title: Functional characterization of SARS-CoV-2 infection suggests a complex inflammatory response and metabolic alterations

text: Covid-19, caused by the SARS-CoV-2 virus, has reached the category of a worldwide pandemic. Even though intensive efforts, no effective treatments or a vaccine are available. Molecular characterization of the transcriptional response in Covid-19 patients could be helpful to identify therapeutic targets. In this study, RNAseq data from peripheral blood mononuclear cell samples from Covid-19 patients and healthy controls was analyzed from a functional point of view using probabilistic graphical models. Two networks were built: one based on genes differentially expressed between healthy and infected individuals and another one based on the 2,000 most variable genes in terms of expression in order to make a functional characterization. In the network based on differentially expressed genes, two inflammatory response nodes with different tendencies were identified, one related to cytokines and chemokines, and another one related to bacterial infections. In addition, differences in metabolism, which were studied in depth using Flux Balance Analysis, were identified. SARS-CoV2-infection caused alterations in glutamate, methionine and cysteine, and tetrahydrobiopterin metabolism. In the network based on 2,000 most variable genes, also two inflammatory nodes with different tendencies between healthy individuals and patients were identified. Similar to the other network, one was related to cytokines and chemokines. However, the other one, lower in Covid-19 patients, was related to allergic processes and self-regulation of the immune response. Also, we identified a decrease in T cell node activity and an increase in cell division node activity. In the current absence of treatments for these patients, functional characterization of the transcriptional response to SARS-CoV-2 infection could be helpful to define targetable processes. Therefore, these results may be relevant to propose new treatments. Author Summary SARS-CoV-2 infection caused Covid-19 which has reached the category of a worldwide pandemic. However, no treatments or vaccines are still available. For this reason, it is still necessary the molecular study of this disease. In this study, we reanalyzed data from peripheral blood mononuclear cells from Covid-19 patients and healthy controls using computational techniques that allow the study of differential biological processes and metabolic pathways. The results suggested a complex inflammatory response, involving genes related to response to bacterial infection and allergic processes, and alterations in metabolic pathways such as glutamate metabolism, cysteine and methionine metabolism or tetrahydrobiopterin metabolism. These processes could be used in the future as therapeutic targets in Covi-19 infection.


title: Characterizing the transmission and identifying the control strategy for COVID-19 through epidemiological modeling

text: The outbreak of the novel coronavirus disease, COVID-19, originating from Wuhan, China in early December, has infected more than 70,000 people in China and other countries and has caused more than 2,000 deaths. As the disease continues to spread, the biomedical society urgently began identifying effective approaches to prevent further outbreaks. Through rigorous epidemiological analysis, we characterized the fast transmission of COVID-19 with a basic reproductive number 5.6 and proved a sole zoonotic source to originate in Wuhan. No changes in transmission have been noted across generations. By evaluating different control strategies through predictive modeling and Monte carlo simulations, a comprehensive quarantine in hospitals and quarantine stations has been found to be the most effective approach. Government action to immediately enforce this quarantine is highly recommended.


Covid-19: UK budget gives £94 a week statutory sick pay to self-isolators and their carers


title: Ad hoc laboratory-based surveillance of SARS-CoV-2 by real-time RT-PCR using minipools of RNA prepared from routine respiratory samples

text: We report a laboratory-based surveillance for SARS-CoV-2 using minipools of respiratory samples submitted for routine diagnostics. We tested a total of 70 minipools resembling 700 samples shortly before the upsurge of cases in Germany. We identified one SARS-CoV-2 positive patient. Our approach proved its concept, is easily adaptable and resource-saving.


title: Coronavirus epidemic: prediction and controlling measures

text: The COVID-19 outbreak has caused over 1.7 million (still increasing) confirmed cases globally as of April 10th, 2020. The levels of spread and severity of the virus lead to a wide-spread political and economic turmoil. We believe that two critical contributing factors need to be taken into account by the authorities to make effective decisions for controlling the spread of the virus: (i) being familiar with the most effective controlling measures and (ii) having a mathematical model to predict the spread of the virus. In this study, we provided information regarding both of these crucial factors. First, we investigated the importance of different measures such as quarantine, isolation, face mask, social distancing, etc. in controlling the virus in various countries. We then present a mathematical model to predict the spread of the virus in different countries. Our prediction shows an excellent match with the actual data up to now.


title: The Distal Polybasic Cleavage Sites of SARS-CoV-2 Spike Protein Enhance Spike Protein-ACE2 Binding

text: The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a crucial role in binding the human cell receptor ACE2 that is required for viral entry. Many studies have been conducted to target the structures of RBD-ACE2 binding and to design RBD-targeting vaccines and drugs. Nevertheless, mutations distal from the SARS-CoV-2 RBD also impact its transmissibility and antibody can target non-RBD regions, suggesting the incomplete role of the RBD region in the spike protein-ACE2 binding. Here, in order to elucidate distant binding mechanisms, we analyze complexes of ACE2 with the wild type spike protein and with key mutants via large-scale all-atom explicit solvent molecular dynamics simulations. We find that though distributed approximately 10 nm away from the RBD, the SARS-CoV-2 polybasic cleavage sites enhance, via electrostatic interactions and hydration, the RBD-ACE2 binding affinity. A negatively charged tetrapeptide (GluGluLeuGlu) is then designed to neutralize the positively charged arginine on the polybasic cleavage sites. We find that the tetrapeptide GluGluLeuGlu binds to one of the three polybasic cleavage sites of the SARS-CoV-2 spike protein lessening by 34% the RBD-ACE2 binding strength. This significant binding energy reduction demonstrates the feasibility to neutralize RBD-ACE2 binding by targeting this specific polybasic cleavage site. Our work enhances understanding of the binding mechanism of SARS-CoV-2 to ACE2, which may aid the design of therapeutics for COVID-19 infection. TOC: The SARS-CoV-2 spike protein-ACE2 complex showing the polybasic cleavage sites


title: Impact of the COVID-19 Pandemic on Adult Mental Health

text: The outbreak of the Novel Coronavirus (COVID-19) in December 2019 has progressed to the status of a global pandemic, with countries across the seven continents adversely affected and the number of human cases exceeding two million. With no available vaccine, the treatment is primarily symptomatic for those affected and preventative for those at risk. Most countries have taken action to curtail the spread of COVID-19 through measures such as lockdowns, social distancing and voluntary self-isolation. Whilst necessary, such measures and the disease itself, may have an adverse impact on mental health. In view of research from previous pandemic crises, it is known that such situations are likely to increase stress levels and have negative psychiatric effects. The impact is likely to be felt by the general public, sufferers of COVID-19, their families and friends, persons with pre-existing mental health conditions and healthcare workers.


title: What to do when a patient infected with covid-19 needs an operation: A Pre-surgery, Peri-surgery and Post-surgery Guide/ COVID-19 ile Enfekte Bir Hastasının Operasyona İhtiyacı Olduğunda Ne Yapmalıyız: Cerrahi Öncesi, Cerrahi Sırası ve Cerrahi Sonrası Rehberi

text: The virus, called COVID-19, which has emerged in China in December 2019, has been known to spread through droplets and close contact, and has evolved into a pandemic today. It is also known that in all patients who have come into contact with COVID-19, the infection is not severe and may even occur without symptoms. There is no consensus yet on how to take measures to protect the patient and the surgeon in case of diseases requiring urgent or elective surgery, and how preoperative preparation, perioperative phase, and postoperative care should be performed. The aim of this study was to prepare a guide on how the surgeon should behave in patients whose operation is mandatory in light of the available data.


title: Real-time RT-PCR for the detection of SARS-CoV-2 nucleic acid/ 实时荧光RT-PCR方法检测新型冠状病毒核酸结果分析

text: Objective: To investigate the performance of real-time RT-PCR for the detection of SARS-CoV-2 nucleic acid in clinical diagnosis of COVID-19. Methods: Laboratory test data and basic case information of Henan COVID-19 cases were collected from the China's Infectious Disease Information System as of March 5, 2020. All information was entered by local hospitals and Center for Disease Control and Prevention (CDC). Local hospitals or country CDC were responsible for sampling and municipal CDC was responsible for nucleic acid testing. Results: A total of 6 714 specimens were detected and the positive rate of SARS-CoV-2 nucleic acid was 23.82%. The specimens were collected from 1 200 confirmed cases, 2 178 suspected cases and 77 asymptomatic cases. The nucleic acid diagnosis rate of COVID-19 was 36.96% (1 277/3 455). In all cases, the positive rates of SARS-CoV-2 nucleic acid in nasal swabs, sputum samples and throat swabs were 19.38%, 28.59% and 23.53%, respectively (χ2=15.896, P<0.01). The positive rate of SARS-CoV-2 nucleic acid in confirmed COVID-19 cases was 63.10%. The positive rates in nasal swabs, sputum samples and throat swabs were 50.80%, 58.71% and 65.21 (χ2=18.612, P<0.01). The positive rates of SARS-CoV-2 nucleic acid were 43.51%, 23.98%, 22.82%, 12.17%, 14.46% and 13.21% in samples collected on the day of symptom onset and one week, two weeks, three weeks, four weeks, five weeks and above five weeks after the onset, respectively. The positive rates in confirmed cases were respectively 89.03%, 86.57%, 52.30%, 17.53%, 17.69% and 24.14% at those time points. Conclusions: Real-time RT-PCR is the most effective method for early pathogenic diagnosis of COVID-19. The highest detection rate of nucleic acid is achieved within one week after the onset of COVID-19, and the latest time for nucleic acid detection is 38 d after the onset.


Ventilation and other strategies for COVID-19 patients


docid: faixawpn

title: Social media and smartphone app use predicts maintenance of physical activity during Covid-19 enforced isolation in psychiatric outpatients

text: Public health professionals have raised concerns that the social and physical distancing measures implemented in response to the Covid-19 pandemic may negatively impact health in other areas, via both decreased physical activity and increased social isolation. Here, we investigated whether increased engagement with digital social tools may help mitigate effects of enforced isolation on physical activity and mood, in a naturalistic study of at-risk individuals. Passively sensed smartphone app use and actigraphy data, collected from a sample of psychiatric outpatients both before and during imposition of strict lockdown conditions (N=163), were analysed using Gaussian graphical models: a form of network analysis which gives insight into the predictive relationships between measures across timepoints. Within-individuals, we found evidence of a positive predictive path between digital social engagement, general smartphone use, and physical activity - selectively under lockdown conditions. Further, we observed a positive relationship between social media use and total daily steps across individuals during (but not prior to) lockdown. We interpret these findings in terms of individuals using these digital tools to harness online social support structures, which may help guard against negative effects of in-person social deprivation and other pandemic-related stress. Monitoring of these measures is low burden and unintrusive and therefore, given appropriate consent, could potentially help identify individuals who are failing to engage this mechanism, providing a route to early intervention in this and other vulnerable populations.


title: Computational Electrostatics Predict Variations in SARS-CoV-2 Spike and Human ACE2 Interactions

text: SARS-CoV-2 is a novel virus that is presumed to have emerged from bats to crossover into humans in late 2019. As the global pandemic ensues, scientist are working to evaluate the virus and develop a vaccine to counteract the deadly disease that has impacted lives across the entire globe. We perform computational electrostatic simulations on multiple variants of SARS-CoV-2 spike protein s1 in complex with human angiotensin-converting enzyme 2 (ACE2) variants to examine differences in electrostatic interactions across the various complexes. Calculations are performed across the physiological pH range to also examine the impact of pH on these interactions. Two of six spike protein s1 variations having greater electric forces at pH levels consistent with nasal secretions and significant variations in force across all five variants of ACE2. Five out of six spike protein s1 variations have relatively consistent forces at pH levels of the lung, and one spike protein s1 variant that has low potential across a wide range of pH. These predictions indicate that variants of SARS-CoV-2 spike proteins and human ACE2 in certain combinations could potentially play a role in increased binding efficacy of SARS-CoV-2 in vivo.


docid: uatweoke

title: Temporal patterns in electrical nerve stimulation: burst gap code shapes tactile frequency perception

text: We have described a novel temporal encoding mechanism in the somatosensory system, where tactile pulses grouped into periodic bursts create a perceived frequency based on the duration of the silent gap between bursts, rather than the mean rate or the periodicity. This coding strategy may offer new opportunities for transmitting information to the brain using various sensory neural prostheses and brain-machine interfaces. However, it was not known whether the same coding mechanisms apply when electrical, rather than mechanical, stimulation is used. Here, we demonstrate that the predictions of the burst gap coding model for frequency perception apply to burst stimuli delivered with electrical pulses, re-emphasising the importance of the temporal structure of spike patterns in neural processing and perception of tactile stimuli. Reciprocally, the electrical stimulation data confirm that the results observed with mechanical stimulation do indeed depend on neural processing mechanisms in the central nervous system and are not due to mechanical effects in the skin or afferent population activation patterns. Our results suggest that spike intervals contribute to perceived frequency with perceptual weights that depend on their duration, and that a generalised frequency processing system would explain the constancy of vibrotactile frequency perception across different receptor types.


title: The First Month Spread of COVID-19 in Madagascar

text: Using the officially published data and aware of the unclear source and inaccurate number of samples, we present a first and (for the moment) unique attempt to study the spread of the pandemic COVID-19 in Madagascar. The approach has been tested by predicting the number of contaminated persons until 20 days after fitting the inputs data collected within 15 days using standard least {chi}2-fit method. Encouraged by this first test, we add the new data collected within 30 days and give prevision until 33 days. The present data show an approximate linear increase of about (4-5) infected persons per day while the analysis signals an eventual near future stronger growth. These results may also be interpreted as the lowest values of the real cases due to the insufficient number of samples (about 2200 for 20 millions of population). A comparison with some other approaches is done. Some social, economical and political impacts of COVID-19 and confinement for Madagascar and Worldwide are shortly discussed.


title: Impact of COVID-19 large scale restriction on environment and economy in Indonesia

text: COVID-19 has a severe and widespread impact, especially in Indonesia COVID-19 was first reported in Indonesia on March 03, 2020 then rapidly spread to all 34 provinces by April 09, 2020 Since then, COVID-19 is declared a state of national disaster and health emergency This research analyzes the difference of CO, HCHO, NO2, and SO2 density in Jakarta, West Java, Central Java, and South Sulawesi before and during the pandemic Also, this study assesses the effect of large scale restrictions on the economic growth during COVID-19 pandemic in Indonesia In a nutshell, the results on Wilcoxon and Fisher test by significance level alpha=5% as well as odds ratio showed that there are significant differences of CO density in all regions with highest odds ratio in East Java (OR=9 07), significant differences of HCHO density in DKI Jakarta, East Java, and South Sulawesi There are significant differences of NO2 density before and during public activities limitation in DKI Jakarta, West Java, East Java, and South Sulawesi However, the results show that there are no significant differences of SO2 density in all regions In addition, this research shows that there are significant differences of retail, grocery and pharmacy, and residental mobility before and during the COVID-19 pandemic in Indonesia This research also shows that during the COVID-19 pandemic there are severe economic losses, industry, companies, and real disruptions are severe for all levels of life due to large scale restrictions (C) 2020 GJESM All rights reserved


title: COVID-19 in healthcare workers in three hospitals in the South of the Netherlands, March 2020

text: Background: Ten days after the first reported case of SARS-CoV-2 infection in the Netherlands, 3.9% of healthcare workers (HCWs) in nine hospitals located in the South of the Netherlands tested positive for SARS-CoV-2 RNA. The extent of nosocomial transmission that contributed to the HCW infections was unknown. Methods: We combined epidemiological data, collected by means of structured interviews of HCWs, with whole genome sequencing (WGS) of SARS-CoV-2 in clinical samples from HCWs and patients in three of nine hospitals that participated in the HCW screening, to perform an in-depth analysis of sources and modes of transmission of SARS -CoV-2 in HCWs and patients. Results: A total of 1,796 out of 12,022 HCWs (15%) of the three participating hospitals were screened, based on clinical symptoms, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete genome sequences of 50 HCWs and 18 patients. Most sequences grouped in 3 clusters, with 2 clusters displaying local circulation within the region. The observed patterns are most consistent with multiple introductions into the hospitals through community acquired infections, and local amplification in the community. Conclusions: Although direct transmission in the hospitals cannot be ruled out, the data does not support widespread nosocomial transmission as source of infection in patients or healthcare workers.


title: Pharmacological interventions for COVID-19: Protocol for a Rapid Living Systematic Review with network meta-analysis

text: CONTEXT AND OBJECTIVE: Coronavirus disease 2019 (COVID-19) has emerged in China in December 2019 and rapidly spread. Although extraordinary efforts have been made on research regarding pharmacological interventions, none have proven effective. This is the protocol for a rapid living systematic review that aims to compare the effectiveness and safety of different pharmacological interventions for the treatment of COVID-19. METHODS: rapid living systematic review methodology with Network Meta-Analysis following the recommendations of Cochrane Handbook. We will include randomized controlled trials (RCT) and quasi-RCTs that evaluate single and/or combined pharmacological interventions at any dose for the treatment of COVID-19. We will search PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, Scopus and SciELO to identify potentially eligible studies. No language restrictions will be used in the selection. We will perform the critical appraisal of included studies with the Risk of Bias tool and the certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).


title: Characterization of SARS-CoV-2 viral diversity within and across hosts

text: In light of the current COVID-19 pandemic, there is an urgent need to accurately infer the evolutionary and transmission history of the virus to inform real-time outbreak management, public health policies and mitigation strategies. Current phylogenetic and phylodynamic approaches typically use consensus sequences, essentially assuming the presence of a single viral strain per host. Here, we analyze 621 bulk RNA sequencing samples and 7,540 consensus sequences from COVID-19 patients, and identify multiple strains of the virus, SARS-CoV-2, in four major clades that are prevalent within and across hosts. In particular, we find evidence for (i) within-host diversity across phylogenetic clades, (ii) putative cases of recombination, multi-strain and/or superinfections as well as (iii) distinct strain profiles across geographical locations and time. Our findings and algorithms will facilitate more detailed evolutionary analyses and contact tracing that specifically account for within-host viral diversity in the ongoing COVID-19 pandemic as well as future pandemics.


title: How an Australian researcher ended up in the spotlight at a White House coronavirus briefing

text: When Craig Dalton heard that his name came up at a nationally televised White House press briefing Monday, the medical epidemiologist at the University of Newcastle in Australia says “I didn’t believe it ” Dalton did a quick websearch and his disbelief transformed into amazement “Turned out, it was actually true,” he told ScienceInsider Dalton’s unexpected moment in the media spotlight came as Deborah Birx, the White House’s coronavirus response coordinator, and Anthony Fauci, the head of the National Institute of Allergy and Infectious Diseases, stepped to the White House lectern to describe a new set of guidelines that the U S government would be distributing as part of its effort to slow the spread of coronavirus 2019 (COVID-2019) in the United States


title: Prevalence of facemask use among general public when visiting wet market during Covid-19 pandemic: An observational study.

text: Background In late December 2019, an outbreak of a novel coronavirus disease (COVID-19; previously known as 2019-nCoV) was epidemiologically linked to seafood and wet animal wholesale market in Wuhan, Hubei, China. This has instigated stigma among the general population as the wet market is viewed as a high-risk location for getting infected with coronavirus. Objective This study investigated the prevalence of facemask use among general population visiting the wet market. This study also investigated the demographic factors contributing to unacceptable facemask practice. Setting This prospective observational study was done among visitor to a district wet market selling range of live or freshly slaughtered animals during COVID-19 pandemic outbreak. Methods Individuals entering through dedicated entry point were observed for the type, category and practice of wearing personal protective equipment. Inclusion criteria for this study were any individuals entering the wet market. Subjects were categorized into two groups of acceptable and unacceptable facemask practice. The Pearson chi-square was used to test for differences in investigated variables in the univariate setting and Binary Logistic regression model was used in the multivariate setting. Main outcome measure Prevalence, acceptance practice and odds ratio of unacceptance of facemask use. Results Among 1697 individuals included in the final analysis, 1687 (99.7%) was observed wearing facemask with 1338 (78.8%) using medical-grade facemask. Among them, 1615 (95.7%) individuals facemask practice was acceptable while the reaming 72 (4.3%) individuals were observed with unacceptable facemask practice. Individuals using medical-grade facemask and high-risk age group are 6.4 times (OR=6.40; 95% CI, 2.00-20.43; p=.002) and 2.06 times practice (OR=2.06; 95% CI, 1.08-3.94; p=.028). More likely to practice unacceptable facemask use respectively. Conclusion High saturation of facemask among the general population is an adequate indicator of public hygiene measures strategy which can help to mitigate the COVID-19 epidemic impact. Alarmingly, the unacceptable facemask practice among high-risk population raises the need for a targeted approach by healthcare authorities to ensure satisfactory facemask use.


title: Clinical and behavioural characteristics of self-isolating healthcare workers during the COVID-19 pandemic: a single-centre observational study

text: Objectives:To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19. Design: A cross-sectional, single-centre study. Setting: A large, teaching hospital based in Central London with tertiary infection services. Participants: 236 HCWs completed a survey distributed by internal staff email bulletin. 167 were female and 65 male. Measures: Information on symptomatology, exposures and health-seeking behaviour were collected from participants by self-report. Results: The 236 respondents reported illness compatible with COVID-19 and there was an increase in illness reporting during March 2020. Diagnostic swabs were not routinely performed. Cough (n=179, 75.8%), fever (n=138, 58.5%), breathlessness (n=84, 35.6%) were reported. Anosmia was reported in 42.2%. Fever generally settled within 1 week (n=110, 88%). Several respondents remained at home and did not seek formal medical attention despite reporting severe breathlessness and measuring hypoxia (n=5/9, 55.6%). 2 patients required hospital admission but recovered following oxygen therapy. 84 respondents (41.2%) required greater than the obligated 7 days off work and 9 required greater than 3 weeks off. Conclusion: There was a significant increase in staff reporting illness compatible with possible COVID-19 during March 2020. Conclusions cannot be drawn about exact numbers of confirmed cases due to lack of diagnostic swabbing. There were significant numbers of respondents reporting anosmia; as well as early non-specific illness prior to onset of cough and fever. This may represent pre-symptomatic HCWs who are likely to be infectious and thus criteria for isolation and swabbing should be broadened. The study also revealed concerning lack of healthcare seeking in respondents with significant red flag symptoms (severe breathlessness, hypoxia). This should be addressed urgently to reduce risk of severe disease being detected late. Finally, this study should inform trusts that HCWs may require longer than 7 days off work to recover from illness.


title: “Amantadine disrupts lysosomal gene expression; potential therapy for COVID19”

text: SARS-coronavirus 2 is the causal agent of the COVID-19 outbreak. SARS-Cov-2 entry into a cell is dependent upon binding of the viral spike (S) protein to cellular receptor and on cleavage of the spike protein by the host cell proteases such as Cathepsin L and Cathepsin B. CTSL/B are crucial elements of lysosomal pathway and both enzymes are almost exclusively located in the lysosomes.CTSL disruption offers potential for CoVID-19 therapies. The mechanisms of disruption include: decreasing expression of CTSL, direct inhibition of CTSL activity and affecting the conditions of CTSL environment (increase pH in lysosomes). We have conducted a high throughput drug screen gene expression analysis to identify compounds that would downregulate the expression of CTSL/CTSB. One of the top significant results shown to downregulate the expression of the CTSL gene is Amantadine. Amantadine was approved by the US Food and Drug Administration in 1968 as a prophylactic agent for influenza and later for Parkinson’s disease. It is available as a generic drug.. Amantadine in addition to downregulating CTSL appears to further disrupt lysosomal pathway, hence interfering with the capacity of the virus to replicate. It acts as a lysosomotropic agent altering the CTSL functional environment. We hypothesize that Amantadine could decrease the viral load in SARS-CoV-2 positive patients and as such it may serve as a potent therapeutic decreasing the replication and infectivity of the virus likely leading to better clinical outcomes. Clinical studies will be needed to examine the therapeutic utility of amantadine in COVID-19 infection.


docid: atisrhas

title: Virus survival in evaporated saliva microdroplets deposited on inanimate surfaces

text: The novel coronavirus respiratory syndrome (COVID-19) has now spread worldwide. The relative contribution of viral transmission via fomites is still unclear. SARS-CoV-2 has been shown to survive on inanimate surfaces for several days, yet the factors that determine its survival on surfaces are not well understood. Here we combine microscopy imaging with virus viability assays to study survival of three bacteriophages suggested as good models for human respiratory pathogens: the enveloped Phi6 (a surrogate for SARS-CoV-2), and the non-enveloped PhiX174 and MS2. We measured virus viability in human saliva microdroplets, SM buffer, and water following deposition on glass surfaces at various relative humidities (RH). Although saliva microdroplets dried out rapidly at all tested RH levels (unlike SM that remained hydrated at RH ≥ 57%), survival of all three viruses in dry saliva microdroplets was significantly higher than in water or SM. Thus, RH and hydration conditions are not sufficient to explain virus survival, indicating that the suspended medium, and association with saliva components in particular, likely affect physicochemical properties that determine virus survival. The observed high virus survival in dry saliva deposited on surfaces, under a wide range of RH levels, can have profound implications for human public health, specifically the COVID-19 pandemic.


Non-pharmaceutical interventions for epidemic outbreaks – any evidence?/ Nicht-pharmakologische maßnahmen bei epidemien – gibt es evidenz?


title: Comparative analysis of antiviral efficacy of FDA-approved drugs against SARS-CoV-2 in human lung cells: Nafamostat is the most potent antiviral drug candidate

text: Drug repositioning represents an effective way to control the current COVID-19 pandemic. Previously, we identified 24 FDA-approved drugs which exhibited substantial antiviral effect against SARS-CoV-2 in Vero cells. Since antiviral efficacy could be altered in different cell lines, we developed an antiviral screening assay with human lung cells, which is more appropriate than Vero cell. Comparative analysis of antiviral activities revealed that nafamostat is the most potent drug in human lung cells (IC50 = 0.0022µM).


title: Medical oxygen demand soars

text: Gases companies worldwide have ramped up delivery of gas cylinders and are installing new on-site liquid oxygen tanks and supply systems in hospitals as demand surges for medical oxygen to treat patients with COVID-19 The European Industrial Gases Association says members such as Air Liquide and Linde are experiencing 5–10 times the usual demand for medical O2 To meet the demand spike in the US, companies are installing tanks at established and pop-up hospitals around the country Air Products recently put a 40,000 L medical O2 tank and a 14,000 L reserve tank at a pop-up hospital at the USTA Billie Jean King National Tennis Center in New York City The facility has 400 beds In Italy and eastern France, Air Liquide has seen 4–6 times the normal demand for medical oxygen Despite the surge, the company says it doesn’t anticipate supply shortages Linde, Germany’s biggest supplier of medical gases,


title: Transmissibility of coronavirus disease 2019 (COVID-19) in Chinese cities with different transmission dynamics of imported cases

text: Background: Monitoring the time-varying reproduction number (Rt) of the disease is useful in determining whether there is sustained transmission in a population. In this study, we examined Rt of COVID-19 and compared its transmissibility between different intervention periods in Hangzhou and Shenzhen. Methods: Daily aggregated counts of confirmed imported and local cases between January 1, 2020 and March 13, 2020 were analysed. A likelihood function was constructed to estimate Rt, accounting for imported cases. Results: Although Hangzhou had fewer number of cases than Shenzhen, Shenzhen had higher proportion of imported cases than Hangzhou (83% vs 29%). Since the epidemic of COVID-19 in Shenzhen was dominated by imported cases, Rt was kept below unity through time. On the contrary, Rt was greater than unity in Hangzhou from 16 January to 7 February due to the surge in local cases. Credits to the Wuhan lockdown and outbreak response measures following the local lockdown, Rt decreased steadily and dropped below unity in mid-February. Conclusion: The lockdown measures and local outbreak responses helped reduce the potential of local transmission in Hangzhou and Shenzhen. Meanwhile, cities with similar epidemic trend could have different transmission dynamics given the variation in imported cases.


title: Medical Abortion Care During a Pandemic

text: In keeping with federal policy, our state’s laws do not permit medical abortion via telemedicine, not even during the coronavirus disease 2019 (COVID-19) outbreak, a decision that endangers the lives of women, clinical staff, nurses, and doctors. It also ties dedicated professionals to the clinic instead of being available to emergency rooms, bedsides, and intensive care units, knowing if their clinic doors close vulnerable women may be driven to desperate acts. Instead of 6 feet we could have been 3000 miles apart. Nearly 39% of abortions in the United States are medical abortions. Instructions, medication prescriptions, and routine follow-up can all be safely done remotely. When an examination or ultrasound are necessary, it can be accomplished with minimal staff and patient exposure. Instead, I am caught in a Kafkaesque moment in an already surreal time. Making medical abortion part of telemedicine during the COVID-19 pandemic could save the lives of women, nurses, staff, and doctors. Maybe yours, maybe even mine.


title: Scientists have turned the structure of the coronavirus into music

text: You’ve probably seen dozens of images of the novel coronavirus—now responsible for 1 million infections and tens of thousands of deaths Now, scientists have come up with a way for you to hear it: by translating the structure of its famous spike protein into music


title: SARS-CoV-2 in human milk is inactivated by Holder pasteurization but not cold storage

text: As the COVID-19 pandemic evolves, human milk banks worldwide continue to provide donor human milk to vulnerable infants who lack access to mothers own milk. Under these circumstances, ensuring the safety of donor human milk is paramount, as the risk of vertical transmission of SARS-CoV-2 is not well understood. Here, we investigate the inactivation of SARS-CoV-2 in human milk by pasteurisation, and the stability of SARS-CoV-2 in human milk under cold storage (freezing or refrigeration). Following heating to 63{degrees}C or 56{degrees}C for 30 minutes, SARS-CoV-2 replication competent (i.e. live) virus was undetected in both human milk and the control medium. Cold storage of SARS-CoV-2 in human milk (either at 4{degrees}C or -30{degrees}C) did not significantly impact infectious viral load over a 48 hour period. Our findings demonstrate that SARS-CoV-2 can be effectively inactivated by Holder pasteurisation, and confirm that existing milk bank processes will effectively mitigate the risk of transmission of SARS-COV-2 to vulnerable infants through pasteurised donor human milk.


title: The Enhanced Danger of Physicians’ Off-Label Prescribing During a Public Health Emergency

text: The COVID-19 pandemic represents a major challenge to both technologically advanced and resource-poor countries There are currently no effective treatments for severe disease other than supportive care and advanced life support measures, including the use of mechanical ventilators With the urgency and necessity bred from desperation, there have been many calls to utilize unproven therapies, such as hydroxychloroquine, for which little evidence of efficacy exists We have previously argued that such off-label use, while legal, is problematic (and even dangerous) and have suggested several regulatory remedies that could protect patients and advance their interests while preserving the reasonable authority of physicians to do what they and their patients think is the best course of action In this essay we ask whether the special conditions existing in a public healthcare crisis, such as the current pandemic, would justify a relaxing of our argument and permit ongoing unregulated off-label use We outline at least four areas of concern, all of which can be exacerbated by the widespread distress and despair amongst doctors, patients and other stakeholders We contend that, if anything, these conditions warrant even more caution and scrutiny of this practice


title: THE EMOTIONAL IMPACT OF THE ASRM GUIDELINES ON FERTILITY PATIENTS DURING THE COVID-19 PANDEMIC

text: Objective: To survey fertility patients' agreement with ASRM recommendations during the COVID-19 pandemic and the emotional impact on them. Design: An online survey was sent to current fertility patients Setting: New York City academic fertility practice at the epicenter of the COVID-19 pandemic Patient(s): Fertility patients seen within the last year Intervention(s): None Main Outcome Measure(s): Patient agreement with the ASRM recommendations during the COVID-19 pandemic and the emotional impact rated on a Likert scale Result(s): A total of 518 patients completed the survey for a response rate of 17%. Fifty percent of respondents had a cycle canceled due to the COVID-19 pandemic. Of those who had a cycle cancelled, 85% of respondents found it to be moderately to extremely upsetting with 22% rating it to be equivalent to the loss of a child. There was no difference on the emotional impact based on the type of cycle cancelled. Fifty-five percent of patients agreed that diagnostic procedures such as hysterosalpingograms should be cancelled while 36% of patients agreed all fertility cycles should be cancelled. Patients were slightly more likely to agree with the ASRM guidelines if they have an upcoming cycle cancelled (p = 0.041). Of all respondents 82% would have preferred to have the option to start a treatment cycle in consultation with their doctor. Conclusion(s): Given the severity of the COVID-19 pandemic, the physical, financial and emotional impact of this unprecedented threat cannot be underestimated in our fertility patients. Key Word(s): COVID-19, novel coronavirus, ASRM, mental health, infertility


title: Clinical Characteristics and Risk factors for developed COVID-19 patients transferring to designated hospital from Jianghan Fangcang shelter Hospital: a retrospective, observational study

text: Background The outbreak of coronavirus disease 2019 (COVID-19) has become a world-wide emergency. Fangcang shelter hospitals have been applied in COVID-19 to ease ongoing shortage of medical resources in Wuhan since February 2020. Methods This study enrolled all cases (no=1848) with mild or moderate type of COVID-19 in Fangcang shelter hospital of Jianghan in Wuhan from Feb 5th to Mar 9th, 2020. Diagnosis of COVID-19 was based on the National health commission of China. Epidemiological history, comorbidity, vital signs, symptoms and signs were recorded in detail. Laboratory tests included biochemical indicators and nucleic acid tests by throat swabs have been performed as well. Findings A total of 1327 patients reached the criteria of isolation release. Meanwhile, 521 patients have been transferred to the designated hospitals for further treatment, including severe type, fever more than 3 days, and severe comorbidity. The case-severity rate (rate of mild or moderate type transforming to severe type) was 3.0% in the shelter hospital. The patients from mild or moderate type to severe type showed the following clinical characteristics: the median incubation (onset to shelter) period was 10 days; they were all symptomatic at admission; fever, cough, and fatigue were the most common symptoms; hypertension, diabetes and coronary heart diseases were common co-morbidities; most of the patients had elevated levels of CRP at ill onset with 33.3% over 10 mg per L; bilateral distribution and ground-glass opacity were the most common manifestations in chest CT. Interpretation The potential risk factors of fever, fatigue, high level of C-reactive protein were the risk factors to identify the progression of COVID-19 patients with mild or moderate type. Fangcang shelter hospitals have substantially reduced the time from the onset of severe symptoms transfer to a designated hospital. Early application of the Fangcang shelter hospital may contribute to decrease the ratio of mild transforming to severe patients. Funding No specific grant from any funding was applied to this research.


title: EU science chief defends record after ouster over coronavirus plans

text: Last week’s noisy resignation of Mauro Ferrari as president of the €2 2 billion European Research Council (ERC)—the European Union’s foremost funder of basic research—revealed a rift over its approach to research on the coronavirus pandemic Ferrari’s departure, just 3 months into the job, also showed the limits of an ERC president’s power to influence the course of a funding agency that prides itself on its independence On 7 April, the same day Ferrari stepped down as ERC president and chair of its Scientific Council, he released a statement to the Financial Times, saying he had “lost faith in the system” and was upset by ERC’s unwillingness to set up a “special program” to address the COVID-19 pandemic But the next day, the 19 other members of the science council hit back In a sharp statement, the council said Ferrari “displayed a complete lack of appreciation for the raison d’être of the ERC ” It also suggested that Ferrari had neglected his duties to attend to personal projects in the United States It said the council unanimously called for his resignation on 27 March


title: Chinese effective control and other countries uncharted challenge against COVID-19: an epidemiological and modelling study

text: Background: On the present trajectory, COVID is inevitably becoming a global epidemic, leading to concerns regarding the pandemic potential in China and other countries. Objective: In this study, we use the time-dependent reproduction number (Rt) to comprise the COVID transmissibility across different countries. Methods: We used data from Jan 20, 2019, to Feb 29, 2020, on the number of newly confirmed cases, obtained from the reports published by the CDC, to infer the incidence of infectious over time. A two-step procedure was used to estimate the Rt. The first step used data on known index-secondary cases pairs, from publicly available case reports, to estimate the serial interval distribution. The second step estimated the Rt jointly from the incidence data and the information data in the first step. Rt was then used to simulate the epidemics across all major cities in China and typical countries worldwide. Results: Based on a total of 126 index-secondary cases pairs from 4 international regions, we estimated that the serial interval for SARS-2-CoV was 4.18 (IQR 1.92 - 6.65) days. Domestically, Rt of China, Hubei province, Wuhan had fallen below 1.0 on 9 Feb, 10 Feb and 13 Feb (Rt were 0.99 {+/-} 0.02, 0.99 {+/-} 0.02 and 0.96 {+/-} 0.02), respectively. Internationally, as of 26 Feb, statistically significant periods of COVID spread (Rt >1) were identified for most regions, except for Singapore (Rt was 0.92 {+/-} 0.17). Conclusions: The epidemic in China has been well controlled, but the worldwide pandemic has not been well controlled. Worldwide preparedness and vulnerability against COVID-19 should be regarded with more care.


title: Basic and effective reproduction numbers of COVID-19 cases in South Korea excluding Sincheonji cases

text: In February and March 2020, COVID-19 epidemic in South Korea met a large black swan effect by a Sincheonji cult mass infection in Daegu-Gyeongbuk area. The black swan made it difficult to evaluate that the current policies for infection prevention including social distancing, closing schools, hand washing, and wearing masks good enough or not. Therefore, in this study, we evaluated basic reproduction number (R0) and time-dependent reproduction number (Rt) of confirmed cases based on various kinds of populations, including total, Daegu-Geyoengbuk, except-Daegu-Gyeongbuk, Sincheonji, and except-Sincheonji. In total, it seems the infection is going to be under control, but this is never true because in the except-Sincheonji and except-Daegu-Geyongbuk cases, R0 is still above 1.0, and Rt is drifting around 1.0. This study could be used to determine government policies in the near future.


title: Sudden hyposmia as a prevalent symptom of COVID-19 infection.

text: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has recently caused a pandemic that has involved Italy as the second worldwide nation in terms of infected patients and deaths. The clinical manifestation of Covid-19 ranges from asymptomatic carrier status to severe pneumonia. Asymptomatic individuals in Covid-19 are those who are carriers of the virus but do not show clinical symptoms and are able to transmit the disease in the same degree as symptomatic carriers. In order to contain contagions is of supreme importance to identify asymptomatic patients because this subpopulation is one of the main factors contributing to the spread of this disease. We report on six Italian patients with COVID-19 who presented sudden hyposmia as the only or most prominent disease manifestation, without upper or lower respiratory tract involvement or other major features of the disease. A supra-threshold olfaction test confirmed the hyposmia in all patients. The onset of hyposmia during a Covid-19 outbreak should be considered as a warning sign of an infection that requires a diagnostic test for Covid-19


title: Feasibility of Xiaochaihu Decoction on fever induced by coronavirus disease 2019 (COVID-19) based on network pharmacology/ 基于网络药理学的小柴胡汤治疗新型冠状病毒肺炎（COVID-19）发热的可行性探讨

text: Objective: The aim of this article was to study the potential antivirus and fever reducing mechanisms of Xiaochaihu Decoction (XCHD) on novel coronavirus pneumonia based on network pharmacology and molecular docking method. Methods: Firstly, the potential targets and pathways of XCHD on fever were analyzed using network pharmacology. Compounds and potential targets in XCHD were screened using TCMSP and PharmMapper databases. The targets in fever reducing were identified from OMMI and Genecards databases. The protein-protein interaction network was established by String database to analyze key targets. The gene oncology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) analysis of key targets were also conducted to generate the relative pathways based on DAVID and KOBAS 3.0 databases, respectively. The compound-target-pathway network was established using Cytoscape 3.2.7. In addition, we used molecular docking method to identify the crucial compounds with higher connectivity on SARS-CoV-2 and the angiotensin-converting enzyme 2 (ACE2). ACE2 has been identified as the key target of SARS-CoV-2 entering cells. The possible binding sites of compounds on SARS-CoV-2 and ACE2 were predicted. Results: Network pharmacology analysis indicated that 165 active compounds and 168 relative targets were selected. A total of 7006 targets related to fever were identified. In addition, 141 potential targets of XCH on fever were identified. Totally, 292 GO terms of XCHD on fever and 30 pathways were identified using GO and KEGG analysis. Furthermore, molecular docking indicated that main active compounds in XCHD exhibited higher affinity with both SARS-CoV-2 and ACE2. Beta-sitosterol, stigmasterol, 3’-hydroxy-4’-O-methylglabridin were top three candidates with highest affinity. Conclusion: In summary, our study identified the potential mechanisms of XCHD on fever. Besides, Beta-sitosterol, stigmasterol, 3’-hydroxy-4’-O-methylglabridin could be the key compounds to exert anti-viral effects against SARS-CoV-2. Our prediction also provided the research fields to further study the mechanisms of XCH on SARS-CoV-2 infection in future.


title: Screening for SARS-CoV-2 infections with colorimetric RT-LAMP and LAMP sequencing

text: The SARS-CoV-2 (COVID-19) pandemic poses a significant public-health problem. In order to control the pandemic, rapid tests for detecting existing infections and assessing virus spread are critical. Approaches to detect viral RNA based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) hold outstanding promise towards greatly simplified and broadly applicable testing methods. RT-LAMP assays appear more robust than qPCR-based methods and only require incubation at a constant temperature, thus eliminating the need for sophisticated instrumentation. Here, we tested a two-color RT-LAMP protocol using clinical SARS-CoV-2 samples and also established a protocol that does not require prior RNA isolation ("swab-to-RT-LAMP"). Our study is based on several hundred clinical patient samples with a wide range of viral loads, thus allowing, for the first time, to accurately determine the sensitivity and specificity of the RT-LAMP assay for the detection of SARS-CoV-2 in patients. We found that RT-LAMP can reliably detect SARS-CoV-2 samples with a qPCR threshold cycle number (CT value) of up to 30 in the standard RT-qPCR assay. We used both, either purified RNA or direct pharyngeal swab specimens and showed that RT-LAMP assays have, despite a decreased sensitivity compared to RT-qPCR, excellent specificity. We also developed a multiplexed LAMP-sequencing protocol as a validation and backup procedure to double-check the results of visual RT-LAMP assays. LAMP-sequencing is fully scalable and can assess the results of thousands of LAMP reactions in parallel. We propose decentralised COVID-19 testing as a routine to allow facilities and institutions to return to near-to-full functionality.


title: A Stratified Model to Quantify the Effects of Containment Policies on the Spread of COVID-19

text: The SARS-Cov-2 virus is spreading fast all over the world and has already imposed a significant social and economic cost in many countries. Different countries have utilised a variety of containment policies with an emphasis on social distancing as a strategy to stop the spread of COVID-19. Quantifying the effects of such policies in different time-scales and comparing the efficacy of various available policies is of utmost importance for policy-makers in different countries. That is even more important when the policy-makers want to plan for long-term strategies and to weigh each option based on its epidemiological effects and socio-economic costs. In the absence of detailed knowledge of the interactions between individuals in a population and the characteristics of the SARS-Cov-2 virus, quantifying the effects of these policies is very difficult. Hence, there is an immediate need for models that can predict the spread of COVID-19 in a population, without the need for such detailed information. In this manuscript, a method is presented that can be used to predict the spread of COVID-19 in any country and under any containment policy imposed separately on different groups in the population. The method tunes the parameters of a known stratified model based on the available data on the spread of COVID-19. The model includes a set of nonlinear ordinary differential equations and is easy to simulate and easy to understand. As it is presented in this manuscript, the population is divided into age-groups. But given the availability of the data, there is no reason to limit the stratification into only age-groups and we can consider any relevant groups. To estimate the parameters of the model such that it reflects the characteristics of the spread of COVID-19 in a population, the method relies on an optimisation scheme. More specifically, the optimisation scheme estimates the contact rates between different age groups in the population. But a very important and useful feature of the model is that the estimated parameters for one population can be translated and used for any other population with a known age-structure, which in this day and age, includes almost any country or city in the world. Also, it is shown that the method is quite insensitive to the underlying assumptions in the optimisation scheme and also to deliberate or non-deliberate errors that might have occurred in collecting the data. The capabilities of the model are demonstrated using a case study under different containment policies, from an uncontained population to mitigation and suppression policies. Also, we can use the model to quantify the effects of strategies which include switching between different containment policies at pre-determined points in time. The model allows us to quantify the effects of each of these policies on the spread of the disease in a population, in particular, the instantaneous and total numbers of infectious individuals in a population which are important parameters for policy-makers. The simulation results, as explained in the following, provide some insight into various policies and some of the results are possibly counter-intuitive for many people. For example, the model predicts that closing down schools and universities without any other containment policy imposed on older age-groups has almost no impact on the number of patients that might need support-care in hospitals. The method provides an easy-to-use tool to use the information collected on the spread of COVID-19 in a country or region and then use that information in another population which might not have been as widely affected by the disease yet.


Learning From Disasters: The CoVID-19 Fallout on Spine Care


‘Reality is an activity of the most august imagination’. When the world stops, it’s not a complete disaster–we can hear the birds sing!


title: SARS-Cov-2 RNA Found on Particulate Matter of Bergamo in Northern Italy: First Preliminary Evidence

text: In previous communications, we have hypothesized the possibility that SARS-CoV-2 virus could be present on particulate matter (PM) during the spreading of the infection, consistently with evidence already available for other viruses. Here, we present the first results of the analyses that we have performed on 34 PM10 samples of outdoor/airborne PM10 from an industrial site of Bergamo Province, collected with two different air samplers over a continuous 3-weeks period, from February 21st to March 13th. We can confirm to have reasonably demonstrated the presence of SARS-CoV-2 viral RNA by detecting highly specific RtDR gene on 8 filters in two parallel PCR analyses. This is the first preliminary evidence that SARS-CoV-2 RNA can be present on outdoor particulate matter, thus suggesting that, in conditions of atmospheric stability and high concentrations of PM, SARS-CoV-2 could create clusters with outdoor PM and, by reducing their diffusion coefficient, enhance the persistence of the virus in the atmosphere. Further confirmations of this preliminary evidence are ongoing, and should include real-time assessment about the vitality of the SARS-CoV-2 as well as its virulence when adsorbed on particulate matter. At the present, no assumptions can be made concerning the correlation between the presence of the virus on PM and COVID-19 outbreak progression. Other issues to be specifically addressed are the average concentrations of PM eventually required for a potential boost effect of the contagion (in case it is confirmed that PM might act as a carrier for the viral droplet nuclei), or even the theoretic possibility of immunization consequent to minimal dose exposures at lower thresholds of PM.


docid: tmchpkzi

title: Plasmin cascade mediates thrombolytic events in SARS-CoV-2 infection via complement and platelet-activating systems

text: Recently emerged beta-coronavirus, SARS-CoV-2 has resulted in the current pandemic designated COVID-19. COVID-19 manifests as severe illness exhibiting systemic inflammatory response syndrome, acute respiratory distress syndrome (ARDS), thrombotic events, and shock, exacerbated further by co-morbidities and age1–3. Recent clinical reports suggested that the pulmonary failure seen in COVID-19 may not be solely driven by acute ARDS, but also microvascular thrombotic events, likely driven by complement activation4,5. However, it is not fully understood how the SARS-CoV-2 infection mechanisms mediate thrombotic events, and whether such mechanisms and responses are unique to SARS-CoV-2 infection, compared to other respiratory infections. We address these questions here, in the context of normal lung epithelia, in vitro and in vivo, using publicly available data. Our results indicate that plasmin is a crucial mediator which primes interactions between complement and platelet-activating systems in lung epithelia upon SARS-CoV-2 infection, with a potential for therapeutic intervention.


title: Incorporating and Addressing Testing Bias Within Estimates of Epidemic Dynamics for SARS-CoV-2

text: The disease burden of SARS-CoV-2 as measured by tests from various countries present varying estimates of infection and fatality rates. Models based on these acquired data may suffer from systematic errors and large estimation variances due to the biases associated with testing and lags between the infection and death counts. Here, we present an augmented compartment model to predict epidemic dynamics while explicitly modeling for the sampling bias involved in testing. Our simulations show that sampling biases in favor of patients with higher disease manifestation could significantly affect direct estimates of infection and fatality rates calculated from the numbers of confirmed cases and deaths, and serological testing can partially mitigate these biased estimates. We further recommend a strategy to obtain unbiased estimates, calculating the dependence of expected confidence on a randomized sample size, showing that relatively small sample sizes can provide statistically significant estimates for SARS-CoV-2 related death rates.


title: A comprehensive analysis of R0 with different lockdown phase during covid-19 in India

text: Background: World Health organization declared Covid-19 as an outbreak, hence preventive measure like lockdown should be taken to control the spread of infection. This study offers an exhaustive analysis of the reproductive number (R0) in India with major intervention for COVID-19 outbreaks and analysed the lockdown effects on the Covid-19. Methodology: Covid-19 data extracted from Ministry of Health and Family Welfare, Government of India. Then, a novel method implemented in the incidence and Optimum function in desolve package to the data of cumulative daily new confirmed cases for robustly estimating the reproduction number in the R software. Result: Analysis has been seen that the lockdown was really quite as effective, India has already shown a major steady decline. The growth rate has fluctuated about 20 percent with trend line projections in various lockdown. A comparative analysis gives an idea of decline in value of R0 from 1.73 to 1.08. Annotation plot showing the predicted R0 values based on previous lockdown in month of June and July. Conclusion: Without lockdown, the growth might not have been contained in India and may have gone into the exponential zone. We show that, the lockdown in India was fairly successful. The effect partial lifting of the lockdown (unlock) is also seen in the results, in terms of increment in R0 values. Hence this study provides a platform for policy makers and government authorities for implementing the strategies to prevent the spread of infection.


title: Lockdown may partially halt the spread of 2019 novel coronavirus in Hubei province, China

text: We present a timely evaluation of the impact of lockdown on the 2019-nCov epidemic in Hubei province, China. The implementation appears to be effective in reducing about 60% of new infections and deaths, and its effect also appears to be sustainable even after its removal. Delaying its implementation reduces its effectiveness. However, the direct economic cost of such a lockdown remains to be seen and whether the model is replicable in other Chinese regions remains a matter of further investigation.


title: Property valuation in the UK: material uncertainty and COVID-19

text: Purpose: An understanding of uncertainty has always been an integral part of property valuations. No valuation is certain, and the valuer needs to convey to the user of the valuation in the degree of uncertainty pertaining to the market value. Design/methodology/approach: This practice briefing is a short overview of the importance of understanding uncertainty in valuation in normal markets and the particular difficulties now with the material uncertainty created by the COVID-19 pandemic. Findings: This paper discusses how important it is for the valuer and the client to communicate and understand the uncertainty in the market at any point of time. The COVID-19 has had a significant impact on property values and the importance of clarity within valuation reports. Practical implications: This paper looks at the importance of placing capital and rental value changes due to material uncertainty in valuation reports. Originality/value: This provides guidance on how professional bodies are advising their members, around the world, on how to report valuations and market value in the context of material uncertainty.


title: Comparison of SARS-CoV2 N gene real-time RT-PCR targets and commercially available mastermixes

text: We aim to test four one-step RT real-time mastermix options for use in SARS-CoV2 real-time PCR, with three primer/probe assays targeting the N gene. The lower limit of detection is determined using a SARS CoV2 N gene RNA transcript dilution series (to 1 copy/µl) and verified using 74 nose and throat swabs. The N2 assay demonstrates the most sensitive detection of SARS-Cov-2 RNA. Three of the four mastermixes performed well, with the Takara One Step PrimeScript™ III RT-PCR Kit mastermix demonstrating improved performance at the lower limit of detection.


title: Multiple known and a novel parvovirus associated with an outbreak of feline diarrhea and vomiting

text: An unexplained outbreak of feline diarrhea and vomiting, negative for common enteric viral and bacterial pathogens, was subjected to viral metagenomics and PCR. We characterized from fecal samples the genome of a novel chapparvovirus we named fechavirus that was shed by 8/17 affected cats and different feline bocaviruses shed by 9/17 cats. Also detected were nucleic acids from attenuated vaccine viruses, members of the normal feline virome, viruses found in only one or two cases, and viruses likely derived from ingested food products. Epidemiological investigation of disease signs, time of onset, and transfers of affected cats between three facilities support a possible role for this new chapparvovirus in a highly contagious feline diarrhea and vomiting disease.


title: CONTAIN: An open-source shipping container laboratory optimised for automated COVID-19 diagnostics

text: The COVID-19 pandemic has challenged diagnostic systems globally. Expanding testing capabilities to conduct population-wide screening for COVID-19 requires innovation in diagnostic services at both the molecular and industrial scale. No report to-date has considered the complexity of laboratory infrastructure in conjunction with the available molecular assays to offer a standardised solution to testing. Here we present CONTAIN. A modular biosafety level 2+ laboratory optimised for automated RT-qPCR COVID-19 testing based on a standard 40ft shipping container. Using open-source liquid-handling robots and RNA extraction reagents we demonstrate a reproducible workflow for RT-qPCR COVID-19 testing. With five OT2 liquid handlers, a single CONTAIN unit reaches a maximum daily testing capacity of 2400 tests/day. We validate this workflow for automated RT-qPCR testing, using both synthetic SARS-CoV-2 samples and patient samples from a local NHS hospital. Finally, we discuss the suitability of CONTAIN and its flexibility in a range of diagnostic testing scenarios including high-density urban environments and mobile response units. Visual abstract


title: Lung expression of genes encoding SARS-CoV-2 cell entry molecules and antiviral restriction factors: interindividual differences are associated with age and germline variants

text: Germline variants in genes involved in SARS-CoV-2 cell entry (i.e. ACE2 and TMPRSS2) may influence the susceptibility to infection, as may polymorphisms in genes involved in the innate host response to viruses (e.g. APOBEC3 family). We searched for polymorphisms acting, in lung tissue, as expression quantitative trait loci (eQTLs) for 15 candidate COVID-19 susceptibility genes, selected for their roles in virus cell entry and host antiviral responses. No significant eQTLs were identified for ACE2 and TMPRSS2 genes, whose expression levels did not associate with either sex or age of the 408 patients whose non-diseased lung tissue was analyzed. Instead, we identified seven cis-eQTLs (FDR<0.05) for APOBEC3D and APOBEC3G (rs139296, rs9611092, rs139331, rs8177832, rs17537581, rs61362448, and rs738469). The genetic control of the expression of APOBEC3 genes, which encode enzymes that interfere with virus replication, may explain interindividual differences in risk or severity of viral infections. Future studies should investigate the role of host genetics in COVID-19 patients using a genome-wide approach, to identify other genes whose expression levels are associated with susceptibility to SARS-CoV-2 infection or COVID-19 severity. Author summary Identification of expression quantitative trait loci (eQTLs) has become commonplace in functional studies on the role of individual genetic variants in susceptibility to diseases. In COVID-19, it has been proposed that individual variants in SARS-CoV-2 cell entry and innate host response genes may influence the susceptibility to infection. We searched for polymorphisms acting, in non-diseased lung tissue of 408 patients, as eQTLs for 15 candidate COVID-19 susceptibility genes, selected for their roles in virus cell entry and host antiviral responses. Seven cis-eQTLs were detected for APOBEC3D and APOBEC3G genes, which encode enzymes that interfere with virus replication. No significant eQTLs were identified for ACE2 and TMPRSS2 genes. Therefore, the identified eQTLs may represent candidate loci modulating interindividual differences in risk or severity of SARS-CoV-2 virus infection.


docid: pbddwyyi

title: Skepticism and rumor spreading: the role of spatial correlations

text: Critical thinking and skepticism are fundamental mechanisms that one may use to prevent the spreading of rumors, fake-news and misinformation. We consider a simple model in which agents without previous contact with the rumor, being skeptically oriented, may convince spreaders to stop their activity or, once exposed to the rumor, decide not to propagate it as a consequence, for example, of fact-checking. We extend a previous, mean-field analysis of the combined effect of these two mechanisms, active and passive skepticism, to include spatial correlations. This can be done either analytically, through the pair approximation, or simulating an agent-based version on diverse networks. Our results show that while in mean-field there is no coexistence between spreaders and susceptibles (although, depending on the parameters, there may be bistability depending on the initial conditions), when spatial correlations are included, because of the protective effect of the isolation provided by removed agents, coexistence is possible.


title: Deep learning-based model for detecting 2019 novel coronavirus pneumonia on high-resolution computed tomography: a prospective study

text: Background: Computed tomography (CT) is the preferred imaging method for diagnosing 2019 novel coronavirus (COVID19) pneumonia. Our research aimed to construct a system based on deep learning for detecting COVID-19 pneumonia on high resolution CT, relieve working pressure of radiologists and contribute to the control of the epidemic. Methods: For model development and validation, 46,096 anonymous images from 106 admitted patients, including 51 patients of laboratory confirmed COVID-19 pneumonia and 55 control patients of other diseases in Renmin Hospital of Wuhan University (Wuhan, Hubei province, China) were retrospectively collected and processed. Twenty-seven consecutive patients undergoing CT scans in Feb, 5, 2020 in Renmin Hospital of Wuhan University were prospectively collected to evaluate and compare the efficiency of radiologists against 2019-CoV pneumonia with that of the model. Findings: The model achieved a per-patient sensitivity of 100%, specificity of 93.55%, accuracy of 95.24%, PPV of 84.62%, and NPV of 100%; a per-image sensitivity of 94.34%, specificity of 99.16%, accuracy of 98.85%, PPV of 88.37%, and NPV of 99.61% in retrospective dataset. For 27 prospective patients, the model achieved a comparable performance to that of expert radiologist. With the assistance of the model, the reading time of radiologists was greatly decreased by 65%. Conclusion: The deep learning model showed a comparable performance with expert radiologist, and greatly improve the efficiency of radiologists in clinical practice. It holds great potential to relieve the pressure of frontline radiologists, improve early diagnosis, isolation and treatment, and thus contribute to the control of the epidemic.


title: Ecological processes underlying the emergence of novel enzootic cycles—arboviruses in the neotropics as a case study

text: Pathogens originating from wildlife (zoonoses) pose a significant public health burden, comprising the majority of emerging infectious diseases. Efforts to control and prevent zoonotic disease have traditionally focused on animal-to-human transmission, or “spillover”. However, in the modern era, increasing international mobility and commerce facilitate the spread of infected humans, non-human animals (hereafter animals), and their products worldwide, thereby increasing the risk that zoonoses will be introduced to new geographic areas. Imported zoonoses can potentially ‘spill back’ to infect local wildlife—a danger magnified by urbanization and other anthropogenic pressures that increase contacts between human and wildlife populations. In this way, humans can function as vectors, dispersing zoonoses from their ancestral enzootic systems to establish reservoirs elsewhere in novel animal host populations. Once established, these enzootic cycles are largely unassailable by standard control measures and have the potential to feed human epidemics. Understanding when and why translocated zoonoses establish novel enzootic cycles requires disentangling ecologically complex and stochastic interactions between the zoonosis, the human population, and the natural ecosystem. We address this challenge by delineating potential ecological mechanisms affecting each stage of enzootic establishment—wildlife exposure, enzootic infection, and persistence—applying existing ecological concepts from epidemiology, invasion biology, and population ecology. We ground our study in the neotropics, where four arthropod-borne viruses (arboviruses) of zoonotic origin—yellow fever, dengue, chikungunya, and Zika viruses—have separately been introduced into the human population. This paper is a step towards developing a framework for predicting and preventing novel enzootic cycles in the face of zoonotic translocations.


title: Infection Control of 2019 Novel Corona Virus Disease (COVID-19) in Cancer Patients undergoing Radiotherapy in Wuhan

text: Background A pandemic of 2019 novel corona virus disease (COVID-19), which was first reported in Wuhan city, has affected more than 100,000 patients worldwide. Patients with cancer are at a higher risk of COVID-19, but currently, there is no guidance on the management of cancer patients during this outbreak. Here, we report the infection control measures and early outcomes of patients who received radiotherapy (RT) at a tertiary cancer centre in Wuhan. Methods We reviewed all patients who were treated at the Zhongnan Hospital of Wuhan University (ZHWU) from Jan 20 to Mar 6, 2020. This preceded the city lock-down date of Jan 23, 2020. Infection control measures were implemented, which included a clinical pathway for managing suspect COVID-19 cases, on-site screening, modifications to the RT facility, and protection of healthcare workers. Primary end-point was infection rate among patients and healthcare staff. Diagnosis of COVID-19 was based on the 5th edition criteria. Findings 209 patients completed RT during the study period. Median age was 55 y (IQR = 48-64). Thoracic, head and neck, and lower gastrointestinal and gynaecological cancer patients consisted the majority of patients. Treatment sites included thoracic (38.3%), head and neck (25.4%), and abdomen and pelvis (25.8%); 47.4%, 27.3%, and 25.4% of treatments were for adjuvant, radical, and palliative indications, respectively. 188 treatments/day were performed prior to the lock-down, in contrast to 12.4 treatments/day post-lock-down. Only one (0.48%) patient was diagnosed with COVID-19 during the study period. No healthcare worker was infected. Interpretation Herein, we show that in a susceptible population to COVID-19, strict infection control measures can curb human-to-human transmission, and ensure timely delivery of RT to cancer patients.


title: Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations

text: Background: Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the values of acute phase inflammation marker C-reactive protein (CRP). Methods: LPV plasma concentrations were prospectively collected in 92 patients hospitalized at our institution. Lopinavir/ritonavir was administered 12 hourly, 800/200 mg on day 1, and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24 and 48 hours. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. Results: The median age of study participants was 59 (range 24 up to 85) years, and 71% were male. The median duration from symptom onset to hospitalization and treatment initiation was 7 days (IQR 4;10) and 8 days (IQR 5;10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 ug/mL (IQR 18.9;31.5). LPV plasma concentrations positively correlated with CRP values (r=0.37, p<0.001), and were significantly lower when tocilizumab was preadministrated. No correlation was found between HCQ concentrations and CRP values. Conclusions: High LPV plasma concentrations were observed in COVID-19 patients. The ratio of calculated unbound drug fraction to published SARS-CoV2 EC50 values indicated insufficient LPV concentrations in the lung. CRP values significantly correlated with LPV but not HCQ plasma concentrations, implying inhibition of cytochrome P450 3A4 (CYP3A4) metabolism by inflammation.


title: Hyperlocal Postcode Based Crowdsourced Surveillance Systems in the COVID-19 Pandemic Response

text: The SARS-CoV-2 pandemic has rapidly saturated healthcare resources across the globe and has led to a restricted screening process, hindering efforts at comprehensive case detection. This has not only facilitated community spread but has also resulted in an underestimation of the true incidence of disease, a statistic which is useful for policy making aimed at controlling the current pandemic and in preparing for future outbreaks. In this perspective, we present a crowdsourced platform developed by us for the true estimation of all SARS-CoV-2 infections in the community, through active self-reporting and layering other authentic datasets. The granularity of data captured by this system could prove to be useful in assisting governments to identify SARS-CoV-2 hotspots in the community facilitating lifting of restrictions in a controlled fashion.


title: Enantiomers of Chloroquine and Hydroxychloroquine Exhibit Different Activities Against SARS-CoV-2 in vitro, Evidencing S-Hydroxychloroquine as a Potentially Superior Drug for COVID-19

text: In all of the clinical trials for COVID-19 conducted thus far and among those ongoing involving chloroquine or hydroxychloroquine, the drug substance used has invariably been chloroquine (CQ) diphosphate or hydroxychloroquine (HCQ) sulfate, i.e., the phosphoric or sulfuric acid salt of a racemic mixture of R- and S-enantiomer (50/50), respectively. As a result, the clinical outcome from previous CQ or HCQ trials were, in fact, the collective manifestation of both R and S-enantiomers with inherent different pharmacodynamic and pharmacokinetic properties, and toxicity liabilities. Our data for the first time demonstrated the stereoselective difference of CQ and HCQ against live SARS-CoV-2 virus in a Biosafety Level 3 laboratory. S-chloroquine (S-CQ) and S-hydroxychloroquine (S-HCQ) were found to be 27% and 60% more active against SARS-CoV-2, as compared to R-CQ and R-HCQ, respectively. With these data and previous work on stereoselective metabolism of CQ and HCQ, we recommend that future clinical studies should employ S-HCQ as a potentially superior drug substance for the treatment of COVID-19 for improved therapeutic index.


Is Pakistan's Response to Coronavirus (SARS-CoV-2) Adequate to Prevent an Outbreak?


title: Short Communication: Vitamin D and COVID-19 infection and mortality in UK Biobank

text: Purpose Vitamin D has been proposed as a potential causal factor in COVID-19 risk. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 mortality, and inpatient confirmed COVID-19 infection, in UK Biobank participants. Methods UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration, were linked to COVID-19 mortality. Univariable and multivariable Cox proportional hazards regression analyses were performed for the association between 25(OH)D and COVID-19 death, and poisson regression analyses for the association between 25(OH)D and severe COVID-19 infection. Results Complete data were available for 341,484 UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection. Vitamin D was associated with severe COVID-19 infection and mortality univariably (mortality HR=0.99; 95% CI 0.98-0.998; p=0.016), but not after adjustment for confounders (mortality HR=0.998; 95% CI=0.99-1.01; p=0.696). Conclusions Our findings do not support a potential link between vitamin D concentrations and risk of severe COVID-19 infection and mortality. Recommendations for vitamin D supplementation to lessen COVID-19 risks may provide false reassurance.


How do healthcare workers in diagnostic imaging minimise risks but maximise performance during the COVID-19 pandemic?


title: Hemogram Data as a Tool for Decision-making in COVID-19 Management: Applications to Resource Scarcity Scenarios

text: Background: COVID-19 pandemics has challenged emergency response systems worldwide, with widespread reports of essential services breakdown and collapse of health care structure. A critical element involves essential workforce management since current protocols recommend release from duty for symptomatic individuals, including essential personnel. Testing capacity is also problematic in several countries, where diagnosis demand outnumbers available local testing capacity. Purpose: This work describes a machine learning model derived from hemogram exam data performed in symptomatic patients and how they can be used to predict qRT-PCR test results. Methods: A Naive-Bayes model for machine learning is proposed for handling different scarcity scenarios, including managing symptomatic essential workforce and absence of diagnostic tests. Hemogram result data was used to predict qRT-PCR results in situations where the latter was not performed, or results are not yet available. Adjusts in assumed prior probabilities allow fine-tuning of the model, according to actual prediction context. Results: Proposed models can predict COVID-19 qRT-PCR results in symptomatic individuals with high accuracy, sensitivity and specificity. Data assessment can be performed in an individual or simultaneous basis, according to desired outcome. Based on hemogram data and background scarcity context, resource distribution is significantly optimized when model-based patient selection is observed, compared to random choice. The model can help manage testing deficiency and other critical circumstances. Conclusions: Machine learning models can be derived from widely available, quick, and inexpensive exam data in order to predict qRT-PCR results used in COVID-19 diagnosis. These models can be used to assist strategic decision-making in resource scarcity scenarios, including personnel shortage, lack of medical resources, and testing insufficiency.


docid: xiynfpuw

title: Hypokalemia and Clinical Implications in Patients with Coronavirus Disease 2019 (COVID-19)

text: BACKGROUND: SARS-CoV-2 has caused a series of COVID-19 globally. SARS-CoV-2 binds angiotensin I converting enzyme 2 (ACE2) of renin-angiotensin system (RAS) and causes prevalent hypokalemia METHODS: The patients with COVID-19 were classified into severe hypokalemia, hypokalemia, and normokalemia group. The study aimed to determine the relationship between hypokalemia and clinical features, the underlying causes and clinical implications of hypokalemia. RESULTS: By Feb 15, 2020, 175 patients with COVID-19 (92 women and 83 men; median age, 46 [IQR, 34-54] years) were admitted to hospital in Wenzhou, China, consisting 39 severe hypokalemia-, 69 hypokalemia-, and 67 normokalemia patients. Gastrointestinal symptoms were not associated with hypokalemia among 108 hypokalemia patients (P>0.05). Body temperature, CK, CK-MB, LDH, and CRP were significantly associated with the severity of hypokalemia (P<0.01). 93% of severe and critically ill patients had hypokalemia which was most common among elevated CK, CK-MB, LDH, and CRP. Urine K+ loss was the primary cause of hypokalemia. severe hypokalemia patients was given 3 g/day, adding up to an average of 34 (SD=4) g potassium during hospital stay. The exciting finding was that patients responded well to K+ supplements when they were inclined to recovery. CONCLUSIONS: Hypokalemia is prevailing in patients with COVID-19. The correction of hypokalemia is challenging because of continuous renal K+ loss resulting from the degradation of ACE2. The end of urine K+ loss indicates a good prognosis and may be a reliable, in-time, and sensitive biomarker directly reflecting the end of adverse effect on RAS system.


title: SARS-CoV-2 triggered neutrophil extracellular traps (NETs) mediate COVID-19 pathology

text: Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to respiratory failure. These patients also develop cytokine storm syndrome, and organ dysfunctions, which is a clinical picture that resembles sepsis. Considering that neutrophil extracellular traps (NETs) have been described as an important factors of tissue damage in sepsis, we investigated whether NETs would be produced in COVID-19 patients and participate in the lung tissue damage. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and respective healthy controls were enrolled. NETs concentration was assessed by MPO-DNA PicoGreen assay or by confocal immunofluorescence. The cytotoxic effect of SARS-CoV-2-induced NETs was analyzed in human epithelial lung cells (A549 cells). The concentration of NETs was augmented in plasma and tracheal aspirate from COVID-19 patients and their neutrophils spontaneously released higher levels of NETs. NETs were also found in the lung tissue specimens from autopsies of COVID-19 patients. Notably, viable SARS-CoV-2 can directly induce in vitro release of NETs by healthy neutrophils in a PAD-4-dependent manner. Finally, NETs released by SARS-CoV-2-activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represent a potential therapeutic target for COVID-19.


title: Containment works

text: Coronavirus Containment works Caroline Ash National governments have taken different approaches in response to the coronavirus disease 2019 (COVID-19) pandemic, ranging from draconian quarantines to laissez-faire mitigation strategies


title: In-silico analysis of SARS-CoV-2 genomes: Insights from SARS encoded non-coding RNAs

text: Recently a novel coronavirus (SARS-CoV-2) emerged from Wuhan, China and has infected more than 571000 people leading to more than 26000 deaths. Since SARS-CoV-2 genome sequences show similarity with those of SARS, we sought to analyze all the available SARS-CoV-2 genomes based on the insights obtained from SARS genome specifically focusing on non-coding RNAs. Here, results are presented from the dual approach i.e identifying host encoded miRNAs that might regulate viral pathogenesis as well as identifying viral encoded miRNAs that might regulate host cell signaling pathways and aid in viral pathogenesis. Analysis utilizing first approach resulted in the identification of 10 host encoded miRNAs that could target the genome of both the viruses (SARS-CoV-2 and SARS reference genome). Interestingly our analysis revealed that there is significantly higher number of host miRNAs that could target SARS-CoV-2 genome as compared to the SARS reference genome. Results from second approach involving SARS-CoV-2 and SARS reference genome identified a set of virus encoded miRNAs which might regulate host signaling pathways. Our analysis further identified a similar “GA” rich motif in SARS-CoV-2 genome that was shown to play a vital role in lung pathogenesis during severe SARS infections. Hence, we successfully identified human and virus encoded miRNAs that might regulate pathogenesis of both these coronaviruses and the fact that more number of host miRNAs could target SARS-CoV-2 genomes possibly reveal as to why this virus follows mild pathogenesis in healthy individuals. We identified non-coding sequences in SARS-CoV-2 genomes that were earlier reported to contribute towards SARS pathology. The study provides insights into the overlapping sequences among these viruses for their effective inhibition as well as identifying new drug targets that could be used for development of new antivirals.


docid: xklbnvom

title: Elevated serum IgM levels indicate poor outcome in patients with coronavirus disease 2019 pneumonia: A retrospective case-control study

text: Background: The coronavirus disease 2019 (COVID-19) pneumonia outbreak began in Wuhan and pandemics tend to occur. Although SARS-CoV-2-specific immunoglobulins have been detected in serum of COVID-19 patients, their dynamics and association with outcomes have not been characterized. Methods: A total of 116 hospitalized patients with confirmed COVID-19 pneumonia and SARS-CoV-2-specific immunoglobulins tested in Tongji hospital were retrospectively investigated. Clinical, laboratory, radiological characteristics and outcomes data were compared between mild-moderate group and died group. Further, a paired case-control study was conducted where each deceased case was matched to three mild-moderate patients of similar age. Findings: Among 116 subjects included, 101 mild-moderate patients survived and 15 cases died. SARS-CoV-2-specific IgM levels peaked in forth week after onset of COVID-19 pneumonia, while serum IgG levels increased over 8 weeks. Serum IgM levels were higher in deceased patients than mild-moderate patients (P = 0.024), but not IgG. Serum IgM levels were negatively correlated with clinical outcome, eosinophil count and albumin levels (r = -0.269, P = 0.003; r = -0.188, P = 0.043; and r = -0.198, P = 0.033, resp.). The area under the ROC curve (AUC) for IgM antibody was 0.681 (95% CI: 0.517-0.845, P = 0.024). In case-control study paired by age, serum IgM was higher in deceased patients than mild-moderate patients (P = 0.019), positively correlated with leucocyte count (r = 0.260, P = 0.045), while negatively correlated with clinical outcome and albumin levels (r = -0.337, P = 0.008; r = -0.265, P = 0.041). AUC for IgM levels was 0.704 (95% CI: 0.534-0.873, P = 0.019). Interpretation: These results indicate that dynamics of SARS-CoV-2 specific IgM and IgG antibodies was similar with that of SARS-CoV, while elevated serum IgM levels indicate poor outcome in patients with COVID-19 pneumonia.


title: Bringing accountability to the peak of the pandemic using linear response theory

text: The peak of the daily new infections in COVID-19 remained qualitative in description and elusive in arrival. Because of the lack of clarity in what to expect from the peak, apart from the hope that one day the peak will be reached, there has been no metric to describe the success of the implemented strategies. We propose a way of predicting the number of infections that can be expected after a lockdown, assuming they come from the asymptomatic cases prior to the lockdown and using linear response theory. These predictions for several western countries faithfully follow the observed infections for several weeks after the lockdown, suggesting universalities in the recovery pattern of several countries. At the same time, the gap between the quantitative predictions of the recovery patterns for New York and Milan and the observations is striking. These gaps which arise even while emulating the recovery patterns of other western countries raise the possibility of an audit of the success of the implemented strategies, and the potential newer sources of infection.


title: Utility of Cloth Masks in Preventing Respiratory Infections: A Systematic Review

text: Background: Using face masks is one of the possible prevention methods against respiratory pathogens. A number of studies and reviews have been performed regarding the use of medical grade masks like surgical masks, N95 respirators etc. However, the use of cloth masks has received little attention. Objectives: The purpose of this review is to analyze the available data regarding the use of cloth masks for the prevention of respiratory infections. We intended to use data from both clinical and non-clinical studies to arrive at our conclusion. Methods: We used PubMed, Cochrane Library and Google Scholar as our source databases. Both clinical and non-clinical studies, which had data regarding the efficacy of cloth masks, were selected. Articles not containing analyzable data including opinion articles, review articles etc. were excluded. After screening the search results, ten studies could be included in our review. Data relevant to our objective was extracted from each study including clinical efficacy, compliance, filtration efficacy etc. Data from some studies were simplified for the purpose of comparison. Extracted data was summarized and categorized for detailed analysis. Qualitative synthesis of the data was performed. But the heterogeneity between the studies did not allow for a meta-analysis. Discussion: The review was limited by a lack of sufficient clinical studies. Lack of standardization between studies was another limitation. Although cloth masks generally perform poorer than the medical grade masks, they may be better than no masks at all. Filtration efficacy varied greatly depending on the material used, with some materials showing a filtration efficacy above 90%. However, leakage could reduce efficacy of masks by about 50%. Standardization of cloth masks and appropriate use is essential for cloth masks to be effective. However, result of a randomized controlled trial suggest that they may be ineffective in the healthcare setting.


title: SARS-CoV-2 has been circulating in northern Italy since December 2019: evidence from environmental monitoring

text: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease COVID-19, a public health emergency worldwide, and Italy is among the world's first and most severely affected countries. The first autochthonous Italian case of COVID-19 was documented on February 21. We investigated the possibility that SARS-CoV-2 emerged in Italy earlier than that date, by analysing 40 composite influent wastewater samples collected - in the framework of other wastewater-based epidemiology projects - between October 2019 and February 2020 from five wastewater treatment plants (WTPs) in three cities and regions in northern Italy (Milan/Lombardy, Turin/Piedmont and Bologna/Emilia Romagna). Twenty-four additional samples collected in the same WTPs between September 2018 and June 2019 were included as blank samples. Viral concentration was performed according to the standard World Health Organization procedure for poliovirus sewage surveillance. Molecular analysis was undertaken with both nested RT-PCR and real-rime RT-PCR assays. A total of 15 positive samples were confirmed by both methods. Of these, 8 were collected before the first autochthonous Italian case. The earliest dates back to 18 December 2019 in Milan and Turin and 29 January 2020 in Bologna. Samples collected in January and February in the three cities were also positive. Our results demonstrate that SARS-CoV-2 was already circulating in northern Italy at the end of 2019. Moreover, it was circulating in different geographic regions simultaneously, which changes our previous understanding of the geographical circulation of the virus in Italy. Our study highlights once again the importance of environmental surveillance as an early warning system, to monitor the levels of virus circulating in the population and identify outbreaks even before cases are notified to the healthcare system.


Responding to the COVID-19 Crisis: Public Policy and Corporate Governance Considerations


Fact Versus Science Fiction: Fighting Coronavirus Disease 2019 Requires the Wisdom to Know the Difference


Genetic Variant Severe Acute Respiratory Syndrome Coronavirus 2 Isolates in Thailand


title: Artificial Intelligence-Assisted Loop Mediated Isothermal Amplification (ai-LAMP) for Rapid and Reliable Detection of SARS-CoV-2

text: Until vaccines and effective therapeutics become available, the practical way to transit safely out of the current lockdown may include the implementation of an effective testing, tracing and tracking system. However, this requires a reliable and clinically validated diagnostic platform for the sensitive and specific identification of SARS-CoV-2. Here, we report on the development of a de novo, high-resolution and comparative genomics guided reverse-transcribed loop-mediated isothermal amplification (LAMP) assay. To further enhance the assay performance and to remove any subjectivity associated with operator interpretation of result, we engineered a novel hand-held smart diagnostic device. The robust diagnostic device was further furnished with automated image acquisition and processing algorithms, and the collated data was processed through artificial intelligence (AI) pipelines to further reduce the assay run time and the subjectivity of the colorimetric LAMP detection. This advanced AI algorithm-implemented LAMP (ai-LAMP) assay, targeting the RNA-dependent RNA polymerase gene, showed high analytical sensitivity and specificity for SARS-CoV-2. A total of ~200 coronavirus disease (CoVID-19)-suspected patient samples were tested using the platform and it was shown to be reliable, highly specific and significantly more sensitive than the current gold standard qRT-PCR. The system could provide an efficient and cost-effective platform to detect SARS-CoV-2 in resource-limited laboratories.