title: Can we apply lessons learned from Ebola experience in West Africa for COVID-19 in lower income countries?

text: The COVID-19 affects vulnerable groups disproportionally in a society where inequities are long-standing issue Weak health system, especially the shortage and maldistribution of capable health workforce will be the main challenge in lower income countries to fight against the COVID-19 Applying the lesson learned and success from the Ebola outbreak in West Africa is important International collaboration with already well functioned local mechanisms, such as the Network of Managers of Health Workforce in Francophone Africa is the key to provide prompt support This approach contributes not only to the short-term COVID-19 control but also long-term strengthening of the sustainable and resilient health system in the lower income countries


docid: atjuumty

title: Treatments administered to the first 9,152 reported cases of COVID19: a systematic review

text: Background The emergence of SARS-CoV-2/2019 novel coronavirus (COVID19) has created a global pandemic with no approved treatments or vaccines. Repurposing existing drugs and rapidly launching clinical trials present the greatest near-term opportunities for mitigating COVID19s impact. Many treatments have already been administered to COVID19 patients but have not been systematically evaluated. We performed a systematic literature review to identify and assess all treatments reported to be administered to COVID19 patients. Methods We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID19 patients published between Dec 1, 2019 and Mar 27, 2020. All studies reporting treatments were included. Data for each paper were manually extracted by two independent extractors. Outcomes included the duration from drug administration to clinically-meaningful response (complete symptom resolution or hospital discharge). Data were analysed descriptively. Results We identified 2,706 articles from single patient case reports to single-centre interventional studies. Of these, 155 studies met inclusion criteria, comprising 9,152 patients from 14 different countries. The cohort was 45.4% female and 98.3% hospitalised, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a response time of 11.7 (1.09) days. Discussion A large number of treatments have been administered to the first 9,152 reported cases of COVID19. Further work is needed to prioritise drugs for investigation in well-controlled clinical trials and treatment protocols. Funding None.


title: Lignocaine’s substantial role in COVID-19 management: Potential remedial and therapeutic implications

text: Background: The outbreak caused by SARS CoV-2 of the recent coronavirus disease-2019 (COVID-19) has been marked as a public health concern with a significant mortality at the global level. Lignocaine a common anesthetic agent being used for pain free surgeries for over a long period of time has expressed extensive characteristic of being an anti-inflammatory, antibacterial, direct spasmolytic, ion channel blocking and repolarization agent. We did a literature review Methodology: Currently compiled over-view has for the first time evaluated the probable curative and therapeutic role of nebulized lignocaine drug against SARS CoV-2 by utilization of PubMed, MEDLINE, NHS Evidence and Web of Science databases. Results: With evidence of nebulized lignocaine being used successfully in respiratory illness before and the established role of low concentration lignocaine as ion channel repolarization agent, we try to interpret and deduce the possible implication of nebulized lignocaine as possible therapeutic agent and a potential cure against SARS-CoV-2 caused respiratory illness by acting as an anti-inflammatory agent during SARS-CoV-2 caused acute lung injury and also possibly as an antiviral drug. Conclusion: By the virtue of possessing anti-inflammatory effect and potential antiviral effects, nebulized lignocaine can be a breakthrough in the management of the current COVID-19 pandemic.


Pandemic times: Learning well in a time of COVID-19


title: Estimate of COVID-19 case prevalence in India based on surveillance data of patients with severe acute respiratory illness

text: In absence of extensive testing for SARS-CoV-2, true prevalence of COVID-19 cases in India remain unknown. In this study, a conservative estimate of prevalence of COVID-19 is calculated based on the age wise COVID-19 positivity rate among patients with severe respiratory illness as reported by Indian Council of Medical Research. Calculations in the study estimates a cumulative number of 17151 COVID-19 positive cases by the end of April 2, 2020.


title: Radiographic Findings and other Predictors in Adults with Covid-19

text: As of March 20, 2020, there were 234,073 confirmed cases of coronavirus disease 2019 (Covid-19) and 9,840 deaths worldwide. Older age and elevated d-dimer are reported risk factors for Covid-19. However, whether early radiographic change is a predictor of fatality remains unknown. We retrospectively reviewed records of all laboratory-confirmed patients admitted to a quarantine unit at Tongji Hospital, a large regional hospital in Wuhan, China, between January 31 and March 5, 2020. The Tongji Hospital ethics committee approved this study. A total of 128 patients were admitted. 102 patients were confirmed to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using RNA detection. As of March 20, 82 confirmed patients were discharged, 15 died, and 5 remained hospitalized. The median age was 57 years (range, 27 - 85), 59 (58%) were male, and 44 (43%) patients had a comorbidity. The most common symptoms were fever, cough, and dyspnea. When compared with survivors, non-survivors were older and more likely to have lymphopenia, elevated lactate dehydrogenase (LDH), elevated d-dimer, and increased hypersensitive troponin I. In a multivariate regression model that included these predictors, older age and elevated LDH were independent risk factors for fatality. Twenty-one survivors and 11 non-survivors had CT scans within the first week. We used severity score to quantify the extent of lung opacification as described in the Supplementary Appendix. The total severity score and number of involved lung lobes within the first week were significantly greater in non-survivors compared to survivors . Using univariate logistic regression analysis, higher total severity score ([≥]15) (odds ratio 53, 95% CI 3-369; p = 0.003), and more involved lung lobes (5 involved lobes) (9, 2-53; p = 0.016) in CT images within the first week were significantly associated with fatality. Moreover, in this subset of patients with CT data within the first week, higher total severity score was the only independent risk factor in a multivariate analysis incorporated the predictors discussed above (older age, lymphocytopenia, elevated LDH, elevated d-dimer, and increased troponin I). For survivors with serial CT scans performed over four weeks, total severity score peaked in the second week. This report suggests that the extent of lung lesions in early CT images is a potential predictor of poor outcome of Covid-19. This will help clinicians to identify the patients with poor prognosis at early stage.


title: Association between consumption of fermented vegetables and COVID-19 mortality at a country level in Europe

text: Background Many foods have an antioxidant activity and nutrition may mitigate COVID-19. Some of the countries with a low COVID-19 mortality are those with a relatively high consumption of traditional fermented foods. To test the potential role of fermented foods in COVID-19 mortality in Europe, we performed an ecological study. Methods The European Food Safety Authority (EFSA) Comprehensive European Food Consumption Database was used to study the country consumption of fermented vegetables, pickled/marinated vegetables, fermented milk, yoghurt and fermented sour milk. We obtained the COVID-19 mortality per number of inhabitants from the Johns Hopkins Coronavirus Resource Center. EuroStat data were used for data on potential confounders at the country level including Gross Domestic Product (GDP) (2019), population density (2018), percentage of people older than 64 years (2019), unemployment rate (2019) and percentage obesity (2014, to avoid missing values). Mortality counts were analyzed with quasi-Poisson regression models - with log of population as an offset - to model the death rate while accounting for over-dispersion. Results Of all the variables considered, including confounders, only fermented vegetables reached statistical significance with the COVID-19 death rate per country. For each g/day increase in the average national consumption of fermented vegetables, the mortality risk for COVID-19 decreased by 35.4% (95% CI: 11.4%, 35.5%). Adjustment did not change the point estimate and results were still significant. Discussion The negative ecological association between COVID-19 mortality and consumption of fermented vegetables supports the a priory hypothesis previously reported. The hypothesis needs to be tested in individual studies performed in countries where the consumption of fermented vegetables is common.


title: Antibody repertoire induced by SARS-CoV-2 spike protein immunogens

text: Multiple vaccine candidates against SARS-CoV-2 based on viral spike protein are under development. However, there is limited information on the quality of antibody response generated following vaccination by these vaccine modalities. To better understand antibody response induced by spike protein-based vaccines, we immunized rabbits with various SARS-CoV-2 spike protein antigens: S-ectodomain (S1+S2) (aa 16-1213), which lacks the cytoplasmic and transmembrane domains (CT-TM), the S1 domain (aa 16-685), the receptor-binding domain (RBD) (aa 319-541), and the S2 domain (aa 686-1213 as control). Antibody response was analyzed by ELISA, Surface Plasmon Resonance (SPR) against different Spike proteins in native conformation, and a pseudovirion neutralization assay to measure the quality and function of the antibodies elicited by the different Spike antigens. All three antigens (S1+S2 ectodomain, S1 domain, and RBD) generated strong neutralizing antibodies against SARS-CoV-2. Vaccination induced antibody repertoire was analyzed by SARS-CoV-2 spike Genome Fragment Phage Display Libraries (SARS-CoV-2 GFPDL), which identified immunodominant epitopes in the S1, S1-RBD and S2 domains. Furthermore, these analyses demonstrated that surprisingly the RBD immunogen elicited a higher antibody titer with 5-fold higher affinity antibodies to native spike antigens compared with other spike antigens. These findings may help guide rational vaccine design and facilitate development and evaluation of effective therapeutics and vaccines against COVID-19 disease. One Sentence Summary SARS-CoV-2 Spike induced immune response


docid: beoseizn

title: Crystal structure of the SARS-CoV-2 non-structural protein 9, Nsp9

text: Many of the proteins produced by SARS-CoV-2 have related counterparts across the Severe Acute Respiratory Syndrome (SARS-CoV) family. One such protein is non-structural protein 9 (Nsp9), which is thought to mediate both viral replication and virulence. Current understanding suggests that Nsp9 is involved in viral genomic RNA reproduction. Nsp9 is thought to bind RNA via a fold that is unique to this class of betacoronoaviruses although the molecular basis for this remains ill-defined. We sought to better characterise the SARS-CoV-2 Nsp9 protein and subsequently solved its X-ray crystal structure, in an apo-form and, unexpectedly, in a peptide-bound form with a sequence originating from a rhinoviral 3C protease sequence (LEVL). The structure of the SARS-CoV-2 Nsp9 revealed the high level of structural conservation within the Nsp9 family. The exogenous peptide binding site is close to the dimer interface and impacted on the relative juxtaposition of the monomers within the homodimer. Together we have established a protocol for the production of SARS-CoV-2 Nsp9, determined its structure and identified a peptide-binding site that may warrant further study from the perspective of understanding Nsp9 function.


Research Issues for Relieving Social Anxiety with COVID-19 Outbreak using Ergonomic Nudge Ideas


docid: dtlwjndn

title: The clinical characteristics and mortal causes analysis of COVID-19 death patients

text: Abstract Purpose: Currently, COVID-19 is causing a large number of deaths globally. However, few researches focused on the clinical features of death patients. This study conducted a retrospective analysis of clinical characteristics and mortal causes in Chinese COVID-19 death patients. Patients and methods: The clinical characteristics of death patients were collected from publicized by local health authorities in China. Expressions of virus targets in human organs were obtained from GTEx database. Results: 159 patients from 24 provinces in China were recruited in our study, including 26 young patients under 60 and 133 aged 60 or older. The median age was 71 years, which indicated that most death patients were elderly. More male patients died of COVID-19 than females (1.65 fold). Hypertension was the most common coexisting disorder and respiratory failure was the most common direct cause of death. Fever (71.19%) and cough (55.08%) were the predominant presenting symptoms. There was one asymptomatic patient. In addition, by comparing young and old patients, heart disease was identified as an important risk factor for death in the aged patients. ACE2 and TMPRSS2 were the targets of SARS-CoV-2, we analyzed their expression in different organs. TMPRSS2 and ACE2 had a high expression in the organs which had corresponding clinical features in death patients. Conclusion: Male, age and heart disease were the main risk factors of death. Beside, asymptomatic patients with serious coexisting disorders may also die of SARS-CoV-2. Thus, more attention should be paid to the old patients with heart disease and asymptomatic patients in the treatment . Keywords: COVID-19, SARS-Cov-2, death, coexisting disorder, cause of death


title: The Institutional and Cultural Context of Cross-National Variation in COVID-19 Outbreaks

text: Background. The COVID-19 pandemic poses an unprecedented and cascading threat to the health and economic prosperity of the world's population. Objectives. To understand whether the institutional and cultural context influences the COVID-19 outbreak. Methods. At the ecological level, regression coefficients are examined to figure out contextual variables influencing the pandemic's exponential growth rate across 96 countries. Results. While a strong institutional context is negatively associated with the outbreak (B = -0.55 ... -0.64, p < 0.001), the pandemic's growth rate is steeper in countries with a quality education system (B = 0.33, p < 0.001). Countries with an older population are more affected (B = 0.46, p < 0.001). Societies with individualistic (rather than collectivistic) values experience a flatter rate of pathogen proliferation (B = -0.31, p < 0.001), similarly for higher levels of power distance (B = -0.32, p < 0.001). Hedonistic values, that is seeking indulgence and not enduring restraints, are positively related to the outbreak (B = 0.23, p = 0.001). Conclusions. The results emphasize the need for public policy makers to pay close attention to the institutional and cultural context in their respective countries when instigating measures aimed at constricting the pandemic's growth.


Herzchirurgie in COVID-19-Zeiten: fachspezifischer Informationsbedarf


title: Nonpharmaceutical interventions for pandemic COVID-19: A cross-sectional investigation of US general public beliefs, attitudes, and actions

text: Nonpharmaceutical interventions (NPIs) represent the primary mitigation strategy for pandemic COVID-19. Despite this, many government agencies and members of the general public may be resistant to NPI adoption. We sought to understand public attitudes and beliefs regarding various NPIs and self-reported adoption of NPIs, and explore associations between NPI performance and the baseline characteristics of respondents. We performed a cross-sectional age-, sex-, and race- stratified survey of the general US population. Of the 1,005 respondents, 37% (95% CI 34.0, 39.9) felt that NPIs were inconvenient, while only 0.9% (95% CI 0.3, 1.5) of respondents believed that NPIs would not reduce their personal risk of illness. Respondents were most uncertain regarding the efficacy of mask and eye protection use, with 30.6% and 22.1%, respectively, unsure whether their use would slow disease spread. On univariate logistic regression analyses, NPI adherence was associated with a belief that NPIs would reduce personal risk of developing COVID-19 (OR 3.06, 95% CI [1.25, 7.48], p=0.014) and with a belief that the NPIs were not difficult to perform (OR 1.79, 95% CI [1.38, 2.31], p<0.0001). Respondents were compliant with straightforward, familiar, and heavily-encouraged NPI recommendations such as hand-washing; more onerous approaches, such as avoiding face touching, disinfecting surfaces, and wearing masks or goggles, were performed less frequently. NPI non-adherence is associated with both outcome expectations (belief that NPIs are effective) and process expectations (belief that NPIs are not overly inconvenient); these findings have important implications for designing public health outreach efforts, where the feasibility, as well as the effectiveness, of NPIs should be stressed.


docid: eerqrqwk

title: The contribution of asymptomatic SARS-CoV-2 infections to transmission - a model-based analysis of the Diamond Princess outbreak

text: Background: Some key gaps in the understanding of SARS-CoV-2 infection remain. One of them is the contribution to transmission from individuals experiencing asymptomatic infections. We aimed to characterise the proportion and infectiousness of asymptomatic infections using data from the outbreak on the Diamond Princess cruise ship. Methods: We used a transmission model of COVID-19 with asymptomatic and presymptomatic states calibrated to outbreak data from the Diamond Princess, to quantify the contribution of asymptomatic infections to transmission. Data available included the date of symptom onset for symptomatic disease for passengers and crew, the number of symptom agnostic tests done each day, and date of positive test for asymptomatic and presymptomatic individuals. Findings: On the Diamond Princess 74% (70-78%) of infections proceeded asymptomatically, i.e. a 1:3.8 case-to-infection ratio. Despite the intense testing 53%, (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. While the data did not allow identification of the infectiousness of asymptomatic infections, assuming no or low infectiousness resulted in posterior estimates for the net reproduction number of an individual progressing through presymptomatic and symptomatic stages in excess of 15. Interpretation: Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. This is essential to consider for countries when assessing the potential effectiveness of ongoing control measures to contain COVID-19.


title: Diagnosis and treatment of acute coronary syndrome during the novel coronavirus infection covid-19 pandemic

text: The novel coronavirus infection COVID-19 pandemic has spread to more than 180 countries. Cardiovascular patients belong to one of the susceptible population cohorts. There is a peculiar pathogenesis and variety of clinical manifestations of COVID-19, as well as difficulties with early diagnosis. Other unresolved issues are routing, surgery and therapy of such patients and comorbidities. Due to absence of well-defined algorithms and guidelines, the treatment of patients with acute coronary syndrome (ACS) in different countries is carried out differently. Interactions between antiviral and coronary artery disease medications are also not completely clear. Based on the available data, the main organizational and therapeutic approaches for ACS during the COVID-19 pandemic are reflected.


title: High COVID-19 incidence among Norwegian travellers returned from Lombardy: implications for travel restrictions

text: On February 27th, three cases of COVID-19 were reported among Norwegians that had recently returned from Lombardy, Italy. Travellers from the region rapidly became the most common source of imported infections in the earliest stage of the Norwegian COVID-19 epidemic. The situation was exacerbated by the unfortunate temporal overlap between the Norwegian winter holidays and intense epidemic spread of COVID-19 in Northern Italy, resulting in a large number of infected travellers. Here we combined flight data on travels between Norway and Lombardy with patient-level data to determine the fraction of travellers returning to Norway that had been infected with SARS-CoV-2. Travellers returning to Norway from Lombardy contracted COVID-19 at incidence rates up to 0.02 per person-day in the period spanning February 21st and March 1st, with a clear uptick in transmission in the middle of the period. This shows an example of the infection risk in tourist destinations being several fold higher than elsewhere in the region. In Norway, this is also supported by high rates of infections among tourists returning from Austria in February and March, despite a low number of reported cases in the country at the time. The massive COVID-19 prevalence among travellers suggest that mandatory quarantine of returning travellers or suspension of non-essential international flights is essential if the aim is to control or suppress the COVID-19 pandemic.


title: Serum protein profiling reveals a landscape of inflammation and immune signaling in early-stage COVID-19 infection

text: Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n=15) and influenza (n=13) patients. We identified a large set of differentially expressed proteins (n=125) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.


title: Dynamical asymmetry exposes 2019-nCoV prefusion spike

text: The novel coronavirus (2019-nCoV) spike protein is a smart molecular machine that instigates the entry of coronavirus to the host cell causing the COVID-19 pandemic. In this study, a structural-topology based model Hamiltonian of C3 symmetric trimeric spike is developed to explore its complete conformational energy landscape using molecular dynamic simulations. The study finds 2019-nCoV to adopt a unique strategy by undertaking a dynamic conformational asymmetry induced by a few unique inter-chain interactions. This results in two prevalent asymmetric structures of spike where one or two spike heads lifted up undergoing a dynamic transition likely to enhance rapid recognition of the host-cell receptor turning on its high-infectivity. The crucial interactions identified in this study are anticipated to potentially affect the efficacy of therapeutic targets. One Sentence Summary Inter-chain-interaction driven rapid symmetry breaking strategy adopted by the prefusion trimeric spike protein likely to make 2019-nCoV highly infective.


title: The effectiveness of social bubbles as part of a Covid-19 lockdown exit strategy, a modelling study

text: Background: During the Covid-19 lockdown, contact clustering in social bubbles may allow extending contacts beyond the household at minimal additional risk and hence has been considered as part of modified lockdown policy or a gradual lockdown exit strategy. We estimated the impact of such strategies on epidemic and mortality risk using the UK as a case study. Methods: We used an individual based model for a synthetic population similar to the UK, that is stratified into transmission risks from the community, within the household and from other households in the same social bubble. The base case considers a situation where non-essential shops and schools are closed, the secondary household attack rate is 20% and the initial reproduction number is 0.8. We simulate a number of strategies including variations of social bubbles, i.e. the forming of exclusive pairs of households, for particular subsets of households (households including children and single occupancy households), as well as for all households. We test the sensitivity of the results to a range of alternative model assumptions and parameters. Results: Clustering contacts outside the household into exclusive social bubbles is an effective strategy of increasing contacts while limiting some of the associated increase in epidemic risk. In the base case scenario social bubbles reduced cases and fatalities by 17% compared to an unclustered increase of contacts. We find that if all households were to form social bubbles the reproduction number would likely increase to 1.1 and therefore beyond the epidemic threshold of one. However, strategies that allow households with young children or single occupancy households to form social bubbles only increased the reproduction number by less than 10%. The corresponding increase in morbidity andmortality is proportional to the increase in the epidemic risk but is largely focussed in older adults independently of whether these are included in the social bubbles. Conclusions: Social bubbles can be an effective way of extending contacts beyond the household limiting the increase in epidemic risk, if managed appropriately.


title: Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping

text: The newly emergent SARS-CoV-2 coronavirus is closely related to SARS-CoV which emerged in 2002. Studies on coronaviruses in general, and SARS in particular, have identified the virus spike protein (S) as being central to virus tropism, to the generation of a protective antibody response and to the unambiguous detection of past infections. As a result of this centrality SARS-CoV-2 S protein has a role in many aspects of research from vaccines to diagnostic tests. We describe a number of recombinant forms of SARS-CoV-2 S expressed in commonly available expression systems and their preliminary use in diagnostics and epitope mapping. These sources may find use in the current and future analysis of the virus and the Covid-19 disease it causes.


title: Epidemiological Determinants of Acute Respiratory Syndrome Coronavirus-2 Disease Pandemic and The Role of the Bacille-Calmette-Guerin Vaccine in Reducing Morbidity and Mortality

text: This study analyzed the determinants of morbidity, mortality, and case fatality rate (CFR) of the ongoing pandemic of severe acute respiratory syndrome coronavirus-2 disease 2019 (COVID-19) Data for 210 countries and territories available in public domains were analyzed in relation to mandatory vaccination with Bacille-Calmette-Guerin (BCG), population density, median age of the country population, health care expenditure per capita, life expectancy at birth, healthy life expectancy, literacy rate, per capita gross domestic production adjusted to purchasing power (PPP), burden of tuberculosis (TB), acquired immunodeficiency disease caused by human immunodeficiency virus (HI V-AIDS), malaria, cardiovascular disease (CVD), neoplasm, diabetes, deaths due to energy-protein (food) deficiency (EPD), and per capita government spending on safe water and sanitation Mandatory BCG vaccination showed a highly significant (p<0 0001) negative correlation with COVID-19 morbidity (r = -0 62) and mortality (r = -0 58) rates, but no significant correlation with CFR The median age of the nation showed a significant (p<0 0001) positive correlation with COVID-19 morbidity (r= 0 40) and mortality (r = 0 34) rates, but no significant correlation with CFR The pandemic resulted in higher morbidity (r= 0 47, p<0 0001) and mortality (r= 0 25, p = 0 01) rates in countries with a higher PPP than in those with a lower PPP COVID-19 CFR and morbidity and mortality rates showed no significant correlation with population density, the burden of malaria or diabetes, or the level of spending on safe water and sanitation Only the burden of TB showed a positive correlation with CFR (r = 0 17, p = 0 05) However, COVID-19 morbidity showed a significant (p =0 05) negative correlation with the burden of TB, HI V-AIDS, CVD, and EPD Mortality and morbidity in COVID-19 patients showed a positive correlation with per capita health expenditure, life expectancy, the burden of neoplasia, and PPP


title: オープンサイエンスの効果と課題―新型コロナウイルスおよびCOVID-19に関する学術界の動向

text: 1．はじめに オープンサイエンスの効果はさまざまに論じられてき た。たとえば経済協力開発機構（OECD）の報告書 1) では， 科学研究の効率化，研究の透明性や質の向上，技術革新の 加速，経済への波及効果，地球規模の課題への取り組み， 共同研究の推進などが挙げられている。 折しも 2019 年 12 月以降，新型コロナウイルス（2019- nCoV）の感染が中国の武漢市から世界中に拡大して「地 球規模の課題」となっている。2020 年 1 月 30 日には世 界保健機関（WHO）が国際的な緊急事態であると宣言し た 2)。これに対して各国・地域の研究者，助成機関，学術 出版社といったステークホルダーが最新の研究成果の公開 と再利用を進めて対策にあたるという，まさに「オープン サイエンス」というべき動きが起きている。そこで本稿は 新型コロナウイルスに関する学術界の動向を概観した上 で，今回の事例におけるオープンサイエンスの効果と課題 について考察したい。なお，本稿の記述は 2020 年 2 月 6 日時点の情報に基づいている（情報が古い箇所もあろうか と思いますが，ご容赦を）。


title: Prioritizing the role of community health workers in the COVID-19 response

text: COVID-19 disproportionately affects the poor and vulnerable Community health workers are poised to play a pivotal role in fighting the pandemic, especially in countries with less resilient health systems Drawing from practitioner expertise across four WHO regions, this article outlines the targeted actions needed at different stages of the pandemic to achieve the following goals: (1) PROTECT healthcare workers, (2) INTERRUPT the virus, (3) MAINTAIN existing healthcare services while surging their capacity, and (4) SHIELD the most vulnerable from socioeconomic shocks While decisive action must be taken now to blunt the impact of the pandemic in countries likely to be hit the hardest, many of the investments in the supply chain, compensation, dedicated supervision, continuous training and performance management necessary for rapid community response in a pandemic are the same as those required to achieve universal healthcare and prevent the next epidemic


title: Problem drinking before and during the COVID-19 crisis in US and UK adults: Evidence from two population-based longitudinal studies

text: Background The impact of the COVID-19 crisis on potentially harmful alcohol consumption is unclear. Aims To test whether the prevalence of problem drinking has changed from before to during the COVID-19 crisis in the US and UK. Design/Setting We examined nationally representative longitudinal data on how problem drinking has changed from pre-pandemic levels among adults in the US (N=7,327; Understanding America Study) and UK (N=12,594; UK Household Longitudinal Study). Methods In the US, we examined rates of consuming alcohol [≥] 4 times in the past week at baseline (March, 2020) and across four waves of follow-up (April-May, 2020). In the UK we assessed the prevalence of consuming alcohol [≥] 4 times per week and weekly heavy episodic drinking using the AUDIT-C at baseline (2017-2019) and during the COVID-19 lockdown (April, 2020). We also tested whether there were specific groups at greater risk of increased problem drinking during the pandemic. Results Among US adults, there was a statistically significant increase in the percentage of participants reporting drinking alcohol [≥] 4 times a week which rose significantly from 11.7% to 17.9% (53% increase, p < .001) as the COVID-19 crisis developed in the US. Among UK adults, the percentage of participants reporting drinking [≥] 4 times a week increased significantly from 14.2% to 23% (62% increase, p < .001) and heavy episodic drinking at least weekly increased significantly from 9.7% to 16.6% (71% increase, p < .001) when compared to pre-COVID-19 lockdown levels. Trends were similar across population demographics, although those aged under 50 years and higher income groups displayed the largest increases. Conclusions The COVID-19 crisis has been associated with substantial increases in problematic drinking in both US and UK adults.


title: Advice from a systems-biology model of the Corona epidemics

text: Using standard systems biology methodologies a 14-compartment dynamic model was developed for the Corona virus epidemic. The model predicts that : (i) it will be impossible to limit lockdown intensity such that sufficient herd immunity develops for this epidemic to die down, (ii) the death toll from the SARS-CoV-2 virus decreases very strongly with increasing intensity of the lockdown, but (iii) the duration of the epidemic increases at first with that intensity and then decreases again, such that (iv) it may be best to begin with selecting a lockdown intensity beyond the intensity that leads to the maximum duration, (v) an intermittent lock down strategy should also work and be more acceptable socially and economically, (vi) an initially intensive but adaptive lockdown strategy should be most efficient, both in terms of its low number casualties and shorter duration, (vii) such an adaptive lockdown strategy offers the advantage of being robust to unexpected imports of the virus, e.g. due to international travel, (viii) the eradication strategy may still be superior as it leads to even fewer deaths and a shorter period of economic lockdown maximum, but should have the adaptive strategy as backup in case of unexpected inflation imports (ix) earlier detection of infections is perhaps the most effective way in which the epidemic can be controlled more readily, whilst waiting for vaccines.


docid: wtqwghon

title: Relative disease burdens of COVID-19 and seasonal influenza in New York City, February 1 - April 18, 2020.

text: Comparisons between the mortality burdens of COVID-19 and seasonal influenza often fail to account for the fact that the United States Centers for Disease Control and Prevention (CDC) reports annual influenza mortality estimates which are calculated based upon a series of assumptions about the underreporting of flu deaths. COVID-19 deaths, in contrast, are being reported as raw counts. In this report, we compare COVID-19 death counts to seasonal influenza death counts in New York City during the interval from February 1 - April 18, 2020. Using this approach, COVID-19 appears to have caused 21.4 times the number of deaths as seasonal influenza during the same period. We also assessed excess mortality in order to verify this finding. New York City has had approximately 13,032 excess all-cause mortality deaths during this time period. We assume that most of these deaths are COVID-19 related. We therefore calculated the ratio of excess deaths (i.e. assumed COVID-19 deaths) to seasonal influenza deaths during the same time interval and found a similar ratio of 21.1 COVID-19 to seasonal influenza deaths. Our findings are consistent with conditions on the ground today. Comparing COVID-19 deaths with CDC estimates of yearly influenza-related deaths would suggest that, this year, seasonal influenza has killed approximately the same number of Americans as COVID-19 has. This does not comport with the realities of the pandemic we see today.


title: Prediction of 2019-nCov in Italy based on PSO and inversion analysis

text: Although China achieved an early victory of controlling the novel coronavirus (2019-nCov), the overseas situation is overwhelming negative, especially in Italy. Up to March 11, 2020, 2019-nCov thoroughly broke out in Italy with over 10,000 confirmed cases notwithstanding the gradually block of the country since March 9, 2020. Estimation of possible infection population and prospective suggestion of handling spread based on exist data are of crucial importance. Considering of the biology parameters obtained based on Chinese clinical data in Wuhan, other scholars' work and real spread feature of 2019-nCov in Italy, we built a more applicable model called SEIJR with log-normal distributed time delay to forecast the trend of spreading. Adopting Particle Swarm Optimization (PSO), we estimated the early period average spreading velocity (0) and conducted inversion analysis of time point (T0) when the virus first hit the Italy. Based on fixed 0 and T0, we then obtained the average spreading velocity 1 after the lock by PSO. For the aim of offering expeditious advice, we generated the prediction trends with different which we considered would be helpful in addressing the infection. Not only solved the complex, nondifferentiable equation of epidemic model, our research also performs well in inversion analysis based on PSO which conveys informative outcomes for further discussion on precatious action. To conclude, the first day of spread is around February 1, 2020 with the early period average spreading velocity 0=0.330 which is higher than most cities in China except Wuhan. After locking the country and attaching great attention to public precaution, the 1 sharply descended to 0.278, indicting the effectiveness of these measures. Furthermore, in order to cope the disease before mid-April, take actions to control the under 0.25 is necessary. Code can be freely download from https://github.com/Summerwork/2019-nCov-Prediction.


COVID-19: An aerosol’s point of view from expiration to transmission to viral-mechanism


title: What we know about the novel coronavirus’s proteins

text: Scientists across the globe are gunning to understand the novel coronavirus, called SARS-CoV-2, and what makes it so contagious and deadly Several members of the coronavirus family infect humans: four cause the common cold, and two—SARS-CoV and MERS-CoV—have triggered dangerous epidemics The novel coronavirus’s closest kin is SARS-CoV, which jumped species from bats to civets to humans to cause the severe acute respiratory syndrome (SARS) epidemic of 2002–3 That SARS outbreak infected just over 8,000 people The current coronavirus pandemic has infected more than 2 million people and killed more than 130,000 as of April 15, according to data from Johns Hopkins University “From a molecular perspective, figuring out why the virus is so much more transmissible than past viruses is where we should be looking right now,” says Robert Kirchdoerfer, a structural biologist at the University of Wisconsin–Madison who studies how coronaviruses fuse with host cells While people infected


title: Co-movement of COVID-19 and Bitcoin: Evidence from wavelet coherence analysis

text: We apply wavelet methods to daily data of COVID-19 world deaths and daily Bitcoin prices from 31th December 2019 to 29th April 2020. We find, especially for the period post April 5, that levels of COVID-19 caused a rise in Bitcoin prices. We contribute to the fast-growing body of work on the financial impacts of COVID-19, as well as to ongoing consideration of whether Bitcoin is a safe haven investment. Our results should be of great interest to both scholars and policy makers, as well as investment professionals interested in the financial implications of both COVID-19 and cryptocurrencies.


title: Global view on virus infection in non-human primates and implication for public health and wildlife conservation

text: The pandemic outbreak and rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not only a threat for humans, but potentially also for many animals. Research has revealed that SARS-CoV-2 and other coronaviruses have been transmitted from animals to humans and vice versa, and across animal species, and hence, attracted public attention concerning host-virus interactions and transmission ways. Non-human primates (NHPs), as our evolutionary closest relatives, are susceptible to human viruses, and a number of pathogens are known to circulate between humans and NHPs. Here we generated global statistics of virus infection in NHPs (VI-NHPs). In total, 121 NHP species from 14 families have been reported to be infected by 139 DNA and RNA viruses from 23 virus families; 74.8 percent of viruses in NHPs have also been found in humans, indicative of the high potential for cross species transmission of these viruses. The top ten NHP species with high centrality in the NHP-virus network are two apes (Pan troglodytes, Pongo pygmaeus), seven Old World monkeys (Macaca mulatta, M. fascicularis, Papio cynocephalus, Lophocebus albigena, Chlorocebus aethiops, Cercopithecus ascanius, C. nictitans) and a lemur (Propithecus diadema). Besides apes, there is a high risk of virus circulation between humans and Old World monkeys, given the wide distribution of many Old World monkey species and their frequent contact with humans. We suggest epidemiological investigations in NHPs, specifically in Old World monkeys with close contact to humans, and other effective measures to prevent this potential circular transmission.


title: COVID-19 pandemic: Impact of lockdown, contact and non-contact transmissions on infection dynamics

text: COVID-19 coronavirus pandemic has virtually locked down the entire world of human population, and through its rapid and unstoppable spread COVID-19 has essentially compartmentalised the population merely into susceptible, exposed, infected and recovered classes. Adapting the classical epidemic modelling framework, two distinct routes of COVID-19 transmission are incorporated into a model: (a) direct person-to-person contact transmission, and (b) indirect airborne and fomites-driven transmission. The indirect non-contact transmission route needs to explored in models of COVID-19 spread, because evidences show that this route of transmission is entirely viable with hugely uncertain level of relative contribution. This theoretical study based on model simulations demonstrates the following: (1) Not incorporating indirect transmission route in the model leads to underestimation of the basic reproduction number, and hence will impact on the COVID-19 mitigation decisions; (2) Lockdown measures can suppress the primary infection peak, but will lead to a secondary peak whose relative strength and time of occurrence depend on the success and duration of the lockdown measures; (3) To make lockdown effective, a considerable level of reduction in both contact and non-contact transmission rates over a long period is required; (4) To bring down the infection cases below any hypothetical health-care capacity, reduction of non-contact transmission rate is key, and hence active measures should be taken to reduce non-contact transmission (e.g., extensive uses of areal and aerosol disinfectant in public spaces to improve contaminated surfaces and air); (5) Any premature withdrawal of lockdown following the sign of a brief retracement in the infection cases can backfire, and can lead to a quicker, sharper and higher secondary peak, due to reactivation of the two transmission routes. Based on these results, this study recommends that any exit policy from lockdown, should take into account the level of transmission reduction in both routes, the absolute scale of which will vary among countries depending on their health-service capacity, but should be computed using accurate time-series data on infection cases and transmission rates.


title: Critical care triaging in the shadow of COVID-19: Ethics considerations

text: Since the World Health Organization declared coronavirus disease 2019 (COVID-19) a Public Health Emergency of International Concern, COVID-19 infection and the associated mortality have increased exponentially, globally. South Africa (SA) is no exception. Concerns abound over whether SA’s healthcare system can withstand a demand for care that is disproportionate to current resources, both in the state and private health sectors. While healthcare professionals in SA have become resilient and adept at making difficult decisions in the face of resource limitations, a surge in COVID-19 cases could place a severe strain on the country’s critical care services and necessitate unprecedented rationing decisions. This could occur at two critical points: access to ventilation, and withdrawal of intensive care in non-responsive or deteriorating cases. The ethical dimensions of decision-making at both junctures merit urgent consideration.


title: Oxygen transfer characteristics of a hollow fiber dialyser: toward possible repurposing of dialysers as blood oxygenators in the context of constrained availability of respiratory support

text: The mass transfer characteristics for oxygen from the gas phase to blood in a hollow fiber renal dialysis unit was investigated in vitro with a view to using such devices to effect respiratory support in patients with viral pneumonia and acute respiratory distress syndrome. In our in vitro experiments, which were severely curtailed by prevailing circumstances, we used water as a substitute on the blood side. The water was saturated rapidly indicating that the system was flow limited rather than diffusion limited for oxygen transfer. Using these findings, we estimated the expected performance with blood and the results suggest that two dialysis units operating in parallel with a pure oxygen gas supply running counter-current to the blood flow, could supply up to 40% of the total required oxygen demand rate in an adult patient. While not studied, carbon dioxide elimination is likely to be feasible as well. It is thus possible that hollow fiber dialysis units operating with suitable roller pumps in a veno-venous access configuration, could serve as a cost-effective and readily available alternative or adjunct for respiratory support in the face of severe resource constraints. Verification and extension of our study is needed by well resourced laboratories who are still able to function during this unprecedented period of restrictions. If, after further studies and clinical considerations, this approach appears feasible, then consideration may be given to clinical deployment of this tech- nique in desperate situations where no alternative exists to preserve life.


title: Nowcasting and Forecasting the Spread of COVID-19 and Healthcare Demand In Turkey, A Modelling Study

text: Abstract Background: A new type of coronavirus (later named Sars-Cov-2) drew attention on 31 December 2019 after the reporting of 27 unidentified pneumonia cases detected in Wuhan, China to the World Health Organization (WHO). Rapid progression of the COVID-19 pandemic has revealed the necessity of epidemic modeling studies to evaluate the course of the epidemic and its burden on the health system. This study aims to estimate the total number of infected people, evaluate the consequences of social interventions on the healthcare system and predict the expected number of cases, intensive care needs, hospitalizations and mortality rates in Turkey according to possible scenarios via the SEIR-based epidemic modeling method. Methods: This study was carried out in three dimensions. In the first, the actual number of people infected in the community has been estimated using the number of deaths in Turkey. In the second, the expected total numbers of infected people, total deaths, total hospitalizations, and intensive care unit (ICU) bed needs have been predicted in case of no intervention. In third, the distribution of the expected number of infected people and deaths, ICU and non-ICU bed needs over time has predicted based on SEIR modeling. A simulator (TURKSAS) has been developed and predictions made in 4 scenarios for Turkey. Results: According to deaths, the estimated number of infected people in Turkey on March 21 was 123,030. In the case of no intervention (1st scenario), the expected total number of infected people is 72,091,595, the total number of deaths is 445,956, the attack rate is 88.1%, the mortality ratio is 0.54%. The ICU bed capacity in Turkey is expected to exceed 4.4-fold and non-ICU bed capacity exceeds 3.21-fold. In 2nd and 3rd scenarios according to the calculations made by considering the social compliance rates of the NPIs, the value of R0 is estimated to decrease from 3 to 1.38 level. Compliance with NPIs makes a 94,303 difference in the expected number of deaths. In both scenarios, the predicted peak value of occupied ICU and non-ICU beds remains below Turkey healthcare capacity. While this study conducted, curfew for >65 and <20 age groups were in force in Turkey. If the curfew is declared for the 21-64 age population (4th scenario), the R0 value drops below 1 (0.98), the expected deaths are 14,230 and the peak values of daily ICU and non-ICU bed demand are below the healthcare capacity. Discussion: Modeling epidemics with assumptions supported by scientific literature and establishing decision support systems based on objective criteria is an important requirement. According to scientific data for the population of Turkey, the situation is not expected to be of worse than predictions presented in the second dimension. Predictions show that 16 million people can be prevented from being infected and 100,000 deaths can be prevented by full compliance with the measures taken. Complete control of the pandemic is possible by keeping R0 below 1. For this, additional evidence-based measures are needed.


title: Estimating and forecasting COVID-19 attack rates and mortality

text: {We describe a model for estimating past and current infections as well as future deaths due to the ongoing COVID-19 pandemic. The model does not use confirmed case numbers and is based instead on recorded numbers of deaths and on the age-specific population distribution. A regularized deconvolution technique is used to infer past infections from recorded deaths. Forecasting is based on a compartmental SIR-type model, combined with a probability distribution for the time from infection to death. The effect of non-pharmaceutical interventions (NPIs) is modelled empirically, based on recent trends in the death rate. The model can also be used to study counterfactual scenarios based on hypothetical NPI policies.


title: COVID-19 lockdowns cause global air pollution declines with implications for public health risk

text: The lockdown response to COVID-19 has caused an unprecedented reduction in global economic activity. We test the hypothesis that this has reduced tropospheric and ground-level air pollution concentrations using satellite data and a network of >10,000 air quality stations. After accounting for the effects of meteorological variability, we find remarkable declines in ground-level nitrogen dioxide (NO2: -29 % with 95% confidence interval -44% to -13%), ozone (O3: -11%; -20% to -2%) and fine particulate matter (PM2.5: -9%; -28% to 10%) during the first two weeks of lockdown (n = 27 countries). These results are largely mirrored by satellite measures of the troposphere although long-distance transport of PM2.5 resulted in more heterogeneous changes relative to NO2. Pollutant anomalies were related to short-term health outcomes using empirical exposure-response functions. We estimate that there was a net total of 7400 (340 to 14600) premature deaths and 6600 (4900 to 7900) pediatric asthma cases avoided during two weeks post-lockdown. In China and India alone, the PM2.5-related avoided premature mortality was 1400 (1100 to 1700) and 5300 (1000 to 11700), respectively. Assuming that the lockdown-induced deviations in pollutant concentrations are maintained for the duration of 2020, we estimate 0.78 (0.09 to 1.5) million premature deaths and 1.6 (0.8 to 2) million pediatric asthma cases could be avoided globally. While the state of global lockdown is not sustainable, these findings illustrate the potential health benefits gained from reducing 'business as usual' air pollutant emissions from economic activities.


title: An easily adopted murine model of distal pancreatectomy for investigating immunotherapy efficacy in resectable pancreatic adenocarcinoma

text: Background Although surgery provides the greatest therapeutic benefit to eligible pancreatic ductal adenocarcinoma (PDAC) patients it does not significantly improve survival for the majority of patients. Unfortunately our understanding of the therapeutic benefit of combining surgery with different treatment modalities including promising immunotherapeutics is limited by the current lack of easily adopted surgical models. The purpose of this study was to develop a surgically resectable model of PDAC in immunocompetent mice for use in preclinical investigations. Materials and Methods Surgically resectable orthotopic tumors were generated by injecting Pan02 cells into the tail of the pancreas. Fifteen days post implantation the primary tumors and tail of the pancreas were resected by laparotomy while preserving the spleen. Splenic function, tumor growth, immune phenotyping and survival were assessed following surgical resection of the primary tumor mass. Results As expected orthotopic tumor implants recapitulated many of the major histological hallmarks of PDAC including disrupted lobular structure and vascular invasion. Preservation of splenic immune cell viability and function was not associated with improved survival following surgery alone. However, pre-operative vaccination with GVAX was associated with improved survival which was not impacted by surgery. Conclusion This represents the first murine model of surgically resectable murine model of PDAC which recapitulates known pathological hallmarks of human disease in an immune competent model while allowing spleen preservation. This relatively simple and easily adopted approach provides an ideal platform to examine the efficacy of potential immunotherapy combinations for PDAC surgery patients.


COVID-19, Public Health Measures, Legal Considerations: A Medical Perspective


title: Ethnicity, comorbidity, socioeconomic status, and their associations with COVID-19 infection in England: a cohort analysis of UK Biobank data

text: Objectives: Recent data suggest higher COVID-19 rates and severity in Black, Asian, and minority ethnic (BAME) communities. The mechanisms underlying such associations remain unclear. We aimed to study the association between ethnicity and risk of COVID-19 infection and disentangle any correlation with socioeconomic deprivation or previous comorbidity. Design: Prospective cohort. Setting: UK Biobank linked to Hospital Episode Statistics (HES) and COVID-19 tests until 14 April 2020. Participants: UK Biobank participants from England, excluding drop-outs and deaths. Main measures: COVID-19 infection based on a positive PCR test. Ethnicity was self-reported and classified using Office of National Statistics groups. Socioeconomic status was based on index of multiple deprivation quintiles. Comorbidities were self-reported and completed from HES. Analyses: Multivariable Poisson analysis to estimate incidence rate ratios of COVID-19 infection according to ethnicity, adjusted for socioeconomic status, alcohol drinking, smoking, body mass index, age, sex, and comorbidity. Results: 415,582 participants were included, with 1,416 tested and 651 positive for COVID-19. The incidence of COVID-19 was 0.61% (95% CI: 0.46%-0.82%) in Black/Black British participants, 0.32% (0.19%-0.56%) in other ethnicities, 0.32% (0.23%-0.47%) in Asian/Asian British, 0.30% (0.11%-0.80%) in Chinese, 0.16% (0.06%-0.41%) in mixed, and 0.14% (0.13%-0.15%) in White. Compared with White participants, Black/Black British participants had an adjusted relative risk (RR) of 3.30 (2.39-4.55), Chinese participants 3.00 (1.11-8.06), Asian/Asian British participants 2.04 (1.36-3.07), other ethnicities 1.93 (1.08-3.45), and mixed ethnicities 1.07 (0.40-2.86). Socioeconomic status (adjusted RR 1.93 (1.51-2.46) for the most deprived), obesity (adjusted RR 1.04 (1.02-1.05) per kg/m2) and comorbid hypertension, chronic obstructive pulmonary disease, asthma, and specific renal diseases were also associated with increased risk of COVID-19. Conclusions: COVID-19 rates in the UK are higher in BAME communities, those living in deprived areas, obese patients, and patients with previous comorbidity. Public health strategies are needed to reduce COVID-19 infections among the most susceptible groups.


title: Does sub-Saharan Africa truly defy the forecasts of the COVID-19 pandemic? Response from population data

text: Introduction. Since its identification, the COVID-19 infection has caused substantial mortality and morbidity worldwide, but sub-Saharan Africa seems to defy the predictions. We aimed to verify this hypothesis using strong statistical methods. Methods. We conducted a cross-sectional study comparing the projected and actual numbers as well as population proportions of COVID-19 cases in the 46 sub-Saharan African countries on May 1st, May 29th (4 weeks later) and June 26th (8 weeks later). The source of the projected number of cases was a publication by scientists from the Center for Mathematical Modeling of Infectious Diseases of the London School of Hygiene & Tropical Medicine, whereas the actual number of cases was obtained from the WHO situation reports. We calculated the percentage difference between the projected and actual numbers of cases per country. Further, N-1 chi-square tests with Bonferroni correction were used to compare the projected and actual population proportion of COVID-19 cases, along with the 95% confidence interval of the difference between these population proportions. All statistical tests were 2-sided, with 0.05 used as threshold for statistical significance. Results. On May 1st, May 29th and June 26th, respectively 40 (86.95%), 45 (97.82%) and 41 (89.13%) of the sub-Saharan African countries reported a number of confirmed cases that was lower than the predicted number of 1000 cases for May 1st and 10000 for both May 29th and June 26th. At these dates, the population proportions of confirmed Covid-19 cases were significantly lower (p-value <0.05) than the projected proportions of cases. Across all these dates, South-Africa always exceeded the predicted number and population proportion of COVID-19 infections. Conclusion. Sub-Saharan African countries did defy the dire predictions of the COVID-19 burden. Preventive measures should be further enforced to preserve this positive outcome.


title: Protective elements of mental health status during the COVID-19 outbreak in the Portuguese population

text: The outbreak of COVID-19 might produce dramatic psychological effects on the individuals' life. In this study, we aimed to explore the elements that may reduce the negative effects on mental health of the quarantine period imposed by most governments during this worldwide crisis. We conducted an online survey to evaluate demographic, lifestyle and mental health variables in the Portuguese population. We observed that factors related with living conditions, maintaining the work either online or in the workplace, frequency of exercise and absence of a previous psychological or physic disorders are protective features of psychological well-being (anxiety, depression, stress and obsessive-compulsive symptoms). Finally, the individuals previously receiving psychotherapeutic support exhibited better psychological indicators if they did not interrupt the process as a consequence of the outbreak. Our results indicate that the practice of physical exercise, reduced consumption of COVID-19 information and the implementation of remote mental healthcare measures might prevent larger impacts on mental health during the COVID-19 outbreak.


title: Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host-glycosylation target

text: Mammalian protein N-linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition and function. N-linked glycans are synthesized from Glc3Man9GlcNAc2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases. Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and unusually is located within the Golgi, where it allows ER escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II. There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection. Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur upon substrate binding. We reveal structural features of the human enzyme that explain its substrate preference and the mechanistic basis for catalysis. The structures inspired the development of new inhibitors that disrupted host protein N-glycan processing of viral glycans and reduced infectivity of bovine viral diarrhea and dengue viruses in cellular models. These results may contribute to efforts of developing broad-spectrum antiviral agents and bring about a more detailed view of the biology of mammalian glycosylation. SIGNIFICANCE STATEMENT The glycosylation of proteins is a major protein modification that occurs extensively in eukaryotes. Glycosidases in the secretory pathway that trim N-linked glycans play a key role in protein quality control and in the specific modifications leading to mature glycoproteins. Inhibition of glucosidases in the secretory pathway is a proven therapeutic strategy, and one with great promise in the treatment of viral disease. The enzyme endo-α-1,2-mannosidase, MANEA, provides an alternative processing pathway to evade glucosidase inhibitors. We report the 3D structure of human MANEA and complexes with bespoke enzyme inhibitors that we show act as antivirals for bovine viral diarrhea and human dengue viruses. The structure of MANEA will support inhibitor optimization and the development of more potent antivirals.


title: Association of inflammatory markers with the severity of COVID-19

text: Background: The ongoing worldwide epidemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a huge threat to global public health. However, with regard to the effects of inflammatory markers on the severity of COVID-19, studies have reported associations that vary in strength and direction. Aims: In the meta-analysis, we aimed to provide an overview of the association of inflammatory markers with severity of COVID-19. Methods: The following databases were searched: PubMed, Embase, Cochrane Library, Wanfang database and CNKI (China National Knowledge Infrastructure) database until March 20, 2020. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were pooled using random or fixed-effects models. Results: A total of 16 studies were included in our analysis comprising of 3962 patients with COVID-19. Random-effects results demonstrated that patients with COVID-19 in non-severe group had lower levels for CRP (WMD = -41.78 mg/l, 95% CI = [-52.43, -31.13], P < 0.001), PCT (WMD = -0.13 ng/ml, 95% CI = [-0.20, -0.05], P < 0.001), IL-6 (WMD = -21.32 ng/l, 95% CI = [-28.34, -14.31], P < 0.001), ESR (WMD = -8.40 mm/h, 95% CI = [-14.32, -2.48], P = 0.005), SAA (WMD = -43.35 μg/ml, 95% CI = [-80.85, -5.85], P = 0.020) and serum ferritin (WMD = -398.80 mg/l, 95% CI = [-625.89, -171.71], P < 0.001), compared with those in severe group. Moreover, survivors had lower level for IL-6 than non-survivors with COVID-19 (WMD = -4.80 ng/ml, 95% CI = [-5.87, -3.73], P < 0.001). These results were consistent through sensitivity analysis and publication bias assessment. Conclusions: The meta-analysis highlights the association of inflammatory markers with the severity of COVID-19. Measurement of inflammatory markers might help clinicians to monitor and evaluate the severity and prognosis of COVID-19.


title: Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics

text: Prevalent resistance to inhibitors that target the influenza A M2 proton channel has necessitated a continued drug design effort, supported by a sustained study of the mechanism of channel function and inhibition. Recent high-resolution X-ray crystal structures present the first opportunity to see how the adamantyl-amine class of inhibitors bind to M2 and disrupt and interact with the channel’s water network, providing insight into the critical properties that enable their effective inhibition in wildtype M2. In this work, we test the hypothesis that these drugs act primarily as mechanism-based inhibitors by comparing hydrated excess proton stabilization during proton transport in M2 with the interactions revealed in the crystal structures, using the Multiscale Reactive Molecular Dynamics (MS-RMD) methodology. MS-RMD, unlike classical molecular dynamics, models the hydrated proton (hydronium-like cation) as a dynamic excess charge defect and allows bonds to break and form, capturing the intricate interactions between the hydrated excess proton, protein atoms, and water. Through this, we show that the ammonium group of the inhibitors is effectively positioned to take advantage of the channel’s natural ability to stabilize an excess protonic charge and is thus acting as a hydronium-mimic. Additionally, we show that the channel is especially stable in the drug binding region, highlighting the importance of this property for binding the adamantane group. Finally, we characterize an additional hinge point near Val27, which dynamically responds to charge and inhibitor binding. Altogether, this work further illuminates a dynamic understanding of the mechanism of drug inhibition in M2, grounded in the fundamental properties that enable the channel to transport and stabilize excess protons, with critical implications for future drug design efforts. TOC Graphic


title: Age-stratified model of the COVID-19 epidemic to analyze the impact of relaxing lockdown measures: nowcasting and forecasting for Switzerland

text: Compartmental models enable the analysis and prediction of an epidemic including the number of infected, hospitalized and deceased individuals in a population. They allow for computational case studies on non-pharmaceutical interventions thereby providing an important basis for policy makers. While research is ongoing on the transmission dynamics of the SARS-CoV-2 coronavirus, it is important to come up with epidemic models that can describe the main stages of the progression of the associated COVID-19 respiratory disease. We propose an age-stratified discrete compartment model as an alternative to differential equation based S-I-R type of models. The model captures the highly age-dependent progression of COVID-19 and is able to describe the day-by-day advancement of an infected individual in a modern health care system. The fully-identified model for Switzerland not only predicts the overall histories of the number of infected, hospitalized and deceased, but also the corresponding age-distributions. The model-based analysis of the outbreak reveals an average infection fatality ratio of 0.4% with a pronounced maximum of 9.5% for those aged [≥]80 years. The predictions for different scenarios of relaxing the soft lockdown indicate a low risk of overloading the hospitals through a second wave of infections. However, there is a hidden risk of a significant increase in the total fatalities (by up to 200%) in case schools reopen with insufficient containment measures in place.


title: Cellphone tracking could help stem the spread of coronavirus. Is privacy the price?

text: “IT IS POSSIBLE TO STOP THE EPIDEMIC ” That’s the message splashed atop a website built by a University of Oxford team this week to share new research on the spread of the novel coronavirus Below that hopeful statement comes a big caveat: To stop the virus’ spread, health officials need to find and isolate the contacts of infected people—lots of them—and fast Such contact tracing is a mainstay of infectious disease control But the Oxford team is one of several now advocating for a new approach: tapping into cellphone location data to track the spread of infection and warn people who may have been exposed


title: Hydroxychloroquine for the management of COVID-19: Hope or Hype? A Systematic review of the current evidence

text: Purpose: The COVID-19 Pandemic has literally left the world breathless in the chase for Pharmacotherapy. With the vaccine approval likely more than a year away and novel drugs in early clinical trials, repurposing of existing drugs takes the center stage. A potential drug discussed both in geopolitical and global scientific community is hydroxychloroquine (HCQ). We intend to systematically weigh and analyze the existing evidence of HCQ in the light of published and pre-print data available so far. Methods: PubMed Ovid MEDLINE, EMBASE, Google scholar databases and official clinical trial Registries of the United States, China, WHO ICTRP were electronically searched for studies for the use of HCQ in patients with COVID-19. Pre-proof article repositories like MedRxiv, BioRxiv, and ChemRxiv were also included in the search. The literature was critically appraised. Results: Total 71 articles were available as of 15 th April of which articles of relevance (three invitro studies, two open label non-randomized trials, two open label randomized control trials, one follow-up study, three reviews, ten short communications) and 88 clinical trials registered in three clinical trial registries were analyzed. HCQ seems to be efficient in inhibiting of SARS CoV-2 in in-vitro cell lines; there is lack of strong evidence from human studies. Conclusions: The in-vitro cell culture based data of viral inhibition does not suffice for the use of hydroxychloroquine in the patients with COVID-19. Currently literature shows inadequate, low level evidence in human studies. Scarcity of safety and efficacy data warrants medical communities, health care agencies and governments across the world against the widespread use of HCQ in COVID-19 prophylaxis and treatment, until robust evidence becomes available. Keywords: Hydroxychloroquine, SARS-CoV-2, COVID-19, Corona virus, nCov2, systematic review


title: The Use of Adjuvant Therapy in Preventing Progression to Severe Pneumonia in Patients with Coronavirus Disease 2019: A Multicenter Data Analysis

text: ABSTRACT IMPORTANCE Coronavirus disease 2019 (COVID-19) is a global pandemic associated with high mortality and effective treatment to prevent clinical deterioration to severe pneumonia has not yet been well clarified. OBJECTIVE To investigate the role of several adjuvant treatments in preventing severe pneumonia in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS Multicenter, retrospective cohort study of 564 consecutively hospitalized patients with confirmed COVID-19 at Third Xiangya Hospital of Central South University, Changsha Public Health Treatment Center, First Hospital of Yueyang, Junshan People's Hospital of Yueyang, Central Hospital of Shaoyang, Central Hospital of Xiangtan, Second Hospital of Changde, Central Hospital of Loudi, and First Affiliated Hospital of University of South China in Hunan province from January 17, 2020 to February 28, 2020; The final date of follow-up was March 15, 2020. EXPOSURES Nonspecific antivirals (arbidol, lopinavir/ritonavir, and interferon α), antihypertensives, and chloroquine. MAIN OUTCOMES AND MEASURES The development of severe COVID-19 pneumonia; Demographic, epidemiological, clinical, laboratory, radiological, and treatment data were collected and analyzed. RESULTS Of 564 patients, the median age was 47 years (interquartile range, 36-58 years), and 284 (50.4%) patients were men. Sixty-nine patients (12.2%) developed severe pneumonia. Patients who developed severe pneumonia were older (median age of 59 and 45 years, respectively), and more patients had comorbidities including hypertension (30.4% and 12.3%, respectively), diabetes (17.4% and 6.7%, respectively), and cardiovascular disease (8.7% and 3.2%, respectively) and presented with fever (84.1% and 60.4%, respectively) and shortness of breath (10.1% and 3.8%, respectively) compared with those who did not. Nonspecific antiviral therapy did not prevent clinical progression to severe pneumonia, although fewer hypertensive patients on angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARB) therapy developed severe pneumonia in contrast with those on non-ACEI/ARB antihypertensive therapy (1 of 16 [6.3%] patients and 16 of 49 [32.7%] patients, respectively [difference, 26.4%; 95% CI, 1.5% to 41.3%]). Multivariate logistic regression analysis showed that hypertension without receiving ACEI/ARB therapy was an independent risk factor (odds ratio [OR], 2.07; 95% CI, 1.07 to 4.00) for developing severe pneumonia irrespective of age. Besides, none of patients treated with chloroquine developed severe pneumonia, though without significance (difference, 12.0%; 95% CI, -3.5% to 30.0%) by propensity score matching. CONCLUSIONS AND RELEVANCE Hypertensive patients on ACEI or ARB may be protective from severe pneumonia in COVID-19 and hence these therapies should not be ceased unless there is a strong indication or further epidemiological evidence. Though none of the current antiviral and immunoregulation therapy showed benefit in preventing COVID-19 progression, chloroquine deserved further investigation.


title: Preliminary experimental analysis of the surface topography formation during laser polishing H13 tooling steel using statistical characteristics of the surface amplitude distribution

text: Abstract Surface finish is one of the most important quality characteristics of fabricated components. To complement that, laser polishing (LP) is one of the advanced manufacturing surface finishing techniques that has been recently developed and successfully employed for improving surface quality without deteriorating the overall structural form through surface smoothing by melting and redistributing a thin layer of molten material. This paper proposes a statistical digital twin of the LP process and demonstrates the applicability of amplitude distribution statistical characteristics in the experimental analysis of surface topography formation during LP process. Initially, the thermodynamic transformation of the initial surface topography is considered by means of technical cybernetics and machine learning approaches to describe two of the most critical LP process components, namely: thermodynamic melting and solidification of both solid material and surface topography. To exemplify the effective application of statistical amplitude distribution characteristics, LP experiments were conducted with two different laser powers (25 W and 100 W) on flat and ground initial surfaces and resulting surface topographies were measured. Several amplitude distribution characteristics, such as roughness average value, averaged transverse profile as a W-shape, averaged transverse roughness profile, and probability distribution function were calculated. After that, actual molten material area, volume redistribution and final surface quality were comparatively analyzed. It was shown that the proportion between two components of the LP thermodynamic transformation and surface topography is critically dependent on laser power. As such, during low-power conditions (< 25 W), surface quality is predominantly determined by the thermodynamic transformation of initial surface topography and therefore only this component can be used for statistically reliable LP process modelling and digital identification. In summary, amplitude distribution characteristics have several advantages in building a comprehensive understanding of the molten material redistributing along and across LP line.


title: Transmission dynamics and control measures of COVID-19 outbreak in China: a modelling study

text: COVID-19 is reported to have been effectively brought under control in China at its initial start place. To understand the COVID-19 outbreak in China and provide potential lessons for other parts of the world, in this study we combine a mathematical modelling with multiple datasets to estimate its transmissibility and severity and how it was affected by the unprecedented control measures. Our analyses show that before 29th January 2020, the ascertainment rate is 6.9%(95%CI: 3.5 - 14.6%); then it increased to 41.5%(95%CI: 30.6 - 65.1%). The basic reproduction number (R0) was 2.23(95%CI: 1.86 - 3.22) before 8th February 2020; then it dropped to 0.04(95%CI: 0.01 - 0.10). This estimation also indicates that the effect on transmissibility of control measures taken since 23rd January 2020 emerged about two weeks late. The confirmed case fatality rate is estimated at 4.41%(95%CI: 3.65 - 5.30%). This shows that SARS-CoV-2 virus is highly transmissible but less severe than SARS-CoV-1 and MERS-CoV. We found that at the early stage, the majority of R0 comes from the undetected infected people. This implies that the successful control in China was achieved through decreasing the contact rates among people in general populations and increasing the rate of detection and quarantine of the infected cases.


Perceived risk of COVID-19 pandemic: The role of public worry and trust


title: Real-world Experience with Favipiravir for Treatment of COVID-19 in Thailand: Results from a Multi-center Observational Study

text: Background. Favipiravir is a broad-spectrum oral antiviral agent that shows in vitro activity against SARS-CoV-2. Presently, data on the effectiveness and optimal dosage of favipiravir for treating COVID-19 is limited. Methods. We conducted a retrospective observational study of hospitalized adult patients with COVID-19 at five tertiary care hospitals in Thailand. We reviewed patient charts to obtain all necessary data. Results. Among 247 COVID-19 patients, 63 (23.0%) received [≥]1 dose of favipiravir. Of these, 27.0% required an O2-nasal cannula, 9.5% required non-invasive ventilation and/or high-flow O2-therapy, and 6.4% required invasive mechanical ventilation and/or ECMO. The median baseline NEWS2 score was 5(0-16). The Day-7 clinical improvement rate [95%CI] was 66.7%[53.7-78.0%] in all patients, 92.5%[75.7%-99.1%] in patients who did not require O2-supplementation, and 47.2%[0.4%-64.5%] in patients who required O2-supplementation. No life-threatening adverse events were identified. The 28-day mortality rate was 4.8%. Multivariate analysis revealed three poor prognostic factors for Day-7 clinical improvement [odds ratio (95%CI); p-value]: older age [0.94 (0.89 to 0.99); p=0.04], higher baseline NEWS2 score [0.64 (0.47 to 0.88); p=0.006], and lower favipiravir loading dose ([≤]45 mg/kg/day) [0.04 (0.005 to 0.4); p=0.006]. Conclusions. Our study reports the promising effectiveness of favipiravir for treating COVID-19 patients. In addition to older age and a high baseline NEWS2 score, a low loading dose of favipiravir ([≥]45 mg/kg/day) was also identified as a poor prognostic factor for early clinical improvement. Further studies to explore the optimal dose and the optimal timing of drug initiation for favipiravir should be performed.


title: Effectiveness of simulation based teaching of ventilatory management among non-anaesthesiology residents to manage COVID 19 pandemic - A Quasi experimental cross sectional pilot study

text: Background and Aims: Simulation is one of the important learning tools when it comes to skill acquisition and as a supplemental tool for training in high stake situations like COVID-19. The aim of this study is to meet the global requirements of knowledge on ventilatory management, prepare and to evaluate the effectiveness of the teaching module for non-anesthesiology trainees on COVID-19 patients. Methods: Quasi experimental cross sectional pilot study was conducted with a sample of twenty-six trainees. A teaching module was prepared and validated which consisted of lectures, audio-video sessions, demonstrations with hands-on training, debriefing, analytical-phase and reflection. Pre and Post evaluations from student t-test and direct observation of procedural skills (DOPS) were used for knowledge and skill assessment respectively and feedback obtained from Likert's score. Results: Pre- and Post-tests had a mean score of 7.42 ± 2.12 and 14.92 ± 2.9 respectively (P value 0.00001). DOPS included 16 point score, in which 23 trainees (88.4%) met the expectations and above expectations as per training objectives. A five-point Likert's score feedback revealed satisfactory and highly satisfactory scores of 100% (ABG), 96.1% (mechanical ventilation), and 84.6% (ventilation in COVID-19 patients). Overall satisfaction for the workshop among respondents was 100 per cent. Confidences of handling scores were 84.5% (interpreting ABG), 65.3% (maneuvering mechanical ventilation), and 96.15% (intubation in COVID-19 patients). Conclusion: A planned teaching module in ventilation management helps to train non-anaesthesiologists more effectively as a part of COVID-19 preparedness. Simulation with debriefing based training to the medical fraternity is the best alternative in the present pandemic and it will also ensure the safety of health care professionals.


title: Know Your Epidemic, Know Your Response: Covid-19 in the United States

text: We document that during the week of March 10-16, the Covid-19 pandemic fundamentally affected the perceptions of U.S. residents about the health risks and socioeconomic consequences entailed by the pandemic. During this week, it seems, "everything changed." Not only did the pandemic progress rapidly across the United States, but U.S. residents started to realize that the threat was real: increasing Covid-19 caseloads heightened perceptions of infection risks and excess mortality risks, concerns about the economic implications increased substantially, and behavioral responses became widespread as the pandemic expanded rapidly in the U.S. In early to mid-March 2020, average perceptions about the coronavirus infection risks are broadly consistent with projections about the pandemic, while expectations about dying conditional on infection and expectations about Covid-19-related excess mortality during the next months are possibly too pessimistic. However, some aspects of Covid-19 perceptions are disconcerting from the perspective of implementing and sustaining an effective societal response to the pandemic. For instance, the education gradient in expected infection risks entails the possibility of having different perceptions of the reality of the pandemic between people with and without a college education, potentially resulting in two different levels of behavioral and policy-responses across individuals and regions. Unless addressed by effective health communication that reaches individuals across all social strata, some of the misperceptions about Covid-19 epidemic raise concerns about the ability of the United States to implement and sustain the widespread and harsh policies that are required to curtail the pandemic. Our analyses also reveal perceptions of becoming infected with the virus, and dying from Covid-19, were driven upwards by a rapidly increasing national caseload, and perceptions of the economic consequences and the adaptation of social distancing were affected by both national and state-level cases.


title: Remote machine mode detection in cold forging using vibration signal

text: Abstract Detecting machine mode can allow smarter process monitoring systems and more accurate fault prediction without external information. A remote machine monitoring system was installed on a cold heading machine in the factory of an automotive fastener manufacturing company. The process monitoring system was non-intrusive and was designed to measure vibration. The end goal of the study was to predict tool wear, but part classification was required first, as the machine produced multiple parts which produced different vibration signals. The collected vibration data was processed using wavelet transform and passed through a convolutional neural network for part classification. This method achieved part classification accuracy as high as 86% when looking at data for a 1-month period. The results show that meaningful classification features are present in the data using the process monitoring system as designed.


docid: qovbwixf

title: Early risk assessment for COVID-19 patients from emergency department data using machine learning

text: Background Since its emergence in late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic, with more than 4.8 million reported cases and 310 000 deaths worldwide. While epidemiological and clinical characteristics of COVID-19 have been reported, risk factors underlying the transition from mild to severe disease among patients remain poorly understood. Methods In this retrospective study, we analysed data of 820 confirmed COVID-19 positive patients admitted to a two-site NHS Trust hospital in London, England, between January 1st and April 23rd, 2020, with a majority of cases occurring in March and April. We extracted anonymised demographic data, physiological clinical variables and laboratory results from electronic healthcare records (EHR) and applied multivariate logistic regression, random forest and extreme gradient boosted trees. To evaluate the potential for early risk assessment, we used data available during patients' initial presentation at the emergency department (ED) to predict deterioration to one of three clinical endpoints in the remainder of the hospital stay: A) admission to intensive care, B) need for mechanical ventilation and C) mortality. Based on the trained models, we extracted the most informative clinical features in determining these patient trajectories. Results Considering our inclusion criteria, we have identified 126 of 820 (15%) patients that required intensive care, 62 of 808 (8%) patients needing mechanical ventilation, and 170 of 630 (27%) cases of in-hospital mortality. Our models learned successfully from early clinical data and predicted clinical endpoints with high accuracy, the best model achieving AUC-ROC scores of 0.75 to 0.83 (F1 scores of 0.41 to 0.56). Younger patient age was associated with an increased risk of receiving intensive care and ventilation, but lower risk of mortality. Clinical indicators of a patient's oxygen supply and selected laboratory results were most predictive of COVID-19 patient trajectories. Conclusion Among COVID-19 patients machine learning can aid in the early identification of those with a poor prognosis, using EHR data collected during a patient's first presentation at ED. Patient age and measures of oxygenation status during ED stay are primary indicators of poor patient outcomes.


title: How COVID-19 redefines the concept of sustainability

text: In January 2020, the World Health Organization (WHO) declared the outbreak of a new coronavirus disease, COVID-19, to be a public health emergency of international concern. Currently, in several countries globally, this pandemic continues to enforce the temporary closure of all nonessential shops and services aside from supermarkets and pharmacies. Workers in countries that are at a high risk of infection have been asked to work from home, as cities have been placed under lockdown. Even curfews to combat the spread of the virus have been imposed in several countries, with all this signaling an unprecedented disruption of commerce. Companies are facing various challenges regarding health and safety, supply chain, labor force, cash flow, consumer demand and marketing. People in the thousands are dying every day from the virus's symptoms, while a public health issue has forced the world to come to a halt and rethink what a sustainable future for our planet and existence is. These drastic recent events have raised the deliberation by the authors to redefine the concept of sustainability.


Global reach, global risk revisited


title: Plasma IL-6 Levels following Corticosteroid Therapy as an Indicator of ICU Length of Stay in Critically ill COVID-19 Patients

text: Intensive Care Unit (ICU) admissions and mortality in severe COVID-19 patients are driven by cytokine storms and acute respiratory distress syndrome (ARDS). Interim clinical trial results suggest that the corticosteroid dexamethasone displays superior 28-day survival in severe COVID-19 patients requiring ventilation or oxygen. Among 16 patients with plasma IL-6 measurement post-corticosteroid administration, a higher proportion of patients with an IL-6 value over 10 pg/mL have worse outcomes (i.e. ICU Length of Stay > 15 days or death) when compared to 41 patients treated with non-corticosteroid drugs including antivirals, tocilizumab, azithromycin, and hydroxychloroquine (p-value = 0.0024). Given this unexpected clinical association between post-corticosteroid IL-6 levels and COVID-19 severity, we hypothesized that the Glucocorticoid Receptor (GR or NR3C1) may be coupled to IL-6 expression in specific cell types that govern cytokine release syndrome (CRS). Examining single cell RNA-seq data from bronchoalveolar lavage fluid of severe COVID-19 patients and nearly 2 million human cells from a pan-tissue scan shows that alveolar macrophages, smooth muscle cells, and endothelial cells co-express both NR3C1 and IL-6. The mechanism of Glucocorticoid Receptor (GR) agonists mitigating pulmonary and multi-organ inflammation in some COVID-19 patients with respiratory failure, may be in part due to their successful antagonism of IL-6 production within lung macrophages and vasculature.


title: Mathematical modeling of the COVID-19 prevalence in Saudi Arabia

text: The swift precautionary and preventive measures and regulations that were adopted by the Saudi authority has ameliorated the exponential escalation of the SARS-CoV-2 virus spread, decreased the fatality rate and critical cases of COVID-19. Understanding the trend of COVID-19 is crucial to establishing the appropriate precautionary measures to mitigate the epidemic spread. The aim of this paper was to modifying and enhancing the mathematical modeling to guide health authority and assist in an early assessment of the epidemic outbreak and can be utilised to monitor non-pharmaceutical interventions (NPIs). Both ARIMA model and Logistic growth model were developed to study the trend and to provide short and long-term forecasting of the prevalence of COVID-19 cases and dynamics. The data analyzed in this study covered the period between 2nd March and 21st June 2020. Two different scenarios were developed to predict the epidemic fluctuating trends and dynamics. The first scenario covered the period between 2nd March and 28th May when the first peak was observed and immediately declined. The analysis projected that the COVID-19 epidemic to reach a peak by 17th May with a total number of 58,534 infected cases and to end on the 4th August, if lockdown were not interrupted and folks followed the recommended personal and social safety guidelines. The second scenario was simulated because of the sudden sharp spike witnessed in the trend of the new confirmed cases on the last week of May and continue to escalate till the time of current writing-21st June. In the 2nd scenario, the analysis estimated the epidemic to peak on 15th June with a total number of 146,004 infected cases and to end on 29th September, 2020 with a final size of 209,607 (185,757 to 244,310) infected cases, assuming that the NPIs will be maintained while new normal life is resumed carefully. ARIMA and Logistic growth models showed excellent performance in projecting the epidemic prevalence, trends and dynamics at different phases. In conclusion, the analysis presented in this paper will assist policy-makers and health care authorities to evaluate the effect of the NPIs applied and to size the resources needed to manage different phases and cope with the final size of the epidemic estimates and to impose extra precautions.


title: Computational Prediction of Mutational Effects on the SARS-CoV-2 Binding by Relative Free Energy Calculations

text: The ability of coronaviruses to infect humans is invariably associated with their binding strengths to human receptor proteins Both SARS-CoV-2, initially named 2019-nCoV, and SARS-CoV were reported to utilize angiotensin-converting enzyme 2 (ACE2) as an entry receptor in human cells To better understand the interplay between SARS-CoV-2 and ACE2, we performed computational alanine scanning mutagenesis on the “hotspot” residues at protein-protein interfaces using relative free energy calculations Our data suggest that the mutations in SARS-CoV-2 lead to a greater binding affinity relative to SARS-CoV In addition, our free energy calculations provide insight into the infectious ability of viruses on a physical basis, and also provide useful information for the design of antiviral drugs


title: Homologous protein domains in SARS-CoV-2 and measles, mumps and rubella viruses: preliminary evidence that MMR vaccine might provide protection against COVID-19

text: The COVID-19 disease is one of worst pandemics to sweep the globe in recent times. It is noteworthy that the disease has its greatest impact on the elderly. Herein, we investigated the potential of childhood vaccination, specifically against measles, mumps and rubella (MMR), to identify if this could potentially confer acquired protection over SARS-CoV-2. We identified sequence homology between the fusion proteins of SARS-CoV-2 and measles and mumps viruses. Moreover, we also identified a 29% amino acid sequence homology between the Macro (ADP-ribose-1-phosphatase) domains of SARS-CoV-2 and rubella virus. The rubella Macro domain has surface-exposed conserved residues and is present in the attenuated rubella virus in MMR. Hence, we hypothesize that MMR could protect against poor outcome in COVID-19 infection. As an initial test of this hypothesis, we identified that 1) age groups that most likely lack of MMR vaccine-induced immunity had the poorest outcome in COVID-19, and 2) COVID-19 disease burden correlates with rubella antibody titres, potentially induced by SARS-CoV2 homologous sequences. We therefore propose that vaccination of at risk age groups with an MMR vaccination merits further consideration as a time-appropriate and safe intervention.


title: Highly accurate and sensitive diagnostic detection of SARS-CoV-2 by digital PCR

text: BACKGROUND: The outbreak of COVID-19 caused by a novel Coronavirus (termed SARS-CoV-2) has spread to over 140 countries around the world. Currently, reverse transcription quantitative qPCR (RT-qPCR) is used as the gold standard for diagnostics of SARS-CoV-2. However, the positive rate of RT-qPCR assay of pharyngeal swab samples are reported to vary from 30~60%. More accurate and sensitive methods are urgently needed to support the quality assurance of the RT-qPCR or as an alternative diagnostic approach. METHODS：We established a reverse transcription digital PCR (RT-dPCR) protocol to detect SARS-CoV-2 on 194 clinical pharyngeal swab samples, including 103 suspected patients, 75 close contacts and 16 supposed convalescents. RESULTS: The limit of blanks (LoBs) of the RT-dPCR assays were ~1.6, ~1.6 and ~0.8 copies/reaction for ORF 1ab, N and E genes, respectively. The limit of detection (LoD) was 2 copies/reaction. For the 103 fever suspected patients, the sensitivity of SARS-CoV-2 detection was significantly improved from 28.2% by RT-qPCR to 87.4% by RT-dPCR. For close contacts, the suspect rate was greatly decreased from 21% down to 1%. The overall sensitivity, specificity and diagnostic accuracy of RT-dPCR were 90%, 100% and 93 %, respectively. In addition, quantification of the viral load for convalescents by RT-dPCR showed that a longer observation period was needed in the hospital for elderly patients. CONCLUSION: RT-dPCR could be a confirmatory method for suspected patients diagnosed by RT-qPCR. Furthermore, RT-dPCR was more sensitive and suitable for low viral load specimens from the both patients under isolation and those under observation who may not be exhibiting clinical symptoms.


title: Partial Prediction of the Virus COVID-19 Spread in Russia Based on SIR and SEIR Models

text: The possibility to predict the spread of COVID-19 in Russia is studied. Particular goal is to predict the time instant when the number of infected achieves its maximum (peak). Such a partial prediction allows one to use simple epidemoics models: SIR and SEIR. Simplicity and small number of parameters are significant advantages of SIR and SEIR models under conditions of a lack of numerical initial data and structural incompleteness of models. The prediction is carried out according to public WHO datasets from March 10 to April 20, 2020. Comparison of forecast results by SIR and SEIR models are given. In both cases, the peak number of infected persons while maintaining the current level of quarantine measures is forecasted at the end of May 2020 or later. It coincides with the real data obtained in May-June, 2020. The results confirm usefulness of simple nonlinear dynamical models for partial prediction of complex epidemics processes.