title: Broad and differential animal ACE2 receptor usage by SARS-CoV-2

text: The COVID-19 pandemic has caused an unprecedented global public health and economy crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, comparing to the SARS-CoV-2-like CoVs identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human ACE2 as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2 from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activity, respectively. Among the remaining species, ACE2 from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models.


title: Covid19 Surveillance in Peru on April using Text Mining

text: The present outbreak as consequence by coronavirus covid19 has generated an big impact over the world. South American countries had their own limitations, challengues and pandemic has highlighted what needs to improve. Peru is a country with good start with quarantine, social distancing policies but the policies was not enough during the weeks. So, the analysis over April is performed through infoveillance using posts from different cities to analyze what population was living or worried during this month. Results presents a high concern about international context, and national situation, besides Economy and Politics are issues to solve. By constrast, Religion and Transport are not very important for peruvian citizens.


title: Heparin inhibits cellular invasion by SARS-CoV-2: structural dependence of the interaction of the surface protein (spike) S1 receptor binding domain with heparin

text: The dependence of the host on the interaction of hundreds of extracellular proteins with the cell surface glycosaminoglycan heparan sulphate (HS) for the regulation of homeostasis is exploited by many microbial pathogens as a means of adherence and invasion. The closely related polysaccharide heparin, the widely used anticoagulant drug, which is structurally similar to HS and is a common experimental proxy, can be expected to mimic the properties of HS. Heparin prevents infection by a range of viruses if added exogenously, including S-associated coronavirus strain HSR1. Heparin prevents infection by a range of viruses if added exogenously, including S-associated coronavirus strain HSR1. Here, we show that the addition of heparin to Vero cells between 6.25 - 200 μg.ml−1, which spans the concentration of heparin in therapeutic use, and inhibits invasion by SARS-CoV-2 at between 44 and 80%. We also demonstrate that heparin binds to the Spike (S1) protein receptor binding domain and induces a conformational change, illustrated by surface plasmon resonance and circular dichroism spectroscopy studies. The structural features of heparin on which this interaction depends were investigated using a library of heparin derivatives and size-defined fragments. Binding is more strongly dependent on the presence of 2-O or 6-O sulphation, and the consequent conformational consequences in the heparin structure, than on N-sulphation. A hexasaccharide is required for conformational changes to be induced in the secondary structure that are comparable to those that arise from heparin binding. Enoxaparin, a low molecular weight clinical anticoagulant, also binds the S1 RBD protein and induces conformational change. These findings have implications for the rapid development of a first-line therapeutic by repurposing heparin as well as for next-generation, tailor-made, GAG-based antiviral agents against SARS-CoV-2 and other members of the Coronaviridae.


title: Evidence for ethnic inequalities in mortality related to COVID-19 infections: Findings from an ecological analysis of England and Wales

text: Background In the absence of direct data on ethnic inequalities in COVID-19 related mortality in the UK, we examine the relationship between ethnic composition of an area and rate of mortality in the area. Methods Ecological analysis using COVID-19 related mortality rates occurring by 24th April 2020, and ethnic composition of the population, across local authorities in England and Wales. Account is taken of age, population density, area deprivation and pollution. Results For every 1% rise in proportion of the population who are ethnic minority, COVID-19 related deaths increased by 5.10 (3.99 to 6.21) per million. This rise is present for each ethnic minority category examined. The size of this increase is a little reduced in a fully adjusted model, suggesting that some of the association results from ethnic minority people living in more densely populated, more polluted and more deprived areas. This estimate suggests that the average England and Wales COVID-19 related death rate would rise by 25% in a local authority with twice the average number of ethnic minority people. Discussion We find clear evidence that rates of COVID-19 related mortality within a local authority increase as the proportion of the population who are ethnic minority increases. We suggest that this is a consequence of social and economic inequalities, including among key workers, driven by entrenched structural and institutional racism and racial discrimination. We argue that these factors should be central to any investigation of ethnic inequalities in COVID-19 outcomes.


title: Frequency and Distribution of Chest Radiographic Findings in COVID-19 Positive Patients

text: BACKGROUND: Current COVID-19 radiological literature is dominated by CT and a detailed description of chest x-ray (CXR) appearances in relation to the disease time course is lacking. PURPOSE: To describe the time course and severity of the CXR findings of COVID-19 and correlate these with real time reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-Cov-2 nucleic acid. MATERIALS AND METHODS: Retrospective study of COVID-19 patients with RT-PCR confirmation and CXRs admitted across 4 hospitals evaluated between January and March 2020. Baseline and serial CXRs (total 255 CXRs) were reviewed along with RT-PCRs. Correlation with concurrent CTs (total 28 CTs) was made when available. Two radiologists scored each CXR in consensus for: consolidation, ground glass opacity (GGO), location and pleural fluid. A severity index was determined for each lung. The lung scores were summed to produce the final severity score. RESULTS: There were 64 patients (26 men, mean age 56±19 years). Of these, 58, 44 and 38 patients had positive initial RT-PCR (91%, [CI: 81-96%]), abnormal baseline CXR (69%, [CI: 56-80%]) and positive initial RT-PCR with abnormal baseline CXR (59 [CI:46-71%]) respectively. Six patients (9%) showed CXR abnormalities before eventually testing positive on RT-PCR. Sensitivity of initial RT-PCR (91% [95% CI: 83-97%]) was higher than baseline CXR (69% [95% CI: 56-80%]) (p = 0.009). Radiographic (mean 6 ± 5 days) and virologic recovery (mean 8 ± 6 days) were not significantly different (p= 0.33). Consolidation was the most common finding (30/64, 47%), followed by GGO (21/64, 33%). CXR abnormalities had a peripheral (26/64, 41%) and lower zone distribution (32/64, 50%) with bilateral involvement (32/64, 50%). Pleural effusion was uncommon (2/64, 3%). The severity of CXR findings peaked at 10-12 days from the date of symptom onset. CONCLUSION: Chest x-ray findings in COVID-19 patients frequently showed bilateral lower zone consolidation which peaked at 10-12 days from symptom onset.


title: Extraction-free COVID-19 (SARS-CoV-2) diagnosis by RT-PCR to increase capacity for national testing programmes during a pandemic

text: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus disease 2019 (COVID-19), a respiratory tract infection. The standard molecular diagnostic test is a multistep process involving viral RNA extraction and real-time quantitative reverse transcriptase PCR (qRT-PCR). Laboratories across the globe face constraints on equipment and reagents during the COVID-19 pandemic. We have developed a simplified qRT-PCR assay that removes the need for an RNA extraction process and can be run on a real-time thermal cycler. The assay uses custom primers and probes, and maintains diagnostic sensitivity within 98.0% compared to the assay run on a high-throughput, random-access automated platform, the Panther Fusion (Hologic). This assay can be used to increase capacity for COVID-19 testing for national programmes worldwide.


title: Healthcare workers preparedness for COVID-19 pandemic in the occupied Palestinian territory: a cross-sectional survey

text: Background: The coronavirus disease 19 (COVID-19) pandemic threatens to overwhelm the capacity of the vulnerable healthcare system in the occupied Palestinian territory (oPt). Sufficient training of healthcare workers (HCWs) in how to manage COVID-19 and the provision of personal protective equipment (PPE) to enable them to do so will be key tools in allowing oPt to mount a credible response to the crisis. Methods: A cross-sectional study was conducted using a validated online questionnaire. Data collection occurred between March 30, 2020 and April 12, 2020. The primary outcomes was PPE provision and the secondary outcome was HCWs preparedness for the COVID-19 pandemic. Results: Of 138 respondents, only 38 HCWs (27.5%) always had access to facemasks when needed and 15 (10.9%) for isolation gowns. The vast majority of HCWs did not find eye protection (n=128, 92.8%), N95 respirators (n=132, 95.7%), and face shields (n=127, 92%) always available. Compared to HCWs in West Bank, those in the Gaza Strip were significantly less likely to have access to alcohol sanitizers (p=0.026) and gloves (p <0.001). On average, governmental hospitals were significantly less likely to have all appropriate PPE measures than non-governmental institutions (p = 0.001). As for preparedness, only 16 (11.6%) surveyed felt confident in dealing with a potential COVID-19 case. With 57 (41.3%) having received any COVID-19 related training and 57 (41.3%) not having a local hospital protocol. Conclusion: HCWs in oPt are underprepared and severely lacking adequate PPE provision. The lack of local protocols, and training has left HCWs confidence exceedingly low. The lack of PPE provision will exacerbate spread of COVID-19 and deepen the crisis, whilst putting HCWs at risk.


title: Transmission Dynamics of COVID-19 and Impact on Public Health Policy

text: In this work we construct a mathematical model for the transmission and spread of coronavirus disease 2019 or COVID-19. Our model features delay terms to account for (a) the time lapse or latency period between contracting the disease and displaying symptoms, and (b) the time lag in testing patients for the virus due to the limited numbers of testing facilities currently available. We find that the delay introduces a significant disparity between the actual and reported time-trajectories of cases in a particular region. Specifically, the reported case histories lag the actual histories by a few days. Hence, to minimize the spread of the disease, lockdowns and similarly drastic social isolation measures need to be imposed some time before the reported figures are approaching their peak values. We then account for the social reality that lockdowns can only be of a limited duration in view of practical considerations. We find that the most effective interval for imposing such a limited-time lockdown is one where the midpoint of the lockdown period coincides with the actual peak of the spread of the disease in the absence of the lockdown. We further show that the true effectivity of imposing a lockdown may be misrepresented and grossly underestimated by the reported case trajectories in the days following the action.


Neurologists Prepare to Redeploy on COVID-19 Front Lines Across the Country


title: Analysis of a model for coronavirus spread

text: The spread of epidemics has always threatened humanity. In the present circumstance of the Coronavirus pandemic, a mathematical model is considered. It is formulated via a compartmental dynamical system. Its equilibria are investigated for local stability. Global stability is established for the disease-free point. The allowed steady states are an unlikely symptomatic-infected-free point, which must still be considered endemic due to the presence of asymptomatic individuals; and the disease-free and the full endemic equilibria. A transcritical bifurcation is shown to exist among them, preventing bistability. The disease basic reproduction number is calculated. Simulations show that contact restrictive measures are able to delay the epidemic's outbreak, if taken at a very early stage. However, if lifted too early, they could become ineffective. In particular, an intermittent lock-down policy could be implemented, with the advantage of spreading the epidemics over a longer timespan, thereby reducing the sudden burden on hospitals.


title: Potential Effectiveness and Safety of Antiviral Agents in Children with Coronavirus Disease 2019: A Rapid Review and Meta-Analysis

text: Background: The COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children. Methods: Electronic databases from their inception to March, 31 2020 were searched for randomized controlled trials, clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19. Results: A total of 23 studies of indirect evidence with 6008 patients were included. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality (risk ratio [RR]= 0.77, 95% confidence interval [CI] 0.45 to 1.30) and probability of negative PCR test (RR=0.98, 95 CI% 0.82 to 1.18). Arbidol had no benefit on probability of negative PCR test (RR=1.27, 95% CI 0.93 to 1.73). Hydroxychloroquine was not associated with increasing the probability of negative PCR result (RR=0.93, 95% CI 0.73 to 1.18). For adults with SARS, interferon was associated with reduced corticosteroid dose (weighted mean difference [WMD]=-0.14 g, 95% CI -0.21 to -0.07) but had no effect on mortality (RR=0.72, 95% CI 0.28 to 1.88); ribavirin did not reduce mortality (RR=0.68, 95% CI % 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR=0.87, 95% CI 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions. Conclusions: There is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials. Keywords: Antiviral agents; children; COVID-19; meta-analysis; rapid review.


title: Data-driven analysis on the simulations of the spread of COVID-19 under different interventions of China

text: Objectives Since February 2020, COVID-19 has spread rapidly to more than 200 countries in the world. During the pandemic, local governments in China implemented different interventions to efficiently control the spread of the epidemic. Characterizing transmission of COVID-19 under some typical interventions is to help countries develop appropriate interventions. Methods We established compartmental model that allowed the number of infected and infectious to be unknown and the effective reproduction number to change over time, thus the effects of policies could be reasonably reflected and estimated. By using the epidemic data of three representative cities of China (Wuhan, Wenzhou and Shenzhen), we migrated the estimated policy modes to other countries. Results The smallest expected cumulative confirmed cases under different interventions would be 5936 with 95% CI (5012,6966) for South Korea, 146012 with 95% CI (140504, 154264) for Italy, and 400642 with 95% CI (390331,409431) for the United States until May 31, 2020, respectively. Conclusions Based on the simulation of epidemic in South Korea, Italy and the United States, it is reasonable that South Korea and Italy continue to maintain their current policies, while the implementation of interventions of Wenzhou may significantly decrease the magnitude of the outbreak of COVID-19 for the United States.


title: A topic analysis of traditional and social media news coverage of the early COVID-19 pandemic and implications for public health communication

text: Knowledge gaps may initially exist among scientists, medical and public health professionals during pandemics, which are fertile grounds for misinformation in news media. We characterized and compared COVID-19 coverage in newspapers, television, and social media, and discussed implications for public health communication strategies that are relevant to an initial pandemic response. We conducted a Latent Dirichlet Allocation (LDA), an unsupervised topic modelling technique, analysis of 3,271 newspaper articles, 40 cable news shows transcripts, 96,000 Twitter posts, and 1,000 Reddit posts during March 4 - 12, 2020, a period chronologically early in the timeframe of the COVID-19 pandemic. Coverage of COVID-19 clustered on topics such as epidemic, politics, and the economy, and these varied across media sources. Topics dominating news were not predominantly health-related, suggesting a limited presence of public health in news coverage in traditional and social media. Examples of misinformation were identified particularly in social media. Public health entities should utilize communication specialists to create engaging informational content to be shared on social media sites. Public health officials should be attuned to their target audience to anticipate and prevent spread of common myths likely to exist within a population. This will help control misinformation in early stages of pandemics.


title: Social media as a tool for scientific updating at the time of COVID pandemic

text: In the face of the rapid evolution of the COVID-19 pandemic, healthcare professionals on the frontline are in urgent need of frequent updates in the accomplishment of their practice. Hence, clinicians started to search for prompt, valid information on sources parallel to academic journals publications. Aim of this work is to investigate the extent of this phenomenon. We administered an anonymous online cross-sectional survey to 645 Italian clinicians. 369 questionnaires were returned. 19,5% (n=72) of respondents were younger than 30 years-old; 49,3% (n=182) worked in Infectious Diseases, Internal Medicine or Respiratory Medicine departments, 11.5% (n=42) in Intensive Care Unit and 7.4% (n=27) were general practitioner. 70% (n=261) of respondents reported that their use of social media to seek medical information increased during the pandemic. 39.3% (n = 145) consistently consulted Facebook groups and 53.1% (n = 196) Whatsapp chats. 47% (n = 174) of respondents reported that information shared on social media had a consistent impact on their daily practice. In the present study, we found no difference in social media usage between age groups or medical specialties. Given the urgent need for scientific update in face of the present health emergency, these findings may help understanding how clinicians access new evidences and implement them in their daily practice.


title: A quality evaluation of guidelines on five different viruses causing public health emergencies of international concern

text: This project aims to evaluate the methods and reporting quality of practice guidelines of five different viruses that have caused Public Health Emergencies of International Concern (PHEIC) over 20 past years: the severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), Zika virus and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We systematically searched databases, guideline websites and government health agency websites from their inception to February 02, 2020 to extract practice guidelines for SARS-CoV, Ebola virus, MERS-CoV, Zika virus, SARS-CoV-2 and the diseases they caused. The literature was screened independently by four researchers. Then, fifteen researchers evaluated the quality of included guidelines using the AGREE-?U (Appraisal of Guidelines for Research and Evaluation ?U, for methodological quality) instrument and RIGHT (Reporting Items for practice Guidelines in Healthcare, for reporting quality) statement. Finally, a total of 81 guidelines were included, including 21 SARS-CoV guidelines, 11 Ebola virus (EBOV) guidelines, 9 MERS-CoV guidelines, 10 Zika Virus guidelines and 30 SARS-CoV-2 guidelines. The evaluation of the methodological quality indicated that the mean scores of each domain for guidelines of each virus were all below 60%, the scores for guidelines in the domains of ?gclarity of presentation?h being the highest and in the ?geditorial independence?h lowest. The mean reporting rate of each domain for guidelines of each virus was also less than 60%: the reporting rates for the domain ?gbackground?h were highest, and for the domain ?gfunding and interests?h lowest. The methodological and reporting quality of the practice guidelines for SARS-CoV, Ebola virus, MERS-CoV, Zika virus and SARS-CoV-2 guidelines tend to be low. We recommend to follow evidence-based methodology and the RIGHT statement on reporting when developing guidelines.


title: Cross-Country Comparison of Case Fatality Rates of COVID-19/SARS-COV-2

text: OBJECTIVES: Case fatality rates (CFR) and recovery rates are important readouts during epidemics and pandemics. In this article, an international analysis was performed on the ongoing coronavirus disease 2019 (COVID-19) pandemic. METHODS: Data were retrieved from accurate databases according to the user’s guide of data sources for patient registries, CFR and recovery rates were calculated for each country. A comparison of CFR between countries with total cases ≥ 1,000 was observed for 12(th) and 23(rd) March. RESULTS: Italy’s CFR was the highest of all countries studied for both time points (12(th) March, 6.22% versus 23(rd) March, 9.26%). The data showed that even though Italy was the only European country reported on 12(rd) March, Spain and France had the highest CFR of 6.16 and 4.21%, respectively, on 23(rd) March, which was strikingly higher than the overall CFR of 3.61%. CONCLUSION: Obtaining detailed and accurate medical history from COVID-19 patients, and analyzing CFR alongside the recovery rate, may enable the identification of the highest risk areas so that efficient medical care may be provided. This may lead to the development of point-of-care tools to help clinicians in stratifying patients based on possible requirements in the level of care, to increase the probabilities of survival from COVID-19 disease.


title: Lockdown and isolation: Psychological aspects of covid-19 pandemic in the general population

text: As of March 2020, the respiratory disease caused by SARS-CoV-2 coronavirus has been declared a “pandemic” by the WHO. In an effort to stem the spread of the virus, governments around the world have ordered more or less restrictive isolation measures. If lockdown and social isolation have proven to be quite effective in terms of physical containment, mental health appears undermined by the onset of feelings such as uncertainty, fear, and despair. Likely, in the near future, mental health professionals will be called to face a “parallel pandemic” of acute stress disorders, post-traumatic stress disorder, emotional disturbance, sleep disorders, depressive syndromes and eventually suicides.


title: Spatial-temporal variations of atmospheric factors contribute to SARS-CoV-2 outbreak

text: The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) reached over two million confirmed cases worldwide, and numbers are still growing at a fast rate. The majority of new infections are now being reported outside of China, where the outbreak officially originated in December 2019 in Wuhan. Despite the wide outbreak of the infection, a remarkable asymmetry is observed in the number of cases and in the distribution of the severity of the COVID-19 symptoms in patients with respect to the countries/regions. In the early stages of a new pathogen outbreak, it is critical to understand the dynamics of the infection transmission, in order to follow contagion over time and project the epidemiological situation in the near future. While it is possible to reason that observed variation in the number and severity of cases stem from the initial number of infected individuals, the difference in the testing policies and social aspects of community transmissions, the factors that could explain high discrepancy in areas with a similar level of healthcare still remain unknown. Here we introduce a binary classifier based on an artificial neural network that can help in explaining those differences and that can be used to support the design of containment policies. We propose that air pollutants, and specifically particulate matter (PM) 2.5 and ozone, are oppositely related with the SARS-CoV-2 infection frequency and could serve as surrogate markers to complement the infection outbreak anticipation.


title: Dynamics of the SARS-CoV-2 epidemic in the earliest-affected areas in Italy: 1 Mass screening for SARS-CoV-2 serological positivity (SARS-2-SCREEN).

text: Background Several municipalities in the Lombardy Region have been affected by the SARS-CoV-2 infection since the earliest stages of the epidemic. To date, 89442 confirmed cases have been diagnosed in Lombardy, and mortality in several municipalities has already surpassed that of the past decade. Currently, the true extent of the SARS-CoV-2 infection remains unknown as several affected subjects may have been asymptomatic or have presented mild disease, thus not resulting in the identified COVID-19 cases. Methods This cross-sectional study aims to define the spread of infection within the population by determining the seroprevalence of IgG antibodies directed against SARS-CoV-2 by rapid immunochromatographic testing and subsequent confirmation by serology on venous blood by liquid phase immunochemical testing, also allowing to compare the two methods. Testing will be performed on adults and minors residing, domiciled or working in several municipalities of the Lombardy Region, involved in the initial stages of the epidemic. The study will include rapid finger-prick testing and venous sampling for antibodies against SARS-CoV-2, and nasopharyngeal swabbing (NPS). Concurrent notification of test results will occur via the regional healthcare information system (SISS). Discussion This study was developed with the desire to understand the seroprevalence of SARS-CoV-2 infection and the epidemiological transmission characteristics of this virus. Understanding the spread and severity of the disease could help in the implementation of effective infection surveillance containment and countermeasures facilitating the identification of cases that have been exposed to the virus and the traceability of contacts. This study has been approved by the Ethics Committee of the University of Milan (35/2020).


title: Automatic Detection of COVID-19 and Pneumonia from Chest X-Ray using Transfer Learning

text: In this study, a dataset of X-ray images from patients with common viral pneumonia, bacterial pneumonia, confirmed Covid-19 disease was utilized for the automatic detection of the Coronavirus disease. The point of the investigation is to assess the exhibition of cutting edge convolutional neural system structures proposed over the ongoing years for clinical picture order. In particular, the system called Transfer Learning was received. With transfer learning, the location of different variations from the norm in little clinical picture datasets is a reachable objective, regularly yielding amazing outcomes. The datasets used in this trial. Firstly, a collection of 24000 X-ray images includes 6000 images for confirmed Covid-19 disease,6000 confirmed common bacterial pneumonia and 6000 images of normal conditions. The information was gathered and expanded from the accessible X-Ray pictures on open clinical stores. The outcomes recommend that Deep Learning with X-Ray imaging may separate noteworthy biomarkers identified with the Covid-19 sickness, while the best precision, affectability, and particularity acquired is 97.83%, 96.81%, and 98.56% individually.


title: Susceptibility and Sustainability of India against CoVid19: a multivariate approach

text: Purpose: We are currently in the middle of a global crisis. Covid19 pandemic has suddenly threatened the existence of human life. Till date, as no medicine or vaccine is discovered, the best way to fight against this pandemic is prevention. The impact of different environmental, social, economic and health parameters is unknown and under research. It is important to identify the factors which can weaken the virus, and the nations which are more vulnerable to this virus. Materials and Methods: Data of weather, vaccination trends, life expectancy, lung disease, number of infected people in the pre-lockdown and post-lockdown period of highly infected nations are collected. These are extracted from authentic online resources and published reports. Analysis is done to find the possible impact of each parameter on CoVid19. Results: CoVid19 has no linear correlation with any of the selected parameters, though few parameters have depicted non-linear relationship in the graphs. Further investigations have shown better result for some parameters. A combination of the parameters results in a better correlation with infection rate. Conclusions: Though depending on the study outcome, the impact of CoVid19 in India can be predicted, the required lockdown period cannot be calculated due to data limitation.


title: Automated and semi-automated contact tracing: Protocol for a rapid review of available evidence and current challenges to inform the control of COVID-19

text: Introduction Traditional approaches to case-finding, case isolation, and contact tracing methods have so far proved insufficient on their own to prevent the development of local epidemics of COVID-19 in many high-income countries despite relatively advanced public health systems. As a result, many governments have resorted to widespread social distancing measures and mass quarantines ('lock-downs') to reduce transmission and to prevent healthcare systems from being overwhelmed. However, such measures impose heavy human and societal costs. Automated or semi-automated digital contact tracing, in conjunction with scaled-up community testing, has been proposed as a key part of exit strategies from lockdowns. However, the effectiveness of these approaches to contact tracing is unclear, and to be effective, trusted, and widely adopted such technology must overcome several challenges. Methods and analysis We will perform a rapid systematic review to assess the effectiveness of automated and semi-automated digital tools for contact tracing, and identify key considerations for successful implementation, to inform the control of COVID-19. We will search PubMed, EMBASE, EBSCO Medical COVID information portal, OVID Global Health, Cochrane Library, medRxiv, BioRxiv, and arXiv for peer-reviewed and pre-print papers on automated or semi-automated digital tools for contact tracing of COVID-19, another respiratory disease with pandemic potential (limited to SARS, MERS, or pandemic influenza), or Ebola, in human populations. Studies will be eligible if published in English between 1 January 2000 and 14 April 2020. We will synthesise study findings narratively and will consider meta-analysis if >=3 suitable studies with comparable interventions and outcomes are available. Ethics and dissemination Ethical approval is not required for this review. We plan to disseminate findings via pre-print, journal publication, through social media and web-based platforms and through direct stakeholder engagement.


title: Potential interference of hydroxychloroquine-glucuronide metabolite on therapeutic drug monitoring of hydroxychloroquine using a mass spectrometry detector

text: Keywords: glucuronide;hydroxychloroquine;interference;mass spectrometry EN glucuronide hydroxychloroquine interference mass spectrometry 1165 1167 3 06/15/20 20200701 NES 200701 To the Editor, Due to a new coronavirus the world has been experiencing an infectious disease for several weeks However, few data are available concerning the phase II hydroxychloroquine-glucuronide (HCQ-Glu) metabolite [[6]], [[7]] [Extracted from the article] Copyright of Clinical Chemistry & Laboratory Medicine is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )


title: Coronaviruses: a paradigm of new emerging zoonotic diseases

text: A novel type of coronavirus (2019-nCoV) infecting humans appeared in Wuhan, China, at the end of December 2019. Since the identification of the outbreak the infection quickly spread involving in one month more than 31,000 confirmed cases with 638 death. Molecular analysis suggest that 2019-nCoV could be originated from bats after passaging in intermediate hosts, highlighting the high zoonotic potential of coronaviruses.


Confronting and Governing the Public Health Emergency


title: Effectiveness of stay-in-place-orders during COVID-19 pandemic: Evidence from US border counties.

text: Recent studies on US counties, with varying effect sizes, show that stay-in-place-orders (SIPOs) are associated with a decline in new COVID-19 cases. Our estimation approach relies on county-pairs across state-borders where one state has SIPO whereas the other state does not, controls for matched county-pair fixed effects and day of observation fixed-effects. The county-pair sample from southern, mid-western, and mountain region states (from March 1, 2020 to April 25, 2020) shows that daily COVID-19 incidence case growth rate is 1.994 percentage points lower for counties in SIPO states relative to those bordering in non-SIPO states. Specifically, we find SIPO reduced daily growth rates by 1.97, 2.14, 2.03, and 2.27 percentage points after 1 to 5 days, 6 to 10 days, 11 to 15 days, and 16 to 20 days, respectively. Our effect sizes are much smaller than in the previous studies with the caveat that states in the northeast and on the west coast could not be included in the border county-pair specification. We find limited evidence of heterogeneous effects in counties with a higher population density, percentage of black or Hispanic residents, proportion of population over 65 years, and social association rates in a county. Nor do we find evidence of meaningful differences in effects of SIPO by county Gini index, unemployment, or GDP. The results of this study could further inform policymakers in making decisions on SIPO extensions or lifting of such orders.


title: Whole-Genome Sequences of the Severe Acute Respiratory Syndrome Coronavirus-2 obtained from Romanian patients between March and June of 2020

text: Impact of mutations on the evolution of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) are needed for ongoing global efforts to track and trace the current pandemic, in order to enact effective prevention and treatment options. SARS-Co-V-2 viral genomes were detected and sequenced from 18 Romanian patients suffering from coronavirus disease-2019. Viral Spike S glycoprotein sequences were used to generate model structures and assess the role of mutations on protein stability. We integrated the phylogenetic tree within the available European SARS-Co-V-2 genomic sequences. We further provide an epidemiological overview of the pre-existing conditions that are lethal in relevant Romanian patients. Non-synonymous mutations in the viral Spike glycoprotein relating to infectivity are constructed in models of protein structures. Continuing search to limit and treat SARS-CoV-2 benefit from our contribution in delineating the viral Spike glycoprotein mutations, as well as from assessment of their role on protein stability or complex formation with human receptor angiotensin-converting enzyme 2. Our results help implement and extend worldwide genomic surveillance of coronavirus disease-2019.


Clinic Reopening Post-Coronavirus Disease 2019: Precaution of a Plastic Surgery Clinic in China


title: Age-dependent effects in the transmission and control of COVID-19 epidemics

text: The COVID-19 pandemic has shown a markedly low proportion of cases among children. Age disparities in observed cases could be explained by children having lower susceptibility to infection, lower propensity to show clinical symptoms, or both. We evaluate these possibilities by fitting an age-structured mathematical model to epidemic data from six countries. We estimate that clinical symptoms occur in 25% (95% CrI: 19-32%) of infections in 10-19-year-olds, rising to 76% (68-82%) in over-70s, and that susceptibility to infection in under-20s is approximately half that of older adults. Accordingly, we find that interventions aimed at children may have a relatively small impact on total cases, particularly if the transmissibility of subclinical infections is low. The age-specific clinical fraction and susceptibility we have estimated has implications for the expected global burden of COVID-19 because of demographic differences across settings: in younger populations, the expected clinical attack rate would be lower, although it is likely that comorbidities in low-income countries will affect disease severity. Without effective control measures, regions with older populations may see disproportionally more clinical cases, particularly in the later stages of the pandemic.


title: Understanding olfactory dysfunction in COVID-19: Expression of ACE2, TMPRSS2 and Furin in the nose and olfactory bulb in human and mice

text: Background Anosmia is a frequent symptom in coronavirus disease 2019 (COVID-19) patients that generally resolves within weeks. In contrast, the anosmia caused by other upper respiratory infections affects a small proportion of patients and may take months to resolve or never resolve. The mechanisms behind COVID-19-induced olfactory dysfunction remain unknown. Here, we address the unique pathophysiology of COVID-19-associated olfactory dysfunction. Methods The expression of ACE2 (virus binding receptor) and TMPRSS2 and Furin (host cell proteases facilitating virus entry) was examined in the nasal mucosa, composed of respiratory mucosa (RM), olfactory mucosa (OM), and olfactory bulb (OB) of mouse and human tissues using immunohistochemistry and gene analyses. Results Co-expression of ACE2, TMPRSS2, and Furin was observed in the RM and in the OM, especially in the supporting cells of the olfactory epithelium and the Bowman’s glands. Notably, the olfactory receptor neurons (ORNs) in the OM were positive for ACE2 but almost negative for TMPRSS2 and Furin. Cells in the OB expressed ACE2 strongly and Furin weakly, and did not express TMPRSS2. All three gene expressions were confirmed in the nasal mucosa and OB. Conclusions ACE2 was widely expressed in all tissues, whereas TMPRSS2 and Furin were expressed only in certain types of cells and were absent in the ORNs. These findings, together with clinical reports, suggest that COVID-19-related anosmia occurs mainly through sensorineural and central dysfunction and, to some extent, conductive olfactory dysfunction. The expression of ACE2, but not TMPRSS2 or Furin, in ORNs may explain the early recovery from anosmia.


title: First study on mental distress in Brazil during the COVID-19 crisis

text: Objective: We aim to provide the first evidence of mental distress and its associated predictors among adults in the ongoing COVID-19 crisis in Brazil. Methods: We conducted a primary survey of 638 adults in Brazil on March 25-28, 2020, about one month (32 days) after the first COVID-19 case in South America was confirmed in Sao Paulo. Results: In Brazil, 52% (332) of the sampled adults experienced mild or moderate distress, and 18.8% (120) suffered severe distress. Adults who were female, younger, more educated, and exercised less report-ed higher levels of distress. The distance from the Brazilian epicenter of Sao Paulo inter-acted with age and workplace attendance to predict the level of distress. The typhoon eye effect was stronger for people who were older or attended their workplace less. The most vulnerable adults were those who were far from the epicenter and did not go to their workplace in the week before the survey. Conclusion: Identifying the predictors of distress enables mental health services to better target finding and helping the more mentally vulnerable adults during the ongoing COVID-19 crisis.


title: St George's COVID shield for use by ENT surgeons performing tracheostomies

text: Healthcare workers are at increased risk of exposure to COVID-19. The majority of cases are acquired through inhalation of infected respiratory particles, contamination with infected surfaces or whilst performing aerosol-generating procedures. Basic infection prevention measures are essential to protect healthcare workers from contracting the disease when managing patients; consequently global demand for personal protective equipment (PPE) has exceeded supply in many regions. We present a novel, innovative polycarbonate shield designed for ENT clinicians performing tracheostomies. Clinical investigations using the shield demonstrated a sixteen-fold decrease in the number of particles detected at the position of the operating surgeon when the shield was used (particle size 0.3m; with shield 27,000 versus 439,000 without shield). The shield, used with appropriate PPE, could therefore help to minimise exposure to aerosol generated particles such as during tracheostomies on patients with COVID-19.


title: Evolving Epidemiology and Effect of Non-pharmaceutical Interventions on the Epidemic of Coronavirus Disease 2019 in Shenzhen, China

text: Previous studies have demonstrated the characteristics of patients with 2019 novel coronavirus disease (COVID-19). However, the effect of non-pharmaceutical interventions on the epidemic in Shenzhen, China remains unknown. Individual data of 417 cases were extracted from the epidemiological investigations and the National Infectious Disease Information System between January 1, 2020 and February 29, 2020. On the basis of important interventions, the epidemic was divided into four periods (January 1-15, January 16-22, January 23-February 5 and after February 6). We used a susceptible-exposed-infectious-asymptomatic-recovered model to evaluate the effect of interventions. Results suggested that about 53.7% were imported from Wuhan. The median age was 47 years and 52.8% were women. Severity risk increased with age and associated with male and co-existing disorders. The attack rate peaked in the third period and drastically decreased afterwards across sex, age groups and geographic regions. Children younger than 5 years showed a higher attack rate than those aged of 6~19. The effective reproductive number decreased from 1.44 to 0.05 after the highest level emergency response since January 23. Overall, the non-pharmaceutical interventions have effectively mitigated the COVID-19 outbreak in Shenzhen, China. These findings may facilitate the introduction of public health policies in other countries and regions.


title: Comparison of transmissibility of coronavirus between symptomatic and asymptomatic patients: Reanalysis of the Ningbo Covid-19 data

text: We investigate the transmissibility of coronavirus for symptomatic and asymptomatic patients using the Ningbo Covid-19 data1. Through more in-depth and comprehensive statistical analysis, we conclude that there is no difference in the transmission rates of coronavirus between the symptomatic and asymptomatic patients, which is consistent with the original findings in Chen et al.1


title: How to reduce epidemic peaks keeping under control the time-span of the epidemic

text: One of the main challenges of the measures against the COVID-19 epidemic is to reduce the amplitude of the epidemic peak without increasing without control its timescale. We investigate this problem using the SIR model for the epidemic dynamics, for which reduction of the epidemic peak I(P) can be achieved only at the price of increasing the time t(P) of its occurrence and its entire time-span t(E). By means of a time reparametrization we linearize the equations for the SIR dynamics. This allows us to solve exactly the dynamics in the time domain and to derive the scaling behaviour of the size, the timescale and the speed of the epidemics, by reducing the infection rate α and by increasing the removal rate β by a factor of λ. We show that for a given value of the size (I(P), the total, I(E) and average [Formula: see text] number of infected), its occurrence time t(P) and entire time-span t(E) can be reduced by a factor 1/λ if the reduction of I is achieved by increasing the removal rate instead of reducing the infection rate. Thus, epidemic containment measures based on tracing, early detection followed by prompt isolation of infected individuals are more efficient than those based on social distancing. We apply our results to the COVID-19 epidemic in Northern Italy. We show that the peak time t(P) and the entire time span t(E) could have been reduced by a factor 0.9 ≤ 1/λ ≤ 0.34 with containment measures focused on increasing β instead of reducing α.


title: COVID-19 Utilization and Resource Visualization Engine (CURVE) to Forecast In-Hospital Resources

text: Background: The emergence of COVID-19 has created an urgent threat to public health worldwide. With rapidly evolving demands on healthcare resources, it is imperative that healthcare systems have the ability to access real-time local data to predict, plan, and effectively manage resources. Objective: To develop an interactive COVID-19 Utilization and Resource Visualization Engine (CURVE) as a data visualization tool to inform decision making and guide a large health system's proactive pandemic response. Methods: We designed and implemented CURVE using R Shiny to display real-time parameters of healthcare utilization at Atrium Health with projections based upon locally derived models for the COVID-19 pandemic. We used the CURVE app to compare predictions from two of our models: one created before and one after the statewide stay-at-home and social distancing orders (denoted before- and after-SAH-order model). We established parameter settings for best-, moderate-, and worst-case scenarios for pandemic spread and resource use, leveraging two locally developed forecasting models to determine peak date trajectory, resource use, and root mean square error (RMSE) between observed and predicted results. Results: CURVE predicts and monitors utilization of hospital beds, ICU beds, and number of ventilators in the context of up-to-date local resources and provides Atrium Health leadership with timely, actionable insights to guide decision-making during the COVID-19 pandemic. The after-SAH-order model demonstrated the lowest RMSE in total bed, ICU bed, and patients on ventilators. Conclusions: CURVE provides a powerful, interactive interface that provides locally relevant, dynamic, timely information to guide health system decision making and pandemic preparedness.


title: Case fatality rate in COVID-19: a systematic review and meta-analysis

text: Background: Estimating the prevalence of severe or critical illness and case fatality of COVID-19 outbreak in December, 2019 remains a challenge due to biases associated with surveillance, data synthesis and reporting. We aimed to address this limitation in a systematic review and meta-analysis and to examine the clinical, biochemical and radiological risk factors in a meta-regression. Methods: PRISMA guidelines were followed. PubMed, Scopus and Web of Science were searched using pre-specified keywords on March 07, 2020. Peer-reviewed empirical studies examining rates of severe illness, critical illness and case fatality among COVID-19 patients were examined. Numerators and denominators to compute the prevalence rates and risk factors were extracted. Random-effects meta-analyses were performed. Results were corrected for publication bias. Meta-regression analyses examined the moderator effects of potential risk factors. Results: The meta-analysis included 29 studies representing 2,090 individuals. Pooled rates of severe illness, critical illness and case fatality among COVID-19 patients were 15%, 5% and 0.8% respectively. Adjusting for potential underreporting and publication bias, increased these estimates to 26%, 16% and 7.4% respectively. Increasing age and elevated LDH consistently predicted severe / critical disease and case fatality. Hypertension; fever and dyspnea at presentation; and elevated CRP predicted increased severity. Conclusions: Risk factors that emerged in our analyses predicting severity and case fatality should inform clinicians to define endophenotypes possessing a greater risk. Estimated case fatality rate of 7.4% after correcting for publication bias underscores the importance of strict adherence to preventive measures, case detection, surveillance and reporting.


Immunotherapy Answers the Call to Fight the COVID-19 Virus


title: Lower State COVID-19 Deaths and Cases with Earlier School Closure in the U.S.

text: This study quantifies the relationship between school closure timing and COVID-19 deaths and cases in the general population in all U.S. states. COVID-19 has higher symptomatic infection rates among the elderly, suggesting school closures could be unrelated to transmission. However, predicting daily cumulative COVID-19 deaths by state, earlier school closure is related to fewer deaths per capita and slower growth in deaths per capita. Results are similar for COVID-19 cases per capita.


title: A flexible target-specific anti-infection therapeutic platform that can be applied to different microbial species

text: The emergence of new microbial pathogens, including drug-resistant strains, complicates treatment, thereby threatening global health. We demonstrated a photoimmuno-antimicrobial strategy (PIAS) that eliminated antibody-targets using a photo-activated anti-pathogen antibody generating mechanical stress that damaged the target’s binding sites. PIAS is effective against many pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), the fungal pathogen Candida albicans, and viral particles irrespective of their species or drug-resistance status. Animal experiments demonstrated that PIAS saved mice from fatal infections; microbiome and histochemical analyses indicated no apparent effect on normal host microflora and tissues in PIAS-treated mice. Resistance to PIAS was not observed during the eight years of this study. As a new type of anti-infection therapy, PIAS may contribute to advances in anti-infection strategies.


Open book? In India, where people are forced to download a tracking app to get paid, journalists are worried about it also being used to access their contacts


title: CAN-NPI: A Curated Open Dataset of Canadian Non-Pharmaceutical Interventions in Response to the Global COVID-19 Pandemic

text: Non-pharmaceutical interventions (NPIs) have been the primary tool used by governments and organizations to mitigate the spread of the ongoing pandemic of COVID-19. Natural experiments are currently being conducted on the impact of these interventions, but most of these occur at the subnational level - data not available in early global datasets. We describe the rapid development of the first comprehensive, labelled dataset of 1640 NPIs implemented at federal, provincial/territorial and municipal levels in Canada to guide COVID-19 research. For each intervention, we provide: a) information on timing to aid in longitudinal evaluation, b) location to allow for robust spatial analyses, and c) classification based on intervention type and target population, including classification aligned with a previously developed measure of government response stringency. This initial dataset release (v1.0) spans January 1st, and March 31st, 2020; bi-weekly data updates to continue for the duration of the pandemic. This novel dataset enables robust, inter-jurisdictional comparisons of pandemic response, can serve as a model for other jurisdictions and can be linked with other information about case counts, transmission dynamics, health care utilization, mobility data and economic indicators to derive important insights regarding NPI impact.


title: Peripheral blood immune status at clinical onset correlates with severity of Coronavirus Disease 2019

text: The Coronavirus Disease 2019 (COVID-19) pandemic is a global threat to healthcare systems, requiring hospitalization in sub intensive and intensive care for respiratory syndrome in 25-30% of patients and accounting for a lethality up to 15%. In this retrospective study the clinical characteristics of 215 COVID-19 patients were correlated with the peripheral blood immune status. Different groups of COVID-19 patients may be identified on the basis of clinical behavior and a strong correlation between groups and age and comorbidities as well as with the immune profile is demonstrated. A lower age correlates with a lower severity of the disease differentiating between patients who may be quarantined at home and those requiring hospitalization. An older age (>82 years) together with a higher number of comorbidities is associated to a very severe prognosis. The absolute number of CD3+, CD4+, CD8+ T lymphocytes was progressively decreasing according to the severity of the disease and a CD3+ and CD8+ threshold indicating very severe cases is suggested.


title: Estimation of instant case fatality rate of COVID-19 in Wuhan and Hubei based on daily case notification data

text: Background The outbreak of coronavirus disease 2019 (COVID-19) initially appeared and has most rapidly spread in Wuhan, China. The case fatality rate is the most direct indicator to assess the hazards of an infectious disease. We aimed to estimate the instant fatality rate and cure rate of COVID-19 in Wuhan City and its affiliated Hubei Province. Methods We collected the daily case notification data of COVID-19 from Dec 8, 2019 to Mar 10, 2020 in Wuhan City and Hubei Province officially announced by the Chinese authority. The numbers of daily confirmed/deaths/cured cases and the numbers of daily cumulative confirmed/deaths/cured cases were obtained. The death time and cure time of COVID-19 patients were calculated based on the dates of diagnosis, death and discharge of individual cases. Then the estimated diagnosis dates of deaths and cured cases were obtained on the basis of the median death or medium cure time, respectively. Finally, the instant fatality rate of COVID-19 was calculated according to the numbers of deaths and cured cases on the same estimated diagnosis dates. Results From Jan 1, 2020 to Feb 22, 2020 in Wuhan City, the instant case fatality rate of COVID-19 was 3.4%～19.5% and the instant cured rate was 80.0%～96.6%. The average fatality rate reached 11.4% while the average cure rate was 88.6%. During the same period in Hubei Province, the instant case fatality rate was 3.8%～16.6% and the instant cured rate was 83.4%～96.6%. The average fatality rate and the average cure rate were 9.2% and 91.8%, respectively. Conclusions The fatality rate and cure rate of COVID-19 in Wuhan City and Hubei Province were underestimated. Wuhan showed higher fatality rate and cure rate than the whole Hubei Province did.


title: Portable and accurate diagnostics for COVID-19: Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection

text: The COVID-19 pandemic has crudely demonstrated the value of massive and rapid diagnostics. By the first week of April, more than 900,000 positive cases of COVID-19 have been reported worldwide, although this number could be greatly underestimated. In the case of an epidemic emergency, the first line of response should be based on commercially available and validated resources. Here, we demonstrate the combined use of the miniPCR, a commercial compact and portable PCR device recently available on the market, and a commercial well-plate reader as a diagnostic system for detecting SARS-CoV-2 nucleic acids. We used the miniPCR to detect and amplify SARS-CoV-2 DNA sequences using the sets of initiators recommended by the World Health Organization for targeting three different regions that encode for the N protein. Prior to amplification, samples were combined with a DNA intercalating reagent (i.e., EvaGreen Dye). Sample fluorescence after amplification was then read using a commercial 96-well plate reader. This straightforward method allows the detection and amplification of SARS-CoV-2 nucleic acids in the range of ~625 to 2 x 105 DNA copies. The accuracy and simplicity of this diagnostics strategy may provide a cost-efficient and reliable alternative for COVID-19 pandemic testing, particularly in underdeveloped regions where RT-qPCR instrument availability may be limited. The portability, ease of use, and reproducibility of the miniPCR makes it a reliable alternative for deployment in point-of-care SARS-CoV-2 detection efforts during pandemics.


title: Genomic, geographic and temporal distributions of SARS-CoV-2 mutations

text: The COVID-19 pandemic is the most significant public health issue in recent history. Its causal agent, SARS-CoV-2, has evolved rapidly since its first emergence in December 2019. Mutations in the viral genome have critical impacts on the adaptation of viral strains to the local environment, and may alter the characteristics of viral transmission, disease manifestation, and the efficacy of treatment and vaccination. Using the complete sequences of 1,932 SARS-CoV-2 genomes, we examined the genomic, geographic and temporal distributions of aged, new, and frequent mutations of SARS-CoV-2, and identified six phylogenetic clusters of the strains, which also exhibit a geographic preference in different continents. Mutations in the form of single nucleotide variations (SNVs) provide a direct interpretation for the six phylogenetic clusters. Linkage disequilibrium, haplotype structure, evolutionary process, global distribution of mutations unveiled a sketch of the mutational history. Additionally, we found a positive correlation between the average mutation count and case fatality, and this correlation had strengthened with time, suggesting an important role of SNVs on disease outcomes. This study suggests that SNVs may become an important consideration in virus detection, clinical treatment, drug design, and vaccine development to avoid target shifting, and that continued isolation and sequencing is a crucial component in the fight against this pandemic. Significance Statement Mutation is the driving force of evolution for viruses like SARS-CoV-2, the causal agent of COVID-19. In this study, we discovered that the genome of SARS-CoV-2 is changing rapidly from the originally isolated form. These mutations have been spreading around the world and caused more than 2.5 million of infected cases and 170 thousands of deaths. We found that fourteen frequent mutations identified in this study can characterize the six main clusters of SARS-CoV-2 strains. In addition, we found the mutation burden is positively correlated with the fatality of COVID-19 patients. Understanding mutations in the SARS-CoV-2 genome will provide useful insight for the design of treatment and vaccination.


title: Outbreak of Novel Coronavirus (SARS-CoV-2): First Evidences From International Scientific Literature and Pending Questions

text: On 31 December, 2019, a cluster of 27 pneumonia cases of unknown etiology was reported by Chinese health authorities in Wuhan City (China) [ ]


title: Seasonal weight changes in laboratory ferrets

text: Ferrets (Mustela putorius furo) are a valuable animal model used in biomedical research. Ferrets undergo significant variation in body weight seasonally, affected by photoperiod, and these variations make it difficult to use weight as an indicator of health status. To overcome this requires a better understanding of these seasonal weight changes. We provide a normative weight data set for the female ferret accounting for seasonal changes, and also investigate the effect of fluid regulation on weight change. Female ferrets (n=39) underwent behavioural testing from May 2017 to August 2019 and were weighed daily while housed in an animal care facility with controlled light exposure. In the winter (October to March), animals experienced 10 hours of light and 14 hours of dark, while in summer (March to October), this contingency was reversed. Individual animals varied in their body weight from approximately 700 to 1200 g. However, weights fluctuated with light cycle, with animals losing weight in summer, and gaining weight in winter such that they fluctuated between approximately 80% and 120% of their long term average weight. Ferrets were weighed as part of their health assessment while experiencing water regulation for behavioural training. Water regulation superimposed additional weight changes on these seasonal fluctuations, with weight loss during the 5 day water regulation period being greater in summer than winter. These data establish a normative benchmark for seasonal weight variation in female ferrets that can be incorporated into the health assessment of an animal’s condition.


title: Detection of SARS-CoV-2 RNA by multiplex RT-qPCR

text: The current RT-qPCR assay recommended for SARS-CoV-2 testing in the United States requires analysis of three genomic targets per sample: two viral and one host. To simplify testing and reduce the volume of required reagents, we developed a multiplex RT-qPCR assay to detect SARS-CoV-2 in a single reaction. We used existing N1, N2, and RP primer and probe sets by the CDC, but substituted fluorophores to allow multiplexing of the assay. The cycle threshold (Ct) values of our multiplex RT-qPCR were comparable to those obtained by the singleplex assay adapted for research purposes. Low copies (>500 copies / reaction) of SARS-CoV-2 RNA were consistently detected by the multiplex RT-qPCR. Our novel multiplex RT-qPCR improves upon current singleplex diagnostics by saving reagents, costs, time and labor.


title: Robust, general purpose, digital power line hum filter which is free of deformations and which can be applied to large transients

text: Power line interference (“hum noise”) is a common source of noise in recorded biological data. It has a highly constant frequency with harmonics and little variation in amplitude and wave shape. In contrast to stochastic noise it is phasic, i.e., the phase relation remains constant across long intervals. In digital recordings, the measurement frequency is typically very close to a multiple of the hum frequency (50 or 60 Hz). Common filters introduce various kinds of distortions and errors. The here proposed subtraction method makes use of the specific properties of power line hum. For this, it computes a moving estimate of the hum noise by taking the periodic median of the high-pass filtered signal. The resulting periodic median subtraction (PMS) filter reliably removes hum of any harmonic composition, even if the ground frequency is lacking. The filter is completely free of border artifacts. It does not introduce distortions, even if around sharp transients such as in force plate recordings of jumping. The filter is validated on recorded and artificial data. The errors are quantified. The results also show that the errors of hum filters generally increase with the high-frequency content of the data. Thus, the removal of hum from a force plate recording generally gives better results than from an EMG recoding. Compared to other filters, the errors of the PMS filter are generally lower than the best hum filters currently known.


title: Estimating Force of Infection from Serologic Surveys with Imperfect Tests

text: The force of infection, or the rate at which susceptible individuals become infected, is an important public health measure for assessing the extent of outbreaks and the impact of control programs. Here we present methods for estimating force of infection from serological surveys of infections which produce lasting immunity, taking into account imperfections in the test used, and uncertainty in such imperfections. The methods cover both single serological surveys, in which age is a proxy for time at risk, and repeat surveys in the same people, in which the force of infection is estimated more directly. Fixed values can be used for the sensitivity and specificity of the tests, or existing methods for belief elicitation can be used to include uncertainty in these values. The latter may be applicable, for example, when the specificity of a test depends on co-circulating pathogens, which may not have been well characterized in the setting of interest. We illustrate the methods using data from two published serological studies of dengue.


title: Belief of Previous COVID-19 Infection and Unclear Government Policy are Associated with Reduced Willingness to Participate in App-Based Contact Tracing: A UK-Wide Observational Study of 13,000 Patients

text: Background: Contact tracing and lockdown are health policies being used worldwide to combat the coronavirus (COVID-19). While easing lockdown, the UK National Health Service (NHS) launched its Track and Trace Service at the end of May 2020, and aims by end of June 2020 also to include app-based notification and advice to self-isolate for those who have been in contact with a person known to have COVID-19. To be successful, such an app will require high uptake, the determinants and willingness for which are unclear but essential to understand for effective public health benefit. Objectives: To measure the determinants of willingness to participate in an NHS app-based contact tracing programme using a questionnaire within the Care Information Exchange (CIE) - the largest patient-facing electronic health record in the NHS. Methods: Observational study of 47,708 registered NHS users of the CIE, 27% of whom completed a novel questionnaire asking about willingness to participate in app-based contact tracing, understanding of government advice, mental and physical wellbeing and their healthcare utilisation -- related or not to COVID-19. Descriptive statistics are reported alongside univariate and multivariable logistic regression models, with positive or negative responses to a question on app-based contact tracing as the dependent variable. Results: 26.1% of all CIE participants were included in the analysis (N = 12,434, 43.0% male, mean age 55.2). 60.3% of respondents were willing to participate in app-based contact tracing. Out of those who responded "no", 67.2% stated that this was due to privacy concerns. In univariate analysis, worsening mood, fear and anxiety in relation to changes in government rules around lockdown were associated with lower willingness to participate. Multivariable analysis showed that difficulty understanding government rules was associated with a decreased inclination to download the app, with those scoring 1-2 and 3-4 in their understanding of the new government rules being 45% and 27% less inclined to download the contact tracing app, respectively; when compared to those who rated their understanding as 5-6/10 (OR for 1-2/10 = 0.57 [CI 0.48 - 0.67]; OR for 3-4/10 = 0.744 [CI 0.64 - 0.87]), whereas scores of 7-8 and 9-10 showed a 43% and 31% respective increase. Those reporting an unconfirmed belief of having previously had and recovered from COVID-19 were 27% less likely to be willing to download the app; belief of previous recovery from COVID-19 infection OR 0.727 [0.585 - 0.908]). Conclusions: In this large UK-wide questionnaire of wellbeing in lockdown, a willingness for app-based contact tracing is 60% - close to the estimated 56% population uptake, and substantially less than the smartphone-user uptake considered necessary for an app-based contact-tracing to be an effective intervention to help suppress an epidemic. Given this marginal level of support over an appropriate age range, the impacts of difficulty comprehending government advice and a policy of not testing to confirm self-reported COVID-19 infection during lockdown indicate that uncertainty in communication and diagnosis in adopted public health policies will negatively impact the effectiveness of a government contact tracing app.


title: Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China

text: In December 2019, cases of unidentified pneumonia with a history of exposure in the Huanan Seafood Market were reported in Wuhan, Hubei Province. A novel coronavirus, SARS-CoV-2, was identified to be accountable for this disease. Human-to-human transmission is confirmed, and this disease (named COVID-19 by World Health Organization (WHO)) spread rapidly around the country and the world. As of 18 February 2020, the number of confirmed cases had reached 75,199 with 2009 fatalities. The COVID-19 resulted in a much lower case-fatality rate (about 2.67%) among the confirmed cases, compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Among the symptom composition of the 45 fatality cases collected from the released official reports, the top four are fever, cough, short of breath, and chest tightness/pain. The major comorbidities of the fatality cases include hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic bronchitis. The source of the virus and the pathogenesis of this disease are still unconfirmed. No specific therapeutic drug has been found. The Chinese Government has initiated a level-1 public health response to prevent the spread of the disease. Meanwhile, it is also crucial to speed up the development of vaccines and drugs for treatment, which will enable us to defeat COVID-19 as soon as possible.


Remdesivir and COVID-19: What are the implications for Africa?


On the importance of science to society: A call for government action


title: Molecular Characterization and Amino Acid Homology of Nucleocapsid (N) Protein in SARS-CoV-1, SARS-CoV-2, MERS-CoV, and Bat Coronavirus

text: Coronavirus disease - 2019 (COVID-19) pandemic, due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is posing a severe bio threat to the entire world Nucleocapsids of SARS-CoV-2 and the related viruses were studied for gene and amino acid sequence homologies In this study, we established similarities and differences in nucleocapsids in SARS-CoV-2, severe acute respiratory syndrome - coronavirus-1 (SARS-CoV-1), bat coronavirus (bat-CoV) and Middle East respiratory syndrome - coronavirus (MERS-CoV) We conducted a detailed analysis of the nucleocapsid protein amino acid and gene sequence encoding it, found in various coronavirus strains After thoroughly screening the different nucleocapsids, we observed a close molecular homology between SARS-CoV-1 and SARS-CoV-2 More than 95% sequence similarity was observed between the two SARS-CoV strains Bat-CoV and SARS-CoV-2 showed 92% sequence similarity MERS-CoV and SARS-CoV-2 nucleocapsid analysis indicated only 65% identity Molecular characterization of nucleocapsids from various coronaviruses revealed that SARS-CoV 2 is more related to SARS-CoV 1 and bat-CoV SARS-CoV 2 exhibited less resemblance with MERS-CoV SARS-CoV 2 showed less similarity to MERS-CoV Thus, either SARS-CoV-1 or bat-CoV may be the source of SARS-CoV-2 evolution Moreover, the existing differences in nucleocapsid molecular structures in SARS-CoV-2 make this virus more virulent and highly infectious, which means that the non-identical SARS-CoV-2 genes (which are absent in SARS-CoV-1 and bat-CoV) are responsible for COVID-19 severity We observed that SARS-CoV-2 nucleocapsid from different locations varied in amino acid sequences This revealed that there are many SARS-CoV-2 subtypes/subsets currently circulating globally This study will help to develop antiviral vaccine and drugs, study viral replication and immunopathogenesis, and synthesize monoclonal antibodies that can be used for precise COVID-19 diagnosis, without false-positive/false-negative results


Bioinsecurities: disease interventions, empire, and the government of species


title: Examine the impact of weather and ambient air pollutant parameters on daily case of COVID-19 in India.

text: The present study presents a view on exploring the relationship pattern between COVID 19 daily cases with weather parameters and air pollutants in mainland India. We consider mean temperature, relative humidity, solar radiation, rainfall, wind speed, PM2.5, PM10, SO2, NO2 and CO as independent variable and daily COVID 19 cases as dependent variable for 18 states during 18th march to 30th April, 2020.After dividing the dataset for 0 to 10 day, 10 to 25 days and 0 to 44 days, the current study applied Akaike s Information Criteria (AIC) and Generalized Additive Model (GAM) to examine the kind of relationship between independent variables with COVID 19 cases. Initially GAM model result shows variables like temperature and solar radiation has positive relation (p<0.05) in 0 to 10 days study with daily cases. In 25 days dataset it significantly shows that temperature has positive relation above 23 degree centigrade, SO2 has a negative relationship and relative humidity has negative (between 30% to 45% and > 60%) and a positive relationship (45% to 60%) with COVID 19 cases (p=0.05). 44 days dataset has six parameters includes temperature as positive, relative humidity as negative (between 0 to 45%) and then positive (after >45%), NO2 as Positive (0 to 35 microgram/m3) followed by negative trend (after > 40 microgram/m3), SO2 and rainfall as negative relation. After sensitive analysis, it is found that weather variables like relative humidity, solar radiation and rainfall are more sensitive than temperature and wind speed. Whereas pollutants like NO2, PM2.5, PM10 and CO are more sensitive variables than SO2 in this study. In summary this study finds temperature, relative humidity, solar radiation, wind speed, SO2, PM2.5, and CO may be important factors associated with COVID 19 pandemic. Keywords: Weather parameter, Air pollutants, Daily COVID 19 cases, Akaike s Information Criteria (AIC), Generalized Additive Model (GAM) and Sensitive analysis.


title: COVID-19 is expanding global consciousness and the sustainability of travel and tourism

text: The sustainable development model has largely failed to address the social and environmental challenges of the 21 stcentury. True sustainability will only occur when it is valued as a part of the taken-for-granted daily life of individuals and cultures across the globe. This has not yet happened because humanity has not evolved a global consciousness quickly enough to match the global advances in telecommunications and transportation technologies that have created a socially and economically ever-shrinking planet. Travel and tourism contributes to the expansion of global consciousness, although only in a haphazard and unintentional manner. The COVID-19 pandemic is a result of planetary time-space compression and is forcing an expansion in human consciousness that will make humankind better able to address global problems. There will still be considerable diversity on the planet, as now, but the pandemic will stimulate growing numbers of people, businesses and governments to adopt new ways of thinking, behaving and operating that are more closely aligned with the goals of sustainable development. This could be further enhanced if travel and tourism were to adopt the expansion and awakening of global conscious as a fundamental and transformational value in the products and experiences that it offers.


title: Triage assessment of cardiorespiratory risk status based on measurement of the anaerobic threshold, and estimation by patient-reported activity limitation

text: BACKGROUND: Rapid triaging, as in the current COVID-19 pandemic, focuses on age and pre-existing medical conditions. In contrast, preoperative assessments use cardiopulmonary exercise testing (CPET) to categorise patients to higher and lower risk independent of diagnostic labels. Since CPET is not feasible in population-based settings, our aims included evaluation of a triage/screening tool for cardiorespiratory risk. METHODS: CPET-derived anaerobic thresholds were evaluated retrospectively in 26 patients with pulmonary arteriovenous malformations (AVMs) who represent a challenging group to risk-categorise. Pulmonary AVM-induced hypoxaemia secondary to intrapulmonary right-to-left shunts, anaemia from underlying hereditary haemorrhagic telangiectasia and metabolic equivalents derived from the 13-point Veterans Specific Activity Questionnaire (VSAQ) were evaluated as part of routine clinical care. Pre-planned analyses evaluated associations and modelling of the anaerobic threshold and patient-specific variables. RESULTS: In the 26 patients (aged 21-77, median 57 years), anaerobic threshold ranged from 7.6-24.5 (median 12.35) ml.min-1kg-1 and placed more than half of the patients (15, 57.7%) in the >11 ml.min-1kg-1 category suggested as lower-risk for intra-abdominal surgeries. Neither age nor baseline SpO2 predicted anaerobic threshold, or lower/higher risk categories, either alone or in multivariate analyses, despite baseline oxygen saturation (SpO2) ranging from 79 to 99 (median 92)%, haemoglobin from 108 to 183 (median 156)g.L-1. However, lower haemoglobin, and particularly, arterial oxygen content and oxygen pulse were associated with increased cardiorespiratory risk: Modelling a haemoglobin increase of 25g.L-1 placed a further 7/26 (26.9%) patients in a lower risk category. For patients completing the VSAQ, derived metabolic equivalents were strongly associated with anaerobic threshold enabling risk evaluations through a simple questionnaire. CONCLUSIONS: Baseline exercise tolerance may override age and diagnostic labels in triage settings. These data support approaches to risk reduction by aerobic conditioning and attention to anaemia. The VSAQ is suggested as a rapid screening tool for cardiorespiratory risk assessment to implement during triage/screening.


title: Forecasting COVID-19 pandemic in Poland according to government regulations and people behavior

text: The coronavirus disease 2019 (COVID-19) outbreak is a worldwide pandemic problem that started in China in December 2019 and within a few months spread to all continents. Very high infectivity of SARS-CoV-2 virus and substantial disease severity caused medical care capacity shortage in many countries. Therefore, real-time epidemic forecasting of the COVID-19 is useful to plan public health strategies like country lockdown and healthcare reorganization. We used extended susceptible-infected-removed (eSIR) model to predict the epidemic trend of COVID-19 in Poland under different scenarios of the lockdown and lockdown removal. We used time-series data of SARS-CoV-2 infection from March 4 to May 22 2020. Our forecast includes the impact of a timeline of preventive measures introduced in Poland. Using eSIR algorithm we estimated the basic reproductive number and a total number of infections under different epidemic trend scenarios. Using eSIR modeling we estimated that the basic reproductive number in Poland concerning different scenarios of the lockdown removal is in a range of 3.91-4.79. The lowest predicted number of infected cases would be 263 900 (0 - 1 734 200, 95%CI) if the strict protective measures were maintained until the end of September. However, under different scenarios of precautions removal, a total number of infected cases may exceed one million within the next year. Relatively early introduction of strong precautions in Poland significantly slowed down epidemic spread in Poland in comparison with other European countries like Italy or Spain. However, early removal of protective measures may result in a significant increase in infection. Data shows that the number of new COVID-19 cases in Poland beyond May 18 is linear what could be a prognosis of a duration of the epidemic exceeding 300 days.


title: Scientists are drowning in COVID-19 papers. Can new tools keep them afloat?

text: Timothy Sheahan, a virologist studying COVID-19, wishes he could keep pace with the growing torrent of new scientific papers about the disease and the novel coronavirus that causes it But there are just too many—more than 4000 alone last week “I’m not keeping up,” says Sheahan, who works at the University of North Carolina, Chapel Hill “It’s impossible ” A loose-knit army of data scientists, software developers, and journal publishers is pressing hard to change that Backed by large technology firms and the White House, they are racing to create digital collections holding thousands of freely available papers that could be useful to ending the pandemic, and scrambling to build data-mining and search tools that can help researchers quickly find the information they seek And the urgency is growing: By one estimate, the COVID-19 literature published since January has reached more than 23,000 papers and is doubling every 20 days—among the biggest explosions of scientific literature ever


title: Developmental pathways regulate cytokine-driven effector and feedback responses in the intestinal epithelium

text: The intestinal tract is a common site for infection, and it relies on an appropriate immune response to defend against pathogens. The intestinal epithelium has an important role in effector responses, which is coordinated by immune-type specific cytokines. It is incompletely understood how cytokines drive epithelial responses. Here, using organoid-cytokine co-cultures, we provide a comprehensive analysis of how key cytokines affect the intestinal epithelium, and relate this to in vivo infection models. We use imaging, based on a convolutional neural network, and transcriptomic analysis to reveal that cytokines use developmental pathways to define intestinal epithelial effector responses. For example, we find IL-22 and IL-13 dichotomously induce goblet cells, in which only IL-13 driven goblet cells are associated with NOTCH signaling. We further show that IL-13 induces BMP signalling to act as a negative feedback loop in IL-13 induced tuft cell hyperplasia, an important aspect of type 2 immunity. Together, we show that targeting developmental pathways may be a useful tool to tailor epithelial effector responses that are necessary for immunity to infection.


title: Association between SARS-CoV-2 infection, exposure risk and mental health among a cohort of essential retail workers in the United States

text: Objectives: To investigate SARS-CoV-2 (the virus causing COVID-19) infection and exposure risks among grocery retail workers, and to investigate their mental health state during the pandemic. Methods: This cross-sectional study was conducted in May 2020 in a single grocery retail store in Massachusetts, USA. We assessed workers personal/occupational history and perception of COVID-19 by questionnaire. The health outcomes were measured by nasopharyngeal SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) results, GAD-7 (General Anxiety Disorder-7) and PHQ-9 (Patient Health Questionnaire-9). Results: Among 104 workers tested, twenty-one (20%) had positive viral assays. Seventy-six percent positive cases were asymptomatic. After multi-variate adjustments, employees with direct customer exposure had an odds of 4.7 (95% CI 1.2 to 32.0) being tested positive for SARS-CoV-2, while smokers had an odds of 0.1 (95% CI 0.01 to 0.8) having positive assay. As to mental health, the prevalence of anxiety and depression (i.e. GAD-7 score > 4 or PHQ-9 score >4) was 24% and 8%, respectively. After adjusting for potential confounders, those able to practice social distancing consistently at work had odds of 0.2 (95% CI 0.1 to 0.7) and 0.1 (95% CI 0.01 to 0.6) screening positive for anxiety and depression, respectively. Conclusions: We found a considerable asymptomatic SARS-CoV-2 infection rate among grocery workers. Employees with direct costumer exposure were 5 times more likely to test positive for SARS-CoV-2, while cigarette smokers were 90% less likely to have positive assays. Those able to practice social distancing consistently at work had significantly lower risk of anxiety or depression.


title: New Soluble Angiopoietin Analog of C4BP-ANG1 Prevents Pathological Vascular Leakage

text: Vascular leak is a key driver of organ injury in diseases such as Acute Respiratory Distress Syndrome caused by viruses, including COVID-19. Strategies that reduce enhanced permeability and vascular inflammation are promising therapeutic targets. Activation of the Angiopoietin-1 (Angpt1)-Tie2 tyrosine kinase signaling pathway is an important regulator of vascular quiescence. Here we describe the design and construction of a new soluble ANGPT1 mimetic that is a potent activator of endothelial Tie2 in vitro and in vivo. Using a chimeric fusion strategy, we replaced the extracellular matrix (ECM) binding and oligomerization domain of ANGPT1 with a heptameric scaffold derived from the C-terminus of serum complement protein C4-binding protein α (C4BP). We refer to this new fusion protein biologic as C4BP-ANG1, which forms a stable heptamer and induces TIE2 phosphorylation in cultured cells, and in the lung following i.v. injection of mice. Injection of C4BP-ANG1 ameliorates VEGF- and lipopolysaccharide-induced vascular leakage, in keeping with the known functions of Angpt1-Tie2 in maintaining quiescent vascular stability, and therefore is a promising candidate treatment for inflammatory endothelial dysfunction.


title: Broad phenotypic alterations and potential dysfunctions of lymphocytes in COVID-19 recovered individuals

text: Background Lymphopenia is a typical symptom in the COVID-19 patients. While millions of patients are clinical recovered, little is known about the immune status of lymphocytes in these individuals. Methods A clinical recovered cohort (CR) of 55 COVID-19 individuals (discharged from hospital 4 to 11 weeks), and 55 age and sex matched healthy donors cohort (HD) were recruited. Detailed analysis on phenotype of the lymphocytes in peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry. Findings Compared with cohort HD, the CD8+ T cells in cohort CR had higher Teff and Tem, but lower Tc1 (IFN-{gamma}+), Tc2 (IL-4+) and Tc17 (IL-17A+) frequencies. The CD4+ T cells of CR had decreased frequency, especially on the Tcm subset. Moreover, CD4+ T cells of CR expressed lower PD-1 and had lower frequencies of Th1 (IFN-{gamma}+), Th2 (IL-4+), Th17 (IL-17A+) as well as circulating Tfh (CXCR5+PD-1+). Accordingly, isotype-switched memory B cell (IgM-CD20hi) in CR had significantly lower proportion in B cells, though level of activation marker CD71 elevated. For CD3-HLA-DRlo lymphocytes of CR, besides levels of IFN-{gamma}, Granzyme B and T-bet were lower, the correlation between T-bet and IFN-{gamma} became irrelevant. In addition, taken into account of discharged days, all the lowered function associated phenotypes showed no recovery tendency within whole observation period. Interpretation The CR COVID-19 individuals still showed remarkable phenotypic alterations in lymphocytes after clinical recovery 4 to 11 weeks. This suggests SARS-CoV-2 infection imprints profoundly on lymphocytes and results in long-lasting potential dysfunctions.


title: Basic prediction methodology for covid-19: estimation and sensitivity considerations

text: The purpose of the present paper is to present simple estimation and prediction methods for basic quantities in an emerging epidemic like the ongoing covid-10 pandemic. The simple methods have the advantage that relations between basic quantities become more transparent, thus shedding light to which quantities have biggest impact on predictions, with the additional conclusion that uncertainties in these quantities carry over to high uncertainty also in predictions. A simple non-parametric prediction method for future cumulative case fatalities, as well as future cumulative incidence of infections (assuming a given infection fatality risk f), is presented. The method uses cumulative reported case fatalities up to present time as input data. It is also described how the introduction of preventive measures of a given magnitude ρ will affect the two incidence predictions, using basic theory of epidemic models. This methodology is then reversed, thus enabling estimation of the preventive magnitude ρ, and of the resulting effective reproduction number RE. However, the effects of preventive measures only start affecting case fatalities some 3-4 weeks later, so estimates are only available after this time has elapsed. The methodology is applicable in the early stage of an outbreak, before, say, 10% of the community have been infected. Beside giving simple estimation and prediction tools for an ongoing epidemic, another important conclusion lies in the observation that the two quantities f (infection fatality risk) and ρ (the magnitude of preventive measures) have very big impact on predictions. Further, both of these quantities currently have very high uncertainty: current estimates of f lie in the range 0.2% up to 2% ([9], [7]), and the overall effect of several combined preventive measures is clearly very uncertain. The two main findings from the paper are hence that, a) any prediction containing f, and/or some preventive measures, contain a large amount of uncertainty (which is usually not acknowledged well enough), and b) obtaining more accurate estimates of in particular f, should be highly prioritized. Seroprevalence testing of random samples in a community where the epidemic has ended are urgently needed.


title: Rapid response flow cytometric assay for the detection of antibody responses to SARS-CoV-2

text: SARS-CoV-2 has emerged as a previously unknown zoonotic coronavirus that spread worldwide causing a serious pandemic. While reliable nucleic acid-based diagnostic assays were rapidly available, there exists only a limited number of validated serological assays. Here, we evaluated a novel flow cytometric approach based on antigen-expressing HEK 293T cells to assess spike-specific IgG and IgM antibody responses. Analyses of 201 pre-COVID-19 sera proved a high assay specificity in comparison to commercially available CLIA and ELISA systems, while also revealing the highest sensitivity in specimens from PCR-confirmed SARS-CoV-2 infected patients. Additionally, a soluble Angiotensin-Converting-Enzyme 2 (ACE-2) variant was established as external standard to quantify spike-specific antibody responses on different assay platforms. In conclusion, our newly established flow cytometric assay allows sensitive and quantitative detection of SARS-CoV-2-specific antibodies, which can be easily adopted in different laboratories and does not rely on external supply of assay kits.


title: Volume VI Citation Index

text: Unknown


title: Spatial analysis of COVID-19 spread in Iran: Insights into geographical and structural transmission determinants at a province level

text: The Islamic Republic of Iran reported its first COVID-19 cases by 19th February 2020, since then it has become one of the most affected countries, with more than 73,000 cases and 4,585 deaths at the date. Spatial modeling could be used to approach an understanding of structural and sociodemographic factors that have impacted COVID-19 spread at a province-level in Iran. In the present paper, we developed a spatial statistical approach to describe how COVID-19 cases are spatially distributed and to identify significant spatial clusters of cases and how the socioeconomic features of Iranian provinces might predict the number of cases. We identified a cluster of provinces with significantly higher rates of COVID-19 cases around Tehran, which indicated that the spread of COVID-19 within Iran was spatially correlated. Urbanized, highly connected provinces with older population structures and higher average temperatures were the most susceptible to present a higher number of COVID-19 cases. Interestingly, literacy is a protective factor that might be directly related to health literacy and compliance with public health measures. These features indicate that policies related to social distancing, protecting older adults, and vulnerable populations, as well as promoting health literacy, might be targeted to reduce SARS-CoV2 spread in Iran. Our approach could be applied to model COVID-19 outbreaks in other countries with similar characteristics or in case of an upturn in COVID-19 within Iran.


CRISPR tests for coronavirus, unproven therapies and a high-profile resignation


title: Antibodies to SARS/CoV-2 in arbitrarily-selected Atlanta residents

text: We quantitated anti-SARS/CoV-2 IgG and IgM by ELISA in self-collected blood samples (n=142) in arbitrarily-selected metro Atlanta residents, primarily acquaintances of the authors' lab members from 4/17-4/27, 2020. Archived serum (n=34), serum from nucleic acid test (NAT)-positive subjects (n=4), and samples collected from NAT-positive community members (n=4) served to validate the assay. The range of anti-SARS/CoV-2 antibodies in archived and NAT-positive sera indicated need to compromise sensitivity or specificity. Accordingly, we set a cutoff of 4 SD above the mean for IgG and 3 SD above the mean for IgM to indicate that an individual had been exposed, and developed some degree of immunity, to SARS/CoV-2. The IgG cutoff clearly compromised sensitivity but offered high specificity, both of which were harder to gauge for IgM. Based on these cutoffs, excluding subjects whose participation resulted from self-suspected SARS/CoV-2 infection, we found 7.1% positivity for anti-SARS/CoV-2 IgG (3 of 127 subjects) or IgM (6 of 127). While we do not claim this small immune survey is broadly representative of metro Atlanta, and we have greater confidence in the IgG results, which had only 2.4% positivity, it nonetheless demonstrates that persons with antibodies to SARS/CoV-2, who've not suspected they'd been exposed to this virus, can readily be found in various Atlanta area neighborhoods (9 positives were in 8 zip codes). Accordingly, these results support the notion that dissemination of the virus is more widespread than testing would indicate but also suggests that most persons in metro Atlanta remain vulnerable to this virus. More generally, these results support the general utility of sero-surveillance to guide public policy but also highlight the difficulty of discerning if individuals have immunity to SARS/CoV-2.


title: Monitoring and forecasting the number of reported and unreported cases of the COVID-19 epidemic in Brazil using Particle Filter

text: In this paper, we combine algorithm of Liu & West for the Particle Filter (PF) with SIRU-type epidemic model to monitor and forecast cases of Covid-19 in Brazil from February up to September. We filter the number of cumulative reported cases and estimate model parameters and more importantly unreported infectious cases (asymptomatic and symptomatic infectious individuals). The parameters under study are related to the attenuation factor of the transmission rate and the fraction of asymptomatic infectious becoming reported as symptomatic infectious. Initially, the problem is analysed through Particle Swarm Optimization (PSO) based simulations to provide initial guesses, which are then refined by means of PF simulations. Subsequently, two additional steps are performed to verify the capability of the adjusted model to predict and forecast new cases. According to the results, the pandemic peak is expected to take place in mid-June 2020 with about 25,000 news cases per day. As medical and hospital resources are limited, this result shows that public health interventions are essential and should not be relaxed prematurely, so that the coronavirus pandemic is controlled and conditions are available for the treatment of the most severe cases.