title: Tracing Back the Temporal Change of SARS-CoV-2 with Genomic Signatures

text: The coronavirus disease (COVID-19) outbreak starting from China at the end of 2019 and its subsequent spread in many countries have given rise to thousands of coronavirus samples being collected and sequenced till date. To trace back the initial temporal change of SARS-CoV-2, the coronavirus implicated in COVID-19, we study the limited genomic sequences that were available within the first couple of months of its spread. These samples were collected under varying circumstances and highlight wide variations in their genomic compositions. In this paper, we explore whether these variations characterize the initial temporal change of SARS-CoV-2 sequences. We observe that n-mer distributions in the SARS-CoV-2 samples, which were collected at an earlier period of time, predict its collection timeline with approximately 78% accuracy. However, such a distinctive pattern disappears with the inclusion of samples collected at a later time. We further observe that isolation sources (e.g., oronasopharynx, saliva, feces, etc.) could not be predicted by the n-mer patterns in these sequences. Finally, the phylogenetic and protein-alignment analyses highlight interesting associations between SARS-CoV-2 and other coronaviruses.


title: In-Silico evidence for two receptors based strategy of SARS-CoV-2

text: We propose a novel numerical method able to determine efficiently and effectively the relationship of complementarity between portions of protein surfaces. This innovative and general procedure, based on the representation of the molecular iso-electron density surface in terms of 2D Zernike polynomials, allows the rapid and quantitative assessment of the geometrical shape complementarity between interacting proteins, that was unfeasible with previous methods. We first tested the method with a large dataset of known protein complexes obtaining an overall area under the ROC curve of 0.76 in the blind recognition of binding sites and then applied it to investigate the features of the interaction between the Spike protein of SARS-CoV-2 and human cellular receptors. Our results indicate that SARS-CoV-2 uses a dual strategy: its spike protein could also interact with sialic acid receptors of the cells in the upper airways, in addition to the known interaction with Angiotensin-converting enzyme 2.


What to D.O.: Ready for COVID-19 — and Every Chart in the Rack


title: Doxycycline has Distinct Apicoplast-Specific Mechanisms of Antimalarial Activity

text: Doxycycline (DOX) is a key antimalarial drug that is thought to kill Plasmodium falciparum parasites by blocking protein translation in the essential apicoplast organelle. Although parasite resistance to DOX has not emerged, clinical use is primarily limited to prophylaxis due to delayed second-cycle parasite death at 1-3 μM, the DOX concentration readily achieved in human plasma at current dosing. Slow antiparasitic activity is thought to be a fundamental limitation of DOX and other antibiotics that target apicoplast maintenance. We report that slightly higher 8-10 μM DOX concentrations kill parasites with first-cycle activity that blocks apicoplast biogenesis. This faster activity is rescued by exogenous isopentenyl pyrophosphate, an essential apicoplast product, confirming an apicoplast-specific target. Exogenous iron rescues first- but not second-cycle activity by 1 or 10 μM DOX, revealing that first-cycle activity involves a metal-dependent mechanism that is distinct from the canonical delayed-death mechanism. These results provide a new paradigm for understanding fundamental antiparasitic mechanisms of DOX and suggest the possibility of repurposing DOX as a faster-acting antimalarial at higher dosing, which remains well tolerated. Multiple mechanisms of DOX activity would be expected to limit parasite resistance.


title: Analysis of the initial chest high resolution CT manifestations of COVID-19/ 新型冠状病毒肺炎首次胸部高分辨率CT影像分析

text: Objective: To investigate the initial chest high resolution CT (HRCT) manifestations of the patients with COVID-19. Methods: A retrospective analysis of the first chest HRCT images of 106 patients with COVID-19 was performed who were confirmed in our hospital from January 3 to 25, 2020. Lesion distribution, morphology and surrounding involvement were analyzed. Results: The lesions were found on all initial HRCT images of 106 patients, with unilateral lung distribution in 11 cases (10.4%) and bilateral lung distribution in other 95 cases(89.6%), peripheral distribution of lung in 65 cases (61.3%) and peripheral and central distribution in other 41 cases (38.7%). HRCT showed 8 cases (7.5%) with 1 lesion, 5 cases (4.7%) with 2 lesions, and other 93 cases (87.8%) with multiple lesions. HRCT also showed the nodular lesions in 12 cases(11.3%), ground-glass opacities in 94 cases (88.7%), fibrous stripes in 7 cases (6.6%), and mixed lesions in 15 cases (14.2%). Only one lung lobe was involved in 10 cases (9.4%), while more than two lobes were involved in other 96 cases (90.6%). In addition, 24 cases (22.6%) with enlarged mediastinal lymph nodes (over 60 years old in 19 cases, accounting for 79.2%), 3 cases with pleural effusion (2.8 %), 1 case with pericardial effusion (0.9%), and 2 cases with pleural involvement/thickening (1.9%) were found. Patients over 60 years old mostly presented with multiple lesions, various appearances, peripheral and central distributions of lungs, involving multiple lobes, and enlarged mediastinal lymph nodes. Conclusions: Lung COVID-19 lesions can be shown by the initial chest HRCT, which is the preferred imaging method. Thoracic HRCT scans play an important role in the early diagnosis of COVID-19.


title: Tissue distribution of ACE2 protein in Syrian golden hamster (Mesocricetus auratus) and its possible implications in SARS-CoV-2 related studies

text: Recently, the Syrian golden hamster (Mesocricetus auratus) has been demonstrated as a clinically relevant animal model for SARS-CoV-2 infection. However, lack of knowledge about the tissue-specific expression pattern of various proteins in these animals and the unavailability of reagents like antibodies against this species hampers optimal use of these models. The major objective of our current study was to analyze the tissue-specific expression pattern of angiotensin□converting enzyme 2 (ACE2), a proven functional receptor for SARS-CoV-2 in different organs of the hamster. We have adapted immunoblot analysis, immunohistochemistry, and immunofluorescence analysis techniques to evaluate the ACE2 expression pattern in different tissues of the Syrian golden hamster. We found that kidney, small intestine, esophagus, tongue, brain, and liver express ACE2. Epithelium of proximal tubules of kidney and surface epithelium of ileum expresses a very high amount of this protein. Surprisingly, analysis of stained tissue sections for ACE2 showed no detectable expression of ACE2 in the lung or tracheal epithelial cells. Similarly, all parts of the large intestine (caecum, colon, and rectum) were negative for ACE2 expression. Together, our findings corroborate some of the earlier reports related to ACE2 expression pattern in human tissues and also contradicts some others. We believe that the findings of this study will enable the appropriate use of the Syrian golden hamster to carryout SARS-CoV-2 related studies.


title: Household transmission of COVID-19, Shenzhen, January-February 2020

text: Coronavirus disease 2019 has led to more than three million cases globally. Since the first family cluster of COVID-19 cases identified in Shenzhen in early January, most of the local transmission occurred within household contacts. Identifying the factors associated with household transmission is of great importance to guide preventive measures.


title: Randomization amid a pandemic - a critical appraisal regarding convalescent plasma therapy clinical trials for COVID-19 patients

text: Abstract The novel coronavirus disease (COVID-19) is spreading rapidly, a pandemic that has already affected millions of people across the world Currently there are no vaccines or drugs approved for COVID-19 Initial data which are coming from large clinical trials using Hydroxychloroquine, Lopinavir/Ritonavir, Remdesevir, and Favipiravir are not satisfactory against COVID-19 till now and we are in the midst of a worldwide public health threat In this context human convalescent plasma is considered as an option for treatment of COVID-19 disease Convalescent plasma therapy is a classic adaptive immunotherapy which involves the administration of antibodies against COVID-19 to a COVID-19 patient for the purpose of treating the viral disease Over the last two decades, convalescent plasma therapy was used for the treatment of 2003 SARS-CoV-1 epidemic, 2009-2010 H1N1 influenza virus pandemic, the 2012 Middle East Respiratory Syndrome (MERS)-CoV epidemic and 2014-2016 Ebola epidemic


title: Evaluation of WHO listed COVID-19 qPCR primers and probe in silico with 375 SERS-CoV-2 full genome sequences

text: Quantitative reverse-transcription PCR (qRT-PCR) assays remains the gold standard for detection of the SARS-CoV-2 virus because of its sensitivity and specificity. However, successful design of qRT-PCR assays requires accurate viral genome sequences. With mutations accumulating as the virus is transmitted globally, we sought to compare current assays recommended by the World Health Organization with available SARS-CoV-2 genomic sequences in silico. While most sequences were conserved, there were notable mismatches, particularly in assays developed using early sequences when compared to more recent isolates. We recommend that any assay being evaluated for diagnostic tests be compared with prevalent sequence data from the region of proposed testing and that continued publicly accessible sequence information continue to be provided by the research community.


title: A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV

text: The outbreak of COVID-19, which is caused by SARS-CoV-2 virus, continues to spread globally, but there is currently very little understanding of the epitopes on the virus. In this study, we have determined the crystal structure of the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein in complex with CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient. CR3022 targets a highly conserved epitope that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding site can only be accessed when at least two RBDs on the trimeric S protein are in the “up” conformation. Overall, this study provides structural and molecular insight into the antigenicity of SARS-CoV-2. ONE SENTENCE SUMMARY Structural study of a cross-reactive SARS antibody reveals a conserved epitope on the SARS-CoV-2 receptor-binding domain.


title: Prediction of the Epidemic Peak of Covid19 in Egypt, 2020

text: Objectives: Since December 2019 a pandemic of new novel coronavirus has started from Wuhan, China, in Egypt, the first case reported on February 14, 2020. In this study we aimed to predict the time of possible peak and simulate the changes could be happen by the social behavior of Egyptians during Ramadan (the holy month). Methods: SIR and SEIR compartmental models were used to predict the peak time. We simulated different expected scenarios based to examine their effects on the peak timing. Results: We found that the peak most likely to be in middle of June 2020. Simulating different transmission rate probability and R0 the earliest peak could to be in the May 20 and latest one could be in 18 July. The peak shifted much earlier to 11th April 2020 without lockdown and other mitigation strategies. Conclusion: Social behaviors of citizens during the holy month will dramatically affect the peak timing. Mitigations strategies and other lockdown measure helped to delay the expected peak. Keywords: COVID-19; compartmental models; Epidemic peak; Egypt


title: Why does COVID-19 case fatality rate vary among countries?

text: Background While the epidemic of SARS-CoV-2 is spreading worldwide, there is much concern over the mortality rate that the infection induces. Available data suggest that COVID-19 case fatality rate varies temporally (as the epidemic progresses) and spatially (among countries). Here, we attempted to identify key factors possibly explaining the variability in case fatality rate across countries. Methods We used data on the temporal trajectory of case fatality rate provided by the European Center for Disease Prevention and Control, and country-specific data on different metrics describing the incidence of known comorbidity factors associated with an increased risk of COVID-19 mortality at the individual level (Institute for Health Metrics and Evaluation). We also compiled data on demography, economy and political regimes for each country. Findings We first showed that temporal trajectories of case fatality rate greatly vary among countries. We found no evidence for association between comorbidities and case fatality rate at the country level. Case fatality rate was negatively associated with number of hospital beds x1,000 inhabitants. We also report evidence suggesting an association between case fatality rate and the political regime, with democracies suffering from the highest mortality burden, compared to autocratic regimes. However, most of the among-country variance in case fatality rate remained unexplained. Interpretation Overall, these results emphasize the role of socio-economic and political factors as possible drivers of COVID-19 case fatality rate at the country level. Funding None.


title: Dog Savior: Immediate Scent-Detection of SARS-COV-2 by Trained Dogs

text: Molecular tests for viral diagnostics are essential to confront the COVID-19 pandemic, but their production and distribution cannot satisfy the current high demand. Early identification of infected people and their contacts is the key to being able to isolate them and prevent the dissemination of the pathogen; unfortunately, most countries are unable to do this due to the lack of diagnostic tools. Dogs can identify, with a high rate of precision, unique odors of volatile organic compounds generated during an infection; as a result, dogs can diagnose infectious agents by smelling specimens and, sometimes, the body of an infected individual. We trained six dogs of three different breeds to detect SARS-CoV-2 in respiratory secretions of infected patients and evaluated their performance experimentally, comparing it against the gold standard (rRT-PCR). Here we show that viral detection takes one second per specimen. After scent-interrogating 9,200 samples, our six dogs achieved independently and as a group very high sensitivity, specificity, predictive values, accuracy, and likelihood ratio, with very narrow confidence intervals. The highest metric was the negative predictive value, indicating that with a disease prevalence of 7.6%, 99.9% of the specimens indicated as negative by the dogs did not carry the virus. These findings demonstrate that dogs could be useful to track viral infection in humans, allowing COVID-19 free people to return to work safely.


title: Predictors to use mobile apps for monitoring COVID-19 symptoms and contact tracing: A survey among Dutch citizens.

text: Introduction: eHealth applications have been recognized as a valuable tool to reduce COVID-19s effective reproduction number. In this paper, we report on an online survey among Dutch citizens with the goal to identify antecedents of acceptance of a mobile application for COVID-19 symptom recognition and monitoring, and a mobile application for contact tracing. Methods: Next to the demographics, the online survey contained questions focussing on perceived health, fear of COVID-19 and intention to use. We used snowball sampling via posts on social media and personal connections. To identify antecedents of acceptance of the two mobile applications we conducted multiple linear regression analyses. Results: In total, 238 Dutch adults completed the survey. Almost 60% of the responders were female and the average age was 45.6 years (SD=17.4). For the symptom app, the final model included the predictors age, attitude towards technology and fear of COVID-19. The model had an R2 of 0.141. The final model for the tracing app included the same predictors and had an R2 of 0.156. The main reason to use both mobile applications was to control the spread of the COVID-19 virus. Concerns about privacy was mentioned as the main reason not to use the mobile applications. Discussion: Age, attitude towards technology and fear of COVID-19 are important predictors of the acceptance of COVID-19 mobile applications for symptom recognition and monitoring and for contact tracing. These predictors should be taken into account during the development and implementation of these mobile applications to secure acceptance.


title: An Inexpensive RT-PCR Endpoint Diagnostic Assay for SARS-CoV-2 Using Nested PCR: Direct Assessment of Detection Efficiency of RT-qPCR Tests and Suitability for Surveillance

text: With a view to extending testing capabilities for the ongoing SARS-CoV-2 pandemic we have developed a test that lowers cost and does not require real time quantitative reverse transcription polymerase chain reaction (RT-qPCR). We developed a reverse transcription nested PCR endpoint assay (RT-nPCR) and showed that RT-nPCR has comparable performance to the standard RT-qPCR test. In the course of comparing the results of both tests, we found that the standard RT-qPCR test can have low detection efficiency (less than 50%) in a real testing scenario which may be only partly explained by low viral representation in many samples. This finding points to the importance of directly monitoring detection efficiency in test environments. We also suggest measures that would improve detection efficiency.


title: Introduction to the special issue: Why the coronavirus crisis is also a crisis of leadership

text: This editorial introduction argues that the coronavirus crisis is also a crisis of leadership theory and practice. Decision making is particularly hazardous when we have poor evidence to guide us and face unpredictable outcomes. Mainstream leadership theories are of little help, since an environment of radical uncertainty means that leaders have less information, expertise and resources to guide them than is often assumed. Undaunted, populist leaders exploit uncertainty to suggest that simple solutions will work. I suggest that the responses of such leaders have been characterised by incompetent leadership, denialist leadership, panic leadership, othering leadership and authoritarian leadership. I also consider the implications of the crisis for business leadership, suggesting that already strained relationships within organisations are likely to deteriorate still further. Critical leadership studies has an important contribution to make in challenging self-serving theories of business that have come to guide much leadership decision-making. We have an opportunity to do research that really matters, and participate in vital conversations about how the theory and practice of leadership can contribute to better outcomes from the coronavirus crisis, and others still to come.


title: Forecasting of COVID-19 Confirmed Cases in Different Countries with ARIMA Models

text: The epidemic of a novel coronavirus illness (COVID-19) becomes as a global threat. The aim of this study is first to find the best prediction models for daily confirmed cases in countries with high number of confirmed cases in the world and second to predict confirmed cases with these models in order to have more readiness in healthcare systems. This study was conducted based on daily confirmed cases of COVID-19 that were collected from the official website of Johns Hopkins University from January 22th, 2020 to March 1th, 2020. Auto Regressive Integrated Moving Average (ARIMA) model was used to predict the trend of confirmed cases. Stata version 12 was used. Mainland China and Thailand had almost a stable trend. The trend of South Korea was decreasing and will become stable in near future. Iran and Italy had unstable trends. Mainland China and Thailand were successful in haltering COVID-19 epidemic. Investigating their protocol in this control like quarantine should be in the first line of other countries program


The COVID-19 Pandemic at the Intersection of Marketing and Public Policy: JPP&M JPP&M JM & PP


title: Community prevalence of SARS-CoV-2 in England: Results from the ONS Coronavirus Infection Survey Pilot

text: Objective: To estimate the percentage of individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) over time in the community in England and to quantify risk factors. Design: Repeated cross-sectional surveys of population-representative households with longitudinal follow-up if consent given. Setting: England. Participants: 34,992 Individuals aged 2 years and over from 16,722 private residential households. Data were collected in a pilot phase of the survey between 26 April and 28 June 2020. Main outcome measures: Percentage of individuals in the community testing positive for SARS-CoV-2 RNA using throat and nose swabs. Individuals were asked about any symptoms and potential risk factors. Results: The percentage of people in private-residential households testing positive for SARS-CoV-2 reduced from 0.32% (95% credible interval (CrI) 0.19% to 0.52%) on 26 April to 0.08% (95% CrI 0.05% to 0.12%) on 28 June, although the prevalence stabilised near the end of the pilot. Factors associated with an increased risk of testing positive included having a job with direct patient contact (relative exposure (RE) 4.06, 95% CrI 2.42 to 6.77)), working outside the home (RE 2.49, 95% CrI 1.39 to 4.45), and having had contact with a hospital (RE 2.20, 95% CrI 1.09 to 4.16 for having been to a hospital individually and RE 1.95, 95% CrI 0.81 to 4.09 for a household member having been to a hospital). In 133 visits where individuals tested positive, 82 (61%, 95% CrI 53% to 69%) reported no symptoms, stably over time. Conclusion: The percentage of SARS-CoV-2 positive individuals declined between 26 April and 28 June 2020. Positive tests commonly occurred without symptoms being reported. Working outside your home was an important risk factor, indicating that continued monitoring for SARS-CoV-2 in the community will be essential for early detection of increases in infections following return to work and other relaxations of control measures.


title: Use of High Flow Nasal Therapy to Treat Moderate to Severe Hypoxemic Respiratory Failure in COVID-19

text: Abstract Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of High flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission. Methods This was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from March 10, 2020, to April 24, 2020 with moderate to severe respiratory failure treated with High Flow nasal therapy (HFNT). Primary outcome was prevention of intubation. Results Of the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (+13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. SF and chest Xray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital/ventilator associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of VAP/HAP was statistically higher in the progressed to intubation group. Conclusion HFNT use is associated with a reduction in the rate of Invasive mechanical ventilation and overall mortality in patients with COVID-19 infection.


title: Clinical and radiographic features of cardiac injury in patients with 2019 novel coronavirus pneumonia

text: Objective: To investigate the correlation between clinical characteristics and cardiac injury of COVID-2019 pneumonia. Methods: In this retrospective, single-center study, 41 consecutive corona virus disease 2019 (COVID-2019) patients (including 2 deaths) of COVID-2019 in Beijing Youan Hospital, China Jan 21 to Feb 03, 2020, were involved in this study. The high risk factors of cardiac injury in different COVID-2019 patients were analyzed. Computed tomographic (CT) imaging of epicardial adipose tissue (EAT) has been used to demonstrate the cardiac inflammation of COVID-2019. ResultsOf the 41 COVID-2019 patients, 2 (4.88%), 32 (78.05%), 4 (9.75%) and 3 (7.32%) patients were clinically diagnosed as light, mild, severe and critical cases, according to the 6th guidance issued by the National Health Commission of China. 10 (24.4%) patients had underlying complications, such as hypertension, CAD, type 2 diabetes mellites and tumor. The peak value of TnI in critical patients is 40-fold more than normal value. 2 patients in the critical group had the onset of atrial fibrillation, and the peak heart rates reached up to 160 bpm. CT scan showed low EAT density in severe and critical patients. Conclusion: Our results indicated that cardiac injury of COVID-2019 was rare in light and mild patients, while common in severe and critical patients. Therefore, the monitoring of the heart functions of COVID-2019 patients and applying potential interventions for those with abnormal cardiac injury related characteristics, is vital to prevent the fatality.


title: Vitamin C for the treatment of COVID-19: A living systematic review

text: Objective This living systematic review aims to provide a timely, rigorous and continuously updated summary of the evidence available on the role of vitamin C in the treatment of patients with COVID-19. Data sources We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L OVE (Living OVerview of Evidence). L OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal. Eligibility criteria for selecting studies and methods We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. We will include randomised trials evaluating the effect of vitamin C, as monotherapy or in combination with other drugs, versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating vitamin C in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low- or very low-certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will pool the results using meta-analysis and will apply the GRADE system to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it every time the conclusions change or whenever there are substantial updates. Ethics and dissemination No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media. PROSPERO Registration Submitted to PROSPERO (awaiting ID allocation). Keywords COVID-19, severe acute respiratory syndrome coronavirus 2, Coronavirus Infections, Systematic review, vitamin c, ascorbic acid.


title: Molecular architecture of the SARS-CoV-2 virus

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins and the complexes of the spike (S) proteins with the cellular receptor ACE2 or neutralizing antibodies, detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryo-electron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in both pre- and postfusion conformations were determined to average resolutions of 9-11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed highly similar overall processing states of the native glycans to that of the recombinant glycoprotein glycans. The in situ architecture of the ribonucleoproteins (RNP) and its higher-order assemblies were revealed. These characterizations have revealed the architecture of the SARS-CoV-2 virus to an unprecedented resolution, and shed lights on how the virus packs its ~30 Kb long single-segmented RNA in the ~80 nm diameter lumen. Overall, the results unveiled the molecular architecture and assembly of the SARS-CoV-2 in native context.


title: The impact of the undetected COVID-19 cases on its transmission dynamics

text: Objective: The COVID-19 pandemic is currently ongoing. Presently, due to the unavailability of a definitive vaccine to decrease its acquiring, it is essential to understand its transmissibility in the community by undetected cases to control its transmission. This study aims to study this context using mathematical modelling. Methods: A COVID-19 transmission model was framed that estimated the basic reproduction number (R_0, a measurement of disease risk) using the next-generation method. It explored the contribution of exposed and infected (detected and undetected) individuals, and environmental pathogen to the overall risk of infection spreading, utilizing the publicly reported data of this infection in Maharashtra between March 22, 2020, and May 4, 2020. A sensitivity analysis was performed to study the effect of a rising number of undetected cases to R_0. Results: The estimated basic reproduction number is R_0=4.63, which increases rapidly with the rise in the undetected COVID-19 cases. Although the exposed individuals made the largest contribution to infection transmission (R_1=2.42), the contaminated environment also played a significant role. Conclusions: It is crucial to identify the individuals exposed and infected to COVID-19 disease and isolate them to control its transmission. The awareness of the role of fomites in infection transmission is also important in this regard.


title: Case Study: Using Facebook Data to Monitor Adherence to Stay-at-home Orders in Colorado and Utah

text: In the absence of effective treatments or a vaccine, social distancing has been the only public health measure available to combat the COVID-19 pandemic to date. In the US, implementing this response has been left to state, county, and city officials, and many localities have issued some form of a stay-at-home order. Without existing tools and with limited resources, localities struggled to understand how their orders changed behavior. In response, several technology companies opened access to their users' location data. As part of the COVID-19 Data Mobility Data Network, we obtained access to Facebook User data and developed four key metrics and visualizations to monitor various aspects of adherence to stay at home orders. These metrics were carefully incorporated into static and interactive visualizations for dissemination to local officials. All code is open source and freely available at https://github.com/ryanlayer/COvid19


title: Zooming In versus Flying Out: Virtual Residency Interviews in the Era of COVID-19

text: Abstract The 2019 coronavirus disease (COVID-19) pandemic has prompted graduate medical education (GME) programs to revisit the concept of virtual interviews for applicants given uncertainty over the duration of social distancing measures and travel restrictions A ?virtual interview? refers to the process of conducting interactions over a video-conferencing platform instead of the traditional model of traveling to an on-site location with face-to-face interactions


title: Comparison of SARS-CoV-2 infections among 3 species of non-human primates

text: COVID-19, caused by SARS-CoV-2 infection, has recently been announced as a pandemic all over the world. Plenty of diagnostic, preventive and therapeutic knowledges have been enriched from clinical studies since December 2019. However, animal models, particularly non-human primate models, are urgently needed for critical questions that could not be answered in clinical patients, evaluations of anti-viral drugs and vaccines. In this study, two families of non-human primates, old world monkeys (12 Macaca mulatta, 6 Macaca fascicularis) and new world monkeys (6 Callithrix jacchus), were experimentally inoculated with SARS-CoV-2. Clinical signs were recorded. Samples were collected for analysis of viral shedding, viremia and histopathological examination. Increased body temperature was observed in 100% (12/12) M. mulatta, 33.3% (2/6) M. fascicularis and none (0/6) of C. jacchus post inoculation of SARS-CoV-2. All of M. mulatta and M. fascicularis showed chest radiographic abnormality. Viral genomes were detected in nasal swabs, throat swabs, anal swabs and blood from all 3 species of monkeys. Viral shedding from upper respiratory reached the peak between day 6 and day 8 post inoculation. From necropsied M. mulatta and M. fascicularis, tissues showing virus positive were mainly lung, weasand, bronchus and spleen. No viral genome was seen in any of tissues from 2 necropsied C. jacchus. Severe gross lesions and histopathological changes were observed in lung, heart and stomach of SARS-CoV-2 infected animals. In summary, we have established a NHP model for COVID-19, which could be used to evaluate drugs and vaccines, and investigate viral pathogenesis. M. mulatta is the most susceptible to SARS-CoV2 infection, followed by M. fascicularis and C. jacchus. One Sentence Summary M. mulatta is the most susceptible to SARS-CoV-2 infection as compared to M. fascicularis and C. jacchus.


title: SARS-CoV-2 infection: the environmental endurance of the virus can be influenced by the increase of temperature

text: The COVID-19 disease, a respiratory disease transmitted by a new betacoronavirus SARS-CoV-2. As for other viral respiratory agents, SARS-CoV-2 spreads by person to person through respiratory droplets and direct contact and potentially by indirect contact through fomites. The goal of the current study is to evaluate whether the increase of temperature can influence the environmental endurance of SARS-CoV-2.We tested SARS-CoV-2 environmental stability in parallel at room temperature (RT, 20-25 Celsius degrees) and at average maximum temperature of June (JT) estimated at 28 Celsius degrees in Italy. The virus inoculated on plastic surface was harvested at predefined time-points and tested to evaluate viral titres on Vero cells by TCID50. Our results confirm that fomite transmission of the emerging SARS-CoV2 is possible, since the virus remains viable on surfaces up to 84 hours at both RT and JT. Moreover, a remarkable difference between the two temperatures exists, suggesting that virus vitality can be influenced by the environmental temperature. Our results support the hypothesis that in the hot season the increase of temperature could influence the environmental endurance of SARS-CoV2 and reduce Covid-19 transmission probability.


title: Profiling the epigenome at home

text: We recently described CUT&Tag, a general strategy for epigenomic profiing in which antibody-tethered Tn5 transposase integrates DNA sequencing adapters at sites of specific chromatin protein binding or histone modification in intact cells or nuclei. Here we introduce a simplified CUT&Tag method that can be performed at home to help ameliorate the interruption of bench research caused by COVID-19 physical distancing requirements. All steps beginning with frozen nuclei are performed in single PCR tubes through to barcoded library amplication and clean-up, ready for pooling and DNA sequencing. Our CUT&Tag@home protocol has minimal equipment, reagent and supply needs and does not require handling of toxic or biologically active materials. We show that data quality and reproducibility for samples down to ~100 nuclei compare favorably to datasets produced using lab-based CUT&Tag and other chromatin profiling methods. We use CUT&Tag@home with antibodies to trimethylated histone H3 lysine-4, −36, −27 and-9 to comprehensively profile the epigenome of human K562 cells, consisting respectively of active gene regulatory elements, transcribed gene bodies, developmentally silenced domains and constitutively silenced parasitic elements.


title: Interspecies transmission and evolution of the emerging coronaviruses: Perspectives from bat physiology and protein spatial structure

text: Emergent coronaviruses (CoVs) such as SARS-CoV and MERS-CoV have posed great threats to public health worldwide over the past two decades. Currently, the emergence of SARS-CoV-2 as a pandemic causes greater public health concern. CoV diversity is due to the large size and replication mechanisms of the genomes together with having bats as their optimum natural hosts. The ecological behavior and unique immune characteristics of bats are optimal for the homologous recombination of CoVs. The relationship of spatial structural characteristics of the spike protein, a protein that is critical for recognition by host receptors, in different CoVs may provide evidence in explaining the coevolution of CoVs and their hosts. This information may help to enhance our understanding of CoV evolution and thus provide part of the basis of preparations for any future outbreaks.


title: A simple arithmetic rationale for crushing the epidemic curve of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) instead of flattening it

text: Countries with ambitious strategies to "crush the curve" of their epidemic trajectories, to promptly eliminate SARS-CoV-2 transmission at national level, include China, Korea, Japan, Taiwan, New Zealand and Australia. In stark contrast, many of the European countries hit hardest over the last two months, including Italy, Spain, France, Ireland and the United Kingdom, currently appear content to merely "flatten the curve" of their epidemic trajectories so that transmission persists at rates their critical care services can cope with. Here is presented a simple set of arithmetic modelling analyses that explain why preferable crush the "curve strategies", to eliminate transmission within months, would require only a modest amount of additional containment effort when compared to "flatten the curve" strategies that allow epidemics to persist at a steady, supposedly manageable level for years, decades or even indefinitely.


title: The relationship of COVID-19 severity with cardiovascular disease and its traditional risk factors: A systematic review and meta-analysis

text: Background: Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 (COVID-19) is uncertain, in part, because of potential confounding by age and sex. Methods: We performed a systematic review of studies that explored pre-existing CVD and its traditional risk factors as risk factors of severe COVID-19 (defined as death, acute respiratory distress syndrome, mechanical ventilation, or intensive care unit admission). We searched PubMed and Embase for papers in English with original data (≥10 cases of severe COVID-19). Using random-effects models, we pooled relative risk (RR) estimates and conducted meta-regression analyses. Results: Of the 661 publications identified in our search, 25 papers met our inclusion criteria, with 76,638 COVID-19 patients including 11,766 severe cases. Older age was consistently associated with severe COVID-19 in all eight eligible studies, with RR >~5 in >60-65 vs. <50 years. Three studies showed no change in the RR of age after adjusting for covariate(s). In univariate analyses, factors robustly associated with severe COVID-19 were male sex (10 studies; pooled RR=1.73, [95%CI 1.50-2.01]), hypertension (8 studies; 2.87 [2.09-3.93]), diabetes (9 studies; 3.20 [2.26-4.53]), and CVD (10 studies; 4.97 [3.76-6.58]). RR for male sex was likely to be independent of age. For the other three factors, meta-regression analyses suggested confounding by age. Only four studies reported multivariable analysis, but most of them showed adjusted RR ~2 for hypertension, diabetes, and CVD. No study explored renin-angiotensin system inhibitors as a risk factor for severe COVID-19. Conclusions: Despite the potential for confounding, these results suggest that hypertension, diabetes, and CVD are independently associated with severe COVID-19 and, together with age and male sex, can be used to inform objective decisions on COVID-19 testing, clinical management, and workforce planning.


title: Saliva Sample as a Non-Invasive Specimen for the Diagnosis of Coronavirus Disease-2019 (COVID-19): a Cross-Sectional Study

text: Objectives. Amid the increasing number of global pandemic coronavirus disease 2019 (COVID-19) cases, there is a need for a quick and easy method to obtain a non-invasive sample for the detection of this novel coronavirus 2019 (SARS-CoV-2). We aimed to investigate the potential use of saliva samples as a non-invasive tool for the diagnosis of COVID-19. Methods. From 27 March to 4 April, 2020, we prospectively collected saliva samples and a standard nasopharyngeal and throat swab in persons seeking care at an acute respiratory infection clinic in a university hospital during the outbreak of COVID-19. Real-time polymerase chain reaction (RT-PCR) was performed, and the results of the two specimens were compared. Results. Two-hundred pairs of the samples were collected. Sixty-nine (34.5%) patients were male, and the median (interquartile) age was 36 (28-48) years. Using nasopharyngeal and throat swab RT-PCR as the reference standard, the prevalence of COVID-19 diagnosed by nasopharyngeal and throat swab RT-PCR was 9.5%. The sensitivity and specificity of the saliva sample RT-PCR were 84.2% [95% confidence interval (CI) 79.2%-89.3%], and 98.9% (95% CI 97.5-100.3%), respectively. An analysis of the agreement between the two specimens demonstrated 97.5% observed agreement (kappa coefficient 0.851, 95% CI 0.723-0.979; p <0.001). Conclusions. Saliva specimens can be used for the diagnosis of COVID-19. The collection method is non-invasive, and non-aerosol generating. Using a saliva sample as a specimen for the detection of SARS-CoV-2 could facilitate the diagnosis of the disease, which is one of the strategies that helps in controlling the epidemic.


title: Replication of Equine arteritis virus is efficiently suppressed by purine and pyrimidine biosynthesis inhibitors

text: RNA viruses are responsible for a large variety of animal infections. Equine Arteritis Virus (EAV) is a positive single-stranded RNA virus member of the family Arteriviridae from the order Nidovirales like the Coronaviridae. EAV causes respiratory and reproductive diseases in equids. Although two vaccines are available, the vaccination coverage of the equine population is largely insufficient to prevent new EAV outbreaks around the world. In this study, we present a high-throughput in vitro assay suitable for testing candidate antiviral molecules on equine dermal cells infected by EAV. Using this assay, we identified three molecules that impair EAV infection in equine cells: the broad-spectrum antiviral and nucleoside analog ribavirin, and two compounds previously described as inhibitors of dihydroorotate dehydrogenase (DHODH), the fourth enzyme of the pyrimidine biosynthesis pathway. These molecules effectively suppressed cytopathic effects associated to EAV infection, and strongly inhibited viral replication and production of infectious particles. Since ribavirin is already approved in human and small animal, and that several DHODH inhibitors are in advanced clinical trials, our results open new perspectives for the management of EAV outbreaks.


title: The 4C Initiative (Clinical Care for Cardiovascular disease in the COVID-19 pandemic): monitoring the indirect impact of the coronavirus pandemic on services for cardiovascular diseases in the UK

text: Background: The coronavirus (COVID-19) pandemic affects cardiovascular diseases (CVDs) directly through infection and indirectly through health service reorganisation and public health policy. Real-time data are needed to quantify direct and indirect effects. We aimed to monitor hospital activity for presentation, diagnosis and treatment of CVDs during the pandemic to inform on indirect effects. Methods: We analysed aggregate data on presentations, diagnoses and treatments or procedures for selected CVDs (acute coronary syndromes, heart failure, stroke and transient ischaemic attack, venous thromboembolism, peripheral arterial disease and aortic aneurysm) in UK hospitals before and during the COVID-19 epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends. Findings: Nine hospitals across England and Scotland contributed hospital activity data from 28 Oct 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown), and for the same weeks during 2018-2019. Across all hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1-58.6%) and 52.9% (52.2-53.5%) respectively compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown, and fell by 31-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances RR 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020. Interpretation: Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.


title: Efficacy and harms of remdesivir for the treatment of COVID-19: a systematic review and meta-analysis

text: Background: We evaluated the efficacy and safety of remdesivir for the treatment of COVID-19. Methods: Systematic review in five engines, pre-print webpages and RCT registries until May 22, 2020 for randomized controlled trials (RCTs) and observational studies evaluating remdesivir on confirmed, COVID-19 adults with pneumonia and/or respiratory insufficiency. Primary outcomes were all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAE). Secondary outcomes included length of hospital stay, progression of pneumonia, and adverse events (AE). Inverse variance random effects meta-analyses were performed. Results: Two placebo-controlled RCTs (n=1300) and two case series (n=88) were included. All studies used remdesivir 200mg IV the first day and 100mg IV for 9 more days, and followed up until 28 days. Wang et al. RCT was stopped early due to AEs; ACTT-1 was preliminary reported at 15-day follow up. Time to clinical improvement was not decreased in Wang et al. RCT, but median time to recovery was decreased by 4 days in ACTT-1. Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28) and need for invasive ventilation at 14 days (RR 0.57, 95%CI 0.23 to 1.42), but had fewer SAEs (RR 0.77, 95%CI 0.63 to 0.94). AEs were similar between remdesivir and placebo arms. Risk of bias ranged from some concerns to high risk in RCTs. Interpretation: There is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in adult, hospitalized COVID-19 patients. Remdesivir should not be recommended for the treatment of severe COVID-19.


title: Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo

text: SARS-CoV-2 emerged in China at the end of 2019 and has rapidly become a pandemic with roughly 2.7 million recorded COVID-19 cases and greater than 189,000 recorded deaths by April 23rd, 2020 (www.WHO.org). There are no FDA approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA approved drugs. Rapid development and human testing of potential antivirals is greatly needed. A quick way to test compounds with potential antiviral activity is through drug repurposing. Numerous drugs are already approved for human use and subsequently there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV. We found that 17 of these inhibit SARS-CoV-2 at a range of IC50 values at non-cytotoxic concentrations. We directly follow up with seven of these to demonstrate all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we have evaluated two of these, chloroquine and chlorpromazine, in vivo using a mouse-adapted SARS-CoV model and found both drugs protect mice from clinical disease.


title: Perceived Stress and Psychological (Dis)Stress among Indian Endodontists During COVID19 Pandemic Lock down

text: Background: The novel 2019 coronavirus(COVID-19) spreads by respiratory and aerosols. COVID19 driven pandemic causes panic, fear and stress among all strata of society. Like all other medical professions, dentists, particularly endodontists, who are highly exposed to aerosols would be exposed to stress. The aim of this study was to assess the (dis)stress among Indian endodontists and the factors that could influence the (dis)stress. Methods: From 8th April to 16th April 2020, we conducted an online survey in closed endodontic social media using snowball sampling technique, collecting basic demographic data, practice setting and relevant data. Psychological stress and perceived distress were collected through COVID-19 Peri-traumatic Distress Index (CPDI) and Perceived stress scale (PSS). Multinomial regression analysis was performed to estimate relative risk rate and P[≤]0.05 was considered significant. Results: This study had 586 Indian endodontists completing this survey across India. Of these, 311(53.07%) were males, 325(55%) in the age group of 25-35 years, 64%in urban areas, 13.14% in solo-practice and a fourth of them were residents. Female endodontists had high perceived stress (RRR=2.46,P=0.01) as compared to males, as measured by PSS. Younger endodontists<25 years(RRR=9.75;P=0.002) and 25-35years (RRR=4.60;P=0.004) as compared with >45 years age-group had more distress. Exclusive consultants had RRR= 2.90, P=0.02, for mild-to-moderate distress as compared to normal. Factors driving this phenomenon are considered. Conclusions: During the lock down due to COVID-19, 1-in-2 Indian endodontists had distress, as measured by CPDI and 4-in-5 of them had perceived stress, as indicated by PSS. Our model identified certain factors driving the (dis)stress, which would help policy framers to initiate appropriate response.


title: Self-reported taste and smell disorders in patients with COVID-19: distinct features in China

text: Objectives: We aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19. Methods: In this retrospective study, 1,206 laboratory-confirmed COVID-19 patients were included and followed-up by telephone call one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0-10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up. Results: From COVID-19 patients (N = 1,172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. The most common nasal symptom was loss of taste (20.6%, median score = 6), while 11.4% had loss of smell (median score = 5). The incidence of nasal symptom including loss of smell and loss of taste as the first onset symptom was <1% in COVID-19 patients. Loss of smell or taste scores showed no correlation with the scores of other nasal symptoms. Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. non-severe COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks. Conclusion: In the Wuhan COVID-19 cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.


title: COVID-19 related social distancing measures and reduction in city mobility

text: In the absence of any pharmacological intervention, one approach to slowing the COVID-19 pandemic is reducing the contact rate in the population through social distancing. Governments the world over have instituted different measures to increase social distancing but information on their effectiveness in reducing mobility is lacking. We analyzed the mobility data from 41 cities to look at the effect of these interventions. The median mobility across cities on March 2, 2020 was 100% (IQR: 94%, 107%), which decreased to a median of 10% (IQR: 7%, 17%) on March 26, 2020. We found that the mobility decreased on average by 3.4% (95%CI: 3.3%, 3.6%) per day from March 2 through March 26. Social distancing measures decreased the mobility by an additional 23% (95%CI: 20%, 27%). Our study provides initial evidence for the reduction in mobility in cities instituting social distancing measures.


title: COVID-19 Awareness Among Healthcare Students and Professionals in Mumbai Metropolitan Region: A Questionnaire-Based Survey

text: Background and objectives The rapid and extensive spread of the COVID-19 pandemic has become a major cause of concern for the healthcare profession. The aim of this study is to assess the awareness of COVID-19 disease and related infection control practices among healthcare professionals and students in the Mumbai Metropolitan Region. Materials and methods A total of 1562 responders from the Mumbai Metropolitan Region completed a questionnaire-based survey on the awareness, knowledge, and infection control practices related to COVID-19 infection in the healthcare setting. The questionnaire was adapted from the current interim guidance and information for healthcare workers published by the US Centers for Disease Control and Prevention (CDC). Convenient sampling method was used for data collection and the distribution of responses was presented as frequencies and percentages. Descriptive statistics were performed for all groups and subgroups based on the percentage of correct responses. Individual pairwise comparisons were done using the median test for the percentage of correct responses. Results The overall awareness for all subgroups was adequate with 71.2% reporting correct answers. The highest percentage of correct responses were from undergraduate medical students and the lowest was from non-clinical/administrative staff. Less than half of the total respondents could correctly define “close contact.” More than three-fourths of the responders were aware of the various infection control measures like rapid triage, respiratory hygiene, and cough etiquette and having a separate, well ventilated waiting area for suspected COVID-19 patients. However, only 45.4% of the responders were aware of the correct sequence for the application of a mask/respirator, and only 52.5% of the responders were aware of the preferred hand hygiene method for visibly soiled hands. Conclusion There is a need for regular educational interventions and training programs on infection control practices for COVID-19 across all healthcare professions. Occupational health and safety are of paramount importance to minimize the risk of transmission to healthcare students and professionals and provide optimal care for patients.


title: Defect control during femtosecond projection two-photon lithography

text: Abstract Two-photon lithography (TPL) is a photopolymerization-based additive manufacturing technique that enables fabrication of millimeter scale complex three-dimensional (3D) structures with submicron features. Despite this unique capability, TPL has experienced limited industrial adoption due to its low throughput. The recently developed parallel projection technique, called femtosecond projection TPL (FP-TPL), is a promising approach to scale up this process as it increases the throughput up to three orders of magnitude. However, it requires tuning of process parameters, including photopolymer material properties, to minimize over-polymerization-based defects. Here, we show how a modification of the optical projection strategy can be used to control these over-polymerization defects without tuning the photopolymer composition. Through optical modeling of the projection technique, we show that these defects can be minimized by altering the density of the projected mask. In addition, the aspect ratio of the submicron features can by reduced from more than 2 to 1.2. Thus, this optimal projection strategy transforms FP-TPL into a more robust process suitable for high-throughput high-quality 3D printing of micro and nanoscale structures.


title: Risk Factors for Mortality of COVID-19 Patients

text: Background: Lethality rates of COVID-19 are so different between countries and continents. This lethality seems to be very low in Africa and Asia, but exceedingly high in western Europe and North America. Many factors could have a role in this disparity such as comorbidities. Advanced age, obesity, cardiovascular disease, diabetes and cancer were the most frequently cited in the reported COVID-19 data. The main objective was to analyse the association between the COVID-19 mortality and the mentioned factors in 164 countries. Methods: The Data of COVID-19 deaths, latitude degrees, population age distribution, cardiovascular diseases, obesity, diabetes and cancer were extracted from different online sources. For the statistical analysis, we used Spearman to measure the correlation coefficient between numbers of deaths and the mentioned factors until June 29, 2020. Results: The correlation between COVID-19 mortality and latitude, high age, obesity, CVD and number of cancer patients per 100,000 is significant at 0.01 level with r = 0.489, r=0.511, r=0.489, r=0.561 and r=0.536 respectively. The correlation between the number of deaths and diabetes is less strong than the previous ones, and the correlation coefficient is r= 0.154. Conclusion: The great lethality of COVID-19 in western Europe and North America can be explained in part by the highest of age, cancer and CVD percentage in these regions. It seems also plausible that the increased obesity in the USA and vitamin D deficiency in Europe may contribute to increasing the number of COVID-19 deaths.


title: Amgen pursues COVID-19 antibodies

text: Amgen and Adaptive Biotechnologies will work together to identify and develop an antibody therapy for COVID-19 Adaptive aims to screen tens of thousands of antibodies produced by B cells in people who have recovered from COVID-19 and find ones that neutralize the virus that causes it, SARS-CoV-2 Amgen will develop and manufacture the best antibodies to test as therapies Adaptive is also expandinga collaboration with Microsoft to study how T cells respond to the viral infection


title: Optimal COVID-19 epidemic control until vaccine deployment

text: Since Dec 2019, the COVID-19 epidemic has spread over the globe creating one of the greatest pandemics ever witnessed. This epidemic wave will only begin to roll back once a critical proportion of the population is immunised, either by mounting natural immunity following infection, or by vaccination. The latter option can minimise the cost in terms of human lives but it requires to wait until a safe and efficient vaccine is developed, a period estimated to last at least 18 months. In this work, we use optimal control theory to explore the best strategy to implement while waiting for the vaccine. We seek a solution minimizing deaths and costs due to the implementation of the control strategy itself. We find that such a solution leads to an increasing level of control with a maximum reached near the fourth month of the epidemics and a steady decrease until vaccine deployment. This strategy strongly outperforms others with constant or cycling allocations of the same amount of resources to control the outbreak. This work opens new perspectives to mitigate the effects of the ongoing COVID-19 pandemics, and be used as a proof-of-concept in using mathematical modelling techniques to enlighten decision ma


title: Why are most COVID-19 infection curves linear?

text: Many countries have passed their first COVID-19 epidemic peak. Traditional epidemiological models describe this as a result of non-pharmaceutical interventions that pushed the growth rate below the recovery rate. In this new phase of the pandemic many countries show an almost linear growth of confirmed cases for extended time-periods. This new containment regime is hard to explain by traditional models where infection numbers either grow explosively until herd immunity is reached, or the epidemic is completely suppressed (zero new cases). Here we offer an explanation of this puzzling observation based on the structure of contact networks. We show that for any given transmission rate there exists a critical number of social contacts, Dc, below which linear growth and low infection prevalence must occur. Above Dc traditional epidemiological dynamics takes place, as e.g. in SIR-type models. When calibrating our corresponding model to empirical estimates of the transmission rate and the number of days being contagious, we find Dc ~ 7.2. Assuming realistic contact networks with a degree of about 5, and assuming that lockdown measures would reduce that to household-size (about 2.5), we reproduce actual infection curves with a remarkable precision, without fitting or fine-tuning of parameters. In particular we compare the US and Austria, as examples for one country that initially did not impose measures and one that responded with a severe lockdown early on. Our findings question the applicability of standard compartmental models to describe the COVID-19 containment phase. The probability to observe linear growth in these is practically zero.


Comparative genetics of resistance to viruses.


title: Modelling strong control measures for epidemic propagation with networks -- A COVID-19 case study

text: We show that precise knowledge of epidemic transmission parameters is not required to build an informative model of the spread of disease. We propose a detailed model of the topology of the contact network under various external control regimes and demonstrate that this is sufficient to capture the salient dynamical characteristics and to inform decisions. Contact between individuals in the community is characterised by a contact graph, the structure of that contact graph is selected to mimic community control measures. Our model of city-level transmission of an infectious agent (SEIR model) characterises spread via a (a) scale-free contact network (no control); (b) a random graph (elimination of mass gatherings); and (c) small world lattice (partial to full lockdown --"social"distancing). This model exhibits good qualitative agreement between simulation and data from the 2020 pandemic spread of coronavirus. Estimates of the relevant rate parameters of the SEIR model are obtained and we demonstrate the robustness of our model predictions under uncertainty of those estimates. The social context and utility of this work is identified, contributing to a highly effective pandemic response in Western Australia.


title: Knowledge synthesis from 100 million biomedical documents augments the deep expression profiling of coronavirus receptors

text: The COVID-19 pandemic demands assimilation of all available biomedical knowledge to decode its mechanisms of pathogenicity and transmission. Despite the recent renaissance in unsupervised neural networks for decoding unstructured natural languages, a platform for the real-time synthesis of the exponentially growing biomedical literature and its comprehensive triangulation with deep omic insights is not available. Here, we present the nferX platform for dynamic inference from over 45 quadrillion possible conceptual associations extracted from unstructured biomedical text, and their triangulation with Single Cell RNA-sequencing based insights from over 25 tissues. Using this platform, we identify intersections between the pathologic manifestations of COVID-19 and the comprehensive expression profile of the SARS-CoV-2 receptor ACE2. We find that tongue keratinocytes, airway club cells, and ciliated cells are likely underappreciated targets of SARS-CoV-2 infection, in addition to type II pneumocytes and olfactory epithelial cells. We further identify mature small intestinal enterocytes as a possible hotspot of COVID-19 fecal-oral transmission, where an intriguing maturation-correlated transcriptional signature is shared between ACE2 and the other coronavirus receptors DPP4 (MERS-CoV) and ANPEP (α-coronavirus). This study demonstrates how a holistic data science platform can leverage unprecedented quantities of structured and unstructured publicly available data to accelerate the generation of impactful biological insights and hypotheses. The nferX Platform Single-cell resource - https://academia.nferx.com/


title: Accuracy of online symptom checkers and the potential impact on service utilisation

text: Objectives: The aims of this study are firstly to investigate the diagnostic and triage performance of symptom checkers, secondly to assess their potential impact on healthcare utilisation and thirdly to investigate for variation in performance between systems. Setting: Publicly available symptom checkers Participants: Publicly available symptom-checkers were identified. A standardised set of 50 clinical vignettes was developed and systematically run through each system by a non-clinical researcher. Primary and secondary outcome measures: System accuracy was assessed by measuring the percentage of times the correct diagnosis was a) listed first, b) within the top five diagnoses listed and c) listed at all. The safety of the disposition advice was assessed by comparing it with national guidelines for each vignette. Results: Twelve tools were identified and included. Mean diagnostic accuracy of the systems was poor, with the correct diagnosis being listed first on 37.7% (Range 22.2 to 72.0%) of occasions and present in the top five diagnoses on 51.0% (Range 22.2 to 84.0%). 51.0% of systems suggested additional resource utilisation above that recommended by national guidelines (range 18.0% to 61.2%). Both diagnostic accuracy and appropriate resource recommendation varied substantially between systems. Conclusions: There is wide variation in performance between available symptom checkers and overall performance is significantly below what would be accepted in any other medical field, though some do achieve a good level of accuracy and safety of disposition. External validation and regulation are urgently required to ensure these public facing tools are safe.


title: Neurological and Psychological Effects of Coronavirus (COVID-19): An Overview of the Current Era Pandemic

text: Coronavirus disease 2019 (COVID 19) is a catastrophic illness that has significantly altered the world’s panoramic view of medicine. As the number of cases around the globe rise, the COVID-19 research writing has been immediately enhanced by professionals internationally. In this review, we focus on the neurological and psychological effects of COVID-19, which can determine both the severity of coronavirus and its related pandemic respectively. While it is critical to distinguish the neurological manifestations from the psychological effects, the latter is becoming more pervasive due to the fast-expanding outbreak. We conducted a systematic review and included observational retrospective, case-series studies, and surveys to establish the largest pool of valuable research. Articles on these approaches were conducted in PubMed, MEDLINE, and Google scholar. Some gray material was also selected because of the recent nature of the disease. Data collected from the studies have proposed that COVID-19 is not unusual in demonstrating the neurological symptoms, as it proved in the past by its sister coronaviruses such as severe acute respiratory syndrome coronavirus-1 (SARS-COV-1) and Middle Eastern respiratory syndrome coronavirus (MERS-COV). Studies have presented that some patients with COVID-19 also showed neurological signs, such as headache, nausea, vomiting, dizziness, loss of taste and smell, and impaired consciousness. However, it necessary to clarify that the invasion of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) directly or indirectly affects the central nervous system (CNS). Contrarily, the COVID-19 pandemic has affected every single element of life. It has not only changed the individual’s health directly but also has significant psychological, economic, and sociological effects. These issues indicate the disease's extraordinary threat, and we must realize that another pandemic will shortly follow it: that of mental and behavioral illness. Thus, the long-lasting psychological implications of this outbreak deserve further investigation side by side.


title: Risk Factors of the Severity of COVID-19: A Meta-Analysis

text: Background: Although the infection rate of COVID-19 is very high, all the patients getting infected don't always die or go through brutal states. This indicates there may be some factors that possibly boost the severity of COVID-19. Objective: We intend to identify some probable risk factors that are responsible for the severity of COVID-19 using a meta-analysis. Methods: The literature exploration lasted up to 18 April 2020 and through PubMed,Google Scholar, EMBASE, and Cochrane Library we have identified 10 pertinent publications. To paraphrase the outcomes of autonomous researches, we have performed a random-effect meta-analysis. Results: Among 2272 patients' information extracted from the selected literature majority (60%) are male patients. This study found sex (male) (Risk ratio [RR] =1.29, 95% CI, 1.07 to 1.54), hypertension (RR=1.79, 95% CI, 1.57 to 2.04), diabetes (RR=1.57, 95% CI, 1.25 to 1.98), fatigue or myalgia (RR=1.17, 95% CI, 1.02; 1.35), and smoking history (RR=1.71, 95% CI,1.25; 2.35) are potential risk factors for the severity of COVID-19. We found fever (RR=1.21, 95% CI, 0.66 to 2.22), cough (1.13, 95% CI, 0.98 to 1.30), and diarrhea (RR=1.14, 95% CI, 0.93 to 1.40) as insignificant risk factors for COVID-19 severity. Conclusions: The finding of this research may be beneficial to identify patients with higher risks to provide additional medical attention from the very beginning of the treatment.


title: Repositioning Chromones for Early Anti-inflammatory Treatment of COVID-19

text: The COVID-19 pandemic is posing an unprecedented sanitary threat. In the absence of specific vaccines and anti-SARS-CoV-2 drugs, medicines that may assist in tackling the emergency and limiting the high number of fatalities are urgently needed. The repositioning of available drugs to treat COVID-19 is the only and rapid option in the face of the lack of direct antiviral agents and vaccines available. In this light it is important to focus on available drugs, which, based on their pharmacodynamics, could plausibly attenuate viral growth as well as COVID-19’s worst complications. This is the case of chloroquine and tocilizumab which seem to limit virus replication and the severity of interstitial pneumonia, respectively. However, these treatments, particularly those aimed at containing inflammation, are still reserved for the most severe cases. This commentary elaborates on the pharmacological rationale of repositioning the mast cell stabilizer chromones as an adjunctive treatment for SARS‐CoV‐2 infection, and proposes their practical clinical testing as an early, safe, and cost-effective anti-inflammatory intervention in COVID-19 to limit the eventual secondary progression toward life-threatening respiratory complications.


title: Scaling COVID-19 against inequalities: should the policy response consistently match the mortality challenge?

text: Background The mortality impact of COVID-19 has thus far been described in terms of crude death counts. We aimed to calibrate the scale of the modelled mortality impact of COVID-19 using age-standardised mortality rates and life expectancy contribution against other, socially-determined, causes of death in order to inform governments and the public. Methods We compared mortality attributable to suicide, drug poisoning and socioeconomic inequality with estimates of mortality from an infectious disease model of COVID-19. We calculated age-standardised mortality rates and life expectancy contributions for the UK and its constituent nations. Results Mortality from a fully unmitigated COVID-19 pandemic is estimated to be responsible for a negative life expectancy contribution of -5.96 years for the UK. This is reduced to -0.33 years in the fully mitigated scenario. The equivalent annual life expectancy contributions of suicide, drug poisoning and socioeconomic inequality-related deaths are -0.25, -0.20 and -3.51 years respectively. The negative impact of fully unmitigated COVID-19 on life expectancy is therefore equivalent to 24 years of suicide deaths, 30 years of drug poisoning deaths, and 1.7 years of inequality-related deaths for the UK. Conclusion Fully mitigating COVID-19 is estimated to prevent a loss of 5.63 years of life expectancy for the UK. Over 10 years there is a greater negative life expectancy contribution from inequality than around six unmitigated COVID-19 pandemics. To achieve long-term population health improvements it is therefore important to take this opportunity to introduce post-pandemic economic policies to build back better.


Reflections on a pandemicPandemic Adaptive Measures in a Major Trauma Center: Coping With COVID-19


title: Bayesian Inference of COVID-19 Spreading Rates in South Africa

text: The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the need for the development of prompt mitigating responses under conditions of high uncertainty. Fundamental to the design of rapid state reactions is the ability to perform epidemiological model parameter inference for localised trajectory predictions. In this work, we perform Bayesian parameter inference using Markov Chain Monte Carlo (MCMC) methods on the Susceptible-Infected-Recovered (SIR) and Susceptible-Exposed-Infected-Recovered (SEIR) epidemiological models with time-varying spreading rates for South Africa. The results find two change points in the spreading rate of COVID-19 in South Africa as inferred from the confirmed cases. The first change point coincides with state enactment of a travel ban and the resultant containment of imported infections. The second change point coincides with the start of a state-led mass screening and testing programme which has highlighted community-level disease spread that was not well represented in the initial largely traveller based and private laboratory dominated testing data. The results further suggest that due to the likely effect of the national lockdown, community level transmissions are slower than the original imported case driven spread of the disease.


title: Estimating false-negative detection rate of SARS-CoV-2 by RT-PCR

text: Reverse transcription-polymerase chain reaction (RT-PCR) assays are used to test patients and key workers for infection with the causative SARS-CoV-2 virus. RT-PCR tests are highly specific and the probability of false positives is low, but false negatives can occur if the sample contains insufficient quantities of the virus to be successfully amplified and detected. The amount of virus in a swab is likely to vary between patients, sample location (nasal, throat or sputum) and through time as infection progresses. Here, we analyse publicly available data from patients who received multiple RT-PCR tests and were identified as SARS-CoV-2 positive at least once. We identify that the probability of a positive test decreases with time after symptom onset, with throat samples less likely to yield a positive result relative to nasal samples. Empirically derived distributions of the time between symptom onset and hospitalisation allowed us to comment on the likely false negative rates in cohorts of patients who present for testing at different clinical stages. We further estimate the expected numbers of false negative tests in a group of tested individuals and show how this is affected by the timing of the tests. Finally, we assessed the robustness of these estimates of false negative rates to the probability of false positive tests. This work has implications both for the identification of infected patients and for the discharge of convalescing patients who are potentially still infectious.


title: Complete Genome Sequence of a SARS-CoV-2 Strain Isolated in Northern Germany

text: Here, we describe the complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain isolated from an oropharyngeal swab sample from a female patient with COVID-19 who was infected in Hamburg, northern Germany.


title: 'Drawing on Wisdom to Cope with Adversity:' A Systematic Review Protocol of Older Adults' Mental and Psychosocial Health During Acute Respiratory Disease Propagated-Type Epidemics and Pandemics (COVID-19, SARS-CoV, MERS, and Influenza).

text: Background: Mental health has become one of the fundamental priorities during the COVID-19 pandemic. Situations like physical distancing as well as being constantly tagged as the most vulnerable group could expose older adults to mental and psychosocial burdens. Nonetheless, there is little clarity about the impact of the COVID-19 pandemic or similar pandemics in the past on the mental illness, wellbeing, and psychosocial health of the older population compared to other age groups. Objectives: To describe the patterns of older adults' mental and psychosocial health related to acute respiratory disease propagated-type epidemics and pandemics and to evaluate the differences with how other age groups respond. Eligibility criteria: quantitative and qualitative studies evaluating mental illness, wellbeing, or psychosocial health outcomes associated with respiratory propagated epidemics and pandemics exposure or periods (COVID-19, SARS-CoV, MERS, and Influenza) in people 65 years or older. Data source: Original articles published until June 1st, 2020, in any language searched in the electronic healthcare and social sciences database: MEDLINE, Embase, CINAHL, PsycINFO, Scopus, WHO Global literature on coronavirus disease database, China National Knowledge Infrastructure ( - CNKI). Furthermore, EPPI Centre's COVID-19 living systematic map and the publicly available publication list of the COVID-19 living systematic review will be incorporated for preprints and recent COVID-19 publications. Data extraction: Two independent reviewers will extract predefined parameters. The risk of bias will be assessed. Data synthesis: Data synthesis will be performed according to study type and design, type of epidemic and pandemic, types of outcomes (mental health and psychosocial outcomes), and participant characteristics (e.g., sex, race, age, socioeconomic status, food security, presence of dependency in daily life activities independent/dependent older adults). Comparison between sex, race, and other age groups will be performed qualitatively, and quantitatively if enough data is available. The risk of bias and study heterogeneity will be reported for quantitative studies. Conclusion: This study will provide information to take actions to address potential mental health difficulties during the COVID-19 pandemic in older adults and to understand responses on this age group. Furthermore, it will be useful to identify potential groups that are more vulnerable or resilient to the mental-health challenges of the current worldwide pandemic.


title: Trend analysis of the COVID-19 pandemic in China and the rest of the world

text: The recent epidemic of Coronavirus (COVID-19) that started in China has already been "exported" to more than 140 countries in all the continents, evolving in most of them by local spreading. In this contribution we analyze the trends of the cases reported in all the Chinese provinces, as well as in some countries that, until March 15th, 2020, have more than 500 cases reported. Notably and differently from other epidemics, the provinces did not show an exponential phase. The data available at the Johns Hopkins University site seem to fit well an algebraic sub-exponential growing behavior as was pointed out recently. All the provinces show a clear and consistent pattern of slowing down with growing exponent going nearly zero, so it can be said that the epidemic was contained in China. On the other side, the more recent spread in countries like, Italy, Iran, and Spain show a clear exponential growth, as well as other European countries. Even more recently, US -which was one of the first countries to have an individual infected outside China (Jan 21st, 2020)- seems to follow the same path. We calculate the exponential growth of the most affected countries, showing the evolution along time after the first local case. We identify clearly different patterns in the analyzed data and we give interpretations and possible explanations for them. The analysis and conclusions of our study can help countries that, after importing some cases, are not yet in the local spreading phase, or have just started


title: Broad-spectrum antiviral activity of naproxen: from Influenza A to SARS-CoV-2 Coronavirus

text: There is an urgent need for specific antiviral drugs directed against SARS-CoV-2 both to prevent the most severe forms of COVID-19 and to reduce viral excretion and subsequent virus dissemination; in the present pandemic context, drug repurposing is a priority. Targeting the nucleoprotein N of the SARS-CoV-2 coronavirus in order to inhibit its association with viral RNA could be a strategy to impeding viral replication and possibly other essential functions associated with viral N. The antiviral properties of naproxen, belonging to the NSAID family, previously demonstrated against Influenza A virus, were evaluated against SARS-CoV-2. Naproxen binding to the nucleoprotein of SARS-CoV2 was shown by molecular modeling. In VeroE6 cells and reconstituted human primary respiratory epithelium models of SARS-CoV-2 infection, naproxen inhibited viral replication and protected the bronchial epithelia against SARS-CoV-2 induced-damage. The benefit of naproxen addition to the standard of care is tested in an on-going clinical study.


title: Epidemics, Air Travel, and Elimination in a Globalized World: The Case of Measles

text: Although the United States (U.S.) declared measles eliminated in 2000, so long as measles circulates globally, continued importations will trigger sporadic U.S. outbreaks. The United States is highly connected to the rest of the world, and importations occur largely as a result of air travel by U.S. residents and international visitors. We developed a model to assess the risk of measles virus importation from Europe, Asia, and Africa through air travel. We projected 308 (95% prediction interval, 151-518) total measles cases imported from 66 countries during 2006-2015; 290 importations were reported. The model projected a spike in importation risk from Israel during October 2018, coincident with large, importation-triggered outbreaks in New York and New Jersey. Our model shows U.S. importation risk primarily originates from European and Asian countries. Models such as this inform preemptive actions to mitigate infectious disease threats, but only if we prioritize global surveillance and data sharing.


title: Only a combination of social distancing and massive testing can effectively stop COVID-19 progression in densely populated urban areas

text: We present a simple epidemiological model that includes demographic density, social distancing, and efficacy of massive testing and quarantine as main parameters to model the progression of COVID-19 pandemics in densely populated urban areas (i.e., above 10,000 hab km2). Our model demonstrates that effective containment of pandemic progression in densely populated cities is achieved only by combining social distancing, widespread testing, and quarantining of infected subjects. This finding has profound epidemiological significance, and sheds light on the controversy regarding the relative effectiveness of widespread testing and social distancing. Our simple epidemiological simulator can also be used to assess the efficacy of a governmental/societal response to an outbreak. This study has also relevant implications on the concept of smart cities; densely populated areas are hot spots highly vulnerable to epidemic crisis.


title: Estimation of SARS-CoV-2 mortality during the early stages of an epidemic: a modelling study in Hubei, China and northern Italy

text: Background. The epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in Wuhan, China in late 2019 is now pandemic. Reliable estimates of death from coronavirus disease 2019 (COVID-19) are essential to guide control efforts and to plan health care system requirements. The objectives of this study are to: 1) simulate the transmission dynamics of SARS-CoV-2 using publicly available surveillance data; 2) give estimates of SARS-CoV-2 mortality adjusted for bias in the two regions with the world's highest numbers of confirmed Covid-19 deaths: Hubei province, China and northern Italy. Method and Findings. We developed an age-stratified susceptible-exposed-infected-removed (SEIR) compartmental model describing the dynamics of transmission and mortality during the SARS-CoV-2 epidemic. Our model accounts for two biases; preferential ascertainment of severe cases and delayed mortality (right-censoring). We fitted our transmission model to surveillance data from Hubei province (1 January to 11 February 2020) and northern Italy (8 February to 3 March 2020). Overall mortality among all symptomatic and asymptomatic infections was estimated to be 3.0% (95% credible interval: 2.6-3.4%) in Hubei province and 3.3% (2.0-4.7%) in northern Italy. Mortality increased with age; we estimate that among 80+ year olds, 39.0% (95%CrI: 31.1-48.9%) in Hubei province and 89.0% (95%CrI: 56.2-99.6%) in northern Italy dies or will die. Limitations are that the model requires data recorded by date of onset and that sex-disaggregated mortality was not available. Conclusions. We developed a mechanistic approach to correct the crude CFR for bias due to right-censoring and preferential ascertainment and provide adjusted estimates of mortality due to SARS-CoV-2 infection by age group. While specific to the situation in Hubei, China and northern Italy during these periods, these findings will help the mitigation efforts and planning of resources as other regions prepare for SARS-CoV-2 epidemics.


title: Potent programmable antiviral against dengue virus in primary human cells by Cas13b RNP with short spacer and delivery by virus-like particle

text: With sequencing as a standard frontline protocol to identify emerging viruses such zika virus and SARS-CoV2, direct utilization of sequence data to program antivirals against the viruses could accelerate drug development to treat their infections. CRISPR-Cas effectors are promising candidates that could be programmed to inactivate viral genetic material based on sequence data but several challenges such as delivery and design of effective crRNA need to be addressed to realize practical use. Here, we showed that virus-like particle (VLP) could deliver PspCas13b-crRNA ribonucleoprotein (RNP) in nanomolar range to efficiently suppress dengue virus infection in primary human target cells. Shortening spacer length could significantly enhance RNA-targeting efficiency of PspCas13b in mammalian cells compared to the natural length of 30 nucleotides without compromising multiplex targeting by a crRNA array. Our results demonstrate the potentials of applying PspCas13b RNP to suppress RNA virus infection, with implications in targeting host RNA as well.


title: Optimal group based testing strategy for detecting infected individuals: comparison of algorithms

text: We investigate group based testing strategy targeted to identify infected patients by making use of a medical test which equally well applies to single and pooled samples. We demonstrate that, under assumed setting, quick sort grounded testing algorithm allows to reduce average costs, and the reduction is very significant when the infection percentage is low. Although the basic idea of test sampling is known, our major novelty is the rigorous treatment of the model. Another interesting insight following rigorous analysis is that an average number of tests per one individual scales like entropy of the prevalence of infection. One more reason for the paper is the context: taking into account the current situation with the coronavirus, dissemination of renowned ideas and the optimisation of algorithms can be of a great importance and of economical benefit.


title: Life-long persistence of infectious Zika virus: inflammation and behavioral sequela

text: The recent spread of Zika virus (ZIKV) and its association with congenital defects and neurological disorders has created an urgent need to understand the pathogenesis of ZIKV and identify therapeutic strategies that will prevent or eliminate them. The neurodevelopmental defects associated with ZikV infections early in pregnancy are well documented, however the potential defects associated with infections in late pregnancy and perinatal period are less well characterized. Further, the long-term sequelae of these infections are not fully understood. Immunocompetent C57BL/6 mice infected at one day old (P1), which neurodevelopmentally model late pregnancy in humans, develop a transient neurological syndrome including unsteady gait, kinetic tremors, severe ataxia and seizures 10-15 days post-infection (dpi) but symptoms subside after a week, and most animals survive. Despite apparent recovery, MRI of convalescent mice shows reduced cerebellar volume that correlates with altered coordination and motor function as well as hyperactivity and impulsivity. Persistent mRNA levels of pro-inflammatory genes including Cd80, Il-1α, and Ifn-γ together with Cd3, Cd8 and perforin (PrfA), suggested the persistence of a low-grade inflammatory process. Further, the brain parenchyma of convalescent mice harbor multiple small foci with viral antigen, active apoptotic processes in neurons, and cellular infiltrates, surrounded by activated astrocytes and microglia as late as 1-year post-infection. Detection of negative-sense strand viral RNA and replication of virus derived from these convalescent mice by blinded passage in Vero cells confirmed that low levels of live ZikV persist in CNS of convalescent mice life-long. Our studies establish that Zika can establish reservoirs in CNS and suggest that anti-viral treatment that clears virus from the CNS as well as long-term neurological and behavioral monitoring may be needed for patients known to be exposed to ZikV at an early age. Author’s summary The congenital brain malformations associated with ZikV infections early in pregnancy are well documented, however whether apparently asymptomatic perinatal exposure could lead to long term sequelae is not fully understood. Using a non-lethal neonatal mouse model, we examine host-pathogen interactions, anatomical changes and behavioral patterns by following survivors of the acute infection for over 1 year. We discover that infectious Zika virus has the potential to remain in the CNS for life, lodged within small foci surrounded by gliosis and infiltrating immune cells that may act to limit the viral spread, but also interfere with healing and contribute to life-long neuropathic and behavioral sequelae. These results suggest that anti-viral treatment and long-term neurological and behavioral monitoring may be indicated for patients known to have been exposed to Zika virus, regardless of neurodevelopmental disease severity.


Stability of SARS-CoV-2 in different environmental conditions.


title: The medical education level of the administrators of the local health committees in China

text: The outbreak of Coronavirus disease 2019 (COVID-19) caused by the recently emerged Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious challenge for the healthcare system worldwide. We collected information, which were posted online as of February 25, 2020, on demographic characteristics of the directors of provincial and municipal Health Committee in Chinese mainland, and analyzed the education level and medical education background of the directors based on different geographic regions and per capita GDP. We found that the overall information disclosure rate is insufficient (63.39%). The mean age of the directors of provincial and municipal health committee was ~54 years. Among the 277 officials whose information is available, those in economically less-developed regions or remote areas had significantly poorer educational background. Regardless of economic status, the proportion of officials with a background of medical education in most regions was low. A significant amount of the directors of the provincial and municipal health committees in China lacks a background of medical education. This may hinder the efficiency of healthcare and public health administration, which obviously requires personnel with a background of medical training, especially considering the current outbreak of COVID-19.


title: Appendectomy in patient with suspected COVID-19 with negative COVID-19 results: A case report

text: BACKGROUND: Even at present, we are in the middle of the novel coronavirus disease 2019 (COVID-19) pandemic and are facing challenges in trial and error. Presently, emergency surgery for patients with suspected COVID-19 is burdensome not only for patients but also for healthcare workers. Therefore, we established a surveillance system in the emergency room and established principles for managing patients suspected of COVID-19 who require emergency surgery. CASE SUMMARY: A 67-year-old man was diagnosed with appendicitis in March 2020. His wife was diagnosed with COVID-19 10 d earlier, and the patient was in close contact with her. The patient tested negative twice on an upper respiratory COVID-19 reverse transcription–polymerase chain reaction screening test, but chest X-ray and chest computed tomography revealed patchy ground-glass opacity in both upper lobes of the patient’s lungs. The same emergency surgery procedure for patients with confirmed COVID-19 was applied to this patient suspected of having the disease to ensure that surgery was not delayed while waiting for the reverse transcription–polymerase chain reaction results. A few hours after surgery, the upper respiratory tract specimen taken in the emergency room was negative for COVID-19 but the lower respiratory tract specimen was found to be positive for the disease. CONCLUSION: When COVID-19 is suspected, emergency surgery should be performed as for confirmed COVID-19 without delay.


title: Explainable death toll motion modeling: COVID-19 narratives and counterfactuals

text: Models have gained the spotlight in many discussions surrounding COVID-19. The urgency for timely decisions resulted in a multitude of models as informed policy actions must be made even when so many uncertainties about the pandemic still remain. In this paper, we use machine learning algorithms to build intuitive country-level COVID-19 motion models described by death toll velocity and acceleration. Model explainability techniques provide insightful data-driven narratives about COVID-19 death toll motion models $-$ while velocity is explained by factors that are increasing/reducing death toll pace now, acceleration anticipates the effects of public health measures on slowing the death toll pace. This allows policymakers and epidemiologists to understand factors driving the outbreak and to evaluate the impacts of different public health measures. Finally, our models also predict counterfactuals in order to face the challenge of estimating what is likely to happen as a result of an action.