pipeline, Pans Human Sera for SARS-CoV-2 Antigens

text: Serologic assays are needed to determine SARS-CoV-2 seroprevalence, but poor specificity can overestimate exposures. Here, we built a pan-human coronavirus proteome-wide programmable phage display assay (VirScan) to profile coronavirus antigens specifically enriched by 20 COVID-19 patient serum IgG. With ReScan, a new diagnostic development workflow which combines the isolation of phage expressing the most immunogenic peptides with paper-based microarrays manufactured via acoustic liquid handling, we identified 9 candidate antigens from a library of 534 SARS-CoV-2 peptides. These arrays could form the basis of a multiplexed COVID-19 serologic assay with enhanced specificity. ReScan has broad applicability for serologic assay development.


title: Social distancing to slow the U.S. COVID-19 epidemic: an interrupted time-series analysis

text: Background: Social distancing measures to address the U.S. COVID-19 epidemic may have significant health, social, and economic impacts. Objective: To estimate the mean change in state-level COVID-19 epidemic growth before versus after the implementation of statewide social distancing measures. Design: Interrupted time-series analysis. Setting: United States. Measurements: Our primary exposure was time in relation to implementation of the first statewide social distancing measure. The pre-implementation period began 14 days prior to implementation and included up to 3 days after implementation to account for incubation. Post-implementation began 4 days after, up to and including March 30. Our primary outcome was the COVID-19 growth rate, calculated as the log of daily COVID-19 cases minus the log of daily COVID-19 cases on the prior day. Results: All states applied some form of statewide social distancing between March 10-27. The mean daily COVID-19 growth rate decreased beginning four days after implementation of the first statewide social distancing measures, by an additional 0.8% per day; 95% CI, -1.4% to -0.2%; P=0.002). This reduction corresponds to an increase in doubling time of the epidemic from 3.3 days (before) to 5.0 days (at 14 days after implementation). Limitations: Potential bias due to the aggregate nature of the ecological data, potential confounding by contemporaneous changes (e.g., increases in testing), and potential underestimation of social distancing due to spillovers across neighboring states. Conclusion: Statewide social distancing measures were associated with a decrease in U.S. COVID-19 epidemic growth. Based on the size of the epidemic at the time of implementation in each state, social distancing measures were associated with a decrease of 3,090 cases at 7 days, and 68,255 cases at 14 days, after implementation.


COVID-19: Recommendations for Treating MS and Related Disorders


title: A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19

text: The global spread of SARS-CoV-2 requires an urgent need to find effective therapeutics for the treatment of COVID-19. We developed a data-driven drug repositioning framework, which applies both machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. The retrospective study using the past SARS-CoV and MERS-CoV data demonstrated that our machine learning based method can successfully predict effective drug candidates against a specific coronavirus. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 is able to suppress the CpG-induced IL-6 production in peripheral blood mononuclear cells, suggesting that it may also have anti-inflammatory effect that is highly relevant to the prevention immunopathology induced by SARS-CoV-2 infection. Further pharmacokinetic and toxicokinetic evaluation in rats and monkeys showed a high concentration of CVL218 in lung and observed no apparent signs of toxicity, indicating the appealing potential of this drug for the treatment of the pneumonia caused by SARS-CoV-2 infection. Moreover, molecular docking simulation suggested that CVL218 may bind to the N-terminal domain of nucleocapsid (N) protein of SARS-CoV-2, providing a possible model to explain its antiviral action. We also proposed several possible mechanisms to explain the antiviral activities of PARP1 inhibitors against SARS-CoV-2, based on the data present in this study and previous evidences reported in the literature. In summary, the PARP1 inhibitor CVL218 discovered by our data-driven drug repositioning framework can serve as a potential therapeutic agent for the treatment of COVID-19.


title: A translational multiplex serology approach to profile the prevalence of anti-SARS-CoV-2 antibodies in home-sampled blood

text: The COVID-19 pandemic has posed a tremendous challenge for the global community. We established a translational approach combining home blood sampling by finger-pricking with multiplexed serology to assess the exposure to the SARS-CoV-2 virus in a general population. The developed procedure determines the immune response in multiplexed assays against several spike (S, here denoted SPK), receptor binding domain (RBD) and nucleocapsid (NCP) proteins in eluates from dried capillary blood. The seroprevalence was then determined in two study sets by mailing 1000 blood sampling kits to random households in urban Stockholm during early and late April 2020, respectively. After receiving 55% (1097/2000) of the cards back within three weeks, 80% (878/1097) were suitable for the analyses of IgG and IgM titers. The data revealed diverse pattern of immune response, thus seroprevalence was dependent on the antigen, immunoglobulin class, stringency to include different antigens, as well as the required analytical performance. Applying unsupervised dimensionality reduction to the combined IgG and IgM data, 4.4% (19/435; 95% CI: 2.4%-6.3%) and 6.3% (28/443; 95% CI: 4.1%-8.6%) of the samples clustered with convalescent controls. Using overlapping scores from at least two SPK antigens, prevalence rates reached 10.1% (44/435; 95% CI: 7.3%-12.9%) in study set 1 and 10.8% (48/443; 95% CI: 7.9%-13.7%). Measuring the immune response against several SARS-CoV-2 proteins in a multiplexed workflow can provide valuable insights about the serological diversity and improve the certainty of the classification. Combining such assays with home-sampling of blood presents a viable strategy for individual-level diagnostics and towards an unbiased assessment of the seroprevalence in a population and may serve to improve our understanding about the diversity of COVID-19 etiology.


title: Disentangling Increased Testing From Covid-19 Epidemic Spread

text: To design effective disease control strategies, it is critical to understand the incidence of diseases. In the Covid-19 epidemic in the United States (caused by outbreak of the SARS-CoV-2 virus), testing capacity was initially very limited and has been increasing at the same time as the virus has been spreading. When estimating the incidence, it can be difficult to distinguish whether increased numbers of positive tests stem from increases in the spread of the virus or increases in testing. This has made it very difficult to identify locations in which the epidemic poses the largest public health risks. Here, we use a probabilistic model to quantify beliefs about testing strategies and understand implications regarding incidence. We apply this model to estimate the incidence in each state of the United States, and find that: (1) the Covid-19 epidemic is likely to be more widespread than reported by limited testing, (2) the Covid-19 epidemic growth in the summer months is likely smaller than it was during the spring months, and (3) the regions which are at highest risk of Covid-19 epidemic outbreaks are not always those with the largest number of positive test results.


docid: tohbzenc

title: Corona Epidemic in Indian context: Predictive Mathematical Modelling

text: The novel Coronavirus pathogen Covid-19 is a cause of concern across the world as the human-to-human infection caused by it is spreading at a fast pace. The virus that first manifested in Wuhan, China has travelled across continents. The increase in number of deaths in Italy, Iran, USA, and other countries has alarmed both the developed and developing countries. Scientists are working hard to develop a vaccine against the virus, but until now no breakthrough has been achieved. India, the second most populated country in the world, is working hard in all dimensions to stop the spread of community infection. Health care facilities are being updated; medical and paramedical staffs are getting trained, and many agencies are raising awareness on the issues related to this virus and its transmission. The administration is leaving no stone unturned to prepare the country to mitigate the adverse effects. However, as the number of infected patients, and those getting cured is changing differently in different states everyday it is difficult to predict the spread of the virus and its fate in Indian context. Different states have adopted measures to stop the community spread. Considering the vast size of the country, the population size and other socio-economic conditions of the states, a single uniform policy may not work to contain the disease. In this paper, we discuss a predictive mathematical model that can give us some idea of the fate of the virus, an indicative data and future projections to understand the further course this pandemic can take. The data can be used by the health care agencies, the Government Organizations and the Planning Commission to make suitable arrangements to fight the pandemic. Though the model is preliminary, it can be used at regional level to manage the health care system in the present scenario. The recommendations can be made, and advisories prepared based on the predictive results that can be implemented at regional levels.


title: Health and Demographic Impact on COVID-19 Infection and Mortality in US Counties

text: Introduction With the pandemic of COVID-19, the number of confirmed cases and related deaths are increasing in the US. We aimed to understand the potential impact of health and demographic factors on the infection and mortality rates of COVID-19 at the population level. Methods We collected total number of confirmed cases and deaths related to COVID-19 at the county level in the US from January 21, 2020 to April 23, 2020. We extracted health and demographic measures for each US county. Multivariable linear mixed effects models were used to investigate potential correlations of health and demographic characteristics with the infection and mortality rates of COVID-19 in US counties. Results Our models showed that several health and demographic factors were positively correlated with the infection rate of COVID-19, such as low education level and percentage of Black. In contrast, several factors, including percentage of smokers and percentage of food insecure, were negatively correlated with the infection rate of COVID-19. While the number of days since first confirmed case and the infection rate of COVID-19 were negatively correlated with the mortality rate of COVID-19, percentage of elders (65 and above) and percentage of rural were positively correlated with the mortality rate of COVID-19. Conclusions At the population level, health and demographic factors could impact the infection and mortality rates of COVID-19 in US counties.


title: A modular framework for the development of targeted Covid-19 blood transcript profiling panels

text: Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of focused blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates. As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: therapeutic development relevance, SARS biology relevance and immunological relevance. Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients.


title: Potential host range of multiple SARS-like coronaviruses and an improved ACE2-Fc variant that is potent against both SARS-CoV-2 and SARS-CoV-1

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a currently uncontrolled pandemic and the etiological agent of coronavirus disease 2019 (COVID-19). It is important to study the host range of SARS-CoV-2 because some domestic species might harbor the virus and transmit it back to humans. In addition, insight into the ability of SARS-CoV-2 and SARS-like viruses to utilize animal orthologs of the SARS-CoV-2 receptor ACE2 might provide structural insight into improving ACE2-based viral entry inhibitors. Here we show that ACE2 orthologs of a wide range of domestic and wild animals support entry of SARS-CoV-2, as well as that of SARS-CoV-1, bat coronavirus RaTG13, and a coronavirus isolated from pangolins. Some of these species, including camels, cattle, horses, goats, sheep, pigs, cats, and rabbits may serve as potential intermediate hosts for new human transmission, and rabbits in particular may serve as a useful experimental model of COVID-19. We show that SARS-CoV-2 and SARS-CoV-1 entry could be potently blocked by recombinant IgG Fc-fusion proteins of viral spike protein receptor-binding domains (RBD-Fc) and soluble ACE2 (ACE2-Fc). Moreover, an ACE2-Fc variant, which carries a D30E mutation and has ACE2 truncated at its residue 740 but not 615, outperforms all the other ACE2-Fc variants on blocking entry of both viruses. Our data suggest that RBD-Fc and ACE2-Fc could be used to treat and prevent infection of SARS-CoV-2 and any new viral variants that emerge over the course of the pandemic.


4th Global report on adult learning and education – Leave no one behind: Participation, equity and inclusion


title: Applications of qualitative grounded theory methodology to investigate hearing loss: Protocol for a qualitative systematic review

text: ABTRACT Introduction: Hearing loss is a chronic condition affecting 11 million individuals in the UK. People with hearing loss regularly experience difficulties interacting in everyday conversations. These difficulties in communication can result in a person with hearing loss withdrawing from social situations and becoming isolated. While hearing health loss research has largely deployed quantitative methods to investigate various aspects of the condition, qualitative research is becoming more widespread. Grounded theory is a specific qualitative methodology that has been used to establish novel theories on the experiences of living with hearing loss. Method and analysis: The aim of this systematic review is to establish how grounded theory has been applied to investigate the psychosocial aspects of hearing loss. Methods are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) 2015 checklist. Studies included in this review will have applied grounded theory methodology. For a study to be included, it can apply grounded theory as an overarching methodology, or have grounded theory methodology embedded amongst other methodologies. These studies can be in the form of retrospective or prospective studies, before and after comparison studies, RCTs, non-RCTs, cohort studies, prospective observational studies, case-control studies, cross-sectional studies, longitudinal studies, and mixed method studies. Purely quantitative studies, studies that have not applied grounded theory methodology, articles reporting expert opinions, case reports, practice guidelines, case series, conference abstracts, and book chapters will be excluded. Studies included will have adult participants ([≥]18 years) who are either people with an acquired hearing loss, their family and friends (communication partners), or audiologists. The quality of application of grounded theory in each study will be assessed using the Guideline for Reporting and Evaluating Grounded Theory Research Studies (GUREGT). Ethics and dissemination: As only secondary data will be used in this systematic review, ethical approval is not required. No other ethical issues are foreseen. The International Prospective Register of Systematic Reviews (http://www crd.york.ac.uk/PROSPERO) holds the registration record of this systematic review. Findings will be disseminated via peer reviewed publications and at relevant academic conferences. Findings may also be published in relevant professional and third sector newsletters and magazines as appropriate. Data will inform future research and guideline development. Prospero registration number: PROSPERO CRD42019134197 Strengths and limitations of this study: This systematic review is the first to provide a comprehensive critique of the use of grounded theory to investigate hearing loss. The search strategy was formed in collaboration with an information specialist at the University of Nottingham. The PRISMA-P guidelines have directed the considerations and layout of this protocol. Because experiences and articulations of hearing loss are influenced by age, only adult ([≥]18 years) participants (people with hearing loss, communication partners, audiologists) will be considered. The search will not include grey literature. The studies included will only have samples of individuals with hearing loss, rather than full deafness.


title: Severe underestimation of COVID-19 case numbers: effect of epidemic growth rate and test restrictions

text: To understand the scope and development of the COVID-19 pandemic, knowledge of the number of infected persons is essential. Often, the number of "confirmed cases", which is based on positive RT-PCR test results, is regarded as a reasonable indicator. However, limited COVID-19 test capacities in many countries are restricting the amount of testing that can be done. This can lead to the implementation of testing policies that restrict access to COVID-19 tests, and to testing backlogs and delays. As a result, confirmed case numbers can be significantly lower than the actual number of infections, especially during rapid growth phases of the epidemic. This study examines the quantitative relation between infections and reported confirmed case numbers for two different testing strategies, "limited" and "inclusive" testing, in relation to the growth rate of the epidemic. The results indicate that confirmed case numbers understate the actual number of infections substantially; during rapid growth phases where the daily growth rate can reach or exceed 30%, as has been seen in many countries, the confirmed case numbers under-report actual infections by up to 50 to 100-fold.


title: The impact of unplanned school closure on children's social contact: Rapid evidence review

text: Background Emergency school closures are often used as public health interventions during infectious disease outbreaks in an attempt to minimise the spread of infection. However, if children continue to mix with others outside the home during the closures, these measures are unlikely to be effective. Objectives This review aimed to summarise existing literature on children's activities and contacts made outside the home during unplanned school closures. Methods We searched four databases from inception to February 2020 for relevant literature. Main findings were extracted. Results 3,343 citations were screened and 19 included in the review. Activities and social contacts appeared to decrease during closures but contact was still common. All studies reported children leaving the house or being looked after by non-household members. There was some evidence that older child age and parental disagreement with closure were predictive of children leaving the house, and mixed evidence regarding the relationship between infection status and leaving the home. Parental agreement with closure was generally high, but some parents disagreed due to perceived low risk of infection and practical issues regarding childcare and financial impact. Conclusions Evidence suggests that many children continue to leave the house and mix with others during school closures despite public health recommendations to avoid social contact. This review of behaviour during unplanned school closures could be used to improve infectious disease modelling.


title: Did elderly people living in small towns or rural areas suffer heavier disease burden during the COVID-19 epidemic?

text: Background: Health disparities were often overlooked during the emerging epidemic. Objectives: This study examined geographic differences in the rates of health care use and deaths among elderly patients. Methods: Based on individual patient records, multivariate Poisson and logistic models were used to calculate adjusted incidences of COVID-19 and probabilities of emergency department (ED) visits, hospitalizations and deaths. Results: Of 8,203 elderly patients, 11% died. Elderly people living in small metropolitan areas were half as likely to be diagnosed with COVID-19. Elderly female patients living in small metropolitan areas had much lower rates of ED visits (23% vs. 34%; Odds Ratio (OR): 0.58; 95%confidence interval (CI): 0.41-0.81; p=0.002) and hospitalizations (22% vs. 31%; OR: 0.62; 95%CI: 0.44 - 0.87; p=0.006) than those living in large metropolitan areas. Furthermore, those living in non-metropolitan areas were more likely to be hospitalized than those living in large metropolitan areas (44% vs. 33%; OR: 1.46; 95%CI: 1.07-1.99; p=0.016), especially among elderly men (51% vs. 35%; OR:1.86; 95%CI: 1.18-2.93; p=0.008). Finally, there was a significant linear trend in hospitalization rates among elderly male patients (p for trend = 0.01). Conclusions: Profound health disparities exist in the time of emerging epidemic.


title: America Addresses Two Epidemics: Cannabis and Coronavirus and their Interactions: An Ecological Geospatial Study

text: Importance. Covid-19 infection has major international health and economic impacts and risk factors for infection are not completely understood. Cannabis smoking is linked with poor respiratory health, immunosuppression and multiple contaminants. Potential synergism between the two epidemics would represent a major public health convergence. Cigarettes were implicated with disease severity in Wuhan, China. Objective. Is cannabis use epidemiologically associated with coronavirus incidence rate (CVIR)? Design. Cross-sectional state-based multivariable study. Setting. USA. Primary and Secondary Outcome Measures. CVIR. Multivariable-adjusted geospatially-weighted regression models. As the American cannabis epidemic is characterized by a recent doubling of daily cannabis use it was considered important to characterize the contribution of high intensity use. Results. Significant associations of daily cannabis use quintile with CVIR were identified with the highest quintile having a prevalence ratio 5.11 (95%C.I. 4.90-5.33), an attributable fraction in the exposed (AFE) 80.45% (79.61-81.25%) and an attributable fraction in the population of 77.80% (76.88-78.68%) with Chi-squared-for-trend (14,782, df=4) significant at P<10-500. Similarly when cannabis legalization was considered decriminalization was associated with an elevated CVIR prevalence ratio 4.51 (95%C.I. 4.45-4.58), AFE 77.84% (77.50-78.17%) and Chi-squared-for-trend (56,679, df=2) significant at P<10-500. Monthly and daily use were linked with CVIR in bivariate geospatial regression models (P=0.0027, P=0.0059). In multivariable additive models number of flight origins and population density were significant. In interactive geospatial models adjusted for international travel, ethnicity, income, population, population density and drug use, terms including last month cannabis were significant from P=7.3x10-15, daily cannabis use from P=7.3x10-11 and last month cannabis was independently associated (P=0.0365). Conclusions and Relevance. Data indicate CVIR demonstrates significant trends across cannabis use intensity quintiles and with relaxed cannabis legislation. Recent cannabis use is independently predictive of CVIR in bivariate and multivariable adjusted models and intensity of use is interactively significant. Cannabis thus joins tobacco as a SARS2-CoV-2 risk factor.


title: Identifying common pharmacotherapies associated with reduced COVID-19 morbidity using electronic health records

text: Importance: Absent a vaccine or any established treatments for the novel and highly infectious coronavirus-19 (COVID-19), rapid efforts to identify potential therapeutics are required. Objective: To identify commonly-prescribed medications that may be associated with lesser risk of morbidity with COVID-19 across 5 Eastern Massachusetts hospitals. Design: In silico cohort using electronic health records between 7/1/2019 and 4/07/2020. Setting: Outpatient, emergency department and inpatient settings from 2 academic medical centers and 3 community hospitals. Participants: All individuals presenting to a clinical site and undergoing COVID-19 testing. Main Outcome or Measure: Inpatient hospitalization; documented requirement for mechanical ventilation. Results: Among 12,818 individuals with COVID-19 testing results available, 2271 (17.7%) were test-positive, and 707/2271 (31.1%) were hospitalized in one of 5 hospitals. Based on a comparison of ranked electronic prescribing frequencies, medications enriched among test-positive individuals not requiring hospitalization included ibuprofen, valacyclovir, and naproxen. Among individuals who were hospitalized, mechanical ventilation was documented in 213 (30.1%); ibuprofen and naproxen were also more commonly prescribed among individuals not requiring ventilation. Conclusions and Relevance: These preliminary findings suggest that electronic health records may be applied to identify medications associated with lower risk of morbidity with COVID-19, but larger cohorts will be required to address confounding by indication. Larger scale efforts at repositioning may help to identify FDA-approved medications meriting study for prevention of COVID-19 morbidity and mortality.


title: The impact of Coronavirus disease 2019 (COVID-19) on health systems and household resources in Africa and South Asia

text: Background. Coronavirus disease 2019 (COVID-19) epidemics strain health systems and households. Health systems in Africa and South Asia may be particularly at risk due to potential high prevalence of risk factors for severe disease, large household sizes and limited healthcare capacity. Methods. We investigated the impact of an unmitigated COVID-19 epidemic on health system resources and costs, and household costs, in Karachi, Delhi, Nairobi, Addis Ababa and Johannesburg. We adapted a dynamic model of SARS-CoV-2 transmission and disease to capture country-specific demography and contact patterns. The epidemiological model was then integrated into an economic framework that captured city-specific health systems and household resource use. Findings. The cities severely lack intensive care beds, healthcare workers and financial resources to meet demand during an unmitigated COVID-19 epidemic. A highly mitigated COVID-19 epidemic, under optimistic assumptions, may avoid overwhelming hospital bed capacity in some cities, but not critical care capacity. Interpretation. Viable mitigation strategies encompassing a mix of responses need to be established to expand healthcare capacity, reduce peak demand for healthcare resources, minimise progression to critical care and shield those at greatest risk of severe disease.


title: Low albumin levels are associated with poorer outcomes in a case series of COVID-19 patients in Spain: a retrospective cohort study

text: OBJECTIVE To describe the clinical characteristics and epidemiological features of severe (non-ICU) and critically patients (ICU) with COVID-19 at triage, prior hospitalization, in one of the main hospitals in The Balearic Islands health care system. DESIGN Retrospective observational study SETTING Son Llatzer University Hospital in Palma de Mallorca (Spain) PARTICIPANTS Among a cohort of 52 hospitalized patients as of 31 March 2020, 48 with complete demographic information and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test, were analyzed. Data were collected between March 15th, 2020, and March 31th 2020, inclusive of these dates. MAIN OUTCOMES Clinical, vital signs and routine laboratory outcomes at the time of hospitalization, including symptoms reported prior to hospitalization. Demographics and baseline comorbidities were also collected. Mortality was reported at the end of the study. RESULTS 48 patients (27 non-ICU and 21 ICU) resident in Mallorca, Spain (mean age, 66 years, [range, 33-88 years]; 67% males) with positive SARS-CoV-2 infection were analyzed. There were no differences in age or sex among groups (p >.05). Initial symptoms included fever (100%), coughing (85%), dyspnea (76%), diarrhea (42%) and asthenia (21%). The majority of patients in this case series were hospitalized because of low SpO2 (SpO2 below 90%) and presentation of bilateral pneumonia (94%) at triage. ICU patients had a higher prevalence of dyspnea compared to non-ICU patients (95% vs 61%, p = .022). Acute respiratory syndrome (ARDS) was presented in 100% of the ICU-patients. All the patients included in the study required oxygen therapy. ICU-patients had lymphopenia as well as hypoalbuminemia. Inflammatory markers such as lactate dehydrogenase (LDH), C-reactive protein (CRP), and procalcitonin were significantly higher in ICU patients compared to non-ICU (p < .001).Lower albumin levels were associated with poor prognosis measured as longer hospital length (r= -0.472, p <.001) and mortality (r= -0.424, p=.003). Interestingly we also found, that MCV was lower among of those patients who died (p=.0002). As of April 28, 2020, 10 patients (8 ICU and 2 non-ICU) had died (21% mortality) and while 100% of the non-ICU patients had been discharged, 33% of ICU patients still remained hospitalized (5 in ICU and 2 had been transferred to ward). CONCLUSION Critically ill patients with COVID-19 present lymphopenia, hypoalbuminemia as well high levels of inflammation. Lower levels of albumin were associated with poorer outcomes in COVID-19 patients. Albumin might be of importance because of its association with disease severity in patients infected with SARS-CoV-2.


title: Community prevalence of SARS-CoV-2 virus in England during May 2020: REACT study

text: Background England has experienced one of the highest rates of confirmed COVID-19 mortality in the world. SARS-CoV-2 virus has circulated in hospitals, care homes and the community since January 2020. Our current epidemiological knowledge is largely informed by clinical cases with far less understanding of community transmission. Methods The REal-time Assessment of Community Transmission (REACT) study is a nationally representative prevalence survey of SARS-CoV-2 virus swab-positivity in the community in England. We recruited participants regardless of symptom status. Results We found 159 positives from 120,610 swabs giving an average prevalence of 0.13% (95% CI: 0.11%,0.15%) from 1st May to 1st June 2020. We showed decreasing prevalence with a halving time of 8.6 (6.2, 13.6) days, implying an overall reproduction number R of 0.57 (0.45, 0.72). Adults aged 18 to 24 yrs had the highest swab-positivity rates, while those >64 yrs had the lowest. Of the 126 participants who tested positive with known symptom status in the week prior to their swab, 39 reported symptoms while 87 did not, giving an estimate that 69% (61%,76%) of people were symptom-free for the 7 days prior testing positive in our community sample. Symptoms strongly associated with swab-positivity were: nausea and/or vomiting, diarrhoea, blocked nose, loss of smell, loss of taste, headache, chills and severe fatigue. Recent contact with a known COVID-19 case was associated with odds of 24 (16, 38) for swab-positivity. Compared with non-key workers, odds of swab-positivity were 7.7 (2.4, 25) among care home (long-term care facilities) workers and 5.2 (2.9, 9.3) among health care workers. However, some of the excess risk associated with key worker status was explained by recent contact with COVID-19 cases. We found no strong evidence for geographical variability in positive swab results. Conclusion Our results provide a reliable baseline against which the impact of subsequent relaxation of lockdown can be assessed to inform future public health efforts to control transmission.


SPECIAL COVID-19 COVERAGE: The Mind of Medicine: Holding Together the Big and the Small


title: Management of Hemoglobin Disorders During the COVID-19 Pandemic

text: The coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has become a global public health concern after being first reported in China and has subsequently spread worldwide. It causes mild to severe respiratory illness with some flu-like symptoms. The causal virus behind this disease, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), conceivably attacks the receptors of the respiratory system of the human body but has no strict evidence of attacking the blood cells yet. However, patients with hemoglobin disorders (e.g., sickle cell anemia, thalassemia) are vulnerable to this global health situation due to their clinical complications. Such patients are generally more prone to viral and bacterial infections, which can worsen their physical condition. Some of these patients present immunocompromised conditions, e.g., splenectomized or post-transplant patients. Therefore, they should follow some preventive steps such as shielding as well as the general guidelines for the COVID-19 pandemic. Transfusion dependent patients require regular monitoring for iron overload, and iron chelation therapy may be stopped by the physician depending on the situation. This article reviews the management strategies and provides some crucial recommendations for people in the corner with hemoglobin disorders.


title: Measuring voluntary social distancing behavior during the COVID-19 pandemic

text: Staying home is an important part of the effort to contain COVID-19 and limit deaths. Every state in the United States has enacted policies to encourage distancing and staying home. An important question is how these policies interact with individuals voluntary responses to COVID-19 cases and deaths. We find evidence of a non-trivial voluntary response to local and nationally reported COVID-19 cases and deaths.


docid: gokevnzw

title: Mental health issues and psychological crisis interventions during the COVID-19 pandemic and earthquakes in Croatia/ Mentalno zdravlje i psihološke krizne intervencije tijekom COVID-19 pandemije i potresa u Hrvatskoj

text: The newly discovered coronavirus, now called SARS-CoV-2, was first detected in Wuhan, China as a cause of severe acute respiratory syndrome, disease called COVID-19. From the beginning of 2020 it rapidly spread, affecting the whole world, but with a major impact in Europe and North America. At the moment of writing, there are more than 2 million confirmed cases with more than 125.000 confirmed deaths related to COVID-19 globally. In Croatia, there are currently 1.741 confirmed cases with 34 deaths related to the virus. The COVID-19 rapid spread and magnitude of pandemic unleashed panic among people which warrants public health officials to also address the epidemic of fear. Research on the psychological reactions to previous epidemics and pandemics suggests that various psychological factors may play a role in coronaphobia. Nov-elty and uncertainty what the unknown brings is likely the cause of COVID-19 fear. With the sharp increase in number of affected persons by pandemic, both infected or suspected cases in isolation, fear and anxiety grew in general population, which warranted a significant increase in need for psychiatric support for both patients and medical staff. After initial stabilization of the situation and a prompt response to increased needs for mental support, during this time of pandemic, self-isolations and imposed social distancing, the strongest earthquake this city has experienced in the last 140 years hit Croatian capital Zagreb. During these trying times, maintaining good mental health of both medical personnel as well as the general population is crucial for both health and mental damage control. In Croatia, crisis interventions aimed for those most exposed to mental impact of pandemic and natural disasters is limited.


title: Modelling lockdown-induced 2nd COVID waves in France

text: As with the Spanish Flu a century ago, authorities have responded to the current COVID-19 pandemic with extraordinary public health measures. In particular, lockdown and related social distancing policies are motivated in some countries by the need to slow virus propagation down, so that the primary wave of patients suffering from severe forms of COVID infection do not exceed the capacity of intensive care units. But unlocking poses a critical issue because relaxing social distancing may, in principle, generate secondary waves. Ironically however, the dynamic repertoire of established epidemiological models that support this kind of reasoning is limited to single epidemic outbreaks. In turn, predictions regarding secondary waves are tautologically derived from imposing assumptions about changes in the so-called "effective reproduction number". In this work, we depart from this approach and extend the LIST (Location-Infection-Symptom-Testing) model of the COVID pandemic with realistic nonlinear feedback mechanisms that under certain conditions, cause lockdown-induced secondary outbreaks. The original LIST model captures adaptive social distancing, i.e. the transient reduction of the number of person-to-person contacts (and hence the rate of virus transmission), as a societal response to salient public health risks. Here, we consider the possibility that such pruning of socio-geographical networks may also temporarily isolate subsets of local populations from the virus. Crucially however, such unreachable people will become susceptible again when adaptive social distancing relaxes and the density of contacts within socio-geographical networks increases again. Taken together, adaptive social distancing and network unreachability thus close a nonlinear feedback loop that endows the LIST model with a mechanism that can generate autonomous (lockdown-induced) secondary waves. However, whether and how secondary waves arise depend upon the interaction with other nonlinear mechanisms that capture other forms of transmission heterogeneity. We apply the ensuing LIST model to numerical simulations and exhaustive analyses of regional French epidemiological data. In brief, we find evidence for this kind of nonlinear feedback mechanism in the empirical dynamics of the pandemic in France. However, rather than generating catastrophic secondary outbreaks (as is typically assumed), the model predicts that the impact of lockdown-induced variations in population susceptibility and transmission may eventually reduce to a steady-state endemic equilibrium with a low but stable infection rate.


title: Y disruption, autosomal hypomethylation and poor male lung cancer survival

text: Lung cancer is the most frequent cause of cancer death worldwide1. It is male predominant and for reasons that are unknown also associated with significantly worse outcomes in men2. Here we compared gene co-expression networks in affected and unaffected pulmonary tissue derived from 126 patients with Stage IA-IV lung cancer. We observed marked degradation of a sex-associated gene co-expression network in tumour tissue. The disturbance was linked to fractional loss of the Y chromosome and was detected in 28% of male tumours in the discovery dataset and 27% of male tumours in a 123 sample replication dataset. Depression of Y chromosome expression was accompanied by extensive autosomal DNA hypomethylation. The male specific H3K4 demethylase, KDM5D, was identified as an apex hub within this co-expression network. Male patients exhibiting relative tumour KDM5D deficiency had an increased risk of death in the discovery dataset (Hazard Ratio [HR] 3.80, 95% CI 1.40 - 10.3, P=0.009) and in an independent sample of 1,100 male lung tumours (HR 1.67, 95% CI 1.4-2.0, P=1.2x10-10). Our findings identify tumour-specific weakening of male-specific expression, in particular deficiency of KDM5D, as a common replicable prognostic marker and credible mechanism underlying sex disparity in cancer.


title: From Wuhan to COVID-19 Pandemic: An Up-to-Date Review of Its Pathogenesis, Potential Therapeutics, and Recent Advances.

text: The emergence of a novel human coronavirus (SARS-CoV-2) causing severe contagious respiratory tract infections presents a serious threat to public health worldwide. To date, there are no specific antiviral agents available for this disease, currently known as COVID-19. Therefore, genomic sequencing and therapeutic clinical trials are being conducted to develop effective antiviral agents. Several reports have investigated FDA-approved drugs as well as in silico virtual screening approaches such as molecular docking and modeling to find novel antiviral agents. Until now, antiparasitic drugs such as chloroquine have shown the most relevant results. Furthermore, there is an urgent need to understand the pathogenesis of this novel coronavirus, its transmission routes, surface survival and evolution in the environment. So far, the scientific community has indicated a possible transmission of COVID-19 via blood transfusion which is challenging in the case of asymptomatic individuals. Protocols for pathogen inactivation are also needed. In this paper, we reviewed recent findings about this life-threatening pandemic.


title: Connecting BCG Vaccination and COVID-19: Additional Data

text: The reasons for a wide variation in severity of coronavirus disease 2019 (COVID-19) across the affected countries of the world are not known. Two recent studies have suggested a link between the BCG vaccination policy and the morbidity and mortality due to COVID-19. In the present study we compared the impact of COVID-19 in terms of case fatality rates (CFR) between countries with high disease burden and those with BCG revaccination policies presuming that revaccination practices would have provided added protection to the population against severe COVID-19. We found a significant difference in the CFR between the two groups of countries. Our data further supports the view that universal BCG vaccination has a protective effect on the course of COVID-19 probably preventing progression to severe disease and death. Clinical trials of BCG vaccine are urgently needed to establish its beneficial role in COVID-19 as suggested by the epidemiological data, especially in countries without a universal BCG vaccination policy. Keywords: COVID-19, BCG vaccination, case fatality ratio, mortality, low resource countries


title: Projections and early-warning signals of a second wave of the COVID-19 epidemic in Illinois

text: We present two different scenarios for a second wave of the COVID-19 epidemic in Illinois and simulate them using our previously described age-of-infection model, calibrated to real-time hospital and deaths data. In the first scenario we assume that the parameters of the second wave in Illinois would be similar to those currently observed in other states such as Arizona, Florida, and Texas. We estimate doubling times of hospitalizations and test positivity in all states with relevant publicly available data and calculate the corresponding effective reproduction numbers for Illinois. These parameters are remarkably consistent in states with rapidly growing epidemics. We conjecture that the emergence of the second wave of the epidemic in these states can be attributed to superspreading events at large parties, crowded bars, and indoor dining. In our second, more optimistic scenario we assume changes in Illinois state policy would result in successful mitigation of superspreading events and thus would lower the effective reproduction number to the value observed in late June 2020. In this case our calculations show effective suppression of the second wave in Illinois. Our analysis also suggests that the logarithmic time derivatives of COVID-19 hospitalizations and case positivity can serve as a simple but strong early-warning signal of the onset of a second wave.


title: The importance of timing of a population level intervention on COVID-19 mortality

text: COVID-19 poses an immense and immediate threat to global public health. Population level interventions (PLIs) impact this threat, with estimable large effects on reducing mortality. Many countries worldwide have currently zero/low mortality and many have yet to implement such PLIs. The importance of timing of PLI implementation on mortality outcomes is poorly understood. We extracted cumulative country-specific COVID-19 mortality for France, Germany, Italy, Spain and the UK to examine country-specific mortality trends and found that all five countries experienced COVID-19 mortality epidemics initially of exponential nature. We estimated the magnitude of effect on mortality of the nationwide PLI implemented on day 18 of Italy's mortality epidemic and assessed the importance of timing of PLI implementation by computing the effect of implementation of a PLI of this magnitude at various times on subsequent mortality. The nationwide PLI in Italy saved an estimated 6,170 lives by day 30 of the Italian epidemic. Implementing a PLI with this effect magnitude in a country of 60 million people on the day of the first death, and on days 7, 10, 14 and 17 thereafter, compared to implementation on day 18, resulted in substantially greater numbers of lives saved. Implementation on day 1 resulted in an additional 3,477 lives saved, 6,955 intensive care unit admissions and 52,162 hospital admissions prevented, beyond that achieved by implementation on day 18. PLI implementation earlier than day 18 substantially enhances benefit. Intervention on the day of the first mortality event in a country achieves the greatest benefit.


title: Quantification of SARS-CoV-2 and cross-assembly phage (crAssphage) from wastewater to monitor coronavirus transmission within communities

text: Wastewater surveillance of SARS-CoV-2 has become an attractive tool for combating the spread of COVID-19 by assessing the presence or levels of the virus shed in a population. However, the methods to quantify viral RNA and to link those quantities to the level of infection within the community vary. In this study, we sought to identify and optimize scalable methods for recovery of viral nucleic acids from wastewater and attempted to use a constitutive member of the gut virome, human-specific crAssphage, to help account for unknown levels of SARS-CoV-2 decay and dilution in the wastewater infrastructure. Results suggest that ultracentrifugation of a small volume of wastewater through a 50% sucrose cushion followed by total nucleic acid extraction yielded quantifiable virus in an area with a modest number of COVID-19 cases. Further, the ratio of log10(SARS-CoV-2):log10(crAssphage) appears to be associated with the cumulative incidence of COVID-19 in the Syracuse, NY area. In areas where ultracentrifuges are available, these methods may be used to link SARS-CoV-2 quantities in wastewater to levels of transmission within communities with sewer service.


title: Paediatric Dentistry and the coronavirus (COVID-19) response in the North East of England and North Cumbria

text: Introduction: Coronavirus (COVID-19) has dramatically changed the landscape of dentistry including Paediatric Dentistry. This paper explores paediatric patient data within a wider service evaluation completed within an Urgent Dental Care Centre in the North East of England and North Cumbria over a 6-week period. Aim: To assess demand for the service, patient demographics and inform paediatric urgent dental care pathways. Main outcome methods: Data collected included key characteristics of paediatric patients accessing Paediatric Dental Services from 23rd March to 3rd May 2020. Descriptive statistics were used for analysis. Results: There were 369 consultations (207 telephone, 124 face-to-face and 38 Out of Hours consultations). The mean age of children accessing the service was 7 years old. 7% of those attending face-to-face visits were reattenders. The most common diagnoses were irreversible pulpitis and dental trauma. 49% of face-to-face consultations resulted in extractions, 28% with General Anaesthetic, and 21% with Local Anaesthetic. Conclusion: Management of dental emergencies provided by the Urgent Dental Care Centre for paediatric patients has largely been effective and confirmed the efficacy of patient pathways established.


title: No evidence of coronaviruses or other potentially zoonotic viruses in Sunda pangolins (Manis javanica) entering the wildlife trade via Malaysia

text: The legal and illegal trade in wildlife for food, medicine and other products is a globally significant threat to biodiversity that is also responsible for the emergence of pathogens that threaten human and livestock health and our global economy. Trade in wildlife likely played a role in the origin of COVID-19, and viruses closely related to SARS-CoV-2 have been identified in bats and pangolins, both traded widely. To investigate the possible role of pangolins as a source of potential zoonoses, we collected throat and rectal swabs from 334 Sunda pangolins (Manis javanica) confiscated in Peninsular Malaysia and Sabah between August 2009 and March 2019. Total nucleic acid was extracted for viral molecular screening using conventional PCR protocols used to routinely identify known and novel viruses in extensive prior sampling (>50,000 mammals). No sample yielded a positive PCR result for any of the targeted viral families – Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae. In light of recent reports of coronaviruses including a SARS-CoV-2 related virus in Sunda pangolins in China, the lack of any coronavirus detection in our ‘upstream’ market chain samples suggests that these detections in ‘downstream’ animals more plausibly reflect exposure to infected humans, wildlife or other animals within the wildlife trade network. While confirmatory serologic studies are needed, it is likely that Sunda pangolins are incidental hosts of coronaviruses. Our findings further support the importance of ending the trade in wildlife globally.


title: Characterization of Microbial Co-infections in the Respiratory Tract of hospitalized COVID-19 patients

text: Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, microbial composition of the respiratory tract and other infected tissues, as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Method Between January 27 and February 26, 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients (requiring ICU admission and mechanical ventilation), in the Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. Co-infection rates, the prevalence and abundance of microbial communities in these COVID-19 patients were determined. Findings Notably, respiratory microbial co-infections were exclusively found in 84.6% of severely ill patients (11/13), among which viral and bacterial co-infections were detected by sequencing in 30.8% (4/13) and 69.2% (9/13) of the patients, respectively. In addition, for 23.1% (3/13) of the patients, bacterial co-infections with Burkholderia cepacia complex (BCC) and Staphylococcus epidermidis were also confirmed by bacterial culture. Further, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes in one severely ill patient was demonstrated, which might be the primary cause of his disease deterioration and death one month after ICU admission. Interpretation Our findings identified distinct patterns of co-infections with SARS-CoV-2 and various respiratory pathogenic microbes in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking of BCC-associated nosocomial infections are recommended to improve the pre-emptive treatment regimen and reduce fatal outcomes of hospitalized patients infected with SARS-CoV-2. Funding National Science and Technology Major Project of China, National Major Project for Control and Prevention of Infectious Disease in China, the emergency grants for prevention and control of SARS-CoV-2 of Ministry of Science and Technology and Guangdong province, Guangdong Provincial Key Laboratory of Genome Read and Write, Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, and Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics.


title: Brazil Health Care System preparation against COVID-19

text: Background: The coronavirus disease outbreak from 2019 (COVID-19) is associated with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly contagious virus that claimed thousands of lives around the world and disrupted the health system in many countries. The assessment of emergency capacity in every country is a necessary part of the COVID-19 response efforts. Thus, it is extremely recommended to evaluate the health care system to prepare the country to tackle COVID-19 challenges. Methods and Findings: A retrospective and ecological study was performed with data retrieved from the public national healthcare database (DATASUS). Numbers of intensive care unit and infirmary beds, general or intensivists physicians, nurses, nursing technicians, and ventilators from each Regional Health Unity were extracted, and the beds per health professionals and ventilators per population rates were assessed. The accessibility to health services was also performed using a spatial overlay approach to verify regions that lack assistance. It was found that Brazil lacks equity, integrity, and may struggle to assist with high complexity for the COVID-19 patients in many regions of the country. Conclusions: Brazilian health system is insufficient to tackle the COVID-19 in some regions of the country where the coronavirus may be responsible for high rates of morbidity and mortality.


title: Pneumonitis and Multi-Organ System Disease in Common Marmosets (Callithrix jacchus) Infected with the Severe Acute Respiratory Syndrome-Associated Coronavirus

text: Severe acute respiratory syndrome (SARS) is a significant emerging infectious disease. Humans infected with the etiological agent, SARS-associated coronavirus (SARS-CoV), primarily present with pneumonitis but may also develop hepatic, gastrointestinal, and renal pathology. We inoculated common marmosets (Callithrix jacchus) with the objective of developing a small nonhuman primate model of SARS. Two groups of C. jacchus were inoculated intratracheally with cell culture supernatant containing SARS-CoV. In a time course pathogenesis study, animals were evaluated at 2, 4, and 7 days after infection for morphological changes and evidence of viral replication. All animals developed a multifocal mononuclear cell interstitial pneumonitis, accompanied by multinucleated syncytial cells, edema, and bronchiolitis in most animals. Viral antigen localized primarily to infected alveolar macrophages and type-1 pneumocytes by immunohistochemistry. Viral RNA was detected in all animals from pulmonary tissue extracts obtained at necropsy. Viral RNA was also detected in tracheobronchial lymph node and myocardium, together with inflammatory changes, in some animals. Hepatic inflammation was observed in most animals, predominantly as a multifocal lymphocytic hepatitis accompanied by necrosis of individual hepatocytes. These findings identify the common marmoset as a promising nonhuman primate to study SARS-CoV pathogenesis.


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