title: Quantitative measurement of activity of JAK-STAT signaling pathways in blood samples and immune cells to predict innate and adaptive cellular immune response to viral infection and accelerate vaccine development

text: The host immune response determines the clinical course of a viral infection, for example in case of COVID-19 infection. The effectiveness of vaccination also depends on the induced immune response. Currently there is no method to measure the cellular immune response in blood samples. The functional activity of cells of innate and adaptive immune system is determined by coordinated activity of signaling pathways, especially the JAK-STAT pathways. Using a previously described approach we developed mRNA-based tests to measure activity of these signaling pathways, and show that they can be used to measure in a quantitative manner the cellular innate and adaptive immune response to a viral infection or vaccine in whole blood, PBMC, and specific immune cell type samples. Pathway activity level and range in healthy individuals was established, enabling interpretation of a pathway activity score on a patient sample without the need for a reference sample. Evidence is presented that the pathway activity analysis may also be useful for in vitro vaccine development and assessment of vaccine immunogenicity. Other envisioned applications lie in development of immunomodulatory drugs and drug response prediction and monitoring. Tests are expected to be of value in the COVID-19 crisis. In addition to the described Affymetrix microarray-based pathway tests for measuring host immune response, qPCR-based versions are in development; the latter can in principle be performed within three hours in routine hospital labs.


What Does Food Retail Research Tell Us About the Implications of Coronavirus (COVID-19) for Grocery Purchasing Habits?


title: Novel coronavirus infection (Covid-19): Guiding principles for obstetric care under pandemic conditions

text: The literature review analyzes the latest data on the principles of diagnosis and treatment of the novel coronavirus infection, management of pregnancy, childbirth, and the postpartum period during a pandemic, as well as the benefits and risks of breastfeeding with confirmed COVID-19 infection on the basis of the clinical guidelines of the Russian and international professional associations and the results of several basic studies and clinical trials In late 2019, the global medical community faced the new infection transmitted through airborne droplets Being initially identified as one of the acute respiratory viral infections, the novel coronavirus infection was included in the list of diseases that pose a risk to others on January 31, 2020 A little later, on March 11, 2020, the World Health Organization (WHO) stated that the infection reached the level of a pandemic The high-risk group includes the elderly, patients with severe concomitant diseases and immunodeficiency, as well as pregnant women with altered immune responsiveness At the same time, the pregnancy status restricts the use of some methods for instrumental diagnosis and anti-coronavirus therapy An obstetrician-gynecologist is responsible not only for the health of an infected woman, but also for that of her unborn child, therefore the specialist must know all the transmission routes of infection, follow epidemiological precautions, be able to identify early symptoms of the disease, perform thorough clinical assessment and provide timely adequate anti-coronavirus therapy The management of women during pregnancy, childbirth, and postpartum should be carried out according to the potential risk of this infection The paper provides useful algorithms for actions during the initial hospital admission of a pregnant woman, her further examination and treatment


title: Bayesian Adaptive Clinical Trials for Anti-Infective Therapeutics during Epidemic Outbreaks

text: In the midst of epidemics such as COVID-19, therapeutic candidates are unlikely to be able to complete the usual multi-year clinical trial and regulatory approval process within the course of an outbreak. We apply a Bayesian adaptive patient-centered model---which minimizes the expected harm of false positives and false negatives---to optimize the clinical trial development path during such outbreaks. When the epidemic is more infectious and fatal, the Bayesian-optimal sample size in the clinical trial is lower and the optimal statistical significance level is higher. For COVID-19 (assuming a static R0=2 and initial infection percentage of 0.1%), the optimal significance level is 7.1% for a clinical trial of a non-vaccine anti-infective therapeutic clinical trial and 13.6% for that of a vaccine. For a dynamic R0 ranging from 2 to 4, the corresponding values are 14.4% and 26.4%, respectively. Our results illustrate the importance of adapting the clinical trial design and the regulatory approval process to the specific parameters and stage of the epidemic.


title: Reviews of Science for Science Librarians: Vitamins and Trace Elements that May Be Preventive or Ameliorating in This Age of Contagion

text: Prompted by COVID-19, many laypersons now seek information on nutritional support to ward off or help shorten the effects of serious infectious diseases, and are attracted to practices and substances that lack a serious scientific basis. This paper scanned peer-reviewed medical literature to prove a concept: That diets or supplements rich in some vitamins or minerals may indeed be important in managing threats to health caused by a variety of infectious diseases in the past and compares these findings to the current recommendations of the Academy of Nutrition and Dietetics and to research by Zhang and Liu, two China-based pioneers in countering COVID-19. Vitamins A, D, and zinc, are common to both groups and are well supported in the literature. Vitamin C is also a common denominator but has a mixed record of efficacy in dealing with prior infectious outbreaks. Iron has support and do some other vitamins and trace elements. Health science librarians should emphasize that while experts can disagree on particular micronutrients they tend to agree that decisions on protective or curative supplements or diets or should have some basis in fact.


title: A demographic scaling model for estimating the total number of COVID-19 infections

text: Background: The total number of COVID-19 infections is critical information for decision makers when assessing the progress of the pandemic, its implications, and policy options. Despite efforts to carefully monitor the COVID-19 pandemic, the reported number of confirmed cases is likely to underestimate the actual number of infections. We aim to estimate the total number of COVID-19 infections in a straightforward manner using a demographic scaling approach based on life tables. Methods: We use data on total number of COVID-19 attributable deaths, population counts, and life tables as well as information on infection fatality rates as reported in Verity et al. (2020) for Hubei, China. We develop a scaling approach based on life tables and remaining life expectancy to map infection fatality rates between two countries to account for differences in their age structure, health status, and the health care system. The scaled infection fatality rates can be used in combination with COVID-19 attributable deaths to calculate estimates of the total number of infected. We also introduce easy to apply formulas to quantify the bias that would be required in death counts and infection fatality rates in order to reproduce a certain estimate of infections. Findings: Across the 10 countries with most COVID-19 deaths as of April 17, 2020, our estimates suggest that the total number of infected is approximately 4 times the number of confirmed cases. The uncertainty, however, is high, as the lower bound of the 95% prediction interval suggests on average twice as many infections than confirmed cases, and the upper bound 10 times as many. Country-specific variation is high. For Italy, our estimates suggest that the total number of infected is approximately 1 million, or almost 6 times the number of confirmed cases. For the U.S., our estimate of 1.4 million is close to being twice as large as the number of confirmed cases, and the upper bound of 3 million is more than 4 times the number of confirmed cases. For Germany, where testing has been comparatively extensive, we estimate that the total number of infected is only 1.2 times (upper bound: 3 times) than the number of confirmed cases. Comparing our results with findings from local seroprevalence studies and applying our bias formulas shows that some of their infection estimates would only be possible if just a small fraction of COVID-19 related deaths were recorded, indicating that these seroprevalence estimates might not be representative for the total population. Interpretation: As many countries lack population based seroprevalence studies, straightforward demographic adjustment can be used to deliver useful estimates of the total number of infected cases. Our results imply that the total number COVID-19 cases may be approximately 4 times (95%: 2 to 10 times) that of the confirmed cases. Although these estimates are uncertain and vary across countries, they indicate that the COVID-19 pandemic is much more broadly spread than what confirmed cases would suggest, and the number of asymptomatic cases or cases with mild symptoms may be high. In cases in which estimates from local seroprevalence studies or from simulation models exist, our approach can provide a simple benchmark to assess the quality of those estimates.


title: Projection of COVID-19 Cases and Deaths in the US as Individual States Re-open May 4,2020

text: In March and April 2020, control measures enforcing social distancing and restricting individual movement and contact were adopted across the United States in an effort to slow the spread and growth of COVID-19. However, a number of states have now begun to ease these restrictions. Here, we evaluate the effects of loosening stay-at-home orders on COVID-19 incidence and related outcomes. We use a metapopulation model applied at county resolution to simulate the spread and growth of COVID-19 incidence in the United States. We calibrate the model against county-level daily case and death data collected from February 21, 2020 to May 2, 2020, and project the outbreak in 3,142 US counties for 6 weeks into the future. Projections for daily reported cases, daily new infections (both reported and unreported), new and cumulative hospital bed demand, ICU bed and ventilator demand, as well as daily mortality, are generated. We observe a rebound in COVID-19 incidence and deaths beginning in late May, approximately 2 to 4 weeks after states begin to reopen. Importantly, the lag between infection acquisition and case confirmation, coupled with insufficient broader testing and contact tracing, will mask any rebound and exponential growth of the COVID-19 until it is well underway.


title: Data-driven estimation of change points reveal correlation between face mask use and accelerated curtailing of the COVID-19 epidemic in Italy

text: Italy was the first Western country to be seriously affected by COVID-19, and the first to implement drastic measures, which have successfully curtailed the epidemic. To understand which contain measures effected disease dynamics, we estimate change points in COVID-19 dynamics by fitting a compartmental model to official Italian data. Our results indicate that lockdowns managed to cause the epidemic to peak in late March 2020. Surprisingly, we found a change point during the decay from the peak, which does not correspond to obvious drastic legal interventions, but may be explained by widespread promotion and mandatory use of face masks. We confirm these interpretations at regional levels, and find that the gradual reopening of society since early May has caused no change in disease dynamics. We speculate that widespread use of face masks and other protective means has contributed substantially to keeping the number of new Italian COVID-19 cases under control in spite of society turning towards a new normality.


title: Delirium is a presenting symptom of COVID-19 in frail, older adults: a cohort study of 322 hospitalised and 535 community-based older adults

text: Background: Frailty, increased vulnerability to physiological stressors, is associated with adverse outcomes. COVID-19 exhibits a more severe disease course in older, co-morbid adults. Awareness of atypical presentations is critical to facilitate early identification. Objective: To assess how frailty affects presenting COVID-19 symptoms in older adults. Design: Observational cohort study of hospitalised older patients and self-report data for community-based older adults. Setting: Admissions to St Thomas' Hospital, London with laboratory-confirmed COVID-19. Community-based data for 535 older adults using the COVID Symptom Study mobile application. Subjects: Hospital cohort: patients aged 65 and over (n=322); unscheduled hospital admission between March 1st, 2020 - May 5th, 2020; COVID-19 confirmed by RT-PCR of nasopharyngeal swab. Community-based cohort: participants aged 65 and over enrolled in the COVID Symptom Study (n=535); reported test-positive for COVID-19 from March 24th (application launch)- May 8th, 2020. Methods: Multivariate logistic regression analysis performed on age-matched samples from hospital and community-based cohorts to ascertain association of frailty with symptoms of confirmed COVID-19. Results: Hospital cohort: significantly higher prevalence of delirium in the frail sample, with no difference in fever or cough. Community-based cohort: significantly higher prevalence of probable delirium in frailer, older adults, and fatigue and shortness of breath. Conclusions: This is the first study demonstrating higher prevalence of delirium as a COVID-19 symptom in older adults with frailty compared to other older adults. This emphasises need for systematic frailty assessment and screening for delirium in acutely ill older patients in hospital and community settings. Clinicians should suspect COVID-19 in frail adults with delirium.


title: Prevalence and experience of fatigue in survivors of critical illness: A mixed-methods systematic review

text: Objective To investigate the prevalence, experience and management of fatigue in adult survivors of critical illness. Data sources An electronic search was performed on seven databases: CINAHL, Medline, EMBASE, PsycINFO, Emcare, British Nursing Index, and Web of Science. Study selection and data extraction Seventy-six peer-reviewed, English language studies that investigated fatigue or vitality in adult patients admitted to an Intensive Care Unit (ICU) and followed up for any period were included. Extracted data were split into three datasets for analysis: data from vitality domain of SF-36 (dataset A), other quantitative data (dataset B), and qualitative data (dataset C). Methodological quality was assessed using the critical appraisal skills programme (CASP) tools. Data synthesis We adopted a segregated approach to mixed-methods synthesis. We merged all datasets, attributing all results to one of four qualitative themes. These were prevalence and severity, contributing factors, impacts on quality of life, assessment and management. Results The prevalence of fatigue ranged from 13.8 to 80.9 %. Fatigue severity reached its nadir at approximately one month post ICU discharge, improved over time but seldom reached reference population scores. Various biological, disease related and psychological factors associated with fatigue were identified including age, poor pre-morbid status and sleep disturbance. No critical illness specific tool to assess fatigue in ICU survivors was identified. A paucity of evidence based interventions for management of fatigue in ICU survivors were identified despite fatigue negatively impacting on survivors quality of life. Conclusions This mixed method review shows that fatigue is highly prevalent in ICU survivors, negatively impacting their recovery. To date, no ICU specific fatigue assessment tool or targeted intervention has been designed to manage this symptom. Our review has identified factors, which may increase or mitigate against fatigue, along with potential management strategies, which should be used to inform future research and practice.


title: Transcriptomic Similarities and Differences in Host Response between SARS-CoV-2 and Other Viral Infections

text: COVID-19 is a pandemic that shares certain clinical characteristics with other acute viral infections. Here, we studied the whole-blood transcriptomic host response to SARS-CoV-2 and compared it with other viral infections to understand similarities and differences in host response. Using RNAseq we profiled peripheral blood from 24 healthy controls and 62 prospectively enrolled patients with community-acquired lower respiratory tract infection by SARS-Cov-2 within the first 24 hours of hospital admission. We also compiled and curated 23 independent studies that profiled 1,855 blood samples from patients with one of six viruses (influenza, RSV, HRV, ebola, Dengue, and SARS-CoV-1). We show gene expression changes in peripheral blood in patients with COVID-19 versus healthy controls are highly correlated with changes in response to other viral infections (r=0.74, p<0.001). However, two genes, ACO1 and ATL3, show significantly opposite changes between conditions. Pathway analysis in patients with COVID-19 or other viral infections versus healthy controls identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection, and cytokine production for over-expressed genes. Conversely, for under-expressed genes, pathways indicated repression of lymphocyte differentiation and T cell activation. When comparing transcriptome profiles of patients with COVID-19 directly with those with other viral infections, we found 114 and 302 genes were over- or under-expressed, respectively, during COVID-19. Pathways analysis did not identify any significant pathways in these genes, suggesting novel responses to further study. Statistical deconvolution using immunoStates found that M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells, and total B cells showed change consistently in the same direction across all viral infections including COVID-19. Those that increased in COVID-19 but decreased in non-COVID-19 viral infections were CD56bright NK cells, M2 macrophages, and total NK cells. The concordant and discordant responses mapped out here provide a window to explore the pathophysiology of COVID-19 versus other viral infections and show clear differences in signaling pathways and cellularity as part of the host response to SARS-CoV-2.


title: Doubling down on austerity: Framing and coronavirus response

text: Even amid a global pandemic, the ideologies, thought processes, and motivations of public actors can be explained through theory, particularly framing. We argue that the words and symbols used or not used are vitally important to shaping how the public understands, responds to, and navigates our new normal. Moreover, this framing shapes our collective understanding of who or what is valued. We posit that austerity politics at all levels of government has not only helped to create a patchwork system of crisis response, but also explains the variation in framing of the pandemic response as tradeoffs among competing values (e.g., equity versus economy; us versus other; health versus business). The success or failure of these frames can lead to an environment in which administrative evil flourishes.


COVID-19: An update on vaccine development


title: W.A.R.A. (wiring affect with reattach) provided by remote training: First-aid psychological intervention?

text: Wiring Affect with ReAttach (W.A.R.A) is an ultrafast affect-regulation technique that is commonly provided by ReAttach therapists in the proximity of the patient. The benefits of W.A.R.A. are that the intervention is light, brief, and simple in helping to process negative affect. Facing the COVID-19 pandemic and the devastating consequences for mental health, we propose W.A.R.A, amongst other self-regulation strategies, as a first-aid psychological intervention. We immediately started to give access to free online W.A.R.A. training, so professionals, worldwide, can offer W.A.R.A. by remote training and help patients suffering from elevated stress to regulate their negative affect.


The Perfect Storm: Coronavirus (Covid-19) Pandemic Meets Overfat Pandemic


title: In silico approach for designing of a multi-epitope based vaccine against novel Coronavirus (SARS-COV-2)

text: A novel Coronavirus (SARS-COV-2) has now become a global pandemic. Considering the severity of infection and the associated mortalities, there is an urgent need to develop an effective preventive measure against this virus. In this study, we have designed a novel vaccine construct using computational strategies. Spike (S) glycoprotein is the major antigenic component that trigger the host immune responses. Detailed investigation of S protein with various immunoinformatics tools enabled us to identify 5 MHC I and 5 MHC II B-cell derived T-cell epitopes with VaxiJen score > 1 and IC50 value < 100nM. These epitopes were joined with a suitable adjuvant and appropriate linkers to form a multi-epitope based vaccine construct. Further, in silico testing of the vaccine construct for its antigenicity, allergenicity, solubility, and other physicochemical properties showed it to be safe and immunogenic. Suitable tertiary structure of the vaccine protein was generated using 3Dpro of SCRATCH suite, refined with GalaxyRefine, and validated with ProSA, PROCHECK, and ERRAT server. Finally, molecular docking studies were performed to ensure a favorable binding affinity between the vaccine construct and TLR3 receptor. The designed multi-epitope vaccine showed potential to elicit specific immune responses against the SARS-COV-2. However, further wet lab validation is necessary to confirm the actual effectiveness, safety and immunogenic potency of the vaccine construct against derived in this study.


title: Modelling of Covid-19 cases in India using Regression and Time Series models

text: In this article, we analyze the growth pattern of Covid-19 pandemic in India from March 4th to May 15th using regression analysis (exponential and polynomial), auto-regressive integrated moving averages (ARIMA) model as well as Exponential Smoothing and Holt-Winters models. We found that the growth of Covid-19 cases follows a power regime of (t2,t..)after the exponential growth. We have found the optimal change points from where the covid-19 cases shifts their course of growth from exponential to quadratic and then quadratic to linear. We have also found the best fitted regression models using the various criteria like- significant p-values, coefficients of determination R2 values and ANOVA etc. Further, we have searched the best fitting ARIMA model for the data using the AIC (Akaike Information Criterion) and CAIC (Consistent Akaike Information Criterion) and forecasted the number of cases for future days. We have used the usual exponential smoothing and Holt-Winters models for the data. We further found that the ARIMA(2,2,0) model is the best-fitting model for Covid-19 cases in India.


title: Role of Chloroquine and Hydroxychloroquine in the Treatment of COVID-19 Infection- A Systematic Literature Review

text: Background: Coronavirus pandemic is currently a global public health emergency. At present, no pharmacological treatment is known to treat this condition, and there is a need to review the available treatments. Objective: While there have been studies to describe the role of chloroquine and hydroxychloroquine in various viral conditions, there is limited information about the use of them in COVID-19. This systematic review aims to summarize the available evidence regarding the role of chloroquine in treating coronavirus infection. Methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used for this review. A literature search was performed using PUBMED & Google Scholar to find articles about the role of CQ in COVID-19 patients. Results: We included 19 publications (Five published articles, three letters/correspondence, one commentary, five pre-proofs of accepted articles, one abstract of yet to be published article, and four were pre-prints (not yet peer-reviewed) articles) in this systematic review. All the articles mentioned about the role of chloroquine and /or hydroxychloroquine in limiting the infection with SARS-CoV-2 (the virus causing COVID-19). Conclusions: There is theoretical, experimental, preclinical and clinical evidence of the effectiveness of chloroquine in patients affected with COVID-19. There is adequate evidence of drug safety from the long-time clinical use of chloroquine and hydroxychloroquine in other indications. More data from ongoing and future trials will add more insight into the role of chloroquine and hydroxychloroquine in COVID-19 infection.


title: A demographic adjustment to improve measurement of COVID-19 severity at the developing stage of the pandemic

text: The need for accurate statistics has never been felt so deeply as the novel COVID-19 pathogen spreads around the world and quantifying its severity is a primary clinical and public health issue. In Italy, the magnitude and increasing trend of the case-fatality risk (CFR) is fueling the already high levels of public alarm. In this paper, we highlight that the widely used crude CFR is an inaccurate measure of the disease severity since the pandemic is still unfolding. With the goal to improve its comparability over time and across countries at this stage, we then propose a demographic adjustment of the CFR that addresses the bias arising from differential case ascertainment by age. When applied to publicly released data for Italy, we show that until March 16 our adjusted CFR was similar to that of Wuhan, the most affected Chinese region, where COVID-19 has now been contained. This indicates that our adjusted CFR improves its comparability over time, making an important tool to chart the course of the COVID-19 pandemic across countries. Since March 16, the Italian COVID-19 outbreak has entered a new phase, with the northern and southern regions following different trajectories. As a result, our adjusted CFR has been increasing between March 16 and March 20. Data at the subnational level are needed to correctly assess the disease severity in the country at this stage.


title: Blacks/African Americans are 5 Times More Likely to Develop COVID-19: Spatial Modeling of New York City ZIP Code-level Testing Results

text: Introduction. The population and spatial characteristics of COVID-19 infections are poorly understood, but there is increasing evidence that in addition to individual clinical factors, demographic, socioeconomic and racial characteristics play an important role. Methods. We analyzed positive COVID-19 testing results counts within New York City ZIP Code Tabulation Areas (ZCTA) with Bayesian hierarchical Poisson spatial models using integrated nested Laplace approximations. Results. Spatial clustering accounted for approximately 32% of the variation in the data, with hot spots in all five boroughs. Spatial risk did not correspond precisely to population-based rates of positive tests. The strongest univariate association with positive testing rates was the proportion of residents in a ZIP Code Tabulation Area with Chronic Obstructive Pulmonary Disease (COPD). For every one unit increase in a scaled standardized measure of COPD in a community, there was an approximate 8-fold increase in the risk of a positive COVID-19 test in a ZCTA (Incidence Density Ratio = 8.2, 95% Credible Interval 3.7, 18.3). The next strongest association was with the proportion of Black and African American residents, for which there was a nearly five-fold increase in the risk of a positive COVID-19 test. (IDR = 4.8, 95% Cr I 2.4, 9.7). Increases in the proportion of residents older than 65, housing density and the proportion of residents with heart disease were each associated with an approximate doubling of risk. In a multivariable model including estimates for age, COPD, heart disease, housing density and Black/African American race, the only variables that remained associated with positive COVID-19 testing with a probability greater than chance were the proportion of Black/African American residents and proportion of older persons. Conclusions. The population and spatial patterns of COVID-19 infections differ by race, age, physical environment and health status. Areas with large proportions of Black/African American residents are at markedly higher risk that is not fully explained by characteristics of the environment and pre-existing conditions in the population.


title: Neuropsychiatric adverse events of chloroquine: A real-world pharmacovigilance study using the FAERS database

text: Objectives: In early April 2020, the antimalarial drug, chloroquine, has been approved as an emergency treatment for the coronavirus disease 2019 (COVID-19) in the United States and in Europe. Although infrequent, neuropsychiatric symptoms have been reported in patients who received chloroquine for the treatment of malaria or autoimmune diseases. In this study, we investigated these adverse events (AEs) using a large self-reporting database. Materials and Methods: We conducted a disproportionality analysis for the detection of neuropsychiatric AE signals associated with the use of chloroquine (or hydroxychloroquine), reported to FAERS database between the fourth quarter of 2012 and the fourth quarter of 2019. Adjusted reporting odds ratio (ROR) for the development of each of the neuropsychiatric AEs following the use of chloroquine was calculated using a multilevel model. Results: We included 2,389,474 AE cases, among which 520 cases developed neuropsychiatric AE following the use of chloroquine. Exposure to chloroquine was associated with a statistically significant high reporting of amnesia, delirium, hallucinations, depression, and loss of consciousness, (lower 95% confidence interval of the adjusted ROR > 1), although the degree of increase in their ROR was limited. There was no statistically significant high reporting of any other neuropsychiatric AE, including suicide, psychosis, confusion, and agitation. Conclusion: Current pharmacovigilance study results did not suggest any potential link between the use of chloroquine and an increased risk of suicide, psychosis, confusion, and agitation, which would be informative during the emergency use of chloroquine for the treatment of COVID-19.


title: Garment worker rights and the fashion industry’s response to COVID-19

text: In this commentary, we examine the fashion industry’s early responses to COVID-19. Looking across fashion’s global production networks, we argue the fashion industry’s response has been rapid, yet highly inequitable, reflecting—and further entrenching—existing inequalities in the industry.


Working Across Boundaries


title: Discrete SIRIR modelling using empirical infection data shows that SARS-CoV-2 infection provides short-term immunity

text: The novel coronavirus SARS-CoV-2, which causes the COVID-19 disease, is now a global pandemic. Since December 2019, it has infected millions of people, caused the deaths of hundreds of thousands, and resulted in incalculable social and economic damage. Understanding the infectivity and transmission dynamics of the virus is essential for understanding how best to reduce mortality whilst ensuring minimal social restrictions to the lives of the general population. Anecdotal evidence is available, but detailed studies have not yet revealed whether infection with the virus results in immunity. In this work, we have extended the generic SIR framework to analyse empirical infection and fatality data from different regions to investigate the reinfection frequency of the disease. Our model predicts that cases of reinfection should have been observed by now if primary SARS-CoV-2 infection did not protect from subsequent exposure in the short term, however, no such cases have been documented. This work, therefore, provides a useful insight for serological testing strategies, lockdown easing and vaccine design.


title: Knowledge of novel coronavirus (SARS-COV-2) among a Georgian population

text: Introduction Georgia confirmed its first case of SARS-COV-2 infection on February 26, 2020 and by March 31, a total of 110 cases have been reported. Limited understanding about epidemics can lead to panic and disrupt public health efforts to contain transmission. It is important to understand perceptions of the population regarding the disease. This study reports results of a survey designed to understand attitudes and knowledge regarding SARS-COV-2 virus among Georgian population, including health care workers (HCWs). Materials and methods The online survey was conducted using a Facebook advertisement. The target was the whole country and the language used was Georgian. We collected information on demographic data, knowledge of the disease, including perceived differences between coronavirus and influenza. We also included questions to capture the populations perceptions about government preparedness to combat the new coronavirus. Results The survey was open for three days (March 2-4, 2020). 5228 participants completed the survey. Of these, 40.3% were 25-45 years old, 58.2% were female, 20.7% had university degree and 10.3% were HCWs. For 25.8% of respondents, COVID-19 and influenza are the same diseases; 10.9% did not know if they are different. The majority correctly identified the transmission route and symptoms (96.9% and 98.0%, respectively). 19.1% think that Georgia is ready for COVID 19 epidemic, while according to 55% the county is not ready, but HCWs are trying hard to respond properly. For 18% response is inadequate. There was no difference in knowledge between HCWs, non-HCWs and unemployed. 20% of HCWs as well as other study subjects believe that SARS-COV-2 vaccine and medications do exist but are simply not available in Georgia. Conclusion Given that information regarding coronavirus is changing very rapidly, the need to reach people with time-sensitive educational messages as well as prevention strategies is vital.


title: Mortality and use of angiotensin converting enzyme inhibitors in Covid 19 disease - a systematic review.

text: Background. Interest exits concerning the use of angiotensin converting enzyme inhibitors (ACEi) in patients with Covid-19 disease. Objectives. To perform a systematic review on mortality associated to the use of ACEi in patients with Covid 19 disease. Methods. Search in Medline (PubMed) and in ISI Web of Knowledge; use of other sources. Results. A total of 19 articles were evaluated. Four studies were selected and used to produce the meta-analyses. These four studies involved a total number of 1.423 patients treated with ACEi and 11.868 not treated with ACEi. Significant heterogeneity was seen concerning mortality associated to the use of ACEi in the context of Covid-19 disease. One report showed significantly decreased mortality associated to ACEi use, but this finding was not confirmed by the three other studies. No significant difference in mortality was seen in the meta-analysis (ACEi users versus non-users; random effects; odds ratio, 0.93; 95% confidence interval [CI], 0.44 to 1.94; P=0.84). When compared to mortality in patients treated with angiotensin receptor blockers, mortality of patients treated with ACEi was not significantly different, although a trend was noted to exist (odds ratio, 0.74; 95% confidence interval [CI], 0.41 to 1.34; P=0.32). The population studied in the report showing decreased mortality associated to ACEi use had a mean age under 50 years, whereas two other reports had a mean or median patient age over 60 years. Conclusions. The data now presented argue in favor of carrying out clinical trials studying ACEi in Covid-19 patients, to explore the hypothesis that ACEi use has a protective effect in populations with a mean age under 50 years, but not necessarily in those with a mean age over 60 years.


title: Bioinformatics analysis for L polymerase homology of arenaviruses

text: Many pathogenic viruses can transmit between humans and animals as zoonotic infectious often to cause dangerous disease with obvious clinical signs, sometimes globally. However, these outbreaks are generally only dealt with seriously when the viruses concerned have been confirmed and classified as zoonotic. Arenavirus haemorrhagic fever viruses can cause epidemics in some areas of the world. To assess the potential of similar viruses to become zoonotic in the future, bioinformatics of relatively conserved virus proteins, such as the L polymerase of arenaviruses, can be used to identify homology with viruses that might give future outbreaks. In this paper, new and archival metazoan transcriptome sequence data was used as a resource to identify similar sequences to known arenavirus sequences for the purpose of risk prediction. In essence, bioinformatics was utilized to provide a better understanding of the potential evolution and natural history of uncharacterized virus sequences in the GenBank database. Several matches were identified which, along with a reasoned approach to their phyla, was used to provide a likelihood score of their zoonotic potential.


title: Computational Prediction of the Comprehensive SARS-CoV-2 vs. Human Interactome to Guide the Design of Therapeutics

text: Understanding the disease pathogenesis of the novel coronavirus, denoted SARS-CoV-2, is critical to the development of anti-SARS-CoV-2 therapeutics. The global propagation of the viral disease, denoted COVID-19 (“coronavirus disease 2019”), has unified the scientific community in searching for possible inhibitory small molecules or polypeptides. Given the known interaction between the human ACE2 (“Angiotensin-converting enzyme 2”) protein and the SARS-CoV virus (responsible for the coronavirus outbreak circa. 2003), considerable focus has been directed towards the putative interaction between the SARS-CoV-2 Spike protein and ACE2. However, a more holistic understanding of the SARS-CoV-2 vs. human inter-species interactome promises additional putative protein-protein interactions (PPI) that may be considered targets for the development of inhibitory therapeutics. To that end, we leverage two state-of-the-art, sequence-based PPI predictors (PIPE4 & SPRINT) capable of generating the comprehensive SARS-CoV-2 vs. human interactome, comprising approximately 285,000 pairwise predictions. Of these, we identify the high-scoring subset of human proteins predicted to interact with each of the 14 SARS-CoV-2 proteins by both methods, comprising 279 high-confidence putative interactions involving 225 human proteins. Notably, the Spike-ACE2 interaction was the highest ranked for both the PIPE4 and SPRINT predictors, corroborating existing evidence for this PPI. Furthermore, the PIPE-Sites algorithm was used to predict the putative subsequence that might mediate each interaction and thereby inform the design of inhibitory polypeptides intended to disrupt the corresponding host-pathogen interactions. We hereby publicly release the comprehensive set of PPI predictions and their corresponding PIPE-Sites landscapes in the following DataVerse repository: 10.5683/SP2/JZ77XA. All data and metadata are released under a CC-BY 4.0 licence. The information provided represents theoretical modeling only and caution should be exercised in its use. It is intended as a resource for the scientific community at large in furthering our understanding of SARS-CoV-2.


title: Appendix 1 Organisms mentioned in the Handbook

text: Unknown


title: Is Hydroxychloroquine Safe During Pregnancy? Observations from Penn Medicine

text: A novel strain of coronavirus appeared in December 2019. Over the next few months, this novel coronavirus spread throughout the world, being declared a pandemic by the World Health Organization on March 11, 2020. As of this writing (March 28, 2020) over one hundred thousand individuals in the United States of America were confirmed cases. One way of treating the associated disease, COVID-19, is to reuse existing FDA-approved medications. One medication that has shown promise is hydroxychloroquine (HCQ). However, the utility and safety of HCQ among pregnant COVID-19 patients remains a concern.


title: Association of variants within the GST and other genes with anti-tubercular agents related toxicity: a systematic review and meta-analysis

text: Background Individuals receiving treatment with anti-tuberculosis (TB) drugs may experience serious side-effects, such as anti-TB drug-induced hepatotoxicity (ATDH). Genetic variants, such as polymorphisms of the GST gene and other genes, may increase the risk of experiencing such toxicity events. This systematic review and meta-analysis provides a comprehensive evaluation of the evidence base for associations between variants of the GST gene and other genes and toxicity outcomes related to anti-TB drugs. Methods We searched for relevant studies in MEDLINE, PubMed, EMBASE, BIOSIS and Web of Science. We pooled effect estimates for each genotype on each outcome, and stratified all analyses by country. We qualitatively assessed the methodological quality of the included studies. Results We included data from 28 distinct cohorts of patients in the review. The methodological quality of included studies was variable, with several important areas of concern. For GSTM1, patients with the homozygous null genotype were significantly more likely to experience hepatotoxicity than patients with heterozygous or homozygous present genotype (odds ratio [OR]=1.44, 95% confidence interval [CI] 1.15, 1.82). Moderate heterogeneity was observed in this analysis (I2=51.2%). No significant difference was observed for the GSTT1 null polymorphism. For the rs3814057 polymorphism of the PXR gene, both heterozygous genotype and homozygous mutant-type significantly increased hepatotoxicity risk compared with homozygous wild-type (heterozygous versus homozygous wild-type: OR=1.98, 95% CI 1.06, 3.69; I2=0%; homozygous mutant-type versus homozygous wild-type: OR=2.18, 95% CI 1.07, 4.44; I2=0%). Conclusions We found that it is challenging to perform robust synthesis of the evidence base for associations between GST and other genetic variants and toxicity related to anti-TB drugs. We identified significant associations between the GSTM1 null and PXR rs3814057 polymorphisms and ATDH. To the best of our knowledge, no meta-analyses on genetic variants other than variants of the NAT2, CYP2E1, GSTM1 and GSTT1 genes have been published. Our results therefore add to the existing understanding of the association between genetic variants and hepatotoxicity.


title: Humanized Single Domain Antibodies Neutralize SARS-CoV-2 by Targeting Spike Receptor Binding Domain

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across more than 200 countries and regions, leading to an unprecedented medical burden and live lost. SARS-CoV-2 specific antivirals or prophylactic vaccines are not available. Neutralizing antibodies provide efficient blockade for viral infection and are a promising category of biological therapies. Using SARS-CoV-2 spike RBD as a bait, we have discovered a panel of humanized single domain antibodies (sdAbs). These sdAbs revealed binding kinetics with the equilibrium dissociation constant (KD) of 0.7~33 nM. The monomeric sdAbs showed half maximal inhibitory concentration (IC50) of 0.003~0.3 μg/mL in pseudotyped particle neutralization assay, and 0.23~0.50 μg/mL in authentic SARS-CoV-2 neutralization assay. Competitive ligand-binding data suggested that the sdAbs either completely blocked or significantly inhibited the association between SARS-CoV-2 RBD and viral entry receptor ACE2. Finally, we showed that fusion of the human IgG1 Fc to sdAbs improved their neutralization activity by tens of times. These results reveal the novel SARS-CoV-2 RBD targeting sdAbs and pave a road for antibody drug development.


title: Laboratory findings, signs and symptoms, clinical outcomes of Patients with COVID-19 Infection: an updated systematic review and meta-analysis

text: Background and Aim: Coronaviruses disease 2019 (COVID-19), for the first time detected in Wuhan, China, rapidly speared around the world and be a Public Health Emergency of International Concern (PHEIC). The aim of the current survey is collecting laboratory findings, analysis them and reporting a specific pattern for help to COVID-19 diagnosis. Methods: To collect laboratory characteristics, we searched "PubMed" electronic database with the following keywords: "COVID-19" "2019 novel coronavirus" "laboratory findings" "clinical characteristics". Results: Once the initial searches 493 studies were yielded. After removing duplicates studies 480 studies were remained. The 12 studies obtained from the literature, of which 58.3% (7) of studies were case-control, and 41.7% remaining studies were designed as cross-sectional. Conclusion: The result of the current study showed that in the early stage of COVID-19 infection, maybe there are not significant laboratory findings, but with disease progression, the one or more than signs include increasing AST, ALT, LDH, CK, CRP, ESR, WBC, neutrophil, and decreasing Hemoglobin, lymphocyte count, eosinophil count can be seen. Elevating D-dimer and FDP are associated with ARDS development and can be used as prognostic factors. Keywords: COVID-19; laboratory findings; prognostic factors


title: Labs go quiet as researchers brace for long-term coronavirus disruptions

text: Evolutionary biologist Richard Lenski at Michigan State University spends a lot of time thinking about how microbes grow Since 1988, his team has watched populations of Escherichia coli bacteria grow and evolve in the lab through more than 73,000 generations So when cases of COVID-19, caused by the novel coronavirus SARS-CoV-2, appeared in the United States, he knew to expect exponential growth—these first cases were just a hint of what was to come This week, as research institutions around the world brace for a surge in COVID-19 cases and consider their staff and students’ roles in slowing the virus’ spread, Lenski decided to freeze his bacteria and pause the 32-year experiment “I didn’t want people responsible for doing this daily work [of maintaining the bacteria] to feel a pressure to come in when they might not be feeling well,” he says This is “a tiny perturbation” in the scheme of the experiment, which can simply be resumed by unfreezing the bacteria But that disruption is itself the tip of an iceberg Countless labs in a variety of research fields are reconsidering their planned studies—and not all projects can be easily put on ice


title: Asip (Agouti-signaling protein) aggression gene regulate auditory processing genes in mice

text: Covid-19 strategy of lockdown has affected the lives of millions. The strict actions to enclose the epidemic have exposed many households to inner tensions. Domestic violence has been reported to increase during the lockdown. However, the reasons for this phenomenon have not been thoroughly investigated. Melanocortin GPCRs family contribution to aggression is well documented. ASIP (nonagouti) gene plays a vital role in regulating the melanocortin GPCRs family function, and it is responsible for regulating aggression in mice. We conducted a selection analysis of ASIP. We found that it negatively purified from Shark to humans. In order to better asses the effect of this gene in mammals, we performed RNA-seq analysis of a knockout of an ASIP crisper-cas mouse model. We found that ASIP KO in mice upregulates several genes controlling auditory function, including Phox2b, Mpk13, Fat2, Neurod2, Slc18a3, Gon4l Gbx2, Slc6a3(Dat1) Aldh1a7 Tyrp1 and Lbx1. Interestingly, we found that Slc6a5, and Lamp5 as well as IL33, which are associated with startle disease, are also upregulated in response to knocking out ASIP. These findings are indicative of a direct autoimmune effect between aggression-associated genes and startle disease. Furthermore, in order to validate the link between aggression and auditory inputs processing. We conducted psychological tests of persons who experienced lockdown. We found that aggression has risen by 16 % during the lockdown. Furthermore, 3% of the subjects interviewed reported a change in their hearing abilities. Our data shed light on the importance of the auditory input in aggression and open perceptions to interpret how hearing and aggression interact at the molecular neural circuit level.


title: Performing risk stratification for COVID-19 when individual level data is not available, the experience of a large healthcare organization

text: With the global coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need for risk stratification tools to support prevention and treatment decisions. The Centers for Disease Control and Prevention (CDC) listed several criteria that define high-risk individuals, but multivariable prediction models may allow for a more accurate and granular risk evaluation. In the early days of the pandemic, when individual level data required for training prediction models was not available, a large healthcare organization developed a prediction model for supporting its COVID-19 policy using a hybrid strategy. The model was constructed on a baseline predictor to rank patients according to their risk for severe respiratory infection or sepsis (trained using over one-million patient records) and was then post-processed to calibrate the predictions to reported COVID-19 case fatality rates. Since its deployment in mid-March, this predictor was integrated into many decision-processes in the organization that involved allocating limited resources. With the accumulation of enough COVID-19 patients, the predictor was validated for its accuracy in predicting COVID-19 mortality among all COVID-19 cases in the organization (3,176, 3.1% death rate). The predictor was found to have good discrimination, with an area under the receiver-operating characteristics curve of 0.942. Calibration was also good, with a marked improvement compared to the calibration of the baseline model when evaluated for the COVID-19 mortality outcome. While the CDC criteria identify 41% of the population as high-risk with a resulting sensitivity of 97%, a 5% absolute risk cutoff by the model tags only 14% to be at high-risk while still achieving a sensitivity of 90%. To summarize, we found that even in the midst of a pandemic, shrouded in epidemiologic "fog of war" and with no individual level data, it was possible to provide a useful predictor with good discrimination and calibration.


title: The Prevalence of RT-PCR Positivity of SARS-CoV-2 on 10,000 Patients from Three Cities Located on the Eastern of Turkey

text: COVID-19, is caused by SARS-CoV-2, has been started on December/2019 in Wuhan/China and spread all over the world. We analyzed RT-PCR results of 10,000 cases from April-2 to May-30, 2020 in three neighbor cities located on the Eastern of Turkey. The final study population was 7853 cases after excluded screening tests. RT-PCR were performed to detect the SARS-CoV-2-specific RdRp (RNA-dependent-RNA-polymerase) gene fragment. The number of total positive samples out of 7853 were 487; however, the number of non-repeating positive patient was 373 (4.8%). The cough and fever were the most common symptoms in positive cases. The epidemiologic studies should be performed about the prevalence of SARS-CoV-2 infection to better understand the effect of the virus all over the world.


COVID-19 and the Future of Adult Education: An Editorial


title: COVID-19 Pandemic Causing Acute Kidney Injury and Impact on Patients With Chronic Kidney Disease and Renal Transplantation

text: Coronavirus disease 2019 (COVID-19) caused by 2019 novel coronavirus (2019-nCoV) has caused significant mortality and has been declared as a global pandemic by the World Health Organization. The infection mainly presents as fever, cough, and breathing difficulty, and few patients develop very severe symptoms. The purpose of this review is to analyze the impact of the virus on the kidney. COVID-19 infection causes acute kidney injury (AKI) and is an independent risk factor for mortality. Angiotensin-converting enzyme 2 (ACE2) receptors, direct viral damage, and immune-mediated damage play important roles in the pathogenesis. AKI in COVID-19 infection could be from the synergistic effect of virus-induced direct cytotropic effect and cytokine-induced systemic inflammatory response. AKI caused in the viral infection has been analyzed from the available epidemiological studies. The proportion of patients developing AKI is significantly higher when they develop severe disease. Continuous renal replacement therapy (CRRT) is the most used blood purification technique when needed. The impact of COVID-19 infection on chronic kidney disease (CKD) and renal transplant patients is also discussed in the manuscript. No vaccine has been developed against the 2019-nCoV virus to date. The critical aspect of management is supportive care. Several investigative drugs have been studied, drugs approved for other indications have been used, and several clinical trials are underway across the globe. Recently remdesivir has received emergency use authorization by the Food and Drug Administration (FDA) in the USA for use in patients hospitalized with COVID-19. Prevention of the infection holds the key to management. The patients with underlying kidney problems and renal transplant patients are vulnerable to developing COVID-19 infection.


title: Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients

text: Objective Evidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers. Methods Based on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severe versus mild disease, Intensive Care Unit (ICU) versus general ward admission, and expired versus survivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease. Results Cohorts with elevated levels of white blood cells (WBCs) (OR=1.75), neutrophil count (OR=2.62), D-dimer (OR=3.97), prolonged prothrombin time (PT) (OR=1.82), fibrinogen (OR=3.14), erythrocyte sedimentation rate (OR=1.60), procalcitonin (OR=4.76), IL-6 (OR=2.10), and IL-10 (OR=4.93) had higher odds of progression to severe phenotype. Decision tree model (sensitivity=100%, specificity=81%) showed the high performance of neutrophil count at a cut-off value of more than 3.74 x109/L for identifying patients at high risk of severe COVID-19. Likewise, ICU admission was associated with higher levels of WBCs (OR=5.21), neutrophils (OR=6.25), D-dimer (OR=4.19), and prolonged PT (OR=2.18). Patients with high IL-6 (OR=13.87), CRP (OR=7.09), D-dimer (OR=6.36), and neutrophils (OR=6.25) had the highest likelihood of mortality. Conclusions Several hematological and immunological markers, in particular neutrophilic count, could be helpful to be included within the routine panel for COVID-19 infection evaluation to ensure risk stratification and effective management.


title: Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

text: Single-cell RNA profiling of ACE2, the SARS-CoV-2 receptor, had proposed multiple tissue cells as the potential targets of SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic. However, most were not echoed by the patients’ clinical manifestations, largely due to the lack of protein expression information of ACE2 and co-factors. Here, we incorporated the protein information to analyse the expression of ACE2, together with TMPRSS2 and Furin, two proteases assisting SARS-CoV-2 infection, at single cell level in situ, which we called protein-proofed single-cell RNA (pscRNA) profiling. Systemic analysis across 36 tissues revealed a rank list of candidate cells potentially vulnerable to SARS-CoV-2. The top targets are lung AT2 cells and macrophages, then cardiomyocytes and adrenal gland stromal cells, followed by stromal cells in testis, ovary and thyroid. Whereas, the polarized kidney proximal tubule cells, liver cholangiocytes and intestinal enterocytes are less likely to be the primary SARS-CoV-2 targets as ACE2 localizes at the apical region of cells, where the viruses may not readily reach. These findings are in concert with the clinical characteristics of prominent lung symptoms, frequent heart injury, and uncommon intestinal symptoms and acute kidney injury. Together, we provide a comprehensive view on the potential SARS-CoV-2 targets by pscRNA profiling, and propose that, in addition to acute respiratory distress syndrome, attentions should also be paid to the potential injuries in cardiovascular, endocrine and reproductive systems during the treatment of COVID-19 patients.


The remaining unknowns: A determination of the current research priorities for COVID-19 by the global health research community


title: Differences of clinical and imaging findings in multiple generations of secondary COVID-19 infection in Xi'an, China

text: PURPOSE: In the global presence of secondary infections with the coronavirus disease 2019 (COVID-19), little is known about the transmission characteristics of COVID-19 outside Wuhan, China. We evaluated differences in clinic and radiologic findings of multiple generations of COVID-19 infection in Xi'an (Shaanxi, China) to provide more clues for the correct estimate of the disease. METHODS: All COVID-19 infected patients reported in Xi'an up to 10 February 2020 were included for this analysis. Among these cases, clinical and chest CT data of 62 cases were obtained from three hospital in Xi'an. With this information, patients were grouped on basis of exposure history and transmission chains as first-generation, second-generation and third-generation patients. We described clinical characteristics and evaluated CT score/patterns in these COVID-19 cases. RESULTS: There was a clear age differences in multiple generations with COVID-19 infection. Above two thirds of the second-generation (75.0%) and third-generation patients (77.8%) were aged [≥]45 years while 40.0% of first-generation cases at this age (p=0.001). More than half of second-generation patients (52.8%) and third-generation patients (55.6%) have comorbidities and is predominantly hypertensive (22.8% of second-generation vs. 27.8% of third-generation infections). The main exposure of second- and third-generation patients in Xi'an is family exposure (35.2%). For evaluation of CT findings of pulmonary involvement, the total CT score were 4.22{+/-}3.00 in first-generation group, 4.35{+/-}3.03 in second-generation group and 7.62{+/-}3.56 in third-generation group (p<0.001). In all of three generations, the predominant pattern of abnormality observed was organizing pneumonia (65.5% in first-generation group, 61.5% in second-generation group and 71.4% in third-generation group). The average courses of the disease in third-generation infections has obviously extension (22.93{+/-}7.22 days of first-generation, 21.53{+/-}8.31 days of second-generation vs. 31.00{+/-}8.12 days of third-generation group, p=0.004). There were no significant differences of the pulmonary sequelae among three generation patients. CONCLUSION: There is more serious pulmonary infection of COVID-19 pneumonia in second- and third-generation patients, which might be attribute to the elder age and comorbidity of these patients.


title: Characteristics of Ischemic Stroke in COVID-19: A Need for Early Detection and Management

text: Objective: In the setting of the Coronavirus Disease 2019 (COVID-19) global pandemic caused by SARS-CoV-2, a potential association of this disease with stroke has been suggested. We aimed to describe the characteristics of patients who were admitted with COVID-19 and had an acute ischemic stroke (AIS). Methods: This is a case series of PCR-confirmed COVID-19 patients with ischemic stroke admitted to an academic health system in metropolitan Atlanta (USA) between March 24th,2020, and May 5th, 2020. Demographic, clinical, and radiographic characteristics were described. Results: Of 124 ischemic stroke patients admitted during this study period, 8 (6.5%) were also diagnosed with COVID-19. The mean age of patients was 64.3 +/- 6.5 years, 5 (62.5%) male, mean time from last-normal was 4.8 days [SD 4.8], and none received acute reperfusion therapy. All 8 patients had at least one stroke-associated co-morbidity. The predominant pattern of ischemic stroke was embolic; 3 were explained by atrial fibrillation while 5 (62.5%) were cryptogenic. In contrast, cryptogenic strokes were seen in 20 (16.1%) of 124 total stroke admissions during this time. Conclusions: In our case series, ischemic stroke affected COVID-19 patients with traditional stroke risk factors with an age of stroke presentation typically seen in non-COVID populations. We observed a predominantly embolic pattern of stroke with a higher than expected rate of cryptogenic strokes and with a prolonged median time to presentation/symptom recognition limiting the use of acute reperfusion treatments. These results highlight the need for aggressive identification and management of AIS in COVID-19 patients.


title: COVID-19: Doctors, gastroenterology and emotions/ COVID-19: Médicos, gastroenterología y emociones

text: COVID-19 is a pandemic with clinical and emotional implications, sometimes invisible to gastroenterologists. Although dying is part of life, the risk for some doctors may be greater. Specifically, gastroenterologists are affected by the fear of restarting medical check-ups and endoscopic procedures. Amid a sea of information –even with contradictions between different experts— following the guidelines of the Colombian Associations of the Digestive Tract could help reassure doctors and patients. Although the pathologies will continue to appear, the fear of the population to be infected can generate consequences such as delaying the treatment of digestive tract cancers. Physical self-care through protection strategies and the emotional care, are important to help our immune system. Adapting to function during the pandemic, using tele-orientation through digital platforms, is a creative way to reduce collective anxiety.


title: Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). To date, no prophylactic vaccines or approved therapeutic agents are available for preventing and treating this highly transmittable disease. Here we report two monoclonal antibodies (mAbs) cloned from memory B cells of patients recently recovered from COVID-19, and both mAbs specifically bind to the spike (S) protein of SARS-CoV-2, block the binding of receptor binding domain (RBD) of SARS-CoV-2 to human angiotensin converting enzyme 2 (hACE2), and effectively neutralize S protein-pseudotyped virus infection. These human mAbs hold the promise for the prevention and treatment of the ongoing pandemic of COVID-19.


title: Novel Electrodes for Reliable EEG Recordings on Coarse and Curly Hair

text: EEG is a powerful and affordable brain sensing and imaging tool used extensively for the diagnosis of neurological disorders (e.g. epilepsy), brain computer interfacing, and basic neuroscience. Unfortunately, most EEG electrodes and systems are not designed to accommodate coarse and curly hair common in individuals of African descent. This can lead to poor quality data that might be discarded in scientific studies after recording from a broader population set, and for clinical diagnoses, lead to an uncomfortable and/or emotionally taxing experience, and, in the worst cases, misdiagnosis. In this work, we design a system to explicitly accommodate coarse and curly hair, and demonstrate that, across time, our electrodes, in conjunction with appropriate braiding, attain substantially (~10x) lower impedance than state-of-the-art systems. This builds on our prior work that demonstrated that braiding hair in patterns consistent with the clinical standard 10-20 arrangement leads to improved impedance with existing systems.


title: Can the protection be among us? Previous viral contacts and prevalent HLA alleles could be avoiding an even more disseminated COVID-19 pandemic.

text: Background: COVID-19 is bringing scenes of sci-fi movies into real life, and it seems to be far from over. Infected individuals exhibit variable severity, with no relation between the number of cases and mortality, suggesting the involvement of the populational genetic constitution and previous cross-reactive immune contacts in the individuals' disease outcome. Methods: A clustering approach was conducted to investigate the involvement of human MHC alleles with individuals' outcomes. HLA frequencies from affected countries were used to fuel the Hierarchical Clusterization Analysis. The formed groups were compared regarding their death rates. To prospect the T cell targets in SARS-CoV-2, and by consequence, the epitopes that are conferring cross-protection in the current pandemic, we modeled 3D structures of HLA-A*02:01 presenting immunogenic epitopes from SAR-CoV-1, recovered from Immune Epitope Database. These pMHC structures were also compared with models containing the corresponding SARS-CoV-2 epitope, with alphacoronavirus sequences, and with a panel of immunogenic pMHC structures contained in CrossTope. Findings: The combined use of HLA-B*07, HLA-B*44, HLA-DRB1*03, and HLADRB1*04 allowed the clustering of affected countries presenting similar death rates, based only on their allele frequencies. SARS-CoV HLA-A*02:01 epitopes were structurally investigated. It reveals molecular conservation between SARS-CoV-1 and SARS-CoV-2 peptides, enabling the use of formerly SARS-CoV-1 experimental epitopes to inspect actual targets that are conferring cross-protection. Alpha-CoVs and, impressively, viruses involved in human infections share fingerprints of immunogenicity with SARS-CoV peptides. Interpretation: Wide-scale HLA genotyping in COVID-19 patients shall improve prognosis prediction. Structural identification of previous triggers paves the way for herd immunity examination and wide spectrum vaccine development. Funding: This work was supported by the National Council for Scientific and Technological Development (CNPq) and National Council for the Improvement of Higher Education (CAPES) for their support


title: Analysis of mortality in patients of COVID-19: clinical and laboratory parameters

text: Several reports on epidemiological and clinical features of the 2019 coronavirus disease (COVID-19) had been published. However, mortality and morbidity analysis, important for better understanding of the pathogenesis of this disease, are scarce. We examine the clinical and laboratory features of 14 patients who died of COVID-19. The cohort consisted of 11 male and 3 female patients; nine patients aged 70 years or above, and nearly all had underlying diseases. Fever with bilateral pneumonia was the main manifestation. Most patients had consolidations combined with ground glass opacity (GGO) on chest CT scan. Laboratory tests showed lymphocytopenia in 10 patients, high blood glucose in 11, GGT in 5 of the 14 patients, and high LDH in 5 of 6 patients tested. In addition, patients in this cohort had high level of cytokines such as interleukin 6 in all 8 patients tested. The clinical and laboratory parameters in the cohort of fatal cases may be incorporated into future clinical prognosis models, and will be of help in understanding the pathogenesis of this disease.


A Novel Approach of Consultation on 2019 Novel Coronavirus (COVID-19)-Related Psychological and Mental Problems: Structured Letter Therapy


title: Using Behavioral Science to help fight the Coronavirus

text: This rapid, narrative review summarizes useful evidence from behavioral science for fighting the COVID-19 outbreak We undertook an extensive, multi-disciplinary literature search covering five issues: handwashing, face touching, self-isolation, public-spirited behavior, and responses to crisis communication The search identified more than 100 relevant papers We find effective behavioral interventions to increase handwashing, but not to reduce face touching Social supports and behavioral plans can reduce the negative psychological effects of isolation, potentially reducing the disincentive to isolate Public-spirited behavior is more likely with frequent communication of what is “best for all”, strong group identity, and social disapproval of noncompliance Effective crisis communication involves speed, honesty, credibility, empathy, and promoting useful individual actions Risks are probably best communicated through numbers, with ranges to describe uncertainty – simply stating a maximum may bias public perception The findings aim to be useful not only for government and public health authorities, but for organizations and communities


title: Cholinergic relay from punishment- to reward-encoding dopamine neurons signals punishment withdrawal as reward in Drosophila

text: Animals form and update learned associations between otherwise neutral cues and aversive outcomes to predict and avoid danger in changing environments. When a cue later occurs without punishment, this unexpected withdrawal of aversive outcome is encoded as reward, via activation of reward-encoding dopaminergic neurons. Using real-time in vivo functional imaging, optogenetics, behavioral analysis, and electron-microscopy, we identify the neural mechanism through which Drosophila reward-encoding dopaminergic neurons are activated when an olfactory cue is unexpectedly no longer paired with electric shock punishment. Reduced activation of punishment-encoding dopaminergic neurons relieves depression of synaptic inputs to cholinergic neurons, which in turn synaptically increase odor responses of reward-encoding dopaminergic neurons to decrease odor avoidance. These studies reveal for the first time how an indirect excitatory cholinergic synaptic relay from punishment- to reward-encoding dopaminergic neurons encodes the absence of a negative as a positive, revealing a general circuit motif for unlearning aversive memories that could be present in mammals.


title: Elicitation of broadly protective immunity to influenza by multivalent hemagglutinin nanoparticle vaccines

text: Influenza vaccines that confer broad and durable protection against diverse virus strains would have a major impact on global health. However, next-generation vaccine design efforts have been complicated by challenges including the genetic plasticity of the virus and the immunodominance of certain epitopes in its glycoprotein antigens. Here we show that computationally designed, two-component nanoparticle immunogens induce potently neutralizing and broadly protective antibody responses against a wide variety of influenza viruses. The nanoparticle immunogens display 20 hemagglutinin (HA) trimers in a highly immunogenic array, and their assembly in vitro enables precisely controlled co-display of multiple distinct HAs in defined ratios. Nanoparticle immunogens displaying the four HAs of licensed quadrivalent influenza vaccines (QIV) elicited hemagglutination inhibition and neutralizing antibody responses to vaccine-matched strains that were equivalent or superior to commercial QIV in mice, ferrets, and nonhuman primates. The nanoparticle immunogens—but not QIV—simultaneously induced broadly protective antibody responses to heterologous viruses, including H5N1 and H7N9, by targeting the subdominant yet conserved HA stem. Unlike previously reported influenza vaccine candidates, our nanoparticle immunogens can alter the intrinsic immunodominance hierarchy of HA to induce both potent receptor-blocking and broadly cross-reactive stem-directed antibody responses and are attractive candidates for a next-generation influenza vaccine that could replace current seasonal vaccines. One Sentence Summary Nanoparticle immunogens displaying four seasonal influenza hemagglutinins elicit neutralizing antibodies directed at both the immunodominant head and the conserved stem and confer broad protective immunity.


title: Trajectories of depression and anxiety during enforced isolation due to COVID-19: longitudinal analyses of 59,318 adults in the UK with and without diagnosed mental illness

text: Background: There is currently major concern about the impact of the global COVID-19 outbreak on mental health. A number of studies suggest that mental health deteriorated in many countries prior to enforced isolation (lockdown), but it remains unknown how mental health has changed during lockdown. Aims: This study explored trajectories of anxiety and depression over the first two months of lockdown using data from the UK, and compared the experiences of individuals with and without diagnosed mental illness. Methods: Data from 53,328 adults in the UCL COVID -19 Social Study (a well-stratified panel study weighted to population proportions collecting data weekly during the Covid-19 pandemic) were analysed from 21/03/2020-10/05/2020. Growth curve modelling was fitted accounting for socio-demographic and health covariates. Results: 24.4% of the sample had scores indicating moderate-severe anxiety, and 31.4% indicating moderate-severe depressive symptoms. Over the first two months of lockdown, there was only a slight decrease in anxiety levels amongst participants as a whole and a very small decrease in depression levels between weeks 3-6 that then increased again in weeks 7-8. Adults with pre-existing diagnoses of mental health conditions had higher levels of anxiety and depression but there was no evidence of widening inequalities in mental health experiences compared to people without existing mental illness. Conclusions: Results suggest there has been little improvement in depression and only slight improvements in anxiety since lockdown commenced in the UK. These findings suggest greater efforts need to be made to help individuals manage their mental health during the pandemic.


title: Causal Modeling of Twitter Activity During COVID-19

text: Understanding the characteristics of public attention and perception is an essential prerequisite for appropriate crisis management during adverse health events. This is even more crucial during a pandemic such as COVID-19, as primary responsibility of risk management is not centralized to a single institution, but distributed across society. While numerous studies utilize Twitter data in descriptive or predictive context during COVID-19 pandemic, causal modeling of public attention has not been investigated. In this study, we propose a causal inference approach to discover and quantify causal relationships between pandemic characteristics (e.g. number of infections and deaths) and Twitter activity as well as public sentiment. Our results show that the proposed method can successfully capture the epidemiological domain knowledge and identify variables that affect public attention and perception. We believe our work contributes to the field of infodemiology by distinguishing events that correlate with public attention from events that cause public attention.


title: Structural and biochemical characterization of nsp12-nsp7-nsp8 core polymerase complex from COVID-19 virus

text: The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has caused huge number of human deaths. Currently, there are no specific drugs or vaccines available for this virus. The viral polymerase is a promising antiviral target. However, the structure of COVID-19 virus polymerase is yet unknown. Here, we describe the near-atomic resolution structure of its core polymerase complex, consisting of nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembles the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases, and suggests the mechanism for activation by cofactors. Biochemical studies revealed reduced activity of the core polymerase complex and lower thermostability of individual subunits of COVID-19 virus as compared to that of SARS-CoV. These findings provide important insights into RNA synthesis by coronavirus polymerase and indicate a well adaptation of COVID-19 virus towards humans with relatively lower body temperatures than the natural bat hosts.


title: THE ERA OF CORONAVIRUS; KNOWLEDGE, ATTITUDE, PRACTICES, AND BARRIERS TO HAND HYGIENE AMONG MAKERERE UNIVERSITY STUDENTS AND KATANGA COMMUNITY RESIDENTS.

text: Background China reported the Novel Coronavirus at the end of the year 2019 which was, later on, declared a Pandemic by the WHO. Proper hand hygiene was identified as one of the simplest most cost effective Covid-19 control and prevention measures. It is therefore very important to understand the compliance of the community to hand hygiene. Method A descriptive cross-sectional study was conducted among the undergraduate students of Makerere University and residents of Katanga slum from 17th to 22nd of March, 2020. An interviewer guided questionnaire with questions on knowledge, attitude, practice, and barriers to hand hygiene was used in data collection. The collected data was analyzed using Microsoft office excel 2016 and STATA 15 software. A 95% confidence interval was used and statistical significance was P<0.05. Results Only 8.4% of the participants had good knowledge of hand hygiene. 11.7% of the university students had good knowledge compared to 0.9% of the Katanga residents. 29.0% of the participants had a good attitude while 50.1% had a moderate attitude to hand hygiene. University students were 6.3 times (OR: 6.3, 95%C1: (2.1 18.5), P=0.001) more likely to have good knowledge while Katanga residents were 3.6 times (OR: 3.6, 95%C1: (1.5 8.4), P=0.003) more likely to have good attitude to hand hygiene. Only 19.6% accomplished all the seven steps of handwashing. 38.4% of the participants still greeted by handshaking and 60.1% noted lack of soap as a barrier to hand hygiene and 62.9% reported having more than three barriers to hand hygiene. Participants that had been taught handwashing were more likely to have better hand hygiene knowledge and practice. Conclusion Despite a fair attitude, deficiency of knowledge coupled with many barriers such as Lack of soap hindered the Practice of proper hand hygiene. Public health involvement to promote hand hygiene must be promoted.


title: Data-Driven Study of the COVID-19 Pandemic via Age-Structured Modelling and Prediction of the Health System Failure in Brazil amid Diverse Intervention Strategies

text: In this work we propose a data-driven age-structured census-based SIRD-like epidemiological model capable of forecasting the spread of COVID-19 in Brazil. We model the current scenario of closed schools and universities, social distancing of individuals above sixty years old and voluntary home quarantine to show that it led to a considerable reduction in the number of infections as compared with a scenario without any control measures. Notwithstanding, our model predicts that the current measures are not enough to avoid overloading the health system, since the demand for intensive care units will soon surpass the number available. We also show that an urgent intense quarantine might be the only solution to avoid this scenario and, consequently, minimize the number of severe cases and deaths. On the other hand, we demonstrate that the early relaxation of the undergoing isolation measures would lead to an increase of millions of infections in a short period of time and the consecutive collapse of the health system.


title: Health Communication Through News Media During the Early Stage of the COVID-19 Outbreak in China: A Digital Topic Modeling Approach

text: Background : In December 2019, some COVID-19 cases were first reported and soon the disease broke out. As this dreadful disease spreads rapidly, the mass media has been active in community education on COVID-19 by delivering health information about this novel coronavirus. | Methods: We adopted the Huike database to extract news articles about coronavirus from major press media, between January 1st, 2020, to February 20th, 2020. The data were sorted and analyzed by Python software and Python package Jieba. We sought a suitable topic number using the coherence number. We operated Latent Dirichlet Allocation (LDA) topic modeling with the suitable topic number and generated corresponding keywords and topic names. We divided these topics into different themes by plotting them into two-dimensional plane via multidimensional scaling. | Findings: After removing duplicates, 7791 relevant news reports were identified. We listed the number of articles published per day. According to the coherence value, we chose 20 as our number of topics and obtained their names and keywords. These topics were categorized into nine primary themes based on the topic visualization figure. The top three popular themes were prevention and control procedures, medical treatment and research, global/local social/economic influences, accounting for 32.6%, 16.6%, 11.8% of the collected reports respectively. | Interpretation: The Chinese mass media news reports lag behind the COVID-19 outbreak development. The major themes accounted for around half the content and tended to focus on the larger society than on individuals. The COVID-19 crisis has become a global issue, and society has also become concerned about donation and support as well as mental health. We recommend that future work should address the mass media's actual impact on readers during the COVID-19 crisis through sentiment analysis of news data.


title: The SARS-CoV-2 T-cell immunity is directed against the spike, membrane, and nucleocapsid protein and associated with COVID 19 severity

text: Identification of immunogenic targets of SARS-CoV-2 is crucial for monitoring of antiviral immunity and vaccine design. Currently, mainly anti-spike (S)-protein adaptive immunity is investigated. However, also the nucleocapsid (N)- and membrane (M)-proteins should be considered as diagnostic and prophylactic targets. The aim of our study was to explore and compare the immunogenicity of SARS-CoV-2 S-, M- and N-proteins in context of different COVID-19 manifestations. Analyzing a cohort of COVID-19 patients with moderate, severe, and critical disease severity, we show that overlapping peptide pools (OPP) of all three proteins can activate SARS-CoV-2-reactive T-cells with a stronger response of CD4+ compared to CD8+ T-cells. Although interindividual variations for the three proteins were observed, M protein induced the highest frequencies of CD4+ T-cells, suggesting its relevance as diagnostic and vaccination target. Importantly, patients with critical COVID-19 demonstrated the strongest T-cell response, including the highest frequencies of cytokine-producing bi- and trifunctional T-cells, for all three proteins. Although the higher magnitude and superior functionality of SARS-CoV-2-reactive T-cells in critical patients can also be a result of a stronger immunogenicity provided by severe infection, it disproves the hypothesis of insufficient SARS-CoV-2-reactive immunity in critical COVID-19. To this end, activation of effector T-cells with differentiated memory phenotype found in our study could cause hyper-reactive response in critical cases leading to immunopathogenesis. Conclusively, since the S-, M-, and N-proteins induce T-cell responses with individual differences, all three proteins should be evaluated for diagnostics and therapeutic strategies to avoid underestimation of cellular immunity and to deepen our understanding of COVID-19 immunity.


title: Accounting for super-spreading gives the basic reproduction number R0 of COVID-19 that is higher than initially estimated

text: Transmission of infectious diseases is characterized by the basic reproduction number R0, a metric used to assess the threat posed by an outbreak and inform proportionate preventive decision-making. Based on individual case reports from the initial stage of the coronavirus disease 2019 epidemic, R0 is often estimated to range between 2 and 4. In this report, we show that a SEIR model that properly accounts for the distribution of the incubation period suggests that R0 lie in the range 4.4 - 11.7. This estimate is based on the doubling time observed in the near-exponential phases of the epidemic spread in China, United States, and six European countries. To support our empirical estimation, we analyze stochastic trajectories of the SEIR model showing that in the presence of super-spreaders the calculations based on individual cases reported during the initial phase of the outbreak systematically overestimate the doubling time and thus underestimate the actual value of R0.


Potential transmission through aerosols in surgical procedures and blood products


title: Targeted Intracellular Degradation of SARS-CoV-2 RBD via Computationally-Optimized Peptide Fusions

text: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has elicited a global health crisis of catastrophic proportions. With no approved cure or vaccine currently available, there is a critical need for effective antiviral strategies. In this study, we report a novel antiviral platform, through computational design of ACE2-derived peptides which both target the viral spike protein receptor binding domain (RBD) and recruit E3 ubiquitin ligases for subsequent intracellular degradation of SARS-CoV-2 in the proteasome. Our engineered peptide fusions demonstrate robust RBD degradation capabilities in human cells, thus prompting their further experimental characterization and therapeutic development.


title: The first three months of the COVID-19 epidemic: Epidemiological evidence for two separate strains of SARS-CoV-2 viruses spreading and implications for prevention strategies

text: About one month after the COVID-19 epidemic peaked in Mainland China and SARS-CoV-2 migrated from China westward to Europe and then the U.S., the epidemiological data begin to provide important insights into the risks associated with the disease and the effectiveness of intervention strategies. Like other respiratory diseases, including the 2003 SARS epidemic, the virus remains only about two months in any given population, yet the peak incidence and the lethality can vary. The data suggest that at least two strains of the 2020 SARS-CoV-2 virus have evolved during its migration from Mainland China to Europe. South Korea, Iran, and Italy were hit by the more dangerous "SKII" variant. While the epidemic in China is about to end, and in Europe about to level off, the course of the epidemic in the younger US population is still increasing and the peak level will likely depend on which of the strains has entered the US first. The same models that help us to understand the epidemic also help us to choose prevention strategies. While containment merely prolongs the time the disease circulates until the proportion of immune people is high enough for "herd immunity", reducing disease severity, either by vaccination or by early treatment of complications, is the best strategy against a respiratory virus disease.


title: Inferring COVID-19 spreading rates and potential change points for case number forecasts

text: As COVID-19 is rapidly spreading across the globe, short-term modeling forecasts provide time-critical information for decisions on containment and mitigation strategies. A main challenge for short-term forecasts is the assessment of key epidemiological parameters and how they change as first governmental intervention measures are showing an effect. By combining an established epidemiological model with Bayesian inference, we analyze the time dependence of the effective growth rate of new infections. For the case of COVID-19 spreading in Germany, we detect change points in the effective growth rate which correlate well with the times of publicly announced interventions.Thereby, we can (a) quantify the effects of recent governmental measures to mitigating the disease spread, and (b) incorporate analogue change points to forecast future scenarios and case numbers.Our code is freely available and can be readily adapted to any country or region.


title: Suspected COVID-19 in primary care: how GP records contribute to understanding differences in prevalence by ethnicity.

text: Abstract Background The first wave of the London COVID-19 epidemic peaked in April 2020. Attention initially focussed on severe presentations, intensive care capacity, and the timely supply of equipment. General practice has seen a rapid take up of technology to allow virtual consultations, enabling the management of mild and moderate community cases. Aim To quantify the prevalence and time-course of suspected COVID-19 presenting to general practices during the London epidemic. To report disease prevalence by ethnic group, and explore how far differences by ethnicity can be explained by data in the electronic health record (EHR). Design and Setting Cross-sectional study using anonymised data from the primary care records of 1.3 million people registered with 157 practices in four adjacent east London clinical commissioning groups (CCGs). The study area includes 48% of people from ethnic minorities and is in the top decile of social deprivation in England. Method Suspected COVID-19 cases were identified using SNOMED codes. Explanatory variables included age, gender, self-reported ethnicity and measures of social deprivation. Clinical factors included 16 long-term conditions, latest body mass index and smoking status. Results There were 8,985 suspected COVID-19 cases. Ethnicity recording was 78% complete. Univariate analysis showed a two-fold increase in odds of infection for South Asian and Black adults compared to White. In a fully adjusted analysis, including clinical factors, the odds were: South Asian OR 1.93 (95% CI = 1.83 to 2.04) Black OR 1.47 (95% CI 1.38 to 1.57) Conclusions Using data in GP records Black and south Asian ethnicity remain as predictors of community cases of COVID-19, with levels of risk similar to hospital admission cases. Further understanding of these differences requires social and occupational data.


title: Use of a plastic barrier curtain to minimize droplet transmission during tracheal extubation in patients with coronavirus disease

text: The rapid, global spread of coronavirus disease (COVID‐19) has overwhelmed hospital functions in many countries. To ameliorate this crisis, it is important to protect health care providers (HCPs) from COVID‐19. Many intensive care associations advocate guidelines for airway management, since COVID‐19 is considered to spread via droplets from the patient. Additionally, coughing during tracheal intubation and extubation contaminates the area surrounding the patient and increases the risk of infection to HCPs.


title: Clozapine treatment and risk of COVID-19.

text: Background Clozapine, an antipsychotic with unique efficacy in treatment resistant psychosis, is associated with increased susceptibility to infection, including pneumonia. Aims To investigate associations between clozapine treatment and increased risk of COVID-19 in patients with schizophrenia-spectrum disorders who are receiving antipsychotic medications, using electronic health records data, in a geographically defined population in London. Method Using information from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 6,309 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders and were taking antipsychotics at the time on the COVID-19 pandemic onset in the UK. People who were on clozapine treatment were compared with those on any other antipsychotic treatment for risk of contracting COVID-19 between 1 March and 18 May 2020. We tested associations between clozapine treatment and COVID-19 infection, adjusting for gender, age, ethnicity, BMI, smoking status, and SLAM service use. Results Of 6,309 patients, 102 tested positive for COVID-19. Individuals who were on clozapine had increased risk of COVID-19 compared with those who were on other antipsychotic medication (unadjusted HR = 2.62 (95% CI 1.73 - 3.96), which was attenuated after adjusting for potential confounders, including clinical contact (adjusted hazard ratio HR=1.76, 95% CI 1.14 - 2.72). Conclusions These findings provide support for the hypothesis that clozapine treatment is associated with an increased risk of COVID-19. Further research will be needed in other samples to confirm this association. Potential clinical implications are discussed.


title: Getting Humans to do Quantum Optimization - User Acquisition, Engagement and Early Results from the Citizen Cyberscience Game Quantum Moves

text: The game Quantum Moves was designed to pit human players against computer algorithms, combining their solutions into hybrid optimization to control a scalable quantum computer. In this midstream report, we open our design process and describe the series of constitutive building stages going into a quantum physics citizen science game. We present our approach from designing a core gameplay around quantum simulations, to putting extra game elements in place in order to frame, structure, and motivate players' difficult path from curious visitors to competent science contributors. The player base is extremely diverse - for instance, two top players are a 40 year old female accountant and a male taxi driver. Among statistical predictors for retention and in-game high scores, the data from our first year suggest that people recruited based on real-world physics interest and via real-world events, but only with an intermediate science education, are more likely to become engaged and skilled contributors. Interestingly, female players tended to perform better than male players, even though men played more games per day. To understand this relationship, we explore the profiles of our top players in more depth. We discuss in-world and in-game performance factors departing in psychological theories of intrinsic and extrinsic motivation, and the implications for using real live humans to do hybrid optimization via initially simple, but ultimately very cognitively complex games.


title: International Public Health Responses to COVID-19 Outbreak: A Rapid Review

text: BACKGROUND: The outbreak of Coronavirus disease 2019 (COVID-19) has posed a significant threat to many countries. Since the disease does not currently have a particular treatment, there is a compelling need to find substitute means to dominate its expansion. In this rapid review, we aimed to determine some countries’ public responses to the COVID-19 epidemic. METHODS: In this study, academic databases, including MEDLINE, Scopus, and Embase, were investigated. The keywords applied in the search strategy besides the names of each country were: “Public Health,” “Public Response”, “Health Policy”, “COVID-19”, “Novel Coronavirus,” “2019-nCoV”, and “SARS-CoV-2”. The countries included China, Italy, Iran, Spain, South Korea, Germany, France, United States, Australia, Canada, Japan, and Singapore. RESULTS: The total number of retrieved articles in MEDLINE, Scopus, and Embase in April 2020 was 594, and after removing 259 duplicate articles, 335 papers were screened by the experts. After this investigation, 50 articles, in addition to 12 webpages, were extensively reviewed for the results section. Public health strategies and responses can be divided into four main areas, including monitoring, public education, crowd controlling, and care facilities. CONCLUSION: According to the results of the management decisions of some governments on quarantining, social isolation, screening methods, and flight suspensions due to the severity and anonymity of COVID-19, it is highly assured that these strategies would be the most successful approaches to confront the present pandemic. Governments should put in place timely and strict measures to halt the spread and diminish its unintended deadly consequences.


title: The OncoSim-Breast cancer microsimulation model

text: Background: The increasing demand for health care resources requires measures to evaluate the impact of cancer control approaches. A cancer simulation model can help integrate new knowledge to inform clinical and policy decisions. OncoSim-Breast is a breast cancer simulation model. This paper aims to describe the key assumptions in the OncoSim-Breast model and how well it reproduces more recent breast cancer trends and the observed effects in a randomized screening trial. Methods: The OncoSim-Breast model simulates the onset, growth and spread of invasive and ductal carcinoma in situ tumours. The model combines Canadian cancer incidence, mortality, screening program and cost data to project population-level outcomes. Users can change the model input to answer specific policy questions. Here we report three validation exercises. First, we compared the model's projected breast cancer incidence and stage distributions with the observed data in the Canadian Cancer Registry. Second, we compared OncoSim's projected breast cancer mortality with Vital Statistics. Third, we replicated the UK Age trial to compare the model's projections with the trial's observed screening effects. Results: OncoSim-Breast's projected incidence, mortality and stage distribution of breast cancer were close to the observed data in the Canadian Cancer Registry and the Vital Statistics. OncoSim-Breast also reproduced the breast cancer screening effects observed in the UK Age trial. Interpretation: OncoSim-Breast's ability to reproduce the observed population-level breast cancer trends and the screening effects in a randomized trial increases the confidence of using its results to inform policy decisions related to early detection of breast cancer.