title: Estimating the Efficacy of Traffic Blockage and Quarantine for the Epidemic Caused by 2019-nCoV (COVID-19)

text: Background: Since the 2019-nCoV (COVID-19) outbreaks in Wuhan, China, the cumulative number of confirmed cases is increasing every day, and a large number of populations all over the world are at risk. The quarantine and traffic blockage can alleviate the risk of the epidemic and the infections, henceforth evaluating the efficacy of such actions is essential to inform policy makers and raise the public awareness of the importance of self-isolation and quarantine. Method: We collected confirmed case data and the migration data, and introduced the quarantine factor and traffic blockage factor to the Flow-SEIR model. By varying the quarantine factor and traffic blockage factor, we simulated the change of the peak number and arrival time of infections, then the efficacy of these two intervation measures can be analyzed in our simulation. In our study, the self-protection at home is also included in quarantine. Results: In the simulated results, the quarantine and traffic blockage are effective for epidemic control. For Hubei province, the current quarantine factor is estimaed to be 0.405, which means around 40.5% of suceptibles who are close contacting with are in quarantine, and the current traffic blockage factor is estimaed to be 0.66, which indicates around 34% of suceptibles who had flowed out from Hubei. For the other provinces outside Hubei, the current quarantine factor is estimated to be 0.285, and the current traffic blockage factor is estimated to be 0.26. With the quarantine and traffic blockage factor increasing, the number of infections decrease dramatically. We also simulated the start dates of quarantine and traffic blockage at four time points, the simulated results show that the early of warning is also effective for epidemic containing. However, provincial level traffic blockage can only alleviate 21.06% - 22.38% of the peak number of infections. In general, the quarantine is much more effective than the traffic blockage control. Conclusion: Both of quarantine and traffic blockage are effective ways to control the spread of COVID-19. However, the eff icacy of quarantine is found to be much stronger than that of traffic blockage. Considering traffic blockage may also cause huge losses of economy, we propose to gradually deregulate the traffic blockage, and improve quarantine instead. Also, there might be a large number of asymptomatic carriers of COVID-19, the quarantine should be continued for a long time until the epidemic is totally under control.


title: Effect of a one-month lockdown on the epidemic dynamics of COVID-19 in France

text: The COVID-19 epidemic started in the Hubei province in China in December 2019 and then spread around the world reaching the pandemic stage at the beginning of March 2020. Since then, several countries went into lockdown. We estimate the effect of the lockdown in France on the contact rate and the effective reproduction number Re of the COVID-19. We obtain a reduction by a factor 7 (Re=0.47, 95%-CI: 0.45-0.50), compared to the estimates carried out in France at the early stage of the epidemic. We also estimate the fraction of the population that would be infected by the beginning of May, at the official date at which the lockdown should be relaxed. We find a fraction of 3.7% (95%-CI: 3.0-4.8%) of the total French population, without taking into account the number of recovered individuals before April 1st, which is not known. This proportion is seemingly too low to reach herd immunity. Thus, even if the lockdown strongly mitigated the first epidemic wave, keeping a low value of Re is crucial to avoid an uncontrolled second wave (initiated with much more infectious cases than the first wave) and to hence avoid the saturation of hospital facilities. Our approach is based on the mechanistic-statistical formalism, which uses a probabilistic model to connect the data collection process and the latent epidemiological process, which is described by a SIR-type differential equation model.


title: Clinical significance of IgM and IgG test for diagnosis of highly suspected COVID-19 infection

text: Quick, simple and accurate diagnosis of suspected COVID-19 is very important for the screening and therapy of patients. Although several methods were performed in clinical practice, however, the IgM and IgG diagnostic value evaluation was little performed. 57 suspected COVID-19 infection patients were enrolled in our study. 24 patients with positive and 33 patients with negative nucleic acid test. The positive rate of COVID-19 nucleic acid was 42.10%. The positive detection rate of combination of IgM and IgG for patients with COVID-19 negative and positive nucleic acid test was 72.73% and 87.50%. The results were significantly higher than the nucleic acid or IgM, IgG single detection. hsCRP in the COVID-19 nucleic acid negative group showed significantly higher than the positive groups (P=0.0298). AST in the COVID-19 IgM negative group showed significantly lower than the positive groups (P=0.0365). We suggest a quick, simple, accurate aided detection method for the suspected patients and on-site screening in close contact with the population.


title: Traces of SARS-CoV-2 RNA in the Blood of COVID-19 Patients

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third virus that caused coronavirus-related outbreaks over the past 20 years. The outbreak was first reported in December 2019 from Wuhan, China, but rapidly progressed into a pandemic of an unprecedented scale since the 1918 flu pandemic. In addition to respiratory complications in COVID-19 patients, clinical characterizations of severe infection cases indicated a number of other comorbidities, including multiple organ failure (liver, kidney, and heart) and septic shock. In an attempt to elucidate COVID-19 pathogenesis in different human organs, we interrogated the presence of the virus in the blood, or any of its components, which might provide a form of trafficking or hiding to the virus. By computationally analyzing high-throughput sequence data from patients with active COVID-19 infection, we found evidence of traces of SARS-CoV-2 RNA in peripheral blood mononuclear cells (PBMC), while the virus RNA was abundant in bronchoalveolar lavage specimens from the same patients. To the best of our knowledge, the presence of SAR-CoV-2 RNA in the PBMC of COVID-19 patients has not been reported before, and this observation could suggest immune presentation, but discounts the possibility of extensive viral infection of lymphocytes or monocytes.


title: AN AFFORDABLE ANTI-SARS-COV-2 SPIKE ELISA TEST FOR EARLY DETECTION OF IgG SEROCONVERSION SUITED FOR LARGE-SCALE SURVEILLANCE STUDIES IN LOW-INCOME COUNTRIES

text: We describe a cost-effective, scalable technology to produce SARS-COV-2 spike (S) protein based on stable expression in HEK293 cells, and its use to develop a highly specific and sensitive ELISA test. The assay allows early detection of anti-S IgG seroconversion and endpoint titers correlate with virus neutralization. The low-cost S-antigen production, together with sample collection by finger prick and dried blood spots, allowed the development of a half-dollar test that fits the urgent need for large-scale serological surveillance in low-income countries.


title: A Highly Scalable and Rapidly Deployable RNA Extraction-Free COVID-19 Assay by Quantitative Sanger Sequencing

text: There is currently an urgent unmet need to increase coronavirus disease 2019 (COVID-19) testing capability to effectively respond to the COVID-19 pandemic. However, the current shortage in RNA extraction reagents as well as limitations in qPCR protocols have resulted in bottlenecks in testing capacity. Herein, we describe a novel molecular diagnostic for COVID-19 based on Sanger sequencing. This assay uses the addition of a frame-shifted spike-in, a modified PCR master mix, and custom Sanger sequencing data analysis to detect and quantify SARS-CoV-2 RNA at a limit of detection comparable to existing qPCR-based assays, at 10-20 genome copy equivalents. Crucially, our assay was able to detect SARS-CoV-2 RNA from viral particles suspended in transport media that was directly added to the PCR master mix, suggesting that RNA extraction can be skipped entirely without any degradation of test performance. Since Sanger sequencing instruments are widespread in clinical laboratories and commonly have built-in liquid handling automation to support up to 3840 samples per instrument per day, the widespread adoption of qSanger COVID-19 diagnostics can unlock more than 1,000,000 tests per day in the US.


title: SARS-CoV-2 proteins exploit host’s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology

text: The constant rise of the death toll and cases of COVID-19 has made this pandemic a serious threat to human civilization. Understanding of host-SARS-CoV-2 interaction in viral pathogenesis is still in its infancy. In this study we aimed to correlate how SARS-CoV-2 utilizes its proteins for tackling the host immune response; parallelly, how host epigenetic factors might play a role in this pathogenesis was also investigated. We have utilized a blend of computational and knowledgebase approach to elucidate the interplay between host and SARS-CoV-2. Integrating the experimentally validated host interactome proteins and differentially expressed host genes due to SARS-CoV-2 infection, we have taken a blend of computational and knowledgebase approach to delineate the interplay between host and SARS-CoV-2 in various signaling pathways. Also, we have shown how host epigenetic factors are involved in the deregulation of gene expression. Strikingly, we have found that several transcription factors and other epigenetic factors can modulate some immune signaling pathways, helping both host and virus. We have identified miRNA hsa-miR-429 whose transcription factor was also upregulated and targets were downregulated and this miRNA can have pivotal role in suppression of host immune responses. While searching for the pathways in which viral proteins interact with host proteins, we have found pathways like-HIF-1 signaling, autophagy, RIG-I signaling, Toll-like receptor signaling, Fatty acid oxidation/degradation, Il-17 signaling etc significantly associated. We observed that these pathways can be either hijacked or suppressed by the viral proteins, leading to the improved viral survival and life-cycle. Moreover, pathways like-Relaxin signaling in lungs suggests aberration by the viral proteins might lead to the lung pathophysiology found in COVID-19. Also, enrichment analyses suggest that deregulated genes in SARS-CoV-2 infection are involved in heart development, kidney development, AGE-RAGE signaling pathway in diabetic complications etc. might suggest why patients with comorbidities are becoming more prone to SARS-CoV-2 infection. Our results suggest that SARS-CoV-2 integrates its proteins in different immune signaling pathway and other cellular signaling pathways for developing efficient immune evasion mechanisms, while leading the host to more complicated disease condition. Our findings would help in designing more targeted therapeutic interventions against SARS-CoV-2.


title: Prediction of Stability Lobe Diagrams in High-Speed Milling by Operational Modal Analysis

text: Abstract Self-excited regenerative vibration or chatter limits the primary requirements like productivity, surface finish and dimensional accuracy of high-speed machining. It is the most critical factor that severely affects the tool-life and life of the machine tool. Out of several methods followed for suppressing and avoiding chatter, machining conditions chosen with stability lobe diagram is the most reliable way. Stability lobe diagrams are typically generated by knowing specific cutting force coefficients and tool point frequency response functions (FRFs). Inaccurate use of tool point FRFs significantly affects the stable regions of stability lobe diagrams. As tool-point FRFs are influenced by gyroscopic effect, centrifugal force, thermal change in bearing dynamics, etc. during machining, it is important to consider the effect of these factors on tool point FRFs in order to generate accurate stability lobe diagrams. The present work covers a new approach for estimating tool point FRFs during machining operations, employing cutting tool vibration signals. For measuring the vibration at the tip of end mill at different spindle speeds, a non-contact laser vibrometer is used. In order to remove the tooth pass frequency and its harmonics from the measured signals, a comb filter is employed. The filtered signal is subjected to Operational Modal Analysis (OMA) in order to derive tool point FRFs. With the estimated FRFs at different spindle speeds, the stability lobe diagrams are drawn for high-speed milling machine. Comparative study of stability lobe diagrams, drawn with static modal analysis and Operational Modal Analysis, have shown that the cutting conditions chosen from stability lobe diagram derived with OMA, are found to be more realistic for avoiding chatter during high-speed milling applications.


title: Quantifying the social distancing privilege gap: a longitudinal study of smartphone movement

text: Background: In response to the coronavirus pandemic, social distancing became a widely deployed countermeasure in March 2020. We examined whether healthier and wealthier places more successfully implemented social distancing. Methods: Mobile device location data were used to quantify declines in movement by county (n=2,633) in the United States of America, comparing April 15-17 (n=65,544,268 traces) to baseline of February 17 - March 7. Negative binomial regression was used to estimate gradients of privilege across eleven healthcare and economic indicators, adjusting for rurality and stay-at-home mandates. External validation used separate venue-specific data from Google Location Services. Findings: Counties without stay-at-home orders showed a mobility decline of -52.3% (95% CI: -50.3%, -54.3%), slightly less than the decline in mandated areas (-60.8%; 95% CI: -60.0%, -61.6%). Strong linear gradients in privilege were observed. After adjusting for rurality and stay-at-home orders, counties in the highest quintile of social distancing mobility restriction had: 52% less uninsured, 47% more primary care providers, 29% more exercise space, 27% less food insecurity, 26% less child poverty, 17% higher incomes, 14% less overcrowding, 9.6% more racial segregation, 8.2% less youth, 7.4% more elderly, and 6.2% less influenza vaccination, compared to least social distancing areas. Interpretation: Healthier and wealthier counties displayed a social distancing privilege gap, measured via smartphone mobility change. Structural inequities in this key countermeasure will influence immunity, and disease incidence and mortality.


title: Universal Features of Epidemic Models Under Social Distancing Guidelines

text: Different epidemiological models, from the classical SIR system to more sophisticated ones involving population compartments for socially distanced, quarantined, infection aware, asymptomatic infected, and other individuals, share some remarkable dynamic characteristics when contact rates are subject to periodic or one-shot changes. In simple pulsed isolation policies, a linear relationship is found among optimal start time and duration for reduction of the infected peak. If a single interval social distancing starts too early or too late it will be ineffective with respect to decreasing the peak of infection. On the other hand, the nonlinearity of epidemic models leads to non-monotone behavior of the peak of infected population under periodic relaxation policies. This observation led us to hypothesize that an additional single interval social distancing at a proper time can significantly decrease the infected peak of periodic policies, and we verified this improvement.


title: Verification of two Alternative Do-it-yourself Equipment Respirators Seal as COVID-19 Protection (VADERS-CoV): a quality assessment pilot study

text: Background During the ongoing COVID-19 pandemic, healthcare workers are facing shortage in personal protective equipment, especially adequate respirators. Alternative do-it-yourself respirators (ADR) emerge, without any proof of protection. Objective Verify seal potential of two ADR compared to a common FFP2 respirator. Design Quality assessment pilot study. Setting Tertiary Care Hospital. Participants Ten anaesthesiology residents. Interventions Participants performed quantitative face-fit tests (QNFT) with three respirators to evaluate seal. A common FFP2 respirator was used as baseline (control group). ADR tested in this study are an Anaesthesia Face Mask (AFM) and a full-face Modified Snorkelling Mask (MSM) with a 3D-printed connector, both in conjunction with a breathing system filter. Main outcome measures Non-inferior seal performance of ADR over FFP2, assessed by calculated QNFT based on measured individual fit factors, as defined by the Occupational Safety and Health Administration. Results For each respirator a total of 90 individual fit factor measurements were taken. Within the control group, seal failed in 37 (41%) measurements but only in 10 (11%) within the AFM group and in 6 (7%) within the MSM group (P < 0.001 respectively). However, when calculating the final, mean QNFT results, no statistically significant difference was found between respirators. Successful QNFT were determined for 5 out of 10 participants in the control group, for 8 in the AFM group (P = 0.25) and for 7 in the MSM group (P = 0.69). Conclusion Both ADR do have the potential to provide non inferior seal compared to a common FFP2 respirator. While AFM respirators are easily assembled, snorkelling masks must undergo significant but feasible modifications. Our results suggest that those ADR masks might be further investigated as they seem to be viable alternatives for situations when certified respirators are not available.


title: How it all went wrong in the UK

text: The UK's handling of testing, contact tracing, protective equipment and lockdown have left it with one of the highest death rates in the world, reports Adam Vaughan


title: Human leukocyte antigen susceptibility map for SARS-CoV-2

text: We probe how genetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen [HLA] A, B, and C) may affect susceptibility to and severity of severe acute respiratory syndrome 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). We execute a comprehensive in silico analysis of viral peptide-MHC class I binding affinity across all known HLA -A, -B, and -C genotypes for all SARS-CoV-2 peptides. We further explore the potential for cross-protective immunity conferred by prior exposure to four common human coronaviruses. The SARS-CoV-2 proteome is successfully sampled and presented by a diversity of HLA alleles. However, we found that HLA-B*46:01 had the fewest predicted binding peptides for SARS-CoV-2, suggesting individuals with this allele may be particularly vulnerable to COVID-19, as they were previously shown to be for SARS (1). Conversely, we found that HLA-B*15:03 showed the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting it could enable cross-protective T-cell based immunity. Finally, we report global distributions of HLA types with potential epidemiological ramifications in the setting of the current pandemic.


Surgeon’s COVID-19 Traumatic Stress Disorder


title: COVID-19: What are the risks in hypertensive patients?

text: Considering the number of patients affected by SARS-CoV-2, the World Health Organization declared a pandemic on 11 March 2020. A number of publications regarding the course of COVID-19 infection and its relation to comorbidities have appeared since December 2019, when the first cases of atypical pneumonia were diagnosed in China. There is evidence of the higher susceptibility and higher risk of unfavourable outcomes in comorbid patients, including those with hypertension. We summarize the available data on the association with the COVID-19 infection and arterial hypertension, and discuss potential risks, e. g. the risks and benefits of antihypertensive therapy (in particular, related to the blockers of renin-angiotensin-aldosterone system) and the management approaches.


title: Risk of infection and hospitalization by Covid-19 in Mexico: a case-control study

text: Objective. During the onset of a novel epidemic, there are public health priorities that need to be estimated, such as risk factors for infection, hospitalization, and clinical severity to allocate resources and issue health policies. In this work we calculate the risk of infection and hospitalization by Covid-19 conferred by demographic, lifestyle, and co-morbidity factors. Material and methods. This is a case-control study including the tested individuals for SARS-Cov-2 by RT-PCR officially reported by the Health Secretary of Mexico from January 01 to May 8, 2020 (102,875 subjects). Demographic (sex, age, foreign and immigrant status, native speaking, place of residence), life-style (smoking), and co-morbidities [diabetes, obesity, high blood pressure (HBP), asthma, immunosuppression, chronic obstructive pulmonary disease (COPD), cardiovascular disease other than HBP, chronic kidney disease (CKD), and other not specified diseases (other diseases)] variables were included in this study. The risk of infection and hospitalization conferred by each variable was calculated with univariate (ULR) and multivariate (MLR) logistic regression models. Results. The place of residence (OR=4.91 living in Tijuana City), followed by advanced age (OR=6.71 in 61-70 years-old), suffering from diabetes (OR=1.87) or obesity (OR=1.61), being male (OR=1.55), having HBP (OR=1.52), and notoriously being indigenous (OR=1.49) conferred a higher risk of becoming infected by SARS-CoV-2 in Mexico. Unexpectedly, we found that having asthma (OR=0.63), immunosuppression (OR=0.65) or smoking (OR=0.85) are protective factors against infection, while suffering from COPD does not increase the risk for SARS-CoV-2 infection. In contrast, advanced age (OR=11.6 in [≥] 70 years-old) is the main factor for hospitalization due to Covid-19, followed by some co-morbidities, mainly diabetes (OR=3.69) and HBP (OR=2.79), being indigenous (OR=1.89), male sex (OR=1.67) and the place of residence (OR=4.22 for living in Juarez City). Unlike the protective risk against infection, immunosuppression (OR=2.69) and COPD (OR=3.63), contribute to the risk of being hospitalized, while having asthma (OR=0.7) also provides protection against hospitalization. Conclusions. In addition to confirming that older age, diabetes, HBP and obesity are the main risk of infection and hospitalization by Covid-19, we found that being indigenous, immunosuppression, smoking and asthma protect against infection, and the latter also against hospitalization.


title: Amplification of human Î²-glucoronidase gene for appraising the accuracy of negative SARS-CoV-2 RT-PCR results in upper respiratory tract specimens

text: Real-time reverse transcription polymerase-chain reaction (RT-PCR) is the mainstay of Covid-19 diagnosis. False-negative RT-PCR results may hamper clinical management of patients and hinder the adoption of epidemiological measures to control the pandemic. The current study was aimed at assessing whether amplification of {beta}-glucoronidase (GUSB) gene would help estimate the accuracy of SARS-CoV-2 RT-PCR negative results in upper respiratory tract (URT) specimens. URT specimens that tested negative by SARS-CoV-2 RT-PCR displayed higher GUSB RT-PCR cycle thresholds (CT) (P=0.070) than those testing positive (median, 30.7; range, 27.0-40.0, and median 29.7; range 25.5-36.8, respectively), this reflecting poorer cellularity. Receiver operating characteristic (roc) curve analysis indicated that a CT threshold of 31.2 discriminated best between positive and negative SARS CoV-2 RT-PCRs (area under a curve, 0.66; 95% CI, 0.50-0.81; P=0.08). This cut-off yielded a true negative ratio of 89% and accuracy of 70%. The data suggested that amplification of the GUSB gene by RT-PCR may help to appraise the accuracy of negative SARS-CoV-2 RT-PCR results in patients in whom Covid-19 is eventually diagnosed.


A brief review on the possible role of houseflies and cockroaches in the mechanical transmission of coronavirus disease 2019 (Covid-19)


title: Early Experiences With COVID-19 Testing in Transplantation

text: Background The early effects of coronavirus disease 2019 (COVID-19) on transplantation are dramatic: >75% of kidney and liver programs are either suspended or operating under major restrictions To resume transplantation, it is important to understand the prevalence of COVID-19 among transplant recipients, donors, and healthcare workers (HCWs) and its associated mortality Methods To investigate this, we studied severe acute respiratory syndrome coronavirus 2 diagnostic test results among patients with end-stage renal disease or kidney transplants from the Johns Hopkins Health System (n = 235), and screening test results from deceased donors from the Southwest Transplant Alliance Organ Procurement Organization (n = 27), and donors, candidates, and HCWs from the National Kidney Registry and Viracor-Eurofins (n = 253) between February 23 and April 15, 2020 Results We found low rates of COVID-19 among donors and HCWs (0%–1%) who were screened, higher rates of diagnostic tests among patients with end-stage renal disease or kidney transplant (17%–20%), and considerable mortality (7%–13%) among those who tested positive Conclusions These findings suggest the threat of COVID-19 for the transplant population is significant and ongoing data collection and reporting is critical to inform transplant practices during and after the pandemic


title: Lessons from COVID-19 can prepare global tourism for the economic transformation needed to combat climate change

text: The COVID-19 pandemic led to the cessation of almost all international travel in the first half of 2020. A return to pre-pandemic growth patterns will take time and depend on the depth and extent of the recession sparked by COVID-19. The recovery phase will overlap with global efforts to deal with the evolving climate crisis. For the tourism industry to thrive in a future world it must look beyond the temptation of adopting strategies based on a return to the pre-COVID-19 normal of the past and instead seek to understand how it should respond to the emerging transformation of the global economy to carbon neutrality. Many of the lessons that emerged from the pandemic can be applied to strategies to deal with climate change. Of most interest is the success of strategies such as “flattening the curve”. Application of similar strategies plus adoption of the circular economy model to wind back Green House Gas emissions will help avert the global environmental disaster that will occur if global temperatures continue to increase. These strategies point to what a future carbon-neutral economic production system might look like, the path to which could offer the tourism industry numerous opportunities to transform from the current model that favours a high resource consumption model to one that is environmentally friendly and resource neutral.


title: Insight Derived from Molecular Docking and Molecular Dynamics Simulations into the Binding Interactions Between HIV-1 Protease Inhibitors and SARS-CoV-2 3CLpro

text: A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) was identified from respiratory illness patients in Wuhan, Hubei Province, China, which has recently emerged as a serious threat to the world public health Hower, no approved drugs have been found to effectively inhibit the virus Since it has been reported that the HIV-1 protease inhibitors can be used as anti-SARS drugs by tegarting SARS-CoV 3CLpro, we choose six approved anti-HIV-1 drugs to investigate their binding interactions between 3CLpro, and to evaluate their potential to become clinical drugs for the new coronavirus pneumonia (COVID19) caused by SARS-CoV-2 infection The molecular docking results indicate that, the 3CLpro of SARS-CoV-2 has a higher binding affinity for all the studied inhibitors than its SARS homologue Two docking complexes (indinavir and darunavir) with high docking scores were futher subjected to MM-PBSA binding free energy calculations to detail the molecular interactions between these two proteinase inhibitors and the 3CLpro Our results show that darunavir has the best binding affinity with SARS-CoV-2 and SARS-CoV 3CLpro among all inhibitors, indicating it has the potential to become an anti-COVID-19 clinical drug The likely reason behind the increased binding affinity of HIV-1 protease inhibitors toward SARS-CoV2 3CLpro than that of SARS-CoV were investigated by MD simulations Our study provides insight into the possible role of structural flexibility during interactions between 3CLpro and inhibitors, and sheds light on the structure-based design of anti-COVID-19 drugs targeting the SARS-CoV-2 3CLpro


Coronavirus disease 2019 (COVID-19) outbreak: Strengthening the treatment component in health care establishments to minimize case fatality


title: Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches

text: Whole Genome Sequence of four samples from COVID-19 outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, England). The constructed phylogenetic tree indicates probable multiple independent introduction events. The success of future containment measures concernig new introductions will be highly challenging for country due to the significant proportion of BH population living abroad.


title: A how-to-guide to building a robust SARS-CoV-2 testing program at a university-based health system

text: When South Florida became a hotspot for COVID-19 disease in March 2020, we faced an urgent need to develop test capability to detect SARS-CoV-2 infection. We assembled a transdisciplinary team of knowledgeable and dedicated physicians, scientists, technologists and administrators, who rapidly built a multi-platform, PCR- and serology- based detection program, established drive-thru facilities and drafted and implemented guidelines that enabled efficient testing of our patients and employees. This process was extremely complex, due to the limited availability of needed reagents, but outreach to our research scientists and to multiple diagnostic laboratory companies and government officials enabled us to implement both FDA authorized and laboratory developed testing (LDT)-based testing protocols. We analyzed our workforce needs and created teams of appropriately skilled and certified workers, to safely process patient samples and conduct SARS-CoV-2 testing and contact tracing. We initiated smart test ordering, interfaced all testing platforms with our electronic medical record, and went from zero testing capacity, to testing hundreds of healthcare workers and patients daily, within three weeks. We believe our experience can inform the efforts of others, when faced with a crisis situation.


title: Coronavirus Disease (COVID-19): Implications for Cardiovascular and Socially At-risk Populations

text: Dennison Himmelfarb and Baptiste discuss the implications of coronavirus disease (COVID-19) for cardiovascular and socially at-risk populations COVID-19 is an infectious respiratory disease caused by the newly discovered pathogen, SARS-CoV-2, a novel RNA-dependent RNA polymerase betacoronavirus that is thought to derive from bats At this time, there are no specific vaccines or treatments for COVID-19 The best way to prevent and slow transmission is to be well informed about the COVID-19 virus, the disease it causes, and how it spreads


title: Ebselen as a highly active inhibitor of PLProCoV2

text: Since December 2019 a novel a coronavirus identified as SARS-CoV-2 or COV2 has been spreading around the world. On the 16th of May around 4.5 million people got infected and over 300,000 died due to the infection of COV2. The effective treatment remains a challenge. Targeted therapeutics are still under investigation. The papain-like protease (PLPro) from the human SARS-CoV-2 coronavirus is a cysteine protease that plays a critical role in virus replication. Its activity is required to process the viral polyprotein into functional, mature subunits. Moreover, COV2 uses this enzyme to modulate the host’s immune system to its own benefit. Therefore, it represents a highly promising target for the development of antiviral drugs. In this work, we discovered that ebselen, a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity in mammalian cells and cytotoxicity in lower organisms, is a highly active inhibitor of PLProCoV2. We proved that ebselen is a covalent, fast-binding inhibitor of PLProCoV2 exhibiting a low micromolar potency. Furthermore, we identified a difference between PLPro from SARS-CoV-1 (the corona virus which caused the 2002–2004 outbreak, SARS) and SARS-CoV-2 that allows to explain the difference in dynamics of the replication, and, thus, the disease progression. Namely, we present that they show differences in the binding affinity of substrates that we observed through kinetics and molecular docking studies. Using a novel Approximate Bayesian Computation method we were able to find kinetic constants for both enzymes. Molecular modeling study on the structure of the active site and binding mode of the ebselen with SARS and COV2 showed also significant differences that could explain our observation that ebselen is less active and slower bounding with SARS than COV2. In conclusion, we show that ebselen inhibits the activity of the essential viral enzyme papain-like protease (PLpro) from SARS-COV-2 in low micromolar range.


title: Stability of SARS-CoV-2 on Critical Personal Protective Equipment

text: The spread of COVID-19 in healthcare settings is concerning, with healthcare workers representing a disproportionately high percentage of confirmed cases. Although SARS-CoV-2 virus has been found to persist on surfaces for a number of days, the extent and duration of fomites as a mode of transmission, particularly in healthcare settings, has not been fully characterized. To shed light on this critical matter, the present study provides the first comprehensive assessment of SARS-CoV-2 stability on experimentally contaminated personal protective equipment (PPE) widely used by healthcare workers and the general public. Persistence of viable virus was monitored over 21 days on eight different materials, including nitrile medical examination gloves, reinforced chemical resistant gloves, N-95 and N-100 particulate respirator masks, Tyvek, plastic, cotton, and stainless steel. Unlike previous reports, viable SARS-CoV-2 in the presence of a soil load persisted for up to 21 days on experimentally inoculated PPE, including materials from filtering facepiece respirators (N-95 and N-100 masks) and a plastic visor. Conversely, when applied to 100% cotton fabric, the virus underwent rapid degradation and became undetectable in less than 24 hours. These findings underline the importance of appropriate handling of contaminated PPE during and following use in high-risk settings and provide interesting insight into the potential utility of cotton, including cotton masks, in limiting COVID-19 transmission.


title: Experimental Human Metapneumovirus Infection of Cynomolgus Macaques (Macaca fascicularis) Results in Virus Replication in Ciliated Epithelial Cells and Pneumocytes with Associated Lesions throughout the Respiratory Tract

text: A substantial proportion of hitherto unexplained respiratory tract illnesses is associated with human metapneumovirus (hMPV) infection. This virus also was found in patients with severe acute respiratory syndrome (SARS). To determine the dynamics and associated lesions of hMPV infection, six cynomolgus macaques (Macaca fascicularis) were inoculated with hMPV and examined by pathological and virological assays. They were euthanized at 5 (n = 2) or 9 (n = 2) days post-infection (dpi), or monitored until 14 dpi (n = 2). Viral excretion peaked at 4 dpi and decreased to zero by 10 dpi. Viral replication was restricted to the respiratory tract and associated with minimal to mild, multi-focal erosive and inflammatory changes in conducting airways, and increased numbers of macrophages in alveoli. Viral expression was seen mainly at the apical surface of ciliated epithelial cells throughout the respiratory tract, and less frequently in type 1 pneumocytes and alveolar macrophages. Both cell tropism and respiratory lesions were distinct from those of SARS-associated coronavirus infection, excluding hMPV as the primary cause of SARS. This study demonstrates that hMPV is a respiratory pathogen and indicates that viral replication is short-lived, polarized to the apical surface, and occurs primarily in ciliated respiratory epithelial cells.


title: COVID-19: One-month impact of the French lockdown on the epidemic burden

text: On March 16 2020, French authorities ordered a large scale lockdown to counter the COVID-19 epidemic wave rising in the country, stopping non-essential economic, educational, and entertainment activities, maintaining mainly food retailers and healthcare institutions. One month later, the number of new hospitalizations and ICU admissions had reached a plateau and were beginning a slow descent. We developed a spatialized, deterministic, age-structured, and compartmental SARS-CoV-2 transmission model able to reproduce the pre-lockdown dynamic of the epidemic in each of the 13 French metropolitan regions. Thanks to this model, we estimate, at regional and national levels, the total number of hospitalizations, ICU admissions, hospital beds requirements (hospitalization and ICU), and hospital deaths which may have been prevented by this massive and unprecedented intervention in France. If no control measures had been set up, between March 19 and April 19 2020, our analysis shows that almost 23% of the French population would have been affected by COVID-19 (14.8 million individuals). Hence, the French lockdown prevented 587,730 hospitalizations and 140,320 ICU admissions at the national level. The total number of ICU beds required to treat patients in critical conditions would have been 104,550, far higher than the maximum French ICU capacity. This first month of lockdown also permitted to avoid 61,739 hospital deaths, corresponding to a 83.5% reduction of the total number of predicted deaths. Our analysis shows that in absence of any control measures, the COVID-19 epidemic would have had a critical morbidity and mortality burden in France, overwhelming in a matter of weeks French hospital capacities.


title: Adjusted fatality rates of COVID19 pandemic: a comparison across countries

text: Background: A key impact measure of COVID-19 pandemic is the case fatality rate (CFR), but estimating it during an epidemic is challenging as the true number of cases may remain elusive. Objective: To estimate the CFR applying a delay-adjusted method across countries, exploring differences to simple methods and potential correlation to country level variables. Methods: Secondary analysis of publicly available data from countries with [≥]500 cases by April 30th. We calculated CFR adjusting for delay time from diagnosis to death and using simple methods for comparison. We performed a random effects meta-analysis to pooling CFRs for all countries and for those with high testing coverage and low positivity rate. We explored correlation of adjusted CFR with age structure and health care resources at country level. Results: We included 107 countries and the Diamond Princess cruise-ship. The overall delay adjusted CFR was 2.8% (95%CI: 2.1 to 3.1) while naive CFR was 5.1% (95%CI: 4.1 to 6.2). In countries with high testing coverage/low positivity rate the pooled adjusted CFR was 2.1% (95%CI: 1.5 to 3.0), there was a correlation with age over 65 years ({beta} = 0.12; 95%CI: 0.06 to 0.18), but not with number of physician or critical care beds. Naive method underestimated the CFR of the CFR with a median of 1.3% across countries. Conclusion: Our best estimation of CFR across countries is 2% and varies according to the aged population size. Modelers and policy makers may consider these results to assess the impact of lockdowns or other mitigation policies.


title: FAST: a Feasible, Accurate and Speedy Test Strategy for COVID-19

text: As the COVID-19 pandemic continues worldwide, there is an urgent need to detect infected patients as quickly and accurately as possible. Group testing proposed by Technion [2] could improve efficiency greatly. However, the false negative rate (FNR) would be doubled. Using USA as an example, group testing would have over 70,000 false negatives, compared to 35,000 false negatives by individual testing. In this paper, we propose a Flexible, Accurate and Speedy Test (FAST), which is faster and more accurate than any existing tests. FAST first forms small close contact subgroups, e.g. families and friends. It then pools subgroups to form larger groups before RT-PCR test is done. FAST needs a similar number of tests to Technion's method, but could sharply reduce the FNR to a negligible level. Again taking USA as example, FAST reduces the number of false negatives to just 2000 while it is seven times faster than individual testing.


title: Estimating the real-time case fatality rate of COVID-19 using Poisson mixtures model

text: Importance: The case fatality rate (CFR) estimation during the early stage of a disease outbreak is important, but the current estimation methods are heavily biased. Objective: We proposed using a Poisson mixtures model that utilized requires data of deaths, recoveries, and total confirmed cases recorded in each day since the outbreak of a population. Design: We collected data of deaths, recoveries, and total confirmed cases of COVID-19 in Hubei Province, China, and other parts of China up to 10th April 2020. Main Outcome(s) and Measure(s): The CFR of COVID-19 was estimated by minimizing the chi-square goodness-of-fit statistic. Results: Our proposed CRF estimates for Hubei Province became stable on 5th February in the range of 4.5% to 7.0% at which the simple CFR estimators overestimated the actual CFR by more than five folds, and that for the other parts of China (1.5% to 1.6%) were all very close to the actual CFR on the first day of CFR estimation (25th January) at which the simple CFRs were in the range between 15% and 35%. Conclusions and Relevance: Our CFR estimates for Hubei Province and other parts of China were superior to the simple CFR estimators.


title: Update on Coupled Dark Energy and the $H_0$ tension

text: In this work we provide updated constraints on coupled dark energy (CDE) cosmology with Peebles-Ratra (PR) potential and constant coupling strength $\beta$. This modified gravity scenario introduces a fifth force between dark matter particles, mediated by a scalar field that plays the role of dark energy. The mass of the dark matter particles does not remain constant, but changes with time as a function of the scalar field. Here we focus on the phenomenological behavior of the model, and assess its ability to describe updated cosmological data sets that include the Planck 2018 cosmic microwave background (CMB) temperature, polarization and lensing, baryon acoustic oscillations, the Pantheon compilation of supernovae of Type Ia, data on $H(z)$ from cosmic chronometers, and redshift-space distortions. We also study which is the impact of the local measurement of $H_0$ from SH0ES and the strong-lensing time delay data from the H0LICOW collaboration on the parameter that controls the strength of the interaction in the dark sector. We find a peak corresponding to a coupling $\beta>0$ and to a potential parameter $\alpha>0$, more or less evident depending on the data set combination. We show separately the impact of each data set and remark that it is especially CMB lensing the one data set that shifts the peak the most towards $\Lambda$CDM. When a model selection criterion based on the full Bayesian evidence is applied, however, $\Lambda$CDM is still preferred in all cases, due to the additional parameters introduced in the CDE model.


COVID-19 pandemic in India: A clarion call for better preparedness


title: Anti-Spike, anti-Nucleocapsid and neutralizing antibodies in SARS-CoV-2 hospitalized patients and asymptomatic carriers

text: Using longitudinal plasma samples from thirty COVID-19 patients, we observed that virus-specific antibodies are detectable in 100% of patients two weeks after symptom onset. We also show that these patients produced variable levels of neutralizing antibodies which reached a plateau two weeks after symptom onset and then declined in the majority of patients. Furthermore, we report that neutralizing antibodies were undetectable in 56% (14/25) of asymptomatic carriers.


title: ANALYSIS OF CLINICAL RECOVERY-PERIOD AND RECOVERY RATE ESTIMATION OF THE FIRST 1000 COVID-19 PATIENTS IN SINGAPORE

text: COVID-19 has been declared as a global pandemic by the World Health Organization (WHO) on March 11, 2020. In this paper, we investigate various aspects of the clinical recovery of the first 1000 COVID-19 patients in Singapore, spanning from January 23 to April 01, 2020. This data consists of 245 clinically recovered patients. The first part of the paper studies the descriptive statistics and the influence of demographic parameters, namely age and gender, in the clinical recovery-period of COVID-19 patients. The second part of the paper is on identifying the distribution of the length of the recovery-period for the patients. We identify a piecewise analysis of three different periods, identified based on trends of both positive confirmation and clinical recovery of COVID-19. As expected, the overall recovery rate has reduced drastically during the exponential increase of incidences. However, our in-depth analysis shows that there is a shift in the age-group of incidences to the younger population, and the recovery-period of the younger population is considerably lower. Here, we have estimated the recovery rate to be 0.125. Overall, the prognosis of COVID-19 indicates an improvement in recovery rate owing to the government-mandated practices of restricted mobility of the older population and aggressive contact tracing.


title: Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals

text: Memory T cells induced by previous infections can influence the course of new viral infections. Little is known about the pattern of SARS-CoV-2 specific pre-existing memory T cells in human. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in convalescent from COVID-19 (n=24). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then show that SARS-recovered patients (n=23), 17 years after the 2003 outbreak, still possess long-lasting memory T cells reactive to SARS-NP, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we observed a differential pattern of SARS-CoV-2 specific T cell immunodominance in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=18). Half of them (9/18) possess T cells targeting the ORF-1 coded proteins NSP7 and 13, which were rarely detected in COVID-19- and SARS-recovered patients. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to “common cold” human coronaviruses but conserved among animal betacoranaviruses. Thus, infection with betacoronaviruses induces strong and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.


title: Incidence of COVID-19 and Connections with Air Pollution Exposure: Evidence from the Netherlands

text: The fast spread of severe acute respiratory syndrome coronavirus 2 has resulted in the emergence of several hot-spots around the world. Several of these are located in areas associated with high levels of air pollution. This study investigates the relationship between exposure to particulate matter and COVID-19 incidence in 355 municipalities in the Netherlands. The results show that atmospheric particulate matter with diameter less than 2.5 is a highly significant predictor of the number of confirmed COVID-19 cases and related hospital admissions. The estimates suggest that expected COVID-19 cases increase by nearly 100 percent when pollution concentrations increase by 20 percent. The association between air pollution and case incidence is robust in the presence of data on health-related preconditions, proxies for symptom severity, and demographic control variables. The results are obtained with ground-measurements and satellite-derived measures of atmospheric particulate matter as well as COVID-19 data from alternative dates. The findings call for further investigation into the association between air pollution and SARS-CoV-2 infection risk. If particulate matter plays a significant role in COVID-19 incidence, it has strong implications for the mitigation strategies required to prevent spreading.


title: Identification of Patterns in Epidemic Cycles and Methods for Estimating Their Duration: COVID-19 Case Study

text: This paper presents several epidemic cycles of COVID-19 that have practically ended in countries, states and cities and normalize them through simple and well-known numerical methods. It is evident that there is a practically universal pattern between them, in a triangular shape. It is also possible to find similar cycles with very close scales and thus use cases with cycles already closed to predict the end of the cycles still in progress. Three methods are presented and discussed and the case of the city of Rio de Janeiro, Brazil, is presented in more detail.


title: Discovery of potent inhibitors of PLproCoV2 by screening a library of selenium-containing compounds

text: A collection of twelve organoselenium compounds, structural analogues of antioxidant drug ebselen were screened for inhibition of the papain-like protease (PLpro) from the acute respiratory syndrome coronavirus 2 (SARS-CoV-2, CoV2). This cysteine protease, being responsible for the hydrolysis of peptide bonds between specific amino acids, plays a critical role in CoV2 replication and in assembly of new viral particles within human cells. The activity of the PLpro CoV2 is essential for the progression of coronavirus disease 2019 (COVID-19) and it constitutes a key target for the development of anti-COVID-19 drugs. Here, we identified four strong inhibitors that bind favorably to the PLpro CoV2 with the IC50 in the nanomolar range.


title: An epidemiological forecast model and software assessing interventions on COVID-19 epidemic in China

text: We develop a health informatics toolbox that enables public health workers to timely analyze and evaluate the time-course dynamics of the novel coronavirus (COVID-19) infection using the public available data from the China CDC. This toolbox is built upon a hierarchical epidemiological model in which two observed time series of daily proportions of infected and removed cases are emitted from the underlying infection dynamics governed by a Markov SIR infectious disease process. We extend the SIR model to incorporate various types of time-varying quarantine protocols, including government-level macro isolation policies and community-level micro inspection measures. We develop a calibration procedure for under-reported infected cases. This toolbox provides forecast, in both online and offline forms, of turning points of interest, including the time when daily infected proportion becomes smaller than the previous ones and the time when daily infected proportions becomes smaller than that of daily removed proportion, as well as the ending time of the epidemic. An R software is made available for the public, and examples on the use of this software are illustrated. Some possible extensions of our novel epidemiological models are discussed.


title: Looking out for yourself and those around you

text: The coronavirus outbreak is having a profound impact on society, including the veterinary industry As we meet the challenges the outbreak poses, Rosie Allister, Vetlife Helpline Manager, reminds us to look after ourselves and those around us


title: Risk Factors for Clinically Relevant Postoperative Pancreatic Fistula (CR-POPF) after Distal Pancreatectomy: A Single Center Experience

text: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the considerable contributor to major complications after pancreatectomy. The purpose of this study was to evaluate the potential risk factor contributing to CR-POPF following distal pancreatectomy (DP) and discussed the risk factors of pancreatic fistula in order to interpret the clinical importance. All the patients who underwent DP in between January 2011 and January 2020 were reviewed retrospectively in accordance with relevant guidelines and regulations. The univariate and multivariate analysis was performed was performed to test an independent risk factors for pancreatic fistula. P<0.05 was considered statistically significant. In all of the 263 patients with DP, pancreatic fistula was the most common surgical complication 19.0%. The univariate analysis of 18 factors showed that the patients with a malignant tumor, soft pancreas, and patient without ligation of the main pancreatic duct are more likely to develop pancreatic fistula. However, on multivariate analysis the soft texture of the pancreas (OR= 2.381, P= 0.001) and the ligation of main pancreatic duct (OR= 0.388, P= 0.002) were only an independent influencing factor for CR-POPF. As a conclusion, pancreatic fistula was the most common surgical complication after DP, and the texture of pancreas and ligation of main pancreatic duct can influence an incidence of CR-POPF.


title: Reusable Gowns for routine use in hospital and laboratory: a necessity arising of COVID-19 Pandemic

text: COVID-19 pandemic caused by SARS-CoV-2 has started a paradigm shift in working in a hospital or laboratory and airborne precautions have become equally significant as universal blood and body fluid precautions. Use of PPE including surgical masks or N95FFR is becoming a norm and this has led to scarcity of PPE for healthcare workers. We have prepared gowns for healthcare and laboratory workers made from a reusable material and tested with various disinfectants and heat. The cloth could tolerate repeated exposures to heat, alcohol, hypochlorite and hydrogen peroxide, but was damaged by phenol. Since this impermeable material did not allow the air to pass, we used a cool vest made up of indigenous Khadi cloth with pockets containing phase change material. The cost of whole reusable assembly of gown and cap was Indian Rupees 250 (1 USD=76 INR). This can be used in healthcare workers in hospital and community as well as people in diagnostic and research laboratories as a cost effective PPE.


title: Real time estimation of the risk of death from novel coronavirus (2019-nCoV) infection: Inference using exported cases

text: The exported cases of 2019 novel coronavirus (2019-nCoV) infection who were confirmed in other countries provide a chance to estimate the cumulative incidence and confirmed case fatality risk (cCFR) in China. Knowledge of the cCFR is critical to characterize the severity and understand pandemic potential of 2019-nCoV in the early stage of epidemic. Using the exponential growth rate of the incidence, the present study statistically estimated the cCFR and the basic reproduction number, i.e., the average number of secondary cases generated by a single primary case in a naive population. As of 24 January 2020, with 23 exported cases, and estimating the growth rate from 8 December 2019 (scenario 1) and using the data since growth of exported cases (scenario 2), the cumulative incidence in China was estimated at 5433 cases (95% confidence interval (CI): 3883, 7160) and 17780 cases (95% CI: 9646, 28724), respectively. The latest estimates of the cCFR were 4.6% (95% CI: 3.1-6.6) for scenario 1 and 7.7% (95% CI: 4.9-11.3%) for scenario 2, respectively. The basic reproduction number was estimated to be 2.2 (95% CI: 2.1, 2.3) and 3.7 (95% CI: 3.1, 4.3) for scenarios 1 and 2, respectively. Based on the results, we note that current 2019-nCoV epidemic has a substation potential to cause a pandemic. The proposed approach can provide insights into early risk assessment using only publicly available data.


title: Exploring the Parent-Child Landscape Pattern after COVID-19

text: This article discusses the design of parent-child landscape space, in the 5-minute life circle, that is getting more and more attention in the late stage of the new coronavirus (COVID-19) By studying the theory and practice of current parent-child landscape design, combined with the age characteristics of children, it is proposed to divide the parent-child landscape site into 5 small landscape spaces At the same time, the design features and suggested landscape elements of these 5 landscape spaces are listed These 5 small landscape spaces can be enlarged or reduced according to the actual size of the site


title: Temporal clinical and laboratory response to interleukin-6 receptor blockade with Tocilizumab in 89 hospitalized patients with COVID-19 pneumonia

text: Abstract: Background:. Emerging evidence links morbidity and mortality of pandemic COVID-19 pneumonia to an inflammatory cytokine storm. Methods: Eighty nine patients with COVID-19 pneumonia and heightened systemic inflammation (elevated serum C reactive protein and interleukin-6 levels) were treated with Tocilizumab (TCZ), a human monoclonal IgG1 antibody to the interleukin-6 receptor. Results: Clinical and laboratory improvement was seen comparing baseline and 1-2 day post-infusion indices. Among 72 patients not receiving mechanical ventilation, NEWS2 scores fell from 5 to 2 (p <0.001) C reactive protein levels fell from 95 to 14 mg/L (p <0.001) and lymphocyte counts rose from 900 to 1000/uL (p=0.036). Sixty three of 72 patients were discharged from hospital, one patient died, and 8 remained in hospital at time of writing. Among 17 patients receiving mechanical ventilation, despite a rapid decrease in CRP levels from 89 to 35 mg/L (p = 0.014) and early improvements in NEWS2 scores in 10 of 17, ten patients died and seven remain in hospital at time of writing. Overall, mortality was only seen in patients who had markedly elevated CRP levels (>30 mg/L) and low lymphocyte counts (<1000/uL) before TCZ administration. Conclusions: Inflammation and lymphocytopenia are linked to mortality in COVID-19. Inhibition of IL-6 activity by administration of Tocilizumab, an anti IL-6 receptor antibody is associated with rapid improvement in both CRP and lymphocyte counts and in clinical indices. Controlled clinical trials are needed to confirm the utility of IL-6 blockade in this setting. Additional interventions will be needed for patients requiring mechanical ventilation.


title: Case- fatality rate in COVID- 19 patients: A meta-analysis of publicly accessible database

text: A novel coronavirus was reported in Wuhan, China in December 2019 to cause severe acute respiratory symptoms (COVID- 19). In this meta-analysis, we estimated case fatality rate from COVID- 19 infection by random effect meta-analysis model with country level data. Publicly accessible web database WorldOMeter (https://www.worldometers.info/coronavirus/) was accessed on 24th March 2020 GMT and reported total number of cases, total death, active cases and seriously ill/ critically ill patients were retrieved. Primary outcome of this meta-analysis was case fatality rate defined by total number of deaths divided by total number of diagnosed cases. Pooled case fatality rate (95% CI) was 1.78 (1.34- 2.22) %. Between country heterogeneity was 0.018 (p<0.0001). Pooled estimate of composite poor outcome (95% CI) was 4.06 (3.24- 4.88) % at that point of time after exclusion of countries reported small number of cases. Pooled mortality rate (95% CI) was 33.97 (27.44- 40.49) % amongst closed cases (where patients have recovered or died) with. Meta regression analysis identified statistically significant association between health expenditure and mortality amongst closed cases (p=0.037).


Buying Time in a Prosperous Land: Some musings on human-viral relations from the streets of Amsterdam


title: Highly predictive regression model of active cases of COVID-19 in a population by screening wastewater viral load

text: The quantification of the SARS-CoV-2 load in wastewater has emerged as a useful method to monitor COVID-19 outbreaks in the community. This approach was implemented in the metropolitan area of A Coruna (NW Spain), where wastewater from the treatment plant of Bens was analyzed to track the dynamics of the epidemic in a population of 369,098 inhabitants. We developed statistical regression models that allowed us to estimate the number of infected people from the viral load detected in the wastewater with a reliability close to 90%. This is the first wastewater-based epidemiological model that could potentially be adapted to track the evolution of the COVID-19 epidemic anywhere in the world, monitoring both symptomatic and asymptomatic individuals. It can help to understand with a high degree of reliability the true magnitude of the epidemic in a place at any given time and can be used as an effective early warning tool for predicting outbreaks.


title: Scaling analysis of COVID-19 spreading based on Belgian hospitalization data

text: We analyze the temporal evolution of accumulated hospitalization cases due to COVID-19 in Belgium. The increase of hospitalization cases is consistent with an initial exponential phase, and a subsequent power law growth. For the latter, we estimate a power law exponent of ≈ 2.2, which is consistent with growth kinetics of COVID-19 in China and indicative of the underlying small world network structure of the epidemic. Finally, we fit an SIR-X model to the experimental data and estimate the effect of containment policies in comparison to their effect in China. This model suggests that the base reproduction rate has been significantly reduced, but that the number of susceptible individuals that is isolated from infection is very small. Based on the SIR-X model fit, we analyze the COVID-19 mortality and the number of patients requiring ICU treatment over time.


title: Hydroxychloroquine in COVID-19: A systematic review and meta-analysis

text: Abstract Background Hydroxychloroquine is being administered among patients with COVID19 infection in many healthcare systems across the world considering its in vitro effect against the SARS CoV 2 virus. In spite of several observational studies and a few randomized controlled trials, the effect of hydroxychloroquine on patients with COVID 19 infection remains unclear. We undertook this systematic review with meta-analysis to evaluate the efficacy and safety of hydroxychloroquine among patients with COVID 19 infection. Methods We searched PubMed, Embase, the Cochrane Library, Web of Science, medRxiv, and other relevant resources until May 13, 2020. We included randomized controlled trials and observational studies in which hydroxychloroquine was adminstered and compared to a control group. Data were extracted, and quality assessment of the studies was carried out. We evaluated symptomatic progression, mortality, viral clearance, the evolution of changes on chest CT imaging, and adverse events. A fixed or random-effects model was used depending on outcome heterogeneity. Results We included eleven studies including, three randomized controlled trials and eight observational studies. Among these, 2354 patients received hydroxychloroquine alone or in combination, while 1952 did not. Mortality was reported at different points of time. The overall mortality was not significantly different among patients who received hydroxychloroquine compared to the control group (OR: 1.41, 95% CI: 0.76 to 2.62; p = 0.28). Clinical worsening or lack of symptomatic improvement did not differ between patients who received hydroxychloroquine compared to those who did not (OR 1.1, 95% CI: 0.6 to 2.02; p = 0.76). Viral clearance, assessed by RT-PCR, did not differ significantly between the hydroxychloroquine and the control groups (OR: 1.13, CI: 0.26 to 5.01; p = 0.87). The evolution of changes on chest CT imaging was reported only in two studies; a more pronounced improvement was observed with the use of hydroxychloroquine compared to standard care (OR: 2.68, CI: 1.1 to 6.6; P = 0.03). The incidence of adverse events was significantly higher with hydroxychloroquine (OR: 4.1, CI: 1.42 to 11.88; p = 0.009). Conclusions Our meta-analysis does not suggest improvement in clinical progression, mortality, or viral clearance by RT PCR among patients with COVID 19 infection who are treated with hydroxychloroquine. There was a significantly higher incidence of adverse events with hydroxychloroquine use.


title: Fourier spectral density of the coronavirus genome

text: We present an analysis of the coronavirus RNA genome via a study of its Fourier spectral density based on a binary representation of the nucleotide sequence. We find that at low frequencies, the power spectrum presents a small and distinct departure from the behavior expected from an uncorrelated sequence. We provide a couple of simple models to characterize such deviations. Away from a small low-frequency domain, the spectrum presents largely stochastic fluctuations about fixed values and exhibits no other peaks apart from one associated with triplet codon usage. We uncover an interesting, new scaling law for the coronavirus genome: the complexity of the genome scales linearly with the power-law exponent that characterizes the low-frequency domain of the spectral density.


title: Initial experience with short-course corticosteroids in a small cohort of adults with severe COVID-19 in a tertiary care hospital in India

text: Abstract Severe COVID 19 disease is associated with high morbidity and mortality with limited therapeutic options. The role of glucocorticoids in treatment of COVID 19 has been riddled with controversy. The study site has been using glucocorticoids in patients with severe COVID 19 since the first few patients of COVID 19 that were admitted. In the initial cohort of 7 patients with severe COVID disease, use of methylprednisolone in a dose of 30 mg twice daily was associated with rapid improvement in oxygenation and decline in CRP levels. While six patients made a complete clinical recovery, one patient died. There were no secondary infections.


title: The media and their informative role in the face of the coronavirus disease 2019 (COVID-19): Validation of fear perception and magnitude of the issue (MED-COVID-19)

text: Introduction: The media play an important role in the dissemination of information on the 2019 novel coronavirus disease (COVID-19) pandemic. However, it is important to measure whether the population is receiving information that calms it down, as well as whether such news are in accordance with the magnitude of the issue. Objective: To validate a questionnaire that measures the perception of the media and their informative role in the face of COVID-19 pandemic. Methods: A validation process for a questionnaire that measures the perception of the magnitude of this issue and whether it generates fear was carried out. The validation was performed by means of a literature search. Moreover, a first version of the scale was developed, which was assessed by 30 experts (physicians, epidemiologists, among others). After this, an exploratory factor analysis and descriptive statistics were performed. Results: Our scale had 13 initial items; however, one of them was eliminated because of its unsatisfactory level of statistical adequacy. Exploratory factorial analysis and parallel analysis suggested three factors. Results of the KMO coefficient (0.833) and the Bartlett’s test of sphericity (4998.5; gl = 66; p<0.001) were acceptable and significant, which justify the exploratory factorial analysis. The correlation between the factors was >0.4 and robust analyses revealed a satisfactory factorial structure (X2=88.0; p= 0.001; IFC=0.968; GFI=0.992; TLI=0.937; RMSEA=0.123). In the descriptive statistics of the 12 final items, moderate and significant correlations between the items were reported (> 0.5). Conclusion: We generate a scale to validate the perception of how people receive information from the media. Thus, this scale can be used to measure the informative role of the media regarding the COVID-19 pandemic, and may even serve for other similar public health emergencies.


Response of the Istituto Nazionale Tumori of Milan Head & Neck Cancer Unit to the COVID-19 outbreak


title: Chloroquine: Can it be a Novel Drug for COVID-19

text: Coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization. The United States Food and Drug Administration has not approved any drug or vaccine for the treatment of COVID-19; however, reports have emerged from different parts of the world about the potential therapeutic benefits of existing drugs. Chloroquine and phosphate hydroxychloroquine are the drugs currently in the limelight, and recently, the National Task Force for COVID-19 constituted by the Indian Council of Medical Research has recommended the use of antimalarial drug hydroxychloroquine for prophylaxis of severe acute respiratory syndrome-coronavirus 2 infection in selected high-risk individuals. This short write-up explores the potential efficacy and established safety of chloroquine in COVID-19.


title: The in vitro antiviral activity of the anti-hepatitis C virus (HCV) drugs daclatasvir and sofosbuvir against SARS-CoV-2

text: The infection by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes major public health concern and economic burden. Although clinically approved drugs have been repurposed to treat individuals with 2019 Coronavirus disease (COVID-19), the lack of safety studies and limited efficiency as well jeopardize clinical benefits. Daclatasvir and sofosbuvir (SFV) are clinically approved direct-acting antivirals (DAA) against hepatitis C virus (HCV), with satisfactory safety profile. In the HCV replicative cycle, daclatasvir and SFV target the viral enzymes NS5A and NS5B, respectively. NS5A is endowed with pleotropic activities, which overlap with several proteins from SARS-CoV-2. HCV NS5B and SARS-CoV-2 nsp12 are RNA polymerases that share homology in the nucleotide uptake channel. These characteristics of the HCV and SARS-CoV-2 motivated us to further study the activity of daclatasvir and SFV against the new coronavirus. Daclatasvir consistently inhibited the production of infectious SARS-CoV-2 virus particles in Vero cells, in the hepatoma cell line HuH-7 and in type II pneumocytes (Calu-3), with potencies of 0.8, 0.6 and 1.1 μM, respectively. Daclatasvir targeted early events during SARS-CoV-2 replication cycle and prevented the induction of IL-6 and TNF-α, inflammatory mediators associated with the cytokine storm typical of SARS-CoV-2 infection. Sofosbuvir, although inactive in Vero cells, displayed EC50 values of 6.2 and 9.5 μM in HuH-7 and Calu-3 cells, respectively. Our data point to additional antiviral candidates, in especial daclatasvir, among drugs overlooked for COVID-19, that could immediately enter clinical trials.


title: COVID-19 Outbreak in Oman: Model-Driven Impact Analysis and Challenges

text: Motivated by the rapid spread of COVID-19 all across the globe, we have performed simulations of a system dynamic epidemic spread model in different possible situations. The simulation, not only captures the model dynamic of the spread of the virus, but also, takes care of population and mobility data. The model is calibrated based on epidemic data and events specifically of Sultanate of Oman, which can easily be generalized. The simulation results are quite disturbing, indicating that, during a process of stringent social distancing and testing strategies, a small perturbation can lead to quite undesirable outcomes. The simulation results, although consistent in expected outcomes across changing parameters' values, also indicate a substantial mismatch with real numbers. An analysis of what can be the reason of this mismatch is also performed. Within these contradictions, for Oman, regarding the eradication of epidemic, the future is not extremely alarming.


title: The Outcome Impact of Early vs Late HFNC Oxygen Therapy in Elderly Patients with COVID-19 and ARDS

text: Coronavirus disease-2019 (COVID-19) has rapidly spread worldwide. High-flow nasal cannula therapy (HFNC) is a major oxygen supporting therapy for severely ill patients, but information regarding the timing of HFNC application is scarce, especially in elderly patients. We retrospectively analyzed the clinical data of 110 elderly patients ([≥]65 years) who received HFNC from Renmin Hospital of Wuhan University, People's Hospital of Xiantao City and Chinese Medicine Hospital of Shishou City in Hubei Province, China, and from Affiliated Hospital of Guangdong Medical University, People's Hospital of Yangjiang City, People's Hospital of Maoming City in Guangdong Province, China. Of the 110 patients, the median age was 71 years (IQR, 68-78) and 59.1% was male. Thirty-eight patients received HFNC when 200 mmHg < PO2/FiO2 [≤] 300 mmHg (early HFNC group), and 72 patients received HFNC treatment when 100 mmHg < PaO2/FiO2 [≤] 200 mmHg (late HFNC group). Compared with the late HFNC group, patients in the early HFNC group had a lower likelihood of developing severe ARDS, longer time from illness onset to severe ARDS and shorter duration of viral shedding after illness onset, as well as shorter lengths of ICU and hospital stay. Twenty-four patients died during hospitalization, of whom 22 deaths (30.6%) were in the late HFNC group and 2(5.3%) in the early HFNC group. It is concluded that the prognosis was better in severely ill elderly patients with COVID-19 receiving early compared to late HFNC. This suggests HFNC could be considered early in this disease process.


title: Explore the Possible Impact of BCG Vaccination Policy on the Morbidity, Mortality, and Recovery Rates due to COVID-19 Infection.

text: BACKGROUND The Coronavirus Disease-19 (COVID-19) is the new form of an acute infectious respiratory disease and has quickly spread over most continents in the world. Recently, it has been shown that Bacille Calmette-Guerin (BCG) might protect against COVID-19. This study aims to investigate the possible correlation between BCG vaccination and morbidity/mortality/recovery rate associated with COVID-19 infection. METHODS Data of COVID-19 confirmed cases, deaths, recoveries, and population were obtained from https://www.worldometers.info/coronavirus/ (Accessed on 12 June, 2020). To have meaningful comparisons among countries' mortality and recovery rates, we only choose those countries with COVID-19 infected cases at least 200. The Poisson regression and logistic regression were used to explore the relationship between BCG vaccination and morbidity, mortality and recovery rates. RESULTS Among those 158 countries with at least 200 COVID-19 infected cases, there were 141 countries with BCG vaccination information available. The adjusted rates ratio of COVID-19 confirmed cases for Current BCG vaccination vs. non-Current BCG vaccination was 0.339 (with 95% CI= (0.338,0.340)). Moreover, the adjusted odds ratio (OR) of death and recovery after coronavirus infected for Current BCG vaccination vs. non-Current BCG vaccination were 0.258 (with 95% CI= (0.254,0.261)) and 2.151 (with 95% CI= (2.140,2.163)), respectively. CONCLUSIONS That data in this study show the BCG might provide the protection against COVID-19, with consequent less COVID-19 infection and deaths and more rapid recovery. BCG vaccine might bridge the gap before the disease-specific vaccine is developed, but this hypothesis needs to be further tested in rigorous randomized clinical trials.


title: Succumbing to the COVID-19 Pandemic: Healthcare Workers not Satisfied and Intend to Leave Their Jobs

text: Background: Healthcare workers are under such a tremendous amount of pressure during the COVID-19 pandemic that many have become concerned about their jobs and even intend to leave them. It is paramount for healthcare workers to feel satisfied with their jobs and lives during a pandemic. Methods: Between 10 to 30 April, 2020, 240 healthcare workers in Bolivia completed a cross-sectional online survey, which assessed their job satisfaction, life satisfaction, and turnover intention in the ongoing COVID-19 pandemic. Results: The results revealed that their number of office days predicted job satisfaction, life satisfaction, and turnover intention, but the relationships varied by their age. For example, office days of healthcare workers negatively predicted job satisfaction for the young (e.g. at 25 years old: b=-0.21; 95% CI: -0.36 to -0.60) but positively predicted job satisfaction for the old (e.g. at 65 years old: b=0.25; 95% CI: 0.06 to 0.44). Conclusions: These findings provide evidence to enable healthcare organizations to identify staff concerned about job satisfaction, life satisfaction, and turnover intention to enable early actions so that these staff can remain motivated to fight the prolonged COVID-19 pandemic. Keywords: healthcare staff; office days; Latin America; occupational well-being; risk factors; COVID-19


title: International expansion of social enterprises as a catalyst for scaling up social impact across borders

text: Scaling social impact and solutions beyond the local context is argued to embody a key mechanism for social enterprises (SEs) to contribute to the achievement of the sustainable development goals (SDGs) and to generate welfare-enhancing systemic change. In light of this, this article explores the potential of SE international expansion as a catalyst for scaling social impact across borders. From our reading of the literature, we discern three major typologies of cross-border scaling: Control-based, altruism-based, and hybrid. Drawing on a multiple-case study of nine international SEs, we examine why and how SEs deploy these scaling strategies on an international scale; the challenges to maximize social impact across borders associated with each of the scaling strategies, and the resources and actions that SEs can mobilize to manage such challenges associated with international expansion. Contrary to conventional wisdom and mainstream theory depicting SEs as small-sized organizations that suffer from different limitations to expand beyond their traditional national boundaries, our findings illustrate how these organizations can successfully operate on an international scale and simultaneously generate financial, social, and environmental value.


title: Discriminating Mild from Critical COVID-19 by Innate and Adaptive Immune Single-cell Profiling of Bronchoalveolar Lavages

text: How innate and adaptive lung immune responses to SARS-CoV-2 synchronize during COVID-19 pneumonitis and regulate disease severity is poorly established. To address this, we applied single-cell profiling to bronchoalveolar lavages from 44 patients with mild or critical COVID-19 versus non-COVID-19 pneumonia as control. Viral RNA-tracking delineated the infection phenotype to epithelial cells, but positioned mainly neutrophils at the forefront of viral clearance activity during COVID-19. In mild disease, neutrophils could execute their antiviral function in an immunologically ‘controlled’ fashion, regulated by fully-differentiated T-helper-17 (TH17)-cells, as well as T-helper-1 (TH1)-cells, CD8+ resident-memory (TRM) and partially-exhausted (TEX) T-cells with good effector functions. This was paralleled by ‘orderly’ phagocytic disposal of dead/stressed cells by fully-differentiated macrophages, otherwise characterized by anti-inflammatory and antigen-presenting characteristics, hence facilitating lung tissue repair. In critical disease, CD4+ TH1- and CD8+ TEX-cells were characterized by inflammation-associated stress and metabolic exhaustion, while CD4+ TH17- and CD8+ TRM-cells failed to differentiate. Consequently, T-cell effector function was largely impaired thereby possibly facilitating excessive neutrophil-based inflammation. This was accompanied by impaired monocyte-to-macrophage differentiation, with monocytes exhibiting an ATP-purinergic signalling-inflammasome footprint, thereby enabling COVID-19 associated fibrosis and worsening disease severity. Our work represents a major resource for understanding the lung-localised immunity and inflammation landscape during COVID-19.


title: Modeling the dynamics of COVID-19 using Q-SEIR model with age-stratified infection probability

text: We explore the advantage of age-stratifying the population as an improvement on the quarantine-modified SEIR model. We hypothesize that this would project lower cases of infection for the Philippines because of our country's low median age. We introduce the variable U that is multiplied to the incubation rate sigma; when exposed individuals become infected. U is the dot product of the proxy infection probabilities stratified per age group (F) and the population stratified per age group (P) divided by the total population, similar to calculating mathematical expectation. Proxies were taken from two data sets: Hubei, China with a calculated value of U_CHN=0.4447 and Quezon City, Philippines with U_QC=0.5074. When the majority age group, represented by the median age, is far from the age group with the highest number of infections the number of infected individuals decreases and produces a delayed peaking effect. This new method gives a much lower estimate on peak number of infected cases by 65.2% compared with age-stratification alone; and by 75.2% compared with Q-SEIR alone.


title: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update

text: Coronaviruses (CoVs) belong to the family of Coronaviridae, the order Nidovirales, and the genus Coronavirus. They are the largest group of viruses causing respiratory and gastrointestinal infections. Morphologically, CoVs are enveloped viruses containing a non-segmented positive-sense, single-stranded ribonucleic acid (RNA) viruses. CoVs are categorized into four important genera that include Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. A novel member of human CoV that has recently emerged in Wuhan, China, is now formally named as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). This is a unique strain of RNA viruses that have not been previously observed in humans. The virus has wide host adaptability and is capable of causing severe diseases in humans, masked palm civets, mice, dogs, cats, camels, pigs, chickens, and bats. The SARS-CoV-2 typically causes respiratory and gastrointestinal sickness in both humans and animals. It can be transmitted through aerosols and direct/indirect contact, as well as during medical cases and laboratory sample handling. Specific structural proteins, which might be found on the surface of the virus, play an important role in the pathogenesis and development of the complications. The disease is characterized by distinct medical signs and symptoms that include high fever, chills, cough, and shortness of breath or difficulty in breathing. The infected people may also present with other symptoms such as diarrhea, myalgia, fatigue, expectoration, and hemoptysis. It is important from the public health and economic point of view as it affects the growth of the country, which is majorly attributed to the restriction in the movement of the people and the cost associated with the control and prevention of the disease. Since there is no specific therapeutic intervention nor a vaccine available against the virus, supportive management and treatment with non-specific therapeutic agents (repurposed drugs) may provide relief to the patients. Some preventive strategies of the disease include blocking the routes of transmission of the infections, disinfection of instruments used during medical case handling, using personal protective equipment, proper and early diagnosis of the disease, avoiding contact with the sick patients, and quarantine of the infected/exposed people.


title: Visualizing the invisible: The effect of asymptomatic transmission on the outbreak dynamics of COVID-19

text: Understanding the outbreak dynamics of the COVID-19 pandemic has important implications for successful containment and mitigation strategies. Recent studies suggest that the population prevalence of SARS-CoV-2 antibodies, a proxy for the number of asymptomatic cases, could be an order of magnitude larger than expected from the number of reported symptomatic cases. Knowing the precise prevalence and contagiousness of asymptomatic transmission is critical to estimate the overall dimension and pandemic potential of COVID-19. However, at this stage, the effect of the asymptomatic population, its size, and its outbreak dynamics remain largely unknown. Here we use reported symptomatic case data in conjunction with antibody seroprevalence studies, a mathematical epidemiology model, and a Bayesian framework to infer the epidemiological characteristics of COVID-19. Our model learns, in real time, the time-varying contact rate of the outbreak, and projects the temporal evolution and credible intervals of the effective reproduction number and the symptomatic, asymptomatic, and recovered populations. Our study reveals that the outbreak dynamics of COVID-19 are sensitive to three parameters: the effective reproduction number, the ratio between the symptomatic and asymptomatic populations, and the infectious periods of both groups. For three distinct locations, Santa Clara County (CA, USA), New York City (NY, USA), and Heinsberg (NRW, Germany), our model estimates the fraction of the population that has been infected and recovered by May 13, 2020 to 6.2% (95% CI: 3.3%-9.0%), 22.7% (95% CI: 15.7%-29.8%), and 20.5% (95% CI: 17.0%-24.3%). Our method traces the initial outbreak date in Santa Clara County back to January 20, 2020 (95% CI: January 16, 2020 - January 24, 2020). Our results could significantly change our understanding and management of the COVID-19 pandemic: A large asymptomatic population will make isolation, containment, and tracing of individual cases challenging. Instead, if needed, managing community transmission through increasing population awareness, promoting physical distancing, and encouraging behavioral changes could become more relevant.


title: COVID-19 and intracerebral haemorrhage: causative or coincidental?

text: Pneumonia appears to be the most common manifestation of coronavirus disease 2019 (COVID-19), but some extrapulmonary involvement, such as gastrointestinal, cardiac and renal, has been reported. The limited clinical data about the virus's behavior to date, especially extrapulmonary symptoms, suggest that we should be aware of the possibility of initial cerebrovascular manifestations of COVID-19.


title: Recurrent Neural Reinforcement Learning for Counterfactual Evaluation of Public Health Interventions on the Spread of Covid-19 in the world

text: As the Covid-19 pandemic soars around the world, there is urgent need to forecast the expected number of cases worldwide and the length of the pandemic before receding and implement public health interventions for significantly stopping the spread of Covid-19. Widely used statistical and computer methods for modeling and forecasting the trajectory of Covid-19 are epidemiological models. Although these epidemiological models are useful for estimating the dynamics of transmission of epidemics, their prediction accuracies are quite low. Alternative to the epidemiological models, the reinforcement learning (RL) and causal inference emerge as a powerful tool to select optimal interventions for worldwide containment of Covid-19. Therefore, we formulated real-time forecasting and evaluation of multiple public health intervention problems into off-policy evaluation (OPE) and counterfactual outcome forecasting problems and integrated RL and recurrent neural network (RNN) for exploring public health intervention strategies to slow down the spread of Covid-19 worldwide, given the historical data that may have been generated by different public health intervention policies. We applied the developed methods to real data collected from January 22, 2020 to June 28, 2020 for real-time forecasting the confirmed cases of Covid-19 across the world. We forecasted that the number of laboratory confirmed cumulative cases of Covid-19 will pass 26 million as of August 14, 2020.


title: The heart microbiome of insectivorous bats from Central and South Eastern Europe

text: Host associated microbiome not only may affect the individual health-status or provide insights into the species- or group specific bacterial communities but may act as early warning signs in the assessment of zoonotic reservoirs, offering clues to predict, prevent and control possible episodes of emerging zoonoses. Bats may be carriers and reservoirs of multiple pathogens such as viruses, bacteria and parasites, showing in the same time robust immunity against many of them. The microbiota plays a fundamental role on the induction, training and function of the host immune system and the immune system has largely evolved in order to maintain the symbiotic relationship of the host with these diverse microbes. Thus, expanding our knowledge on bat-associated microbiome it can be usefully in understanding bats’ outstanding immune capacities. The aim of this study was to investigate the presence of different bacterial communities in heart tissue of insectivorous bats, Nyctalus noctula, Pipistrellus pipistrellus and Rhinoplophus hipposideros, from Central and Eastern Europe using high-throughput sequencing of variable regions of the 16S rRNA. In addition, species-specific PCRs were used to validate the presence of the vector-borne pathogens Bartonella spp. and Rickettsia spp. In this study we identified a wide variety of bacterial groups, with the most abundant phyla being Proteobacteria and Firmicutes. The results showed that at individual level, the year or location had no effect on the diversity and composition of the microbiome, however host species determined both structure and abundance of the bacterial community. We report the presence of vector-borne bacteria Bartonella spp. in samples of N. noctula and indications of Rickettsia spp. in R. hipposideros. Our results provide a first insight into the bacterial community found in heart tissue of bats from Central and South Eastern Europe.


title: A virus that has gone viral: Amino acid mutation in S protein of Indian isolate of Coronavirus COVID-19 might impact receptor binding and thus infectivity

text: Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002, MERS-CoV in 2012, and the recent outbreak of SARS-CoV-2 late in 2019 (also named as COVID-19 or novel coronavirus 2019 or nCoV2019. Spike(S) protein, one of the structural proteins of this virus plays key role in receptor (ACE2) binding and thus virus entry. Thus, this protein has attracted scientists for detailed study and therapeutic targeting. As the 2019 novel coronavirus takes its course throughout the world, more and more sequence analyses are been done and genome sequences getting deposited in various databases. From India two clinical isolates have been sequenced and the full genome deposited in GenBank. We have performed sequence analyses of the spike protein of the Indian isolates and compared with that of the Wuhan, China (where the outbreak was first reported). While all the sequences of Wuhan isolates are identical, we found point mutations in the Indian isolates. Out of the two isolates one was found to harbour a mutation in its Receptor binding domain (RBD) at position 407. At this site arginine (a positively charged amino acid) was replaced by isoleucine (a hydrophobic amino acid that is also a C-beta branched amino acid). This mutation has been seen to change the secondary structure of the protein at that region and this can potentially alter receptor ding of the virus. Although this finding needs further validation and more sequencing, the information might be useful in rational drug designing and vaccine engineering.


title: Purely data-driven exploration of COVID-19 pandemic after three months of the outbreak

text: It has been three months since the novel coronavirus (COVID-19) pandemic outbreak. Many research studies were carried to understand its epidemiological characteristics in the early phase of the disease outbreak. The current study is yet another contribution to better understand the disease properties by parameter estimation of mathematical SIR epidemic modeling. The authors use Johns Hopkins University dataset to estimate the basic reproduction number of COVID-19 for representative countries (Japan, Germany, Italy, France, and Netherlands) selected using cluster analysis. As a by-product, the authors estimate transmission, recovery, and death rates for each selected country and carry statistical tests to see if there are any significant differences.


title: Self-reported COVID-19 symptoms on Twitter: An analysis and a research resource

text: Objective To mine Twitter to quantitatively analyze COVID-19 symptoms self-reported by users, compare symptom distributions against clinical studies, and create a symptom lexicon for the research community. Materials and methods We retrieved tweets using COVID-19-related keywords, and performed several layers of semi-automatic filtering to curate self-reports of positive-tested users. We extracted COVID-19-related symptoms mentioned by the users, mapped them to standard IDs, and compared the distributions with multiple studies conducted in clinical settings. Results We identified 203 positive-tested users who reported 932 symptoms using 598 unique expressions. The most frequently-reported symptoms were fever/pyrexia (65%), cough (56%), body aches/pain (40%), headache (35%), fatigue (35%), and dyspnea (34%) amongst users who reported at least 1 symptom. Mild symptoms, such as anosmia (26%) and ageusia (24%) were frequently reported on Twitter, but not in clinical studies. Conclusion The spectrum of COVID-19 symptoms identified from Twitter may complement those identified in clinical settings.


title: Risk factors and symptoms stratification and mortality of COVID-19 in population of Nowshera (Pakistan)

text: Background & Objectives: COVID-19 has spread around the globe, and our country is no exception We have been actively observing and managing these patients and have recorded the salient features including risk factors, the presenting complaints and also the trends of mortality We aimed to have risk factors stratification, prevalent symptoms at the time of presentation to the hospital and to determine factors contributing to mortality due to COVID-19 in population of Nowshera (Pakistan) Methodology: In this cross sectional study, 75 cases with returned PCR results were included from 15th February 2020 to 18th April 2020 Data were entered in a format in SPSS version 25, prepared in accordance with the objectives of the study Results: Out of a total of 75 patients, 20 (26 67%) were females and 55 (73 33%) were males The mean age was 36 +/- 18 y Out of these, 29 (38 67%) patients were COVID-19 positive by PCR technique, and 46 (61 33%) were negative The probability of virus detection was higher in male gender (OR = 1 5, Relative Risk (RR) = 1 2) A significant relation of viral infectivity was noted with history of travel to an epidemic area (p = 0 01 OR = 3 85, RR = 1 5) and history of contacts with COVID-19 infected person/s (p = 0 018, OR = 3 5, RR = 2 3) A high mortality rate of 3/29 (10 34%) for positive COVID-19 cases was recorded The probability of worse outcome in term of death in COVID-19 positive patients was (p = 0 5, OR = 2 1) Regarding symptoms selection;contact and travel history without any symptoms has a reliability index (RI) of 12/35 (34%) for infectivity Cough, fever with shortness of breath (RI;8/12(67%) for positive cases followed by fever and cough with RI of 6/10 (60%) cases etc Sore throat (RI;1/13(8%) and flue only (RI;0/3(0%) proved non-reliable symptoms When plotted the survival graphs of COVID positive vs COVID negative cases, a similar pattern was recorded that showed the mortality rate in the positive cases was not solely due to COVID-19, though being opportunistic infection, it would have contributed We recorded refractory COVID-19 in 4/29 (13 79%) cases Conclusion: We conclude that male gender with history of travel to an epidemic area and contact with COVID-19 patients are strong predisposing factors Cough, fever with shortness of breath are reliable symptoms for COVID-19 in our suspects COVID-19 being an opportunistic infection contributes to a higher mortality in respiratory and cardiac patients