title: Ignorance, exclusion, and solidarity in human-virus co-existence during and after COVID-19

text: In virulent times, can we still practice solidarity and avoid exclusion and violence for collective public health? This commentary explores Taiwan’s current and previous encounters with viruses to consider how its historically, locally, and socially contingent making of health practices might inform better global human-virus co-existence for the future.


title: Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2

text: The WHO has declared SARS-CoV-2 outbreak a public health emergency of international concern. However, to date, there was hardly any study in characterizing the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. In this study, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and analyzed their SARS-CoV-2-specific antibody and T cell responses. We observed SARS-CoV-2-specific humoral and cellular immunity in the patients. Both were detected in newly discharged patients, suggesting both participate in immune-mediated protection to viral infection. However, follow-up patients (2 weeks post discharge) exhibited high titers of IgG antibodies, but with low levels of virus-specific T cells, suggesting that they may enter a quiescent state. Our work has thus provided a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in designing an effective vaccine to protect and treat SARS-CoV-2 infection.


title: Syndromic surveillance insights from a symptom assessment app before and during COVID-19 measures in Germany and the United Kingdom: results from repeated cross-sectional analyses

text: Background: Unprecedented lockdown measures have been introduced in countries across the world to mitigate the spread and consequences of COVID-19. While attention has focused on the effects of these measures on epidemiological indicators relating directly to the infection, there is increased recognition of their broader health implications. However, assessing these implications in real time is a challenge, due to limitations of existing syndromic surveillance data and tools. Objective: To explore the added value of mobile phone app-based symptom assessment tools as real time health insight providers to inform public health policy makers. Methods: A comparative and descriptive analysis of the proportion of all self-reported symptoms entered by users during an Ada assessment in Germany and the United Kingdom (UK) was conducted between two periods: before and after the implementation of Phase One COVID-19 measures. Additional analyses were performed to explore the association between symptom trends and seasonality, and symptom trends and weather. Differences in the proportion of unique symptoms between the periods were analyzed using Pearson's Chi-squared test and reported as Log2 Fold Changes (Log2 FC). Results: Between 48,300-54,900 symptomatic users reported 140,500-170,400 symptoms during the Baseline and Measures periods in Germany. Between 34,200-37,400 symptomatic users in the UK reported 112,100-131,900 symptoms during the Baseline and Measures periods. The majority of symptomatic users were female (Germany 68,600/103,200, 66.52%; UK 51,200/71,600, 72.74%). The majority (Germany 68,500/100,000, 68.45%; UK 50,900/68,800, 73.91%) were aged between 10 and 29 years, and about a quarter (Germany 26,200/100,000, 26.15%; UK 14,900/68,800, 21.65%) were between 30-59 years. 103 symptoms were reported either more or less frequently (with statistically significant differences) during the Measures as compared to the Baseline period, and 34 of these were found in both countries. The following mental health symptoms (Log2 FC, P-value) were reported less often during the Measures period: inability to manage constant stress and demands at work (-1.07, P<.001), memory difficulty (-0.56, P<.001), depressed mood (-0.42, P<.001), and impaired concentration (-0.46, P<.001). Diminished sense of taste (2.26, P<.001) and hyposmia (2.20, P<.001) were reported more frequently during the Measures period. None of the 34 symptoms were found to be different between the same dates in 2019. Fourteen of the 34 symptoms had statistically significant associations with weather variables. Conclusions: Symptom assessment apps have an important role to play in facilitating improved understanding of the implications of public health policies such as COVID-19 lockdown measures. Not only do they provide the means to complement and cross-validate hypotheses based on data collected through more traditional channels, they can also generate novel insights through a real-time syndromic surveillance system.


title: Pentoxifylline: An Immunomodulatory Drug for the Treatment of COVID-19

text: Rapidly spreading outbreak of the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is causing serious health concerns worldwide It started as an epidemic in Wuhan, Hubei province, central China, and has now become a pandemic, spreading over most of the continents of the planet The major clinical symptoms of the infection are dry cough, fever, pneumonia, respiratory failure, hypoxia, and in certain cases, even death Alveolar damage and respiratory system failure are observed in severe cases Initial mild infection leads to activation of the immune system in the lungs and accumulation of various inflammatory cells and molecules At a later phase during the infection, a "cytokine storm" causes an Acute Respiratory Distress Syndrome (ARDS), leading to an increase in the production of pro-inflammatory cytokines, migration of a large number of immune cells to the site of infection, and ultimately pulmonary damage The rapid and uncontrolled outbreak requires putative therapeutic drugs for treatment of patients suffering from COVID-19 Amongst the currently used antiviral drugs, such as hydroxychloroquine, lopinavir, remdesivir etc we would like to present an update on another effective drug, pentoxifylline Pentoxifylline has anti-inflammatory, immunomodulatory, anti-viral, and bronchodilatory properties Pentoxifylline is known to reduce cytokine production, immune cell migration, and suppress certain signal transduction pathways (e g NF-kappa beta and STAT3) Thus, it minimizes inflammatory damage in the lung tissues


title: A novel COVID-19 epidemiological model with explicit susceptible and asymptomatic isolation compartments reveals unexpected consequences of timing social distancing

text: Motivated by the current COVID-19 epidemic, this work introduces an epidemiological model in which separate compartments are used for susceptible and asymptomatic "socially distant" populations. Distancing directives are represented by rates of flow into these compartments, as well as by a reduction in contacts that lessens disease transmission. The dynamical behavior of this system is analyzed, under various different rate control strategies, and the sensitivity of the basic reproduction number to various parameters is studied. One of the striking features of this model is the existence of a critical implementation delay in issuing separation mandates: while a delay of about four weeks does not have an appreciable effect, issuing mandates after this critical time results in a far greater incidence of infection. In other words, there is a nontrivial but tight "window of opportunity" for commencing social distancing. Different relaxation strategies are also simulated, with surprising results. Periodic relaxation policies suggest a schedule which may significantly inhibit peak infective load, but that this schedule is very sensitive to parameter values and the schedule's frequency. Further, we considered the impact of steadily reducing social distancing measures over time. We find that a too-sudden reopening of society may negate the progress achieved under initial distancing guidelines, if not carefully designed.


title: SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant

text: One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays revealed that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of more than 15,000 SARS-CoV-2 sequences identified a natural variant, in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients, but also describe a possibility of the emergence of natural SARS-CoV-2 quasispecies with extended ORF3b that may exacerbate COVID-19 symptoms. Highlights ORF3b of SARS-CoV-2 and related bat and pangolin viruses is a potent IFN antagonist SARS-CoV-2 ORF3b suppresses IFN induction more efficiently than SARS-CoV ortholog The anti-IFN activity of ORF3b depends on the length of its C-terminus An ORF3b with increased IFN antagonism was isolated from two severe COVID-19 cases


docid: bneclzag

title: A descriptive study of the current situation of covid-19 in algeria

text: The Novel Coronavirus disease (COVID-19), first detected in Wuhan (China) in December 2019 is quickly spreading across the globe leading to a shocking number of 3,305,595 cases and 235,861 deaths on May 1st, 2020. Algeria is the fourth most affected country in Africa with a number of 4154 positive cases and 453 deaths. The objective of the current manuscript is to describe the actual situation of COVID-19 in Algeria.


docid: zjwmgjsw

title: Teleworking in the context of the Covid-19 crisis

text: This article aims to analyze the implementation of teleworking as a security practice to face the crisis resulting from the Covid-19 disease. The present paper provides both theoretical and practical results. From a theoretical standpoint, the Baruch and Nicholson approach is extended with environmental, safety, and legal factors that explain telework. From a practical perspective, a database of companies that have introduced telework as a measure to face coronavirus in a crisis context has been obtained. In short, the Covid-19 crisis demonstrates how teleworking has been used by companies to ensure their employees' safety and to provide continuity to economic activity. Consequently, safety factors are relevant in the study of teleworking and should be considered in further research.


docid: rxkltaqy

title: ESTIMATION OF COVID-19 CASES IN FRANCE AND IN DIFFERENT COUNTRIES: HOMOGENEISATION BASED ON MORTALITY

text: Every day the authorities of different countries provide an estimate of the number of persons affected by Covid-19 and a count of fatality. We propose to use the fatality reported in each country to provide a better estimate (Ct0-estimated) of the number of cases at a given time t0. Ct0-estimated = (Ft0 / Fr-est) * (1+ [C(est-d) / C(est-3d)])6 With Ft0: number of actual fatalities reported in a country at time t0; Fr-est: estimated fatality rate; C(est-d): estimated fatalities 18 days before t0; C(est-3d): estimated fatalities 21 days before t0. Based on Ct0-estimated calculated using a fatality rate of 2%, we assessed the number of cases April 10th, 2020 in Belgium, China, France, Germany, Iran, Italy, South Korea, Netherlands, Spain, United Kingdom and USA. This number reached 2,872,097 in France and 924,892 persons in Germany. The proposed formulas also make it possible to evaluate the impact of policies to prevent the spread of epidemic on the appearance of new cases.


Life in Emergistan: COVID-19 is a Test for All Physicians


title: Evaluation Of SYBR Green Real Time PCR For Detecting SARS-CoV-2 From Clinical Samples

text: The pandemic caused by SARS-CoV-2 has triggered an extraordinary collapse of healthcare systems and hundred thousand of deaths worldwide. Following the declaration of the outbreak as a Public Health Emergency of International Concern by the World Health Organization (WHO) on January 30th, 2020, it has become imperative to develop diagnostic tools to reliably detect the virus in infected patients. Several methods based on real time reverse transcription polymerase chain reaction (RT-qPCR) for the detection of SARS-CoV-2 genomic RNA have been developed. In addition, these methods have been recommended by the WHO for laboratory diagnosis. Since all these protocols are based on the use of fluorogenic probes and one-step reagents (cDNA synthesis followed by PCR amplification in the same tube), these techniques can be difficult to perform given the limited supply of reagents in low and middle income countries. In the interest of economy, time and availability of chemicals and consumables, the SYBR Green-based detection was implemented to establish a convenient assay. Therefore, we adapted one of WHO recommended Taqman-based one-step real time PCR protocols (from the University of Hong Kong) to SYBR Green. Our results suggest that SYBR-Green detection represents a reliable cost-effective alternative to increase the testing capacity.


title: Prevalence of SARS-CoV-2 infection among asymptomatic healthcare workers in greater Houston: a cross-sectional analysis of surveillance data from a large healthcare system

text: Objective: To determine the prevalence of SARS-CoV-2 infection among asymptomatic COVID-19 facing and non-COVID-19 facing Healthcare Workers (HCWs), with varying job categories across different hospitals. Design: Cross-sectional analysis of a healthcare system surveillance program that included asymptomatic clinical (COVID-19 facing and non-COVID-19 facing), and non-clinical HCWs. A convenience sample of asymptomatic community residents (CR) was also tested. Proportions and 95% confidence intervals (CI) of SARS-CoV-2 positive HCWs are reported. Proportional trend across HCW categories was tested using Chi Square trend test. Logistic regression model-based likelihood estimates of SARS-CoV-2 prevalence among HCWs with varying job functions and across different hospitals are reported as adjusted odds ratios (aOR) and CI. Setting: Healthcare system comprising one tertiary care academic medical center and six large community hospitals across Greater Houston and a community sample. Participants: 2,872 self-reported asymptomatic adult (> 18 years) HCWs and CRs. Exposure: Clinical HCWs in COVID-19 and non-COVID-19 units, non-Clinical HCWs, and CRs. Job categories of Nursing, Providers, Allied Health, Support, and Administration / Research. Seven hospitals in the healthcare system. Main Outcomes: Positive reverse transcriptase polymerized chain reaction (RT-PCR) test for SARS-CoV-2 Results: Among 2,872 asymptomatic HCWs and CRs, 3.9% (CI: 3.2 - 4.7) tested positive for SARS-CoV-2. Mean (SD) age was 40.9 (11.7) years and 73% were females. Among COVID-19 facing HCWs 5.4% (CI: 4.5 - 6.5) were positive, whereas 0.6% (CI: 0.2 - 1.7%) of non COVID-19 facing HCWs and none of the non-clinical HCWs or CRs were positive (Ptrend < 0.001). Among COVID-19 facing HCWs, SARS-CoV-2 positivity was similar for all job categories (p = 0.74). However, significant differences in positivity were observed across hospitals. Conclusions and Relevance: Asymptomatic HCWs with COVID-19 patient exposure had a higher rate of SARS-CoV-2 positive testing than those not routinely exposed to COVID-19 patients and those not engaged in patient care. Among HCWs with routine COVID-19 exposure, all job types had relatively similar infection rates. These data can inform hospital surveillance and infection control practices for patient-facing job classifications and suggest that general environmental exposure within hospitals is not a significant source of asymptomatic SARS-CoV-2 infection.


I can get no desinfection


title: Optimal harvesting for a stochastic regime-switching logistic diffusion system with jumps

text: Abstract The optimization problem of fishing for a stochastic logistic model is studied in this paper. Besides a standard geometric Brownian motion, another two driving processes are taken into account: a stationary Poisson point process and a continuous-time finite-state Markov chain. The classical harvesting problem for this model is a big difficult puzzle since the corresponding Fokker–Planck equations with three types of noise are very difficult to solve. Our main goal of this paper is to work out the optimization problem with respect to stationary probability density. One of the main contributions is to provide a new equivalent approach to overcome this problem. More precisely, an ergodic method is used to show the almost surely equivalency between the time averaging yield and sustainable yield. Results show that the optimal strategy changes with environment. An interesting thing is that the optimal strategy for each state is equivalent to the global optimality.


title: Correcting under-reported COVID-19 case numbers: estimating the true scale of the pandemic

text: The COVID-19 virus has spread worldwide in a matter of a few months, while healthcare systems struggle to monitor and report current cases. Testing results have struggled with the relative capabilities, testing policies and preparedness of each affected country, making their comparison a non-trivial task. Since severe cases, which more likely lead to fatal outcomes, are detected at a higher rate than mild cases, the reported virus mortality is likely inflated in most countries. Lockdowns and changes in human behavior modulate the underlying growth rate of the virus. Under-sampling of infection cases may lead to the under-estimation of total cases, resulting in systematic mortality estimation biases. For healthcare systems worldwide it is important to know the expected number of cases that will need treatment. In this manuscript, we identify a generalizable growth rate decay reflecting behavioral change. We propose a method to correct the reported COVID-19 cases and death numbers by using a benchmark country (South Korea) with near-optimal testing coverage, with considerations on population demographics. We extrapolate expected deaths and hospitalizations with respect to observations in countries that passed the exponential growth curve. By applying our correction, we predict that the number of cases is highly under-reported in most countries and a significant burden on worldwide hospital capacity.


docid: wxagjqbt

title: COVID-19 Vaccine Candidates: Prediction and Validation of 174 SARS-CoV-2 Epitopes

text: The recent outbreak of SARS-CoV-2 (2019-nCoV) virus has highlighted the need for fast and efficacious vaccine development. Stimulation of a proper immune response that leads to protection is highly dependent on presentation of epitopes to circulating T-cells via the HLA complex. SARS-CoV-2 is a large RNA virus and testing of all overlapping peptides in vitro to deconvolute an immune response is not feasible. Therefore HLA-binding prediction tools are often used to narrow down the number of peptides to test. We tested 19 epitope-HLA-binding prediction tools, and using an in vitro peptide MHC stability assay, we assessed 777 peptides that were predicted to be good binders across 11 MHC allotypes. In this investigation of potential SARS-CoV-2 epitopes we found that current prediction tools vary in performance when assessing binding stability, and they are highly dependent on the MHC allotype in question. Designing a COVID-19 vaccine where only a few epitope targets are included is therefore a very challenging task. Here, we present 174 SARS-CoV-2 epitopes with high prediction binding scores, validated to bind stably to 11 HLA allotypes. Our findings may contribute to the design of an efficacious vaccine against COVID-19.


docid: ufoqvoow

title: During Aspergillus infection, neutrophil, monocyte-derived DC, and plasmacytoid DC enhance innate immune defense through CXCR3-dependent crosstalk

text: Aspergillus fumigatus, a ubiquitous mold, is a common cause of invasive aspergillosis (IA) in immunocompromised patients. Host defense against IA relies on lung-infiltrating neutrophils and monocyte-derived dendritic cells (Mo-DCs). Here, we demonstrate that plasmacytoid dendritic cells (pDCs), which are prototypically anti-viral cells, participate in innate immune crosstalk underlying mucosal antifungal immunity. Aspergillus-infected murine Mo-DCs and neutrophils recruited pDCs to the lung by releasing the CXCR3 ligands, CXCL9 and CXCL10, in a Dectin-1/Card9- and type I and III interferon-signaling dependent manner, respectively. During aspergillosis, circulating pDCs entered the lung in response to CXCR3-dependent signals. Via targeted pDC ablation, we found that pDCs were essential for host defense in the presence of normal neutrophil and Mo-DC numbers. Although interactions between pDC and fungal cells were not detected, pDCs regulated neutrophil NADPH oxidase activity and conidial killing. Thus, pDCs act as positive feedback amplifiers of neutrophil effector activity against inhaled mold conidia.


title: A national prospective cohort study of SARS/COV2 pandemic outcomes in the U.S.: The CHASING COVID Cohort

text: Introduction: The Chasing COVID Cohort (C3) study is a US-based, geographically and socio-demographically diverse sample of adults (18 and older) enrolled into a prospective cohort study during the upswing of the U.S. COVID-19 pandemic. Methods: We used internet-based strategies to enroll C3 participants beginning March 28th, 2020. Following baseline questionnaire completion, study participants will be contacted monthly (for 6 months) to complete assessments of engagement in non-pharmaceutical interventions (e.g., use of cloth masks, avoiding large gatherings); COVID-19 symptoms; SARS/COV2 testing and diagnosis; hospitalizations; healthcare access; and uptake of health messaging. Dried blood spot (DBS) specimens will be collected at the first follow-up assessment (last week of April 2020) and at month 3 (last week of June 2020) and stored until a validated serologic test is available. Results: As of April 20, 2020, the number of people that completed the baseline survey and provided contact information for follow-up was 7,070. Participants resided in all 50 US states, the District of Columbia, Puerto Rico, and Guam. At least 24% of participants were frontline workers (healthcare and other essential workers). Twenty-three percent (23%) were 60+ years, 24% were Black or Hispanic, 52% were men, and 52% were currently employed. Nearly 20% reported recent COVID-like symptoms (cough, fever or shortness of breath) and a high proportion reported engaging in non-pharmaceutical interventions that reduce SARS/COV2 spread (93% avoided groups >20, 58% wore masks; 73% quarantined). More than half (54%) had higher risk for severe COVID-19 illness should they become infected with SARS/COV2 based on age, underlying health conditions (e.g., chronic lung disease), or daily smoking. Discussion: A geographically and socio-demographically diverse group of participants was rapidly enrolled in the C3 during the upswing of the SARS/COV2 pandemic. Strengths of the C3 include the potential for direct observation of, and risk factors for, seroconversion and incident COVID disease (among those with or without antibodies to SARS/COV2) in areas of active transmission.


title: Epidemiological and clinical features of 2019-nCoV acute respiratory disease cases in Chongqing municipality, China: a retrospective, descriptive, multiple-center study

text: Background：In January 19, 2020, first case of 2019 novel coronavirus (2019-nCoV) pneumonia (COVID-19) was confirmed in Chongqing municipality, China. Methods：In this retrospective, descriptive, multiple-center study, total of 267 patients with COVID-19 confirmed by real-time RT-PCR in Chongqing from Jan 19 to Feb 16, 2020 were recruited. Epidemiological, demographic, clinical, radiological characteristics, laboratory examinations, and treatment regimens were collected on admission. Clinical outcomes were followed up until Feb 16, 2020. Results：267 laboratory-confirmed COVID-19 patients admitted to 3 designated-hospitals in Chongqing provincial municipality from January 19 to February 16, 2020 were enrolled and categorized on admission. 217 (81.27%) and 50 (18.73%) patients were categorized into non-severe and severe subgroups, respectively. The median age of patients was 48.0 years (IQR, 35.0-65.0), with 129 (48.3%) of the patients were more than 50 years of age. 149 (55.8%) patients were men. Severe patients were significantly older (median age, 71.5 years [IQR, 65.8-77.0] vs 43.0 years [IQR, 32.5-57.0]) and more likely to be male (110 [50.7%] vs 39 [78.0%]) and have coexisting disorders (15 [30.0%] vs 26 [12.0%]). 41 (15.4%) patients had a recent travel to Hubei province, and 139 (52.1%) patients had a history of contact with patients from Hubei. On admission, the most common symptoms of COVID-19 were fever 225(84.3%), fatigue (208 [77.9%]), dry cough (189 [70.8%]), myalgia or arthralgia (136 [50.9%]). Severe patients were more likely to present dyspnea (17 [34.0%] vs 26 [12.0%]) and confusion (10 [20.0%] vs 15 [6.9%]). Rales (32 [12.0%]) and wheezes (20 [7.5%]) are not common noted for COVID-19 patients, especially for the non-severe (11 [5.1%], 10 [4.6%]). 118 (44.2%). Most severe patients demonstrated more laboratory abnormalities. 231 (86.5%), 61 (22.8%) patients had lymphopenia, leukopenia and thrombocytopenia, respectively. CD4+T cell counts decrease was observed in 77.1 % of cases, especially in the severe patients (45, 100%). 53.1% patients had decreased CD+3 T cell counts, count of CD8+T cells was lower than the normal range in part of patients (34.4%). More severe patients had lower level of CD4+ T cells and CD+3 T cells (45 [100.0%] vs 29[56.9%], 31 [68.9%] vs 20 [39.2%]). Most patients had normal level of IL-2, IL-4, TNF-α and INF-γ, while high level of IL-6 and IL-17A was common in COVID-19 patients (47 [70.1%], 35 [52.2%]). Level of IL-6, IL-17A and TNF-α was remarkably elevated in severe patients (32 [84.2%] vs 15 [51.7%], 25 [65.8%] vs 10 [34.5%], 17 [44.7%] vs 5 [17.2%]). All patients received antiviral therapy (267, 100%). A portion of severe patients (38, 76.0%) received systemic corticosteroid therapy. Invasive mechanical ventilation in prone position, non-invasive mechanical ventilation, high-flow nasal cannula oxygen therapy was adopted only in severe patients with respiratory failure (5[10.0%], 35[70.0%], 12[24.0%]). Traditional Chinese medicine was adopted to most of severe patients (43,86.0%). Conclusion:Our study firstly demonstrated the regional disparity of COVID-19 in Chongqing municipality and further thoroughly compared the differences between severe and non-severe patients. The 28-day mortality of COVID-19 patients from 3 designed hospitals of Chongqing is 1.5%, lower than that of Hubei province and mainland China including Hubei province. However, the 28-mortality of severe patients was relatively high, with much higher when complications occurred. Notably, the 28-mortality of critically severe patients complicated with severe ARDS is considerably as high as 44.4%. Therefore, early diagnosis and intensive care of critically severe COVID-19 cases, especially those combined with ARDS, will be considerably essential to reduce mortality.


title: Using transcranial magnetic stimulation to map the cortical representation of lower-limb muscles

text: The aim of this study was to evaluate the extent to which transcranial magnetic stimulation (TMS) can identify discrete cortical representation of lower-limb muscles in healthy individuals. Data were obtained from 16 young healthy adults (12 women, four men; mean [SD] age 23.0 [2.6] years). Motor evoked potentials were recorded from the resting vastus medialis, rectus femoris, vastus lateralis, medial and lateral hamstring, and medial and lateral gastrocnemius muscles on the right side of the body using bipolar surface electrodes. TMS was delivered through a 110-mm double-cone coil at 63 sites over the left hemisphere. Location and size of the cortical representation and the number of discrete peaks were quantified for each muscle. Within the quadriceps muscle group there was a main effect of muscle on anterior-posterior centre of gravity (p = 0.010), but the magnitude of the difference was very small. Within the quadriceps there was a main effect of muscle on medial-lateral hotspot (p = 0.027) and map volume (p = 0.047), but no post-hoc tests were significant. The topography of each lower-limb muscle was complex, displaying multiple peaks that were present across the stimulation grid, and variable across individuals. The results of this study indicate that TMS delivered with a 110-mm double-cone coil could not reliably identify discrete cortical representations of resting lower-limb muscles when responses were measured using bipolar surface electromyography. The characteristics of the cortical representation of lower-limb muscles reported here provide a basis against which to evaluate cortical reorganisation in clinical populations.


title: How to improve adherence with quarantine: Rapid review of the evidence

text: Objectives: The January 2020 outbreak of coronavirus has once again thrown the vexed issue of quarantine into the spotlight, with many countries asking their citizens to self-isolate if they have potentially come into contact with the infection. However, adhering to quarantine is difficult. Decisions on how to apply quarantine should be based on the best available evidence to increase the likelihood of people adhering to protocols. We conducted a rapid review to identify factors associated with adherence to quarantine during infectious disease outbreaks. Study design: Rapid evidence review. Methods: We searched Medline, PsycINFO and Web of Science for published literature on the reasons for and factors associated with adherence to quarantine during an infectious disease outbreak. Results: We found 3163 papers and included 14 in the review. Adherence to quarantine ranged from as little as 0 up to 92.8%. The main factors which influenced or were associated with adherence decisions were the knowledge people had about the disease and quarantine procedure, social norms, perceived benefits of quarantine and perceived risk of the disease, as well as practical issues such as running out of supplies or the financial consequences of being out of work. Conclusions: People vary in their adherence to quarantine during infectious disease outbreaks. To improve this, public health officials should provide a timely, clear rationale for quarantine and information about protocols; emphasise social norms to encourage this altruistic behaviour; increase the perceived benefit that engaging in quarantine will have on public health; and ensure that sufficient supplies of food, medication and other essentials are provided.


title: Detection of IgM and IgG antibodies in patients with coronavirus disease 2019

text: OBJECTIVES: This study aimed to determine the IgM and IgG responses against severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2 in coronavirus disease 2019 (COVID‐19) patients with varying illness severities. METHODS: IgM and IgG antibody levels were assessed via chemiluminescence immunoassay in 338 COVID‐19 patients. RESULTS: IgM levels increased during the first week after SARS‐CoV‐2 infection, peaked 2 weeks and then reduced to near‐background levels in most patients. IgG was detectable after 1 week and was maintained at a high level for a long period. The positive rates of IgM and/or IgG antibody detections were not significantly different among the mild, severe and critical disease groups. Severe and critical cases had higher IgM levels than mild cases, whereas the IgG level in critical cases was lower than those in both mild and severe cases. This might be because of the high disease activity and/or a compromised immune response in critical cases. The IgM antibody levels were slightly higher in deceased patients than recovered patients, but IgG levels in these groups did not significantly differ. A longitudinal detection of antibodies revealed that IgM levels decreased rapidly in recovered patients, whereas in deceased cases, either IgM levels remained high or both IgM and IgG were undetectable during the disease course. CONCLUSION: Quantitative detection of IgM and IgG antibodies against SARS‐CoV‐2 quantitatively has potential significance for evaluating the severity and prognosis of COVID‐19.


title: From Black Death to fatal flu, past pandemics show why people on the margins suffer most

text: When the Black Death arrived in London by January 1349, the city had been waiting with dread for months Londoners had heard reports of devastation from cities such as Florence, where 60% of people had died of plague the year before In the summer of 1348, the disease had reached English ports from continental Europe and begun to ravage its way toward the capital The plague caused painful and frightening symptoms, including fever, vomiting, coughing up blood, black pustules on the skin, and swollen lymph nodes Death usually came within 3 days The city prepared the best way it knew how: Officials built a massive cemetery, called East Smithfield, to bury as many victims as possible in consecrated ground, which the faithful believed would allow God to identify the dead as Christians on Judgment Day Unable to save lives, the city tried to save souls


title: PROJECTING A MATURE EPIDEMIC: A SIMPLE TOOL WITH AN APPLICATION TO COVID-19 DEATHS

text: We describe a new statistical model for the spread of a mature epidemic, i.e. one characterized by an exponentially decaying growth rate of the cumulative number of cases/deaths - the speed of this decay being measured by the growth rate's half-life. If such a pattern is observed during the recent past, then it can be extrapolated. A spreadsheet is made available that allows users to input weekly cumulative numbers of deaths and obtain an estimate of the growth rate's baseline half-life and the corresponding projections. These projections can be compared to those with a larger half-life (if a protracted epidemic is expected, e.g. due to second wave), or with a smaller one (if successful therapies or mitigation efforts reduce transmission). The model is applied to deaths due to COVID-19 in California in May-June 2020.


title: The fiscal value of human lives lost from Novel Coronavirus (2019-nCoV) in China

text: According to the WHO coronavirus disease (COVID-19) situation report 35, as of 24th February 2020, there was a total of 77,262 confirmed COVID-19 cases in China That included 2595 deaths The specific objective of this study was to estimate the fiscal value of human lives lost due to COVID-19 in China as of 24th February 2020 The deaths from COVID-19 had a discounted (at 3%) total fiscal value of Int$ 924,346,795 in China Out of which, 63 2% was borne by people aged 25–49 years, 27 8% by people aged 50–64 years, and 9 0% by people aged 65 years and above The average fiscal value per death was Int$ 356,203 Re-estimation of the economic model alternately with 5% and 10 discount rates led to a reduction in the expected total fiscal value by 21 3% and 50 4%, respectively Furthermore, the re-estimation of the economic model using the world’s highest average life expectancy of 87 1 years (which is that of Japanese females), instead of the national life expectancy of 76 4 years, increased the total fiscal value by Int$ 229,456,430 (24 8%)


title: Multi-chain Fudan-CCDC model for COVID-19 -- a revisit to Singapore's case

text: Background: COVID-19 has been impacting on the whole world critically and constantly since late December 2019. Rapidly increasing infections has raised intense worldwide attention. How to model the evolution of COVID-19 effectively and efficiently is of great significance for prevention and control. Methods: We propose the multi-chain Fudan-CCDC model based on the original single-chain model in [8] to describe the evolution of COVID-19 in Singapore. Multi-chains can be considered as the superposition of several single chains with different characteristics. We identify parameters of models by minimizing the penalty function. Results: The numerical simulation results exhibit the multi-chain model performs well on data fitting. Though unsteady the increments are, they could still fall within the range of 25% fluctuation from simulation results. It is predicted by multi-chain models that Singapore are experiencing a nonnegligible risk of explosive outbreak, thus stronger measures are urgently needed to contain the epidemic. Conclusion: The multi-chain Fudan-CCDC model provides an effective way to early detect the appearance of imported infectors and super spreaders and forecast a second outbreak. It can also explain the data in those countries where the single-chain model shows deviation from the data.


title: MINERVA: A facile strategy for SARS-CoV-2 whole genome deep sequencing of clinical samples

text: The novel coronavirus disease 2019 (COVID-19) pandemic poses a serious public health risk. Analyzing the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from clinical samples is crucial for the understanding of viral spread and viral evolution, as well as for vaccine development. Existing sample preparation methods for viral genome sequencing are demanding on user technique and time, and thus not ideal for time-sensitive clinical samples; these methods are also not optimized for high performance on viral genomes. We have developed MetagenomIc RNA EnRichment VirAl sequencing (MINERVA), a facile, practical, and robust approach for metagenomic and deep viral sequencing from clinical samples. This approach uses direct tagmentation of RNA/DNA hybrids using Tn5 transposase to greatly simplify the sequencing library construction process, while subsequent targeted enrichment can generate viral genomes with high sensitivity, coverage, and depth. We demonstrate the utility of MINERVA on pharyngeal, sputum and stool samples collected from COVID-19 patients, successfully obtaining both whole metatranscriptomes and complete high-depth high-coverage SARS-CoV-2 genomes from these clinical samples, with high yield and robustness. MINERVA is compatible with clinical nucleic extracts containing carrier RNA. With a shortened hands-on time from sample to virus-enriched sequencing-ready library, this rapid, versatile, and clinic-friendly approach will facilitate monitoring of viral genetic variations during outbreaks, both current and future.


title: Nowcasting and Forecasting the Spread of COVID-19 in Iran

text: Introduction: As of early December 2019, COVID-19, a disease induced by SARS-COV-2, has started spreading, originated in Wuhan, China, and now on, have infected more than 2 million individuals throughout the world. Purpose: This study aimed to nowcast the COVID-19 outbreak throughout Iran and to forecast the trends of the disease spreading in the upcoming month. Methods: The cumulative incidence and fatality data were extracted from official reports of the National Ministry of Health and Medical Educations of Iran. To formulate the outbreak dynamics, six phenomenological models, as well as a modified mechanistic Susciptible-Exposed-Infectious-Recovered (SEIR) model, were implemented. The models were calibrated with the integrated data, and trends of the epidemic in Iran was then forecasted for the next month. Results: The final outbreak size calculated by the best fitted phenomenological models was estimated to be in the range of 68,486 to 118,923 cases; however, the calibrated SEIR model estimated that the outbreak would rage again, starting from April 26. Moreover, projected by the mechanistic model, approximately half of the infections have undergone undetected. Conclusion: Although the advanced phenomenological models perfectly fitted the data, they are incapable of applying behavioral aspects of the outbreak and hence, are not reliable enough for authorities' decision adoptions. In contrast, the mechanistic SEIR model alarms that the COVID-19 outbreak in Iran may peak for the second time, consequent to lifting the control measures. This implies that the government may implement a more granular decision making to control the outbreak.


title: First case of placental infection with SARS-CoV-2

text: Background: The effects of Covid-19 in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic Covid-19 complicated by severe preeclampsia and placental abruption. Methods: We analyzed placenta for the presence of SARS-CoV-2 through molecular and immunohistochemical assays and by and electron microscopy, and we measured the maternal antibody response in blood to this infection. Results: SARS-CoV-2 localized predominantly to syncytiotrophoblast cells at the maternal-fetal interface of the placenta. Histological examination of the placenta revealed a dense macrophage infiltrate, but no evidence for vasculopathy typically associated with preeclampsia. Conclusion: This case demonstrates, for the first time, SARS-CoV-2 invasion of the placenta, highlighting the potential for severe morbidity among pregnant women with Covid-19.


title: Performance of fabrics for home-made masks against spread of respiratory infection through droplets: a quantitative mechanistic study

text: Respiratory infections may spread through droplets, airborne particles, and aerosols from infected individuals through coughing, sneezing, and speaking. In the case of Coronavirus Disease 2019 (COVID-19), droplet spread can occur from symptomatic as well as pre-symptomatic and asymptomatic persons. The U.S. Centers for Disease Control and Prevention (CDC) has therefore recently recommended home-made cloth face coverings for use by the general public in areas of significant community-based transmission. Because medical masks and N95 respirators are in short supply, these are to be reserved for healthcare workers. There is, however, little information on the effectiveness of home-made face coverings in reducing droplet dissemination. Here, we ascertained the performance of ten different fabrics, ranging from cotton to silk, in blocking high velocity droplets, using a 3-layered commercial medical mask as a benchmark material. We also assessed their breathability and ability to soak water. We reason that the materials should be as breathable as possible, without compromising blocking efficiency, to reduce air flow through the sides of the mask since such flow would defeat the purpose of the mask. We found that most home fabrics substantially block droplets, even as a single layer. With two layers, blocking performance can reach that of surgical mask without significantly compromising breathability. Furthermore, we observed that home fabrics are hydrophilic to varying degrees, and hence soak water. In contrast, medical masks are hydrophobic, and tend to repel water. Incoming droplets are thus soaked and 'held back' by home fabrics, which might offer an as of yet untapped and understudied advantage of home-made cloth masks. Overall, our study suggests that most double-layered cloth face coverings may help reduce droplet transmission of respiratory infections.


title: Automated Diagnosis of COVID-19 Using Deep Learning and Data Augmentation on Chest CT

text: Background: Coronavirus disease 2019 (COVID-19) has surprised the world since the beginning of 2020, and the rapid growth of COVID-19 is beyond the capability of doctors and hospitals that could deal in many areas. The chest computed tomography (CT) could be serve as an effective tool in detection of COVID-19. Its valuable to develop automatic detection of COVID-19. Material and Methods: The collected dataset consisted of 521 COVID-19 chest CT images, 397 normal chest CT images, 76 bacterial pneumonia chest CT images and 48 SARS chest CT images obtained by exhaustively searching available data on the Internet. Then, these data are divided into three sets, referred to training set, validation set and testing set. Sixteen data augmentation operations are designed to enrich the training set in deep learning training phase. Multiple experiments were conducted to analyze the performance of the model in the detection of COVID-19 both in case of no noisy labels and noisy labels. The performance was assessed by the area under the receiver operating characteristic (AUC), sensitivity, specificity and accuracy. Results: The data augmentation operations on the training set is effective for improvement of the model performance. The area under the receiver operating characteristic curve is 0.9689 with (95% CI: 0.9308, 1) in case of no noisy labels, while the per-exam sensitivity, specificity and accuracy for detecting COVID-19 in the independent testing set are 90.52%, 91.58% and 91.21%, respectively. Besides, the model is robust when part of the training samples is marked incorrectly. The AUC is 92.23% in the case of noisy labels of 10% in the training set. Conclusion A deep learning model with insufficient samples can be developed by using data augmentation in assisting medical workers in making quick and correct diagnosis of COVID-19.


docid: hvujzerj

title: HMGXB4 Targets Sleeping Beauty Transposition to Vertebrate Germinal Stem Cells

text: Transposons are parasitic genetic elements that frequently hijack key cellular processes of the host. HMGXB4 is a Wnt signalling-associated HMG-box protein, previously identified as a transcriptional regulating host factor of Sleeping Beauty (SB) transposition. Here, we establish that HMGXB4 is highly expressed from the zygote stage, and declines after transcriptional genome activation. Nevertheless, HMGXB4 is activated by its own promoter at 4-cell stage, responding to the parental-to-zygotic transition, marks stemness, and maintains its expression during germ cell specification. The HMGXB4 promoter is located at an active chromatin domain boundary. As a vertebrate-specific modulator of SETD1A and NuRF complexes, HMGXB4 links histone H3K4 methyltransferase- and ATP-dependent nucleosome remodelling activities. The expression of HMGXB4 is regulated by the KRAB-ZNF/TRIM28 epigenetic repression machinery. A post-transcriptional modification by SUMOylation diminishes its transcriptional activator function and regulates its nucleolar trafficking. Collectively, HMGXB4 positions SB transposition into an elaborate stem cell-specific transcriptional regulatory mechanism that is active during early embryogenesis and germline development, thereby potentiating heritable transposon insertions in the germline.


title: Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in Rhesus macaques

text: The outbreak of Corona Virus Disease 2019 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) is highly transmitted. The potential extra-respiratory transmission routes remain uncertain. Five rhesus macaques were inoculated with 1×106 TCID50 of SARS-CoV-2 via conjunctival (CJ), intratracheal (IT), and intragastric (IG) routes, respectively. Remarkably, the CJ inoculated-macaques developed mild interstitial pneumonia and viral load was detectable in the conjunctival swabs at 1 days post-inoculation (dpi). Only via IT inoculation, viral load was detected in the anal swab at 1-7 dpi and macaque showed weight loss. However, viral load was undetectable after IG inoculation. Comparatively, viral load was higher in the nasolacrimal system but lesions of lung were relatively mild and local via CJ inoculation compared with that via IT inoculation, demonstrating distinct characteristics of virus dispersion. Both the two routes affected the alimentary tract. Therefore the clinicians need to protect eye while working with patients.


title: Estimating the extent of true asymptomatic COVID-19 and its potential for community transmission: systematic review and meta-analysis

text: Background: The prevalence of true asymptomatic COVID-19 cases is critical to policy makers considering the effectiveness of mitigation measures against the SARS-CoV-2 pandemic. We aimed to synthesize all available research on the asymptomatic rates and transmission rates where possible. Methods: We searched PubMed, Embase, Cochrane COVID-19 trials, and European PMC for pre-print platforms such as MedRxiv. We included primary studies reporting on asymptomatic prevalence where: (a) the sample frame includes at-risk population, and (b) there was sufficiently long follow up to identify pre-symptomatic cases. Meta-analysis used fixed effect and random effects models. Results: We screened 571 articles and included five low risk-of-bias studies from three countries (China (2), USA (2), Italy (1)) that tested 9,242 at-risk people, of which 413 were positive and 65 were asymptomatic. Diagnosis in all studies was confirmed using a RT-qPCR test. The proportion of asymptomatic cases ranged from 6% to 41%. Meta-analysis (fixed effect) found that the proportion of asymptomatic cases was 16% (95% CI: 12% - 20%) overall; higher in non-aged care 19% (15% - 24%), and lower in long-term aged care 8% (4% - 14%). Two studies provided direct evidence of forward transmission of the infection by asymptomatic cases but suggested lower rates than symptomatic cases. Conclusion: Our estimates of the prevalence of asymptomatic COVID-19 cases are lower than many highly publicized studies, but still substantial. Further robust epidemiological evidence is urgently needed, including in sub-populations such as children, to better understand the importance of asymptomatic cases for driving spread of the pandemic.


title: Establishing Prokaryotic Expression System of Angiotensin-Converting Enzyme 2 (ACE2) gene in pigs

text: In this paper, ACE2 gene of pigs was cloned and the purified protein was obtained via the prokaryotic expression system. Polyclonal antibody of high titer and sensitivity was obtained using Wastar rats immunization method and is then used to determine of the expression of ACE2 using immunohistochemistry. The sequence of ACE2 in pigs covered 2418 nucleotides and coded 805 amino acid (aa) residues. Sequence homology analysis showed that the ACE2 sequence in pigs is highly conserved among species at the nucleotide and amino acid levels. Genetic evolution analysis revealed that ACE2 gene in pigs has the shortest genetic distance with that in goats while residing in a totally different branch from that in zebra fishes. Analysis of protein structure predicted that ACE2 protein is a transmembrane secreted protein with high hydrophilicity, containing a signal peptide sequences locating between 1aa to 17aa. The ACE2 fusion protein expressed (under the induction with 1.0 mmol/L IPTG for 10 h) was of approximately 100 kDa and mainly existed in inclusion body. Wastar rats immunization showed that the titer of the anti-ACE2 antiserum in rats was 1: 3200. Western blot showed that the antibody binds specifically. Immunohistochemistry showed that the ACE2 protein was expressed in all major tissues of pigs. It is the first time that polyclonal antibody of ACE2 in pigs was obtained and the expression of ACE2 was confirmed. These results will provide a basis for investigating on ACE2’s biological activity in pigs.


title: Saudi heart association, national heart center and national cardiopulmonary resuscitation committee taskforce statement on cpr and resuscitation during COVID-19 pandemic

text: Corona virus disease 2019 is a global pandemic, which affects around 2million individuals with a high death rate that exceeds 90,000 death cases across the globe. The Saudi Heart Association and the national cardiopulmonary resuscitation committee developed a taskforce to discuss the magnitude of clinical situation and CPR management on COVID-19 patients in a prehospital and in-hospital settings. Meanwhile, the taskforce aims to develop a nation-wide clinical guidance to be used by health care workers and untrained laypersons to resuscitate COVID-19 suspected and diagnosed patients.


title: Hydroxychloroquine (HCQ): an observational cohort study in primary and secondary prevention of pneumonia in an at-risk population

text: Background. Recent studies suggest that hydroxychloroquine (HCQ) could be effective against COVID-19. It is reasonable to expect that if HCQ can prevent or reduce the adverse effects of influenza, it may also reduce the effects of COVID-19 in humans. The objective of this study was to test whether HCQ can prevent or reduce the risk and severity of influenza. Methods. This is an observational cohort study using medico-administrative data from Quebec. Patients included had at least one emergency department (ED) visit in 2012 or 2013, with a prior diagnosis of chronic conditions, and were admissible to the public drug insurance plan. Two sub-cohorts were considered depending on reasons for ED visit: other than influenza or pneumonia (primary prevention) and influenza or pneumonia (secondary prevention). Results. In the primary prevention analysis (n=417,353), patients taking HCQ (n=3,659) had an increased risk of hospitalization for pneumonia in the following year compared to those who did not (5.2% vs. 2.9%; adjusted OR=1.25, p=0.0079). In the secondary prevention analysis (n=27,152), patients taking HCQ (n=392), compared to those who did not had a modest and non-significant increased risk of hospitalization for pneumonia after 30 days (25.8% vs. 22.6%; adjusted OR=1.14, p=0.3177). Interpretation: Based on the assumption that HCQ has similar effects on the COVID-19 as those observed on influenza, we can infer that it will not have positive effects on COVID-19. We should therefore act cautiously before initiating prospective interventional studies on the use of HCQ to reduce adverse effects of COVID-19.


title: Cancer is associated with the severity and mortality of patients with COVID-19: a systematic review and meta-analysis

text: Background: Cancer patients are considered a highly vulnerable population in the COVID-19 epidemic, but the relationship between cancer and the severity and mortality of patients with COVID-19 remains unclear. This study aimed to explore the prevalence of cancer in patients with COVID-19 and to examine whether cancer patients with COVID-19 may be at an increased risk of severe illness and mortality. Methods: A comprehensive electronic search in seven databases was performed, to identified studies reporting the prevalence of cancer in COVID-19 patients, or providing data of cancer between patients with severe or non-severe illness or between non-survivors and survivors. Meta-analyses were performed to estimate the pooled prevalence and odds risk (OR) using the inverse variance method with the random-effects model. Results: Thirty-four studies with 8080 patients were included. The pooled prevalence of cancer in patients with COVID-19 was 2.0% (95% CI: 2.0% to 3.0%). The prevalence in Italy (5.0%), France (6.0%), and Korea (4.0%) were higher than that in China (2.0%). Cancer was associated with a 2.84-fold significantly increased risk of severe illness (OR = 2.84, 95%CI: 1.75 to 4.62, P < 0.001) and a 2.60-fold increased risk of death (OR = 2.60, 95%CI: 1.28 to 5.26, P = 0.008) in patients with COVID-19. Sensitivity analyses showed that the results were stable after excluding studies with a sample size of less than 100. Conclusions: Cancer patients have an increased risk of COVID-19 and cancer was associated with a significantly increased risk of severity and mortality of patients with COVID-19.


title: Breadth of concomitant immune responses underpinning viral clearance and patient recovery in a non-severe case of COVID-19

text: We report the kinetics of the immune response in relation to clinical and virological features of a patient with mild-to-moderate coronavirus disease-19 (COVID-19) requiring hospitalisation. Increased antibody-secreting cells, follicular T-helper cells, activated CD4+ and CD8+ T-cells and IgM/IgG SARS-CoV-2-binding antibodies were detected in blood, prior to symptomatic recovery. These immunological changes persisted for at least 7 days following full resolution of symptoms, indicating substantial anti-viral immunity in this non-severe COVID-19.


Continuing CRISPR Patent Disputes May Be Usurped by Its Potential Role in Fighting Global Pandemics


docid: kkvylfob

title: A rejoinder to misleading articles about misleading media coverage: a case of COVID-19


Public health measures, radiotherapy, and the novel coronavirus outbreak


Maladies cardio-vasculaires chez la femme: il est temps d’agir ! Plaidoyer pour une mobilisation responsable, préventive et sociétale


title: High‐dose, short‐term corticosteroids for ARDS caused by COVID‐19: a case series

text: We report a case series of seven mechanically ventilated patients with acute respiratory distress syndrome (ARDS) caused by coronavirus disease (COVID‐19) who received early treatment with high‐dose, short‐term systemic corticosteroids to prevent cytokine overproduction. Of the seven patients, four were male and median age was 69 years. They were intubated within seven days after admission when their respiratory status rapidly worsened. At that time, we administered 1000 or 500 mg/day for three days of methylprednisolone intravenously, followed by 1 mg/kg and tapered off. The median duration for the total administration of corticosteroids was 13 days. This high‐dose, short‐term corticosteroid therapy enabled extubation of the patients within seven days. Many questions on the clinical management of COVID‐19 remain unanswered, and data on corticosteroid therapy as a choice of treatment are mixed. We present the clinical course of our cases, review the previous evidence, and discuss management.


title: A Modelling Analysis of Strategies for Relaxing COVID-19 Social Distancing

text: Abstract Background: The ability of countries to contain and control COVID-19 virus transmission via social distancing is critical in the absence of a vaccine. Early activation of robust measures has been shown to control the daily infection rate, and consequential pressure on the health care system. As countries begin to control COVID-19 spread an understanding of how to ease social distancing measures to prevent a rebound in cases and deaths is required. Methods: Using COVID-19 transmission data from the outbreak source in Hubei Province, China prior to activation of containment measures, we adapted an established individual-based simulation model of the city of Newcastle, Australia. Simulation of virus transmission in this model, with and without, social distancing measures activated permitted us to quantify social distancing effectiveness. Optimal strategies for relaxing social distancing were determined under two settings: with high numbers of daily cases, as in New York; and where early social distancing activation resulted in limited ongoing transmission, as in Perth, Australia. Findings: In countries where strong social distancing measures were activated after the COVID-19 virus had spread widely, our study found these measures are required to be maintained for significant periods before being eased, to return to a situation where daily case numbers become low. In countries where early responses to the COVID-19 pandemic have been highly successful, as in Australia, we show that a staged relaxation of social distancing prevents a rebound in cases. Interpretation: Modelling studies and direct observation have shown that robust and timely social distancing have the most effect in containing the spread of the COVID-19 virus. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society and economic activity. This study demonstrates the necessity of holding robust social distancing in place until COVID-19 virus transmission has significantly decreased, and how they may then be safely eased.


title: ICU Bed Availability Monitoring and analysis in the Grand Est region of France during the COVID-19 epidemic

text: Background: Reliable information is an essential component for responding to the COVID-19 epidemic, especially regarding the availability of critical care beds (CCBs). We propose three contributions: a) ICUBAM (ICU Bed Availability Monitor), a tool which both collects and visualizes information on CCB availability entered directly by intensivists. b) An analysis of CCB availability and ICU admissions and outcomes using collected by ICUBAM during a 6-week period in the hard-hit Grand Est region of France, and c) Explanatory and predictive models adapted to CCB availability prediction, and fitted to availability information collected by ICUBAM. Methods: We interact directly with intensivists twice a day, by sending a SMS with a web link to the ICUBAM form where they enter 8 numbers: number of free and occupied CCBs (ventilator-equipped) for both COVID-19 positive and COVID-19- negative patients, the number of COVID-19 related ICU deaths and discharges, the number of ICU refusals, and the number of patients transferred to another region due to bed shortages. The collected data are described using univariate and multivariate methods such as correspondence analysis and then modeled at different scales: a medium and long term prediction using SEIR models, and a short term statistical model to predict the number of CCBs. Results: ICUBAM was brought online March 25, and is currently being used in the Grand-Est region by 109 intensivists representing 40 ICUs (95% of ICUs). ICUBAM allows for the calculation of CCB availability, admission and discharge statistics. Our analysis of data describes the evolution and extent of the COVID-19 health crisis in the Grand-Est region: on April 6th, at maximum bed capacity, 1056 ventilator-equipped CCBs were present, representing 211% of the nominal regional capacity of 501 beds. From March 19th to March 31st, average daily COVID-19 ICU inflow was 68 patients/day, and 314 critical care patients were transferred out of the Grand-Est region. With French lockdown starting on March 17th, a decrease of the daily inflow was found starting on April 1st: 23 patients/day during the first fortnight of April, and 7 patients/day during the last fortnight. However, treatment time for COVID-19 occupied CCBs is long: 15 days after the peak on March 31st, only 20% of ICU beds have been freed (50% after 1 month). Region-wide COVID-19 related in-ICU mortality is evaluated at 31%. Models trained from ICUBAM data are able to describe and predict the evolution of bed usage for the Grand-Estregion. Conclusion: We observe strong uptake of the ICUBAM tool, amongst both physicians and local healthcare stakeholders (health agencies, first responders etc.). We are able to leverage data collected with ICUBAM to better understand the evolution of the COVID-19 epidemic in the Grand Est region. We also present how data ingested by ICUBAM can be used to anticipate CCB shortages and predict future admissions. Most importantly, we demonstrate the importance of having a cross-functional team involving physicians, statisticians and computer scientists working both with first-line medical responders and local health agencies. This allowed us to quickly implement effective tools to assist in critical decision-making processes.


title: South Africa flattens its coronavirus curve—and considers how to ease restrictions

text: With South Africa in its third week of a COVID-19 lockdown that will last at least through April, scientists advising the government gave a preview of the next phase of the response in a televised address on Monday evening They offered “a glimpse at the science behind the decision-making,” Minister of Health Zweli Mkhize said during the briefing—and a road map for reopening the country South Africa detected its first novel coronavirus infection on 5 March For the next few weeks, the epidemic followed an exponential curve similar to those in the United Kingdom, the United States, and many other countries On 15 March, the country’s president, Cyril Ramaphosa, declared a national state of emergency banning visitors from high-risk countries, stopping large gatherings, closing more than half of its land borders, and shutting schools On 27 March the country started a 21-day lockdown, closing all borders and confining everyone except those performing essential services to their homes except to buy groceries and medicine or to collect welfare payments


The sustainable development goals in a bioremediation journal context: what a difference a year makes in a post COVID-19 world!


title: Analyzing Covid-19 Data using SIRD Models

text: The goal of this analysis is to estimate the effects of the diverse government intervention measures implemented to mitigate the spread of the Covid-19 epidemic. We use a process model based on a compartmental epidemiological framework Susceptible-Infected-Recovered-Dead (SIRD). Analysis of case data with such a mechanism-based model has advantages over purely phenomenological approaches because the parameters of the SIRD model can be calibrated using prior knowledge. This approach can be used to investigate how governmental interventions have affected the Covid-19-related transmission and mortality rate during the epidemic.


title: Laboratory validation of an RNA/DNA hybrid tagmentation based mNGS workflow on SARS-CoV-2 and other respiratory RNA viruses detection

text: Background: Acute respiratory infection caused by RNA viruses is still one of the main diseases all over the world such as SARS CoV 2 and Influenza A virus. mNGS was a powerful tool for ethological diagnosis. But there were some challenges during mNGS implementation in clinical settings such as time consuming manipulation and lack of comprehensive analytical validation. Methods: We set up CATCH that was a mNGS method based on RNA and DNA hybrid tagmentation via Tn5 transposon. Seven respiratory RNA viruses and three subtypes of Influenza A virus had been used to test capabilities of CATCH on detection and quantification. Analytical performance of SARS CoV 2 and Influenza A virus had been determined with reference standards. We compared accuracy of CATCH with quantitative real time PCR by using clinical 98 samples from 64 COVID19 patients. Results: We minimized the library preparation process to 3 hours and handling time to 35 minutes. Duplicate filtered RPM of 7 respiratory viruses and 3 Influenza A virus subtypes were highly correlated with viral concentration. LOD of SARS CoV 2 was 39.2 copies/test and of Influenza A virus was 278.1 copies/mL. Comparing with quantitative real time PCR, the overall accuracy of CATCH was 91.4%. Sensitivity was 84.5% and specificity was 100%. Meanwhile, there were significant difference of microbial profile in oropharyngeal swabs among critical, moderate patients and healthy controls. Conclusion: Although further optimization is needed before CATCH can be rolled out as a routine diagnostic test, we highlight the potential impact of it advancing molecular diagnostics for respiratory pathogens.


title: From a single host to global spread. The global mobility based modelling of the COVID-19 pandemic implies higher infection and lower detection rates than current estimates.

text: Background: Since the outbreak of the COVID-19 pandemic, multiple efforts of modelling of the geo-temporal transmissibility of the virus have been undertaken, but none succeeded in describing the pandemic at the global level. We propose a set of parameters for the first COVID-19 Global Epidemic and Mobility Model (GLEaM). The simulation starting with just a single pre-symptomatic, yet infectious, case in Wuhan, China, results in an accurate prediction of the number of diagnosed cases after 125 days in multiple countries across three continents. Methods: We have built a modified SIR model and parameterized it analytically, according to the literature and by fitting the missing parameters to the observed dynamics of the virus spread. We compared our results with the number of diagnosed cases in sixeight selected countries which provide reliable statistics but differ substantially in terms of strength and speed of undertaken precautions. The obtained 95% confidence intervals for the predictions fit well to the empirical data. Findings: The parameters that successfully model the pandemic are: the basic reproduction number R0, ~4.4; a latent non-infectious period of 1.1. days followed by 4.6 days of the presymptomatic infectious period; the probability of developing severe symptoms, 0.01; the probability of being diagnosed when presenting severe symptoms of 0.6; the probability of diagnosis for cases with mild symptoms or asymptomatic, 0.001. Also, the higher the testing rate per country, the lower the discrepancy between data (diagnosed cases) and model. Interpretation: Parameters that successfully reproduce the observed number of cases indicate that both R0 and the prevalence of the virus might be underestimated. This is in concordance with the newest research on undocumented COVID-19 cases. Consequently, the actual mortality rate is putatively lower than estimated. Confirmation of the pandemic characteristic by further refinement of the model and screening tests is crucial for developing an effective strategy for the global epidemiological crisis.


Training of volunteer medical assistants for deployment during the COVID-19 pandemic. Recommendations of the BDA and DGAI/ Schulungen von freiwillig medizinischen Helfenden bei Einsatz während der COVID-19-Pandemie


title: COVID-19 in Canada: Predictions for the future and control lessons from Asia

text: COVID-19 has spread with unequal efficiency in various parts of the world. In several European countries including Italy, the increase in the number of COVID-19 cases has followed a consistent, exponential pattern of spread. However, some countries, notably Taiwan and Hong Kong, have achieved a different outcome and have managed to bring the COVID-19 outbreak in their countries rapidly under control, without entering the exponential pattern and with very few cases. They have used several different approaches to COVID-19 outbreak control, including the innovative use of smartphone technology and the widespread use of surgical face masks. We show through our models, that Canada has followed the same, consistent COVID-19 exponential growth pattern that is seen in Italy. Both nationally and in its most heavily affected provinces, there is exponential growth of COVID-19 cases, making it possible to make predictions for the future, if no further interventions are made in public health policy. In particular, we argue for the urgent introduction of surgical face masks in health care and other settings and the harnessing of the power of smartphone technology on a national scale.


title: Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex

text: SARS-CoV-2 is the causative agent of the 2019-2020 pandemic. The SARS-CoV-2 genome is replicated-transcribed by the RNA-dependent RNA polymerase holoenzyme (subunits nsp7/nsp82/nsp12) along with a cast of accessory factors. One of these factors is the nsp13 helicase. Both the holo-RdRp and nsp13 are essential for viral replication and are targets for treating the disease COVID-19. Here we present cryo-electron microscopic structures of the SARS-CoV-2 holo-RdRp with an RNA template-product in complex with two molecules of the nsp13 helicase. The Nidovirus-order-specific N-terminal domains of each nsp13 interact with the N-terminal extension of each copy of nsp8. One nsp13 also contacts the nsp12-thumb. The structure places the nucleic acid-binding ATPase domains of the helicase directly in front of the replicating-transcribing holo-RdRp, constraining models for nsp13 function. We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapeutic development.


Covid-19 pandemic: Will a vaccine be available soon?


title: AKI during COVID-19 infection: low incidence, high risk of death

text: Background: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide and seriously threatens human health since December 2019. However, information about acute kidney injury (AKI) during COVID-19 infection is limited. Some studies thought that presence of AKI is very common and cannot be ignored, while some studies pointed that AKI only is a rare incident during COVID-19 infection. This meta-analysis aimed to find out the truth of COVID-19 related AKI and to provide stronger evidence. Methods: Two authors independently performed a literature search using PubMed, Web of Science, Embase, and Cochrane Library fulfilled the pre-specified criteria until April 25, 2020 to include studies reported the necessary clinic characteristics, then the incidence of AKI, incidence of required RRT, the mortality with AKI and the death risk with AKI during COVID-19 infection were pooled for statistical analysis by Open Meta-Analyst software to get conclusions. Findings: It was found that the incidence of AKI in hospitalized patients with COVID-19 infection is low, only about 3.8%; the in-hospital mortality with AKI in COVID-19 infected patients is reach up to 32.6%; the death risk with AKI in COVID-19 infected patients is about 16.1 times higher than those without AKI. Conclusions: This meta-analysis indicated AKI during COVID-19 infection should be pay more attention, it maybe a strong red flag to death risk. It is still need additional studies to support the conclusions and to explore the AKI mechanism during COVID-19 infection.


title: A cross-sectional study of immune seroconversion to SARS-CoV-2 in front-line maternity health professionals

text: COVID-19, the respiratory disease caused by the SARS-CoV-2, is thought to cause a milder illness in pregnancy with a greater proportion of asymptomatic carriers. This has important implications for the risk of patient-to-staff, staff-to-staff and staff-to patient transmission among health professionals in maternity. The aim of this study was to investigate the prevalence of previously undiagnosed SARS-CoV-2 infection in health professionals from two tertiary-level maternity units in London, UK and to determine associations between HCW characteristics, reported symptoms and serological evidence of prior SARS-CoV-2 infection. 200 anaesthetists, midwives and obstetricians with no previously confirmed diagnosis of COVID-19 were tested for immune seroconversion using laboratory IgG assays. Comprehensive symptom and medical histories were also collected. 5/40 (12.5%; 95% CI: 4.2-26.8) anaesthetists, 7/52 (13.5%; 95% CI: 5.6-25.8%) obstetricians and 17/108 (15.7%; 95% CI: 9.5-24.0%) midwives were seropositive, with an overall total of 29/200 (14.5%; 95% CI: 9.9-20.1%) of maternity healthcare workers testing positive for IgG antibodies against SARS-CoV-2. Of those who had seroconverted, 10/29 (35.5%) were completely asymptomatic. Fever or cough were only present in 6/29 (20.7%) and (10/29 (34.5%) respectively. Anosmia was the most common symptom occurring in 15/29 (51.7%) seropositive participants and was the only symptom that was predictive of positive seroconversion (OR 18; 95% CI 6 to 55). 58.6% of those who were seropositive had not self-isolated at any point and continued to provide patient care in the hospital setting. This study was the largest study of baseline immune seroconversion in maternity healthcare workers conducted to date and reveals that 1 in 6 were seropositive, of whom 1 in 3 were asymptomatic. This has significant implications for the risk of occupational transmission of SARS-CoV-2 for both staff and patients in maternity and regular testing of staff, including asymptomatic staff should be considered to reduce transmission risk.


title: Animal Model Prescreening: Pre-exposure to SARS-CoV-2 impacts responses in the NHP model

text: COVID-19 presents herculean challenges to research and scientific communities for producing diagnostic and treatment solutions. Any return to normalcy requires rapid development of countermeasures, with animal models serving as a critical tool in testing vaccines and therapeutics. Animal disease status and potential COVID-19 exposure prior to study execution may severely bias efficacy testing. We developed a toolbox of immunological and molecular tests to monitor countermeasure impact on disease outcome and evaluate pre-challenge COVID-19 status. Assay application showed critical necessity for animal pre-screening. Specifically, real-time PCR results documented pre-exposure of an African Green Monkey prior to SARS-CoV-2 challenge with sequence confirmation as a community-acquired exposure. Longitudinal monitoring of nasopharyngeal swabs and serum showed pre-exposure impacted both viral disease course and resulting immunological response. This study demonstrates utility in a comprehensive pre-screening strategy for animal models, which captured the first documented case of community-acquired, non-human primate infection. One Sentence Summary Pre-exposure to SARS-CoV-2 affects biomarker responses in animal models, highlighting a need for robust pre-screening protocols prior to medical countermeasure studies.


title: Defining Facets of Social Distancing during the COVID-19 Pandemic: Twitter Analysis

text: Social distancing has been one of the primary mitigation strategies in the United States to control the spread of novel coronavirus disease (COVID-19) and can be viewed as a multi-faceted public health measure. Using Twitter data, we aim to (1) define and quantify the prevalence and evolution of facets of social distancing during the COVID-19 pandemic in the US in a spatiotemporal context and (2) examine the most amplified tweets among social distancing facets. We analyzed a total of 259,529 unique tweets containing "coronavirus" from 115,485 unique users between January 23, 2020 and March 24, 2020 that were identified by the Twitter API as English and U.S.-based. Tweets containing specified keywords (determined a priori) were grouped into six social distancing facets: implementation, purpose, social disruption, adaptation, positive emotions, and negative emotions. Tweets about social disruptiveness were most retweeted, and implementation tweets were most favorited. Social distancing tweets became overall more prevalent in the U.S. from late January to March but were not geographically uniform. In January and February, facets of social distancing appeared in Los Angeles, San Francisco, and Seattle, which were among the first cities impacted by the COVID-19 outbreak. Tweets related to the "implementation" and "negative emotions" facets of social distancing largely dominated in combination with topics of "social disruption" and "adaptation", albeit to a lesser degree. Social distancing can be defined in terms of facets that respond and represent certain moments and events in a pandemic, including travel restrictions and rising COVID-19 case counts. For example, in February, Miami, FL had a low volume of social distancing tweets but grew in March which corresponded with the rise of COVID-19 cases in the city. This suggests that overall volume of social distancing tweets can reflect the relative case count in respective locations.


title: Detection of SARS-CoV-2 in pets living with COVID-19 owners diagnosed during the COVID-19 lockdown in Spain: A case of an asymptomatic cat with SARS-CoV-2 in Europe

text: During April-May 2020, the presence of respiratory syndrome coronavirus 2 (SARS-CoV-2) in pets living with coronavirus disease 2019 (COVID-19) owners was analyzed. From 23 pets, a cat without clinical symptoms showed positive results for SARS-CoV-2 in oropharyngeal swab using three RT-qPCR assays (negative rectal swab). SARS-CoV-2 was not detected in the remaining pets. Our finding suggests that cats may act as asymptomatic dispersers of SARS-CoV-2, although viral transmission from animals to humans seems unlikely.


title: The interpretation of Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia

text: A coronavirus disease 2019 (COVID-19) outbreak has occurred in Wuhan, Hubei province since Dec. 2019. As of Feb. 10, 2020, more than 40,000 cases had been confirmed, nearly 30,000 cases in Hubei alone, and no inflection point in epidemiology appeared. Severe trauma may still occur during the outbreak of the COVID-19. In order to protect the medical personnel involved in emergency treatment and ensuring the timeliness of treatment for trauma patients, The Trauma Surgery Branch of Chinese Medical Doctors' Association (CMDA) organized the drafting of the present expert consensus. This paper interprets the main views of the expert consensus, emphasizes that the safety of health care staff and patients are equally important, and that the treatment strategies and procedures for severe trauma need to be adjusted during the COVID-19 outbreak. The consensus also recommends the use of CT scan, which plays both the role of screening COVID-19 and accurate assessment of trauma, and strengthening the protection of medical staff. The consensus states that medical personnel can be exempted from isolation if they wear standard three-level protective equipment and are not accidentally exposed during the operation. This expert consensus is the first one to systematically review, summarize and analyze the progress of COVID-19 from a surgeon's perspective. It may be used as a reference for medical institutions at all levels to treat patients with severe trauma and perform other kinds of operations during the COVID-19 outbreak.


title: Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis

text: Background: Recently, Coronavirus Disease 2019 (COVID-19) outbreak started in Wuhan, China. Although the clinical features of COVID-19 have been reported previously, data regarding the risk factors associated with the clinical outcomes are lacking. Objectives: To summary and analyze the clinical characteristics and identify the predictors of disease severity and mortality. Methods: The PubMed, Web of Science Core Collection, Embase, Cochrane and MedRxiv databases were searched through February 25, 2020. Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendations were followed. We extracted and pooled data using random-effects meta-analysis to summary the clinical feature of the confirmed COVID-19 patients, and further identify risk factors for disease severity and death. Heterogeneity was evaluated using the I2 method and explained with subgroup analysis and meta-regression. Results: A total of 30 studies including 53000 patients with COVID-19 were included in this study, the mean age was 49.8 years (95% CI, 47.5-52.2 yrs) and 55.5% were male. The pooled incidence of severity and mortality were 20.2% (95% CI, 15.1-25.2%) and 3.1% (95% CI, 1.9-4.2%), respectively. The predictor for disease severity included old age (≥ 50 yrs, odds ratio [OR] = 2.61; 95% CI, 2.29-2.98), male (OR =1.348, 95% CI, 1.195-1.521), smoking (OR =1.734, 95% CI, 1.146-2.626) and any comorbidity (OR = 2.635, 95% CI, 2.098-3.309), especially chronic kidney disease (CKD, OR = 6.017; 95% CI, 2.192-16.514), chronic obstructive pulmonary disease (COPD, OR = 5.323; 95% CI, 2.613-10.847) and cerebrovascular disease (OR = 3.219; 95% CI, 1.486-6.972). In terms of laboratory results, increased lactate dehydrogenase (LDH), C-reactive protein (CRP) and D-dimer and decreased blood platelet and lymphocytes count were highly associated with severe COVID-19 (all for P < 0.001). Meanwhile, old age (≥ 60 yrs, RR = 9.45; 95% CI, 8.09-11.04), followed by cardiovascular disease (RR = 6.75; 95% CI, 5.40-8.43) hypertension (RR = 4.48; 95% CI, 3.69-5.45) and diabetes (RR = 4.43; 95% CI, 3.49-5.61) were found to be independent prognostic factors for the COVID-19 related death. Conclusions: To our knowledge, this is the first evidence-based medicine research to explore the risk factors of prognosis in patients with COVID-19, which is helpful to identify early-stage patients with poor prognosis and adapt effective treatment.


title: COVID-19 Related Mortality: Is the BCG Vaccine Truly Effective?

text: The coronavirus disease 2019 (COVID-19) pandemic has become a worldwide emergency. In the attempt to search for interventions that would improve outcomes, some studies have looked at the potential benefit of BCG vaccination. These past studies have found a statistically significant reduction in COVID-19 related mortality in countries with a current universal bacille Calmette-Guerin (BCG) vaccination policy. However, just as the authors themselves noted, the nature of ecological studies make them very prone to the presence of several confounders. This paper took into account demographic differences, economic differences and the different stages of the pandemic in each country; gathering data from publicly available sources. It was found that no statistically significant difference exists in mortality rates between countries with a current or prior BCG vaccination policy when compared to those that never had such a program. Nevertheless, the immunostimulatory potential of the BCG vaccine might still prove useful in the development of future vaccines or other prophylactic measures.


title: The time-series ages distribution of the reported COVID-2019 infected people suggests the undetected local spreading of COVID-2019 in Hubei and Guangdong provinces before 19th Jan 2020

text: COVID-2019 is broken out in China. It becomes a severe public health disaster in one month. Find the period in which the spreading of COVID-2019 was overlooked, and understand the epidemiological characteristics of COVID-2019 in the period will provide valuable information for the countries facing the threats of COVID-2019. The most extensive epidemiological analysis of COVID-2019 shows that older people have lower infection rates compared to middle-aged persons. Common sense is that older people prefer to report their illness and get treatment from the hospital compared to middle-aged persons. We propose a hypothesis that when the spreading of COVID-2019 was overlooked, we will find more older cases than the middle-aged cases. At first, we tested the hypothesis with 4597 COVID-2019 infected samples reported from 26th Nov 2019 to 17th Feb 2020 across the mainland of China. We found that 19th Jan 2020 is a critical time point. Few samples were reported before that day, and most of them were older ones. Then samples were explosively increased after that day, and many of them were middle-aged people. We have demonstrated the hypothesis to this step. Then, we grouped samples by their residences(provinces). We found that, in the provinces of Hubei and Guangdong, the ages of samples reported before 19th Jan 2020 are significantly higher than the ages of samples reported after that day. It suggests the COVID-2019 may be spreading in Hubei and Guangdong provinces before 19th Jan 2020 while people were unconscious of it. At last, we proposed that the ages distribution of each-day-reported samples could serve as a warning indicator of whether all potential COVID-2019 infected people are found. We think the power of our analysis is limit because 1. the work is data-driven, and 2. only ~5% of the COVID-2019 infected people in China are included in the study. However, we believe it still shows some value for its ability to estimate the possible unfound COVID-2019 infected people.


title: Does weather affect the growth rate of COVID-19, a study to comprehend transmission dynamics on human health

text: The undefendable outbreak of novel coronavirus (SARS-COV-2) lead to a global health emergency due to its higher transmission rate and longer symptomatic duration, created a health surge in a short time. Since Nov 2019 the outbreak in China, the virus is spreading exponentially everywhere. The current study focuses on the relationship between environmental parameters and the growth rate of COVID-19. The statistical analysis suggests that the temperature changes retarded the growth rate and found that -6.28{degrees}C and +14.51{degrees}C temperature is the favorable range for COVID-19 growth. Gutenberg- Richter's relationship is used to estimate the mean daily rate of exceedance of confirmed cases concerning the change in temperature. Temperature is the most influential parameter that reduces the growth at the rate of 13-16 cases/day with a 1{degrees}C rise in temperature.


title: Personal Protective Equipment N95 Facemask Shortage Quick Fix: The Modified Airway From VEntilatoR Circuit (MAVerIC)

text: We are in a crisis where healthcare providers on the frontlines are running out of the appropriate personal protective equipment including N95 masks and power air-purifying respirators. Here, we propose a makeshift filter mask that we call the Modified Airway from VEntilatoR Circuit (MAVerIC) that can be assembled within seconds using widely available supplies routinely utilized by anesthesia providers in the operating room to provide practitioners on the frontlines with the high standard of protection of a N95 mask during the coronavirus disease 2019 (COVID-19) pandemic, and can be easily quantitatively “fit tested” to ensure no significant leak to optimize safety and efficacy.


title: Ultra-Low-Cost Integrated Silicon-based Transducer for On-Site, Genetic Detection of Pathogens

text: Rapid screening and low-cost diagnosis play a crucial role in choosing the correct course of intervention e.g., drug therapy, quarantine, no action etc. when dealing with highly infectious pathogens. This is especially important if the disease-causing agent has no effective treatment, such as the novel coronavirus SARS-CoV-2 (the pathogen causing COVID-19), and shows no or similar symptoms to other common infections. We report a silicon-based integrated Point-of-Need (PoN) transducer (TriSilix) that can chemically-amplify and detect pathogen-specific sequences of nucleic acids (NA) quantitatively in real-time. Unlike other silicon-based technologies, TriSilix can be produced at wafer-scale in a standard laboratory; we have developed a series of methodologies based on metal-assisted chemical (wet) etching, electroplating, thermal bonding and laser-cutting to enable a cleanroom-free low-cost fabrication that does not require processing in an advanced semiconductor foundry. TriSilix is, therefore, resilient to disruptions in the global supply chain as the devices can be produced anywhere in the world. To create an ultra-low-cost device, the architecture proposed exploits the intrinsic properties of silicon and integrates three modes of operation in a single chip: i) electrical (Joule) heater, ii) temperature sensor (i.e. thermistor) with a negative temperature coefficient that can provide the precise temperature of the sample solution during reaction and iii) electrochemical sensor for detecting target NA. Using TriSilix, the sample solution can be maintained at a single, specific temperature (needed for isothermal amplification of NA such as Recombinase Polymerase Amplification (RPA) or cycled between different temperatures (with a precision of ±1.3°C) for Polymerase Chain Reaction (PCR) while the exact concentration of amplicons is measured quantitatively and in real-time electrochemically. A single 4-inch Si wafer yields 37 TriSilix chips of 10×10×0.65 mm in size and can be produced in 7 hours, costing ~US $0.35 per device. The system is operated digitally, portable and low power – capable of running up to 35 tests with a 4000 mAh battery (a typical battery capacity of a modern smartphone). We were able to quantitatively detect a 563-bp fragment (Insertion Sequence IS900) of the genomic DNA of M. avium subsp. paratuberculosis (extracted from cultured field samples) through PCR in real-time with a Limit-of-Detection of 20 fg, equivalent to a single bacterium, at the 30th cycle. Using TriSilix, we also detected the cDNA from SARS-CoV-2 (1 pg), through PCR, with high specificity against SARS-CoV (2003).


title: Understanding COVID-19 spreading through simulation modeling and scenarios comparison: preliminary results.

text: Since late 2019 the world is facing the rapid spreading of a novel viral disease (SARS-CoV-2) provoked by the coronavirus 2 infection (COVID-19), declared pandemic last 12 March 2020. As of 27 March 2020, there were more than 500,000 confirmed cases and 23,335 deaths worldwide. In those places with a rapid growth in numbers of sick people in need of hospitalization and intensive care, this demand has over-saturate the medical facilities and, in turn, rise the mortality rate. In the absence of a vaccine, classical epidemiological measures such as testing, quarantine and physical distancing are ways to reduce the growing speed of new infections. Thus, these measures should be a priority for all governments in order to minimize the morbidity and mortality associated to this disease. System dynamics is widely used in many fields of the biological sciences to study and explain changing systems. The system dynamics approach can help us understand the rapid spread of an infectious disease such as COVID-19 and also generate scenarios to test the effect of different control measures. The aim of this study is to provide an open model (using STELLA® from Iseesystems) that can be customized to any area/region and by any user, allowing them to evaluate the different behavior of the COVID-19 dynamics under different scenarios. Thus, our intention is not to generate a model to accurately predict the evolution of the disease nor to supplant others more robust -official and non-official- from governments and renowned institutions. We believe that scenarios comparison can be an effective tool to convince the society of the need of a colossal and unprecedented effort to reduce new infections and ultimately, fatalities.


title: SARS-CoV-2 infection among returnees on charter flights to Japan from Hubei, China: a report from National Center for Global Health and Medicine

text: Due to the significant spread of a new type of coronavirus (SARS-CoV-2) infection (COVID-19) in China, the Chinese government blockaded several cities in Hubei Province Japanese citizens lost a means of transportation to return back to Japan The National Center for Global Health and Medicine (NCGM) helped the operation of charter flights for evacuation of Japanese residents from Hubei Province, and this article outlines our experiences A total of five charter flights were dispatched, and the majority of returnees (793/829 [95 7%]) were handled at NCGM A large number of personnel from various departments participated in this operation;107 physicians, 115 nurses, 110 clerical staff, and 45 laboratory technicians in total Several medical translators were also involved In this operation, we conducted airborne precautions in addition to contact precautions Eye shields were also used The doctors collecting the pharyngeal swab used a coverall to minimize the risk of body surface contamination from secretions and droplets Enhanced hand hygiene using alcohol hand sanitizer was performed Forty-eight persons were ultimately hospitalized after the triage at NCGM operation, which was more than the number of persons triaged at the airport (n = 34) Of those hospitalized after NCGM triage, 8 3% (4/48 patients) ultimately tested positive for SARS-CoV-2, significantly higher than the positive rate among subjects not triaged (4/48 [8 3%] vs 9/745 [1 2%]: p = 0 0057) NCGM participated in a large-scale operation to evacuate Japanese nationals from the COVID-19 epidemic area We were able to establish a scheme through this experience that can be used in the future


title: Efficacy and Safety of Leflunomide for Refractory COVID-19: An Open-label Controlled Study

text: OBJECTIVE To evaluate the safety and efficacy of leflunomide for the treatment of refractory COVID-19 in adult patients. DESIGN Open-label controlled study SETTING A designated hospital for patients with refractory COVID-19 in Wuhan, China. PARTICIPANTS 27 hospitalized adult patients ([≥]18 years of age) with radiologically confirmed pneumonia and SARS-CoV-2 positive for more than 28 days despite standard care were assigned to receive standard of care (SOC, grp I) or leflunomide + SOC (grp 2). After 2 weeks, grp 1 and grp 2 patients who continued to be SARS-CoV-2-positive received leflunomide for 14 days while continuing SOC. MAIN OUTCOME MEASURES The primary outcomes were the rate of and time to SARS-CoV-2 clearance and the 14-day and 30-day hospital discharge rate. RESULTS Twelve patients enrolled in grp 1 and 15 patients were in grp 2. The 14 days SARS-CoV-2 viral clearance rate was 80.0% (12/15) for grp 2 patients receiving leflunomide versus 16.7% for grp 1 patients (2/12) (P=0.002). By day 14, the median time to SARS-CoV-2 clearance was 6.0 days (range 1-12; IQR 1-12) for grp 2 patients. In grp 1, two patients converted to viral negative on days 1 and 6 (P=0.002). The 14-day discharge rate was 73.3% (11/15) for the grp 2 versus 8.3% (1/12) for grp 1 (P=0.001). The 30-day discharge rate was 100% (15/15) for the grp 2 versus 66.7% (8/12) for grp 1. No severe adverse events or deaths were reported. CONCLUSION Leflunomide is effective in enhancing SARS-CoV-2 clearance and hospital discharge in refractory COVID-19 patients. The addition of leflunomide to SOC did not increase adverse events versus SOC. These preliminary observations underscore a need for a randomized clinical study of leflunomide in SARS-CoV-2 infection.


title: The worldwide air transportation network: Anomalous centrality, community structure, and cities' global roles

text: We analyze the global structure of the world-wide air transportation network, a critical infrastructure with an enormous impact on local, national, and international economies. We find that the world-wide air transportation network is a scale-free small-world network. In contrast to the prediction of scale-free network models, however, we find that the most connected cities are not necessarily the most central, resulting in anomalous values of the centrality. We demonstrate that these anomalies arise because of the multi-community structure of the network. We identify the communities in the air transportation network and show that the community structure cannot be explained solely based on geographical constraints, and that geo-political considerations have to be taken into account. We identify each city's global role based on its pattern of inter- and intra-community connections, which enables us to obtain scale-specific representations of the network.