title: Remote eye-tracking for cognitive telerehabilitation and interactive school tasks in times of COVID-19

text: In the attempt to mitigate the effects of COVID-19 lockdown, most countries have recently authorized and promoted the adoption of e-learning and remote teaching technologies, often with the support of teleconferencing platforms. Unfortunately, not all students can benefit from the adoption of such a surrogate of their usual school. We were asked to devise a way to allow a community of children affected by the Rett genetic syndrome, and thus unable to communicate verbally, in writing or by gestures, to actively participate in remote rehabilitation and special education sessions by exploiting eye-gaze tracking. As not all subjects can access commercial eye-tracking devices, we investigated new ways to facilitate the access to eye gaze-based interaction for this specific case. The adopted communication platform is a videoconferencing software, so all we had at our disposal was a live video stream of the child. As a solution to the problem, we developed a software (named SWYG) that only runs at the "operator" side of the communication, at the side of the videoconferencing software, and does not require to install other software in the child's computer. The preliminary results obtained are very promising and the software is ready to be deployed on a larger base. While this paper is being written, several children are finally able to communicate with their caregivers from home, without relying on expensive and cumbersome devices.


title: Negative Spillovers Across Partnerships for Responsible Innovation: Evidence from the 2014 Ebola Outbreak

text: Abstract Humanity faces ongoing and contemporaneous grand challenges Occasionally, abrupt shocks escalate a grand challenge's salience over others Prior research has advocated forming partnerships to address grand challenges via responsible innovation Yet, it remains unclear how temporal changes in the salience of a grand challenge impact innovation performances of partnerships We address this research gap by bridging the literature on issue salience, responsible innovation and interorganizational relationships We argue that shocks either aid or harm the performance of partnerships for responsible innovation depending on whether their domains are directly or indirectly affected The Ebola outbreak in 2014 sets the empirical context to test our theory We find that while the innovation performance of Ebola partnerships formed after the outbreak rose eleven-fold, the performance of partnerships treating Influenza fell by 84 9 percent Our theory and findings have immediate implications for today's COVID-19 outbreak, cautioning against salience shifts among concurrent grand challenges


title: A rational approach to identifying effective combined anticoronaviral therapies against feline coronavirus

text: Feline infectious peritonitis (FIP), caused by a genetic mutant of feline enteric coronavirus known as FIPV, is a highly fatal disease of cats with no currently available vaccine or FDA-approved cure. Dissemination of FIPV in affected cats results in a range of clinical signs including cavitary effusions, anorexia, fever and lesions of pyogranulomatous vasculitis and peri-vasculitis with or without central nervous system and/or ocular involvement. There is a critical need for effective and approved antiviral therapies against coronaviruses including FIPV and zoonotic coronaviruses such as SARS-CoV-2, the cause of COVID-19. With regards to SARS-CoV-2, preliminary evidence suggests that there may be potential clinical and pathological overlap with feline coronaviral disease including enteric and neurological involvement in some cases. We have screened 89 putative antiviral compounds and have identified 25 compounds with antiviral activity against FIPV, representing a variety of drug classes and mechanisms of antiviral action. Based upon successful combination treatment strategies for human patients with HIV or hepatitis C virus infections, we have identified combinations of drugs targeting different steps of the FIPV life cycle resulting in synergistic antiviral effect. Translationally, we suggest that a combined anticoronaviral therapy (cACT) with multiple mechanisms of action and penetration of all potential anatomic sites of viral infection should be applied towards other challenging to treat coronaviruses, like SARS-CoV-2. Author summary We have screened 89 compounds in vitro for antiviral activity against FIPV. The putative antiviral activity of these compounds was either purported to be a direct effect on viral proteins involved in viral replication or an indirect inhibitory effect on normal cellular pathways usurped by FIPV to aid viral replication. Twenty-five of these compounds were found to have significant antiviral activity. Certain combinations of these compounds were determined to be superior to monotherapy alone.


title: ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels: a Mendelian randomization study

text: Objectives: To use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to provide insight into how these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. Design: Two-sample Mendelian randomization (MR) analysis. Setting: Summary-level genetic association data. Participants: Participants were predominantly of European ancestry. Variants that proxy ACE inhibitor drug effects and cardiometabolic risk factors (body mass index, chronic obstructive pulmonary disease, lifetime smoking index, low-density lipoprotein cholesterol, systolic blood pressure and type 2 diabetes mellitus) were selected from publicly available genome-wide association study data (sample sizes ranging from 188,577 to 898,130 participants). Genetic association estimates for lung expression of ACE2 and TMPRSS2 were obtained from the Gene-Tissue Expression (GTEx) project (515 participants) and the Lung eQTL Consortium (1,038 participants). Genetic association estimates for circulating plasma ACE2 levels were obtained from the INTERVAL study (4,947 participants). Main outcomes and measures: Lung ACE2 and TMPRSS2 expression and plasma ACE2 levels. Results: There were no association of genetically proxied ACE inhibition with any of the outcomes considered here. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in GTEx (p = 4x10-4) and with circulating plasma ACE2 levels in INTERVAL (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations between genetically predicted levels of the other cardiometabolic traits with the outcomes. Conclusions: This study does not provide evidence to support that ACE inhibitor antihypertensive drugs affect lung ACE2 and TMPRSS2 expression or plasma ACE2 levels. In the current COVID-19 pandemic, our findings do not support a change in ACE inhibitor medication use without clinical justification.


title: Heat treatment for reuse of disposable respirators during Covid-19 pandemic: Is filtration and fit adversely affected?

text: A number of methods for decontaminating disposable filtering face piece respirators have been explored for use in health care settings during epidemics where respirators are in short supply, such as the current Covid-19 pandemic. Heating to temperatures above 65 degrees C has been shown to successfully inactivate the SARS-CoV-2 virus on various surfaces. Ovens or similar heating devices are likely already widely available in hospitals globally. We did a quantitative fit test on nine models of FFP2 and FFP3 respirators before and after heat treatment in an oven. These included both flat fold and moulded cup styles. All passed the initial fit test, and all but two passed the post-treatment fit test. This study demonstrates that FFP respirators can still retain both filtration efficiency and fit after wear and heat treatment, but that it is necessary to understand the probability for failure of fit after decontamination. Heat shows promise as a simple and effective way of treating FFP respirators. Further evaluation of longer-term wear and disinfection effectiveness of heat treatment should be done before widespread use.


title: Covid-19 Outbreak – Immediate and long-term impacts on the dental profession

text: The health professions and systems have been challenged evoking heightened reactions around the globe as response to Covid-19. While most heavily impacted, the role of the dental professionals in preventing the transmission and responding to its long-term impacts on dentistry is critically important. This report, while outlining the immediate impact that the Covid-19 outbreak currently has on dental healthcare professionals, it also looks at some heavier impacts that this outbreak might have on the profession of dentistry. As such this manuscript offers some suggestions and recommendations based on personal feeling.


title: Acetazolamide, Nifedipine and Phosphodiesterase Inhibitors: Rationale for Their Utilization as Adjunctive Countermeasures in the Treatment of Coronavirus Disease 2019 (COVID-19)

text: Effective treatments for Coronavirus Disease 2019 (COVID-19) outbreak are urgently needed. While anti-viral approaches and vaccines are being considered immediate countermeasures are unavailable. The aim of this article is to outline a perspective on the pathophysiology of COVID-19 in the context of the currently available clinical data published in the literature. This article appreciates clinical data published on COVID-19 in the context of another respiratory illness - high altitude pulmonary edema (HAPE). Both conditions have significant similarities that portend pathophysiologic trajectories. Following this potential treatment options emerge. Both COVID-19 and HAPE exhibit a decreased ratio of arterial oxygen partial pressure to fractional inspired oxygen with concomitant hypoxia and tachypnea. There also appears to be a tendency for low carbon dioxide levels in both as well. Radiologic findings of ground glass opacities are present in up to 86% of patients with COVID-19 in addition to patchy infiltrates. Patients with HAPE also exhibit patchy infiltrates throughout the pulmonary fields, often in an asymmetric pattern and CT findings reveal increased lung markings and ground glass-like changes as well. Widespread ground-glass opacities are most commonly a manifestation of hydrostatic pulmonary edema. Similarly, elevated fibrinogen levels in both conditions are likely an epiphenomenon of edema formation rather than coagulation activation. Autopsy results of a COVID-19 fatality revealed bilateral diffuse alveolar damage associated with pulmonary edema, pro-inflammatory concentrates, and indications of early-phase acute respiratory distress syndrome (ARDS). HAPE itself is initially caused by an increase in pulmonary capillary pressure and induces altered alveolar-capillary permeability via high pulmonary artery hydrostatic pressures that lead to a protein-rich and mildly hemorrhagic edema. It appears that COVID-19 and HAPE both discretely converge on ARDS. In light of this, a countermeasure that has been shown to be effective in the analogous condition of HAPE is Acetazolamide. Acetazolamide has a myriad of effects on different organ systems, potently reduces hypoxic pulmonary vasoconstriction, improves minute ventilation and expired vital capacity. Other therapeutics to consider that are also directed towards decreased pulmonary pressure include Nifedipine and Phosphodiesterase inhibitors. This review describes COVID-19 in parallel to HAPE. Deranged respiratory parameters that are present in both conditions are highlighted. The utilization of medications found to be effective in HAPE, for the treatment of COVID-19, is proposed. Given the medical emergency of a growing contagion and the thousands of lives at stake, expedient attempts to improve survival are needed. Acetazolamide, Nifedipine and Phosphodiesterase inhibitors may be potential countermeasures.


title: Resource optimization in COVID-19 diagnosis

text: The emergence and rapid dissemination worldwide of a novel Coronavirus (SARS-CoV-2) results in decrease of swabs availability for clinical samples collection, as well as, reagents for RT-qPCR diagnostic kits considered a confirmatory test for COVID-19 infection. This scenario, showed the requirement of improve de diagnostic capacity, so the aim of this study were to verify the possibility of reducing the reaction volume of RT-qPCR and to test cotton swabs as alternative for sample collection. RT-qPCR volumes and RNA sample concentration were optimized without affecting the sensitivity of assays, using both probe-based and intercalation dyes methods. Although rayon swabs showed better performance, cotton swabs could be used as alternative type for clinical sample collection. COVID-19 laboratory diagnosis is important to isolate and restrict the dissemination of virus, so seek for alternatives to decrease the coast of assays improve the control of disease.


title: The psychological impact of sars-cov-2 quarantine: Observations through the lens of the polyvagal theory

text: According to the polyvagal theory, quarantine and social distancing following COVID-19 pandemic may dampen nucleus ambiguuus (NA) activity in the brainstem and hinder homeostatic cardiorespiratory functioning, emotional self-regulation and health. In addition, enduring quarantine may foster heightened implicit vigilance for social threat, emotional dysregulation, poor sleep and immune response, potentially increasing the chance of infections. Promoting activities aimed at increasing NA functioning, like self-compassion, may support emotional self-regulation, adequate immune response and health.


title: Modelling the impact of reducing control measures on the COVID-19 pandemic in a low transmission setting

text: Aims: We assessed COVID-19 epidemic risks associated with relaxing a set of physical distancing restrictions in the state of Victoria, Australia - a setting with low community transmission - in line with a national framework that aims to balance sequential policy relaxations with longer-term public health and economic need. Methods: An agent-based model, Covasim, was calibrated to the local COVID-19 epidemiological and policy environment. Contact networks were modelled to capture transmission risks in households, schools and workplaces, and a variety of community spaces (e.g. public transport, parks, bars, cafes/restaurants) and activities (e.g. community or professional sports, large events). Policy changes that could prevent or reduce transmission in specific locations (e.g. opening/closing businesses) were modelled in the context of interventions that included testing, contact tracing (including via a smartphone app), and quarantine. Results: Policy changes leading to the gathering of large, unstructured groups with unknown individuals (e.g. bars opening, increased public transport use) posed the greatest risk, while policy changes leading to smaller, structured gatherings with known individuals (e.g. small social gatherings) posed least risk. In the model, epidemic impact following some policy changes took more than two months to occur. Model outcomes support continuation of working from home policies to reduce public transport use, and risk mitigation strategies in the context of social venues opening, such as >30% population-uptake of a contact-tracing app, physical distancing policies within venues reducing transmissibility by >40%, or patron identification records being kept to enable >60% contact tracing. Conclusions: In a low transmission setting, care should be taken to avoid lifting sequential COVID-19 policy restrictions within short time periods, as it could take more than two months to detect the consequences of any changes. These findings have implications for other settings with low community transmission where governments are beginning to lift restrictions.


title: Natural and synthetic potential inhibitors of endoribonuclease Nsp15 encoded by Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Computer modeling in silico experiments. p-Coumaric acid, Curcumin and their Boronic acid derivatives compared to Hydroxychloroquine and its Boronic acid derivativ

text: Based on the structural and biochemical characterization of endoribonuclease Nsp15 in crystal structure PDB code 5YVD, I am providing plausible inhibitors of this enzyme. In this report I intent to signal that is possible to inhibit this enzyme by the use of natural occurring compounds and their boronic acid derivatives, compounds with borono B(OH)2 groups. Boronic acids are atracted to serine side chains in the active site of serine proteases, in this case an endoribonuclease. Actual lab tests need to be conducted, nevertheless I venture here to propose four compounds: p-coumaric acid, Curcumin and their boronic acid derivatives with the use of computer modeling, in silico experiments. I also compared the above mentioned compounds to Hydroxychloroquine and its boronic acid derivative. I used AutoDock Vina, UCSF Chimera 1.12, DeepView / Swiss-Pdb Viewer 4 1.0, Sulp 3.0, PubChem, MDL Isis Draw 2.5, OpenBabelGUI 2.2.3, and Microsoft WordPad. As hardware I used a VAIO loptop with Intel Core i5 with Microsoft Windows 8.0, and a Dell loptop Inspiron E 1405 with an Intel Core Duo with Microsoft Windows Xp (off line).


title: Highly sensitive and full-genome interrogation of SARS-CoV-2 using multiplexed PCR enrichment followed by next-generation sequencing

text: Many detection methods have been used or reported for the diagnosis and/or surveillance of COVID-19. Among them, reverse transcription polymerase chain reaction (RT-PCR) is the most commonly used because of its high sensitivity, typically claiming detection of about 5 copies of viruses. However, it has been reported that only 47-59% of the positive cases were identified by some RT-PCR methods, probably due to low viral load, timing of sampling, degradation of virus RNA in the sampling process, or possible mutations spanning the primer binding sites. Therefore, alternative and highly sensitive methods are imperative. With the goal of improving sensitivity and accommodating various application settings, we developed a multiplex-PCR-based method comprised of 343 pairs of specific primers, and demonstrated its efficiency to detect SARS-CoV-2 at low copy numbers. The assay produced clean characteristic target peaks of defined sizes, which allowed for direct identification of positives by electrophoresis. We further amplified the entire SARS-CoV-2 genome from 8 to half a million viral copies purified from 13 COVID-19 positive specimens, and detected mutations through next generation sequencing. Finally, we developed a multiplex-PCR-based metagenomic method in parallel, that required modest sequencing depth for uncovering SARS-CoV-2 mutational diversity and potentially novel or emerging isolates.


title: TMPRSS2 variants and their susceptibility to COVID-19: focus in East Asian and European populations.

text: The manifestation of the COVID-19 varies from absence of symptoms to Severe Acute Respiratory Syndrome. The epidemiological data indicate that infection and mortality rates are greater in European populations in comparison with eastern Asians. To test if epidemiological patterns may be partly determined by human genetic variation, we investigated, by exomic and databank analyses, the variability found in the TMPRSS2 gene in populations from different continents, since this gene is fundamental to virus access into human cells. The functional variants revealed low diversity. The analyses of the variation in the modifiers of gene expression indicate that the European populations may have much higher levels of pulmonary expression of the TMPRSS2 gene and would be more vulnerable to infection by SARS-CoV-2. By contrast, the pulmonary expression of the TMPRSS2 may be reduced in the populations from East Asia, which implies that they are less susceptible to the virus infection and, these genetic features might also favor their better outcomes. The presented data, if confirmed, indicates a potential genetic contribution of TMPRSS2 to individual susceptibility to viral infection, and might also influence COVID-19 outcome.


title: Soccer, World War II and coronavirus: a comparative analysis of how the sport shut down

text: In 2020 the world faces an unprecedented challenge consequence of the coronavirus pandemic. Soccer, arguably, one of the most globalized industries, has reacted to the event by closing down much of its operations. This paper reviews the speed and breadth of such closures and compares it to another major event in history: The Second World War. During the latter, soccer continued operations despite the apparent difficulties. Total closures were, for the most part, temporary, and the sport was practiced whenever possible. The way that soccer operated during the war contrasts with how it has responded to the COVID-19 crisis. In record time, virtually all leagues in the world stopped operations, and for the first time since its foundation, with but a few exceptions, there were no games anywhere in the world.


title: Rapid inactivation of SARS-CoV-2 with LED irradiation of visible spectrum wavelenghts

text: The COVID-19 pandemic has caused a global health crisis. The difficulty to control the viral spread due to the absence of vaccines and prophylactics measures has raised concerns about prevention and control of SARS-CoV-2. Therefore, it becomes more and more crucial the reduction of environmental risk factors through viral inactivation of aerosols and fomites. Photodynamic inactivation of microorganisms by light energy emitted in the visible spectrum region (VIS), not harmful for mammalian cells and safe for humans, has recently been described. A LED-device emitting a special combination of frequencies in the visible light spectrum was tested on SARS-CoV-2 infected cell surnatant dilutions in order to evaluate the antiviral efficacy. This preliminary in vitro study showed for the first time the ability to inactivate SARS-CoV-2 through LED irradiation of visible spectrum wavelengths. If further and more extensive studies will confirm these data, the usage of this LED could potentially have a big impact on the sanitization of virtually all human environments.


Asymptomatic transmission of severe acute respiratory syndrome-coronavirus 2 within a family cluster of 26 cases: Why quarantine is important?


title: Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays

text: Introduction Commercially available SARS-CoV-2 serological assays based on different viral antigens have been approved for the qualitative determination of anti-SARS-CoV-2 antibodies. However, there is limited published data associating the results from commercial assays with neutralizing antibodies. Methods 67 specimens from 48 patients with PCR-confirmed COVID-19 and a positive result by the Roche Elecsys SARS-CoV-2, Abbott SARS-CoV-2 IgG, or EUROIMMUN SARS-CoV-2 IgG assays and 5 control specimens were analyzed for the presence of neutralizing antibodies to SARS-CoV-2. Correlation, concordance, positive percent agreement (PPA), and negative percent agreement (NPA) were calculated at several cutoffs. Results were compared in patients categorized by clinical outcomes. Results The correlation between SARS-CoV-2 neutralizing titer (EC50) and the Roche, Abbott, and EUROIMMUN assays was 0.29, 0.47, and 0.46 respectively. At an EC50 of 1:32, the concordance kappa with Roche was 0.49 (95% CI; 0.23-0.75), with Abbott was 0.52 (0.28-0.77), and with EUROIMMUN was 0.61 (0.4-0.82). At the same neutralizing titer, the PPA and NPA for the Roche was 100% (94-100) & 56% (30-80); Abbott was 96% (88-99) & 69% (44-86); and EUROIMMUN was 91% (80-96) & 81% (57-93) for distinguishing neutralizing antibodies. Patients who died, were intubated, or had a cardiac injury from COVID-19 infection had significantly higher neutralizing titers relative to those with mild symptoms. Conclusion COVID-19 patients generate an antibody response to multiple viral proteins such that the calibrator ratios on the Roche, Abbott, and EUROIMMUN assays are all associated with SARS-CoV-2 neutralization. Nevertheless, commercial serological assays have poor NPA for SARS-CoV-2 neutralization, making them imperfect proxies for neutralization.


title: Determining the replication kinetics and cellular tropism of the ruminant-associated Influenza D virus on primary human airway epithelial cells

text: Influenza viruses are notorious pathogens that frequently cross the species barrier with often severe consequences for both animal and human health. In 2011, a novel member of the Orthomyxoviridae family, Influenza D virus (IDV), was identified in the respiratory tract of diseased swine. Epidemiological surveys revealed that IDV is distributed worldwide among livestock and that IDV-directed antibodies are detected in humans with occupational exposure to livestock. To identify the transmission capability of IDV to humans, we determined the viral replication kinetics and cell tropism using an in vitro respiratory epithelium model of humans. The inoculation of IDV revealed efficient replication kinetics and apical progeny virus release at different body temperatures. Intriguingly, the replication characteristics of IDV revealed many similarities to the human-associated Influenza C virus, including the cell tropism preference for ciliated cells. Collectively, these results might indicate why IDV-directed antibodies are detected among humans with occupational exposure to livestock. One-sentence summary of the conclusion We show that the ruminant-associated Influenza D virus has direct transmission capability to humans.


title: IL6 inhibition in critically ill COVID-19 patients is associated with increased secondary infections

text: Anti-inflammatory therapies such as IL-6 inhibition have been proposed for COVID-19 in a vacuum of evidence-based treatment. However, abrogating the inflammatory response in infectious diseases may impair a desired host response and predispose to secondary infection. To determine whether IL-6 inhibition is associated with an increased occurrence of secondary infections in patients admitted to the intensive care unit (ICU). We retrospectively reviewed the medical record of patients during an 8-week span and compared the incidence of secondary infection in patients who did and did not receive tocilizumab. The study was approved by the IRB. Additionally, we included representative histopathologic post-mortem findings from several COVID-19 cases that underwent autopsy at our institution. The study was conducted in a cohorted COVID-19 ICU at a tertiary care university medical center. Patients 18 years of age or older admitted to the adult COVID-19 intensive care unit with COVID-19 were randomly selected. We reviewed the occurrence and nature of secondary infections and clinical outcomes in patients who did and did not receive tocilizumab. Measures were formulated prior to the study. For autopsy findings, we were interested in the lung pathology. 60 patients were selected of which 28 had received tocilizumab while 32 had not. Receiving tocilizumab was associated with a higher risk of secondary bacterial (64.3% vs. 31.3%, p=0.010) and fungal (7.1% vs. 0%, p=0.096) infections. 7 cases underwent autopsy. In 3 cases, tocilizumab had previously been given. All 3 patients demonstrated evidence of pneumonia on pathology. Of the 4 cases that had not been given tocilizumab, 2 showed evidence of aspiration pneumonia and 2 exhibited diffuse alveolar damage. Experimental therapies are currently being applied to COVID-19 outside of clinical trials. Anti-inflammatory therapies such as anti-IL-6 therapy have the potential to impair viral clearance, predispose to secondary infection, and cause harm. We seek to raise physician awareness of these issues and highlight the need to better understand the immune response in COVID-19.


title: Compassionate Use of Opaganib For Patients with Severe COVID-19

text: Background. Opaganib is a selective sphingosine-kinase (SK)-2 inhibitor with anti-inflammatory and anti-viral properties. Methods. We provided opaganib on a compassionate-use basis to patients with severe COVID-19. Patients who required oxygen support via high-flow nasal cannula (HFNC) were offered the treatment. For comparison, we used a control group with same-sex, same-severity patients. Results. Seven patients received at least one dose of opaganib since April 2, 2020. One patient, who received both hydroxychloroquine and azithromycin, developed diarrhea and all his medications were stopped. This was the only adverse effect possibly related to opaganib. A second patient was weaned of oxygen and discharged after receiving two doses of opaganib. Therefore, five patients were included in this analysis. Baseline characteristics were not significantly different between cases and controls. Patients treated with opaganib had significantly faster increase in lymphocyte count. All other clinical outcomes had a non-statistically significant trend in favor of the treatment group: median time to weaning from HFNC was 10 and 15 days in cases vs. controls (HR= 0.3, 95% CI: 0.07-1.7, p=0.2) ,time to ambient air was 13 vs.14.5 days (HR=0.4, 95% CI: 0.15-1.5), none of the cases required mechanical ventilation compared with 33% of controls. Conclusion. In this small cohort of severe COVID-19 patients, opaganib was safe and well tolerated with improvement in both clinical and laboratory parameters in all treated patients. The efficacy of opaganib for COVID-19 infection should be further tested in randomized placebo-controlled trials.


title: Elevated levels of interleukin-27 in early life compromise protective immunity during neonatal sepsis

text: Neonates are at increased risk for bacterial sepsis as a result of immature immunity. We established that the immune suppressive cytokine interleukin (IL)-27 is elevated in early life. In the present work, we hypothesized that increased levels of IL-27 may predispose the neonatal population to more severe infection during sepsis. In a neonatal sepsis model, systemic IL-27 levels continued to rise during infection. Peripheral tissue analysis revealed systemic IL-27 expression, while myeloid cell profiling identified Gr-1 and F4/80-expressing cells as the most abundant producers of IL-27 during infection. Increased IL-27 levels were consistent with increased mortality that was improved in WSX-1-/- mice that lack a functional IL-27 receptor. Infected WSX-1-/- pups exhibited improved weight gain and reduced morbidity. IL-27 signaling in WT mice promoted increased bacterial burdens and systemic inflammation compared to WSX-1-/- neonates. This was consistent with more efficient bacterial killing by Ly6B.2+ myeloid cells and macrophages from WSX-1-deficient compared to wild-type neonates. Live animal imaging further supported a more severe and disseminated infection in WT neonates. This is the first report to describe the impact of elevated early life IL-27 on the host response in neonates while also defining the cell and tissue sources of cytokine. IL-27 is frequently associated with suppressed inflammation. In contrast, our findings demonstrate that IL-27 promotes inflammation during neonatal sepsis by directly compromising control of bacteria that drive the inflammatory response. Collectively, our results suggest that IL-27 represents a therapeutic target to limit susceptibility and improve infectious outcomes in neonatal sepsis. IMPORTANCE A number of differences in the neonatal immune response compared with adults have been well described. However, a mechanistic understanding of what needs to be overcome in the neonate to generate a more protective immune response during acute bacterial infection has been limited. The work described here helps fill the gap of what is necessary to overcome in order to achieve improved host response to infection. To further the novelty, IL-27 has not previously been attributed to dysfunction or deficiency in neonatal immunity. Our results enhance the understanding of IL-27 biology in the neonatal population while providing evidence that elevated IL-27 levels limit a protective immune response and are detrimental during neonatal sepsis. Strategies aimed at targeting circulating IL-27 concentrations early in life have the potential to improve control of bacterial infection in neonates.


title: Machine Learning the Phenomenology of COVID-19 From Early Infection Dynamics

text: We present a robust data-driven machine learning analysis of the COVID-19 pandemic from its early infection dynamics, specifically infection counts over time. The goal is to extract actionable public health insights. These insights include the infectious force, the rate of a mild infection becoming serious, estimates for asymtomatic infections and predictions of new infections over time. We focus on USA data starting from the first confirmed infection on January 20 2020. Our methods reveal significant asymptomatic (hidden) infection, a lag of about 10 days, and we quantitatively confirm that the infectious force is strong with about a 0.14% transition from mild to serious infection. Our methods are efficient, robust and general, being agnostic to the specific virus and applicable to different populations or cohorts.


title: Medical Students in the Time of COVID-19: opportunities and challenges

text: The spread of COVID-19 has had a substantial impact on healthcare systems around the world. Increased pressure has led to doctors being called out of retirement, as well as a call for volunteers in healthcare settings and within the community. Medical education has been transformed within the space of weeks, with clinical placements cancelled and teaching and examinations moved to an online format. This raises the question of what the role of medical students is during this pandemic.


title: Clinical characterization of respiratory droplet production during common airway procedures using high-speed imaging

text: Background: During the COVID-19 pandemic, a significant number of healthcare workers have been infected with SARS-CoV-2. However, there remains little knowledge regarding droplet dissemination during airway management procedures in real life settings. Methods: 12 different airway management procedures were investigated during routine clinical care. A high-speed video camera (1000 frames/second) was for imaging. Quantitative droplet characteristics as size, distance traveled, and velocity were computed. Results: Droplets were detected in 8/12 procedures. The droplet trajectories could be divided into two distinctive patterns (type 1/2). Type 1 represented a ballistic trajectory with higher speed droplets whereas type 2 represented a random trajectory of slower particles that persisted longer in air. Speaking and coughing lead to a larger amount of droplets than non-invasive ventilation therapy. The use of tracheal cannula filters reduced the amount of droplets. Conclusions: Respiratory droplet patterns generated during airway management procedures follow two distinctive trajectories based on the influence of aerodynamic forces. Speaking and coughing produce more droplets than non-invasive ventilation therapy confirming these behaviors as exposure risks. Even large droplets may exhibit patterns resembling the fluid dynamics smaller airborne aerosols that follow the airflow convectively and may place the healthcare provider at risk.


title: The potential genetic network of human brain SARS-CoV-2 infection

text: The literature reports several symptoms of SARS-CoV-2 in humans such as fever, cough, fatigue, pneumonia, and headache. Furthermore, patients infected with similar strains (SARS-CoV and MERS-CoV) suffered testis, liver, or thyroid damage. Angiotensin-converting enzyme 2 (ACE2) serves as an entry point into cells for some strains of coronavirus (SARS-CoV, MERS-CoV, SARS-CoV-2). Our hypothesis was that as ACE2 is essential to the SARS-CoV-2 virus invasion, then brain regions where ACE2 is the most expressed are more likely to be disturbed by the infection. Thus, the expression of other genes which are also over-expressed in those damaged areas could be affected. We used mRNA expression levels data of genes provided by the Allen Human Brain Atlas (ABA), and computed spatial correlations with the LinkRbrain platform. Genes whose co-expression is spatially correlated to that of ACE2 were then clustered into 16 groups, depending on the organ in which they are the most expressed (as described by the NCBI genes database). The list of organs where genes sharing local over-expression with the ACE2 gene are the most expressed is astonishingly similar to the organs affected by Covid-19.


title: A Method to Identify the Missing COVID-19 Cases in the U.S. and Results for mid-April 2020

text: I use the COVID-19 death rate in South Korea and a method relating the ratio of death rates in a U.S. state to its share of cumulative positive tests to estimate the total cases of COVID-19 in the U.S. and to estimate the extent of infection and the unidentified share of the infected population in each of the lower-48 states and in New York City in mid-April, 2020. I identify a logarithmic relationship between the cumulative death rate in a state and its cumulative positive share of tests. Using this relationship, I find that 4.3-5.4 million people, 1.4-1.7% of the U.S. population, were infected, with rates of infection that ranged from 0.1% in more rural states to 8-10% in New York state and 11-13% in New York City. Only 16-20% of these infected individuals were identified later through testing.


title: Intensive care risk estimation in COVID-19 pneumonia based on clinical and imaging parameters: experiences from the Munich cohort

text: Background: The rapidly evolving dynamics of coronavirus disease 2019 (COVID-19) and the steadily increasing infection numbers require diagnostic tools to identify patients at high risk for a severe disease course. Here we evaluate clinical and imaging parameters for estimating the need of intensive care unit (ICU) treatment. Methods: We collected clinical, laboratory and imaging data from 65 patients with confirmed COVID-19 infection based on PCR positivity. IL-6, CRP, leukocyte and lymphocyte counts were determined in blood samples. Two radiologists evaluated the severity of imaging findings in computed tomography (CT) images on a scale from 1 (no characteristic signs of COVID-19) to 5 (confluent ground glass opacities in over 50% of the lung parenchyma). The volume of affected lung was quantified using commercially available software. Machine learning modelling was performed to estimate the risk for intensive care unit treatment. Findings: Patients with a severe course of COVID-19 had significantly increased IL-6, CRP and leukocyte counts and significantly decreased lymphocyte counts. The radiological severity grading was significantly increased in ICU patients. Multivariate random forest modelling showed a mean +/- standard deviation sensitivity, specificity and accuracy of 0.72 +/- 0.1, 0.86 +/- 0.16 and 0.80 +/- 0.1 and a ROC-AUC of 0.79 +/- 0.1. The most important predictive parameters were affected lung volume, radiological severity score, CRP and IL-6. Summary and Conclusion: Estimation of need for intensive care treatment is possible based on the clinical and radiological parameters.


title: Knowledge and behaviors toward COVID-19 among U.S. residents during the early days of the pandemic

text: Abstract Objective: To test the hypothesis that knowledge of COVID-19 influences participation in different behaviors including self-reports of purchasing more goods than usual, attending large gatherings, and using medical masks. Methods: Cross-sectional online survey of 1,034 U.S. residents age 18+ conducted on March 17, 2020. Results: For every point increase in knowledge, the odds of participation in purchasing more goods (OR=0.88, 95% CI:0.81-0.95), attending large gatherings (OR=0.87, 95%CI: 0.81-0.93), and using medical masks (OR=0.56, 95% CI:0.50-0.62) decreased by 12%, 13%, and 44%, respectively. Gen X and Millennial participants had 56% to 76% higher odds, respectively, of increased purchasing behavior, compared to Baby Boomers. Results suggest politicization of response recommendations. Democrats had 30% lower odds of attending large gatherings (OR=0.70, 95% CI:0.50-0.97), and 48% lower odds of using medical masks (OR=0.52, 95% CI:0.34-0.78), compared to Republicans. Conclusions: This survey is one of the first attempts to study determinants of knowledge and behaviors in response to the COVID-19 pandemic in the U.S. A national, coordinated effort at pandemic response may ensure better compliance with behavioral recommendations to address this public health emergency.


title: High temperature has no impact on the reproduction number and new cases of COVID-19 in Bushehr, Iran

text: Background: COVID-19 was first reported in Iran on February 19, 2020. Bushehr, one of the warmest provinces of Iran, was the last province confirmed to be infected on March 5, 2020. At the beginning of April, Bushehr was announced as a white, coronavirus-free, province. However, increasing the temperature in the next months did not affect the spread of coronavirus and the number of confirmed cases increased during the next months, so that Bushehr was announced as a Red province on June 13, 2020. Methods: This paper aims 1) to estimate the reproduction number of COVID-19 in Bushehr considering COVID-19 reported cases of Bushehr from April to June 12, 2020, using exponential function and SIR epidemic model, and 2) to investigate the impact of temperature on reproduction number and the spread of coronavirus in Bushehr the temperature data. Result: The reproduction number is estimated to be between 2.564 to 2.641. Regarding the increase of the temperature during April to June, the results show that not only was the spread of COVID-19 not reduced but it also increased. Conclusions: Data analysis on this study shows that high temperature has no impact on the reproduction number and does not slow down the spread of coronavirus in Bushehr.


title: US Stimulus funds research

text: A $2 trillion stimulus package to address the economic impact of the coronavirus pandemic, the largest stimulus in US history, was passed by the US Congress and signed by President Donald J Trump Science agencies throughout the federal government received research funding in the Coronavirus Aid, Relief, and Economic Security (CARES) Act This funding for research on COVID-19—the disease caused by the SARS-CoV-2 virus—is on top of an $8 3 billion package passed in early March “This is a much-needed infusion of funding that will advance COVID-19 research already underway at public universities and elsewhere,” Peter McPherson, president of the Association of Public and Land-grant Universities, says in a statement But universities, which have largely moved classes online and closed labs not doing COVID-19 work, had hoped for more support Congress is already discussing another stimulus bill The National Institutes of Health is the largest recipient of research funding, at $945 [truncated]


Healthcare reassessment in a pandemics time: challenges for CF


title: International expansion of a novel SARS-CoV-2 mutant

text: Letter to the editor. There is no abstract. The summary was showed: SARS-CoV-2 has inevitably mutated during its pandemic spread to cause unpredictable effects on COVID-19 and complicate epidemic control efforts. Here we report that a novel SARS-CoV-2 mutation (ORF3a) appears to be spreading worldwide, which deserves close attention.


title: Understanding Epidemic Data and Statistics: A case study of COVID-19

text: The 2019-Novel-Coronavirus (COVID-19) has affected 181 countries and out of about 1197405 confirmed cases (By April 5). Understanding the transmission dynamics of the infection in each country which affected on a daily basis and evaluating the effectiveness of control policies is critical for our further actions. To date, the statistics of COVID-19 reported cases show more than 80 percent of infected had a mild case of disease, while around 14 percent of infected experienced a severe one and about 5 percent are categorized as critical disease victims. Today's report (2020-04-05; daily updates in the prepared website) shows the confirmed cases of COVID-19 in the US, Spain, Italy, and Germany are 308850, 126168, 124632, and 96092; respectively. Calculating the total Case Fatality Rate (CFR) of Italy (2020-04-04), about 13.3% of confirmed cases passed away. Compared to South Korea's rate of 1.8% (7 times lower than Italy) and China's 4% (69% lower than Italy), the CFR of Italy is too high. There are some effective policies that yield significant changes in the trend of cases. The lockdown policy in China, Italy, and Spain (the effect observed after some days), Shutdown of all non-essential companies in Hubei (the effect observed after 5 days), combined policy in South Korea, and reducing working hours in Iran.


title: Low rate of daily smokers in patients with symptomatic COVID-19

text: Background: Identification of prognostic factors in COVID-19 remains a global challenge. The role of smoking is still controversial. Objective: To evaluate the rate of daily smokers in patients with COVID-19. Methods: COVID-19 in-and outpatients from a large French university hospital were systematically interviewed for their smoking status, use of e-cigarette and nicotinic substitutes. The rates of daily smokers in in-and outpatients were compared to those in the 2019 French general population, after standardization for sex and age. Results: The inpatient group was composed of 340 patients, median age 66 years: 203 men (59.7%) and 137 women (40.3%), median age for both 66 years, with a daily smokers rate of 4.1 % CI95% [2.3-6.9] (5.4% of men, 2.2% of women). The outpatient group was composed of 139 patients, median age 44 years: 62 men (44.6%, median age 43 years), and 77 women (55.4%, median age 44 years). The daily smoker rate was 6.1 % CI 95% [2.7-11.6] (5.1% of men, 6.8% of women). In the 2019 French population, the daily smoker rate was 24.0% (27.5% of men, 20.7% of women). Among inpatients, daily smokers represented 2.2% and 3.4% of the 45 dead patients and of the 29 patients transferred to ICU, respectively. The rate of daily smokers was significantly lower in COVID-19 patients, as compared to that in the French general population after standardization by age and sex, with Standardized Incidence Ratios of 0.24 [0.12-0.48] for outpatients and 0.24 [0.14-0.40] for inpatients. Conclusion: Daily smokers rate in patients with symptomatic COVID-19 is lower as compared to the general population


title: Will COVID-19 pandemic diminish by summer-monsoon in India? Lesson from the first lockdown

text: The novel Coronavirus (2019-nCoV) was identified in Wuhan, Hubei Province, China, in December 2019 and has created a medical emergency worldwide. It has spread rapidly to multiple countries and has been declared a pandemic by the World Health Organization. In India, it is already reported more than 18 thousand cases and more than 600 deaths due to Coronavirus disease 2019 (COVID-19) till April 20, 2020. Previous studies on various viral infections like influenza have supported an epidemiological hypothesis that the cold and dry (low absolute humidity) environments favor the survival and spread of droplet-mediated viral diseases. These viral transmissions found attenuated in warm and humid (high absolute humidity) environments. However, the role of temperature, humidity, and absolute humidity in the transmission of COVID-19 has not yet been well established. Therefore the study to investigate the meteorological condition for incidence and spread of COVID-19 infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease is required for India. In this work, we analyze the local weather patterns of the Indian region affected by the COVID-19 virus for March and April months, 2020. We have investigated the effect of meteorological parameters like Temperature, relative humidity, and absolute humidity on the rate of spread of COVID-19 using daily confirm cases in India. We have used daily averaged meteorological data for the last three years (2017-2019) for March and April month and the same for the year 2020 for March 1 to April 15. We found a positive association (Pearsons r=0.56) between temperature and daily COVID-19 cases over India. We found a negative association of humidity (RH and AH) with daily COVID-19 Cases (Persons r=-0.62, -0.37). We have also investigated the role of aerosol in spreading the pandemic across India because its possible airborne nature. For this, we have investigated the association of aerosols (AOD) and other pollutions (NO2) with COVID-19 cases during the study period and also during the first lockdown period (25 March-15 April) in India. We found a negative association in March when there were few cases, but in April, it shows positive association when the number of cases is more (for AOD it was r=-0.41 and r=0.28 respectively). During the lockdown period, aerosols (AOD) and other pollutants (NO2; an indicator of PM2.5) reduced sharply with a percentage drop of about 36 and 37, respectively. This reduction may have reduced the risk for COVID-19 through air transmission due to the unavailability of aerosol particles as a base. HYSPLIT forward trajectory model also shows that surface aerosols may travel up to 4 km according to wind and direction within three h of its generation. If coronavirus becomes airborne as suggested by many studies, then it may have a higher risk of transmission by aerosols particles. So relaxing in the lockdown and environmental rules in terms of pollutant emissions from power plants, factories, and other facilities would be a wrong choice and could result in more COVID-19 incidences and deaths in India. Therefore the current study, although limited, suggests that it is doubtful that the spread of COVID-19 would slow down in India due to meteorological factors, like high temperature and high humidity. Because a large number of cases have already been reported in the range of high Tem, high Relative, and high absolute humidity regions of India. Thus our results in no way suggest that COVID-19 would not spread in warm, humid regions or during summer/monsoon. So effective public health interventions should be implemented across India to slow down the transmission of COVID-19. If COVID-19 is indeed sensitive to environmental factors, it could be tested in the coming summer-monsoon for India. So the only summer is not going to help India until monsoon is coming. Only government mitigations strategies would be helpful, whether its lockdown, aggressive and strategic testing, medical facilities, imposing social distancing, encouraging to use face mask or monitoring by a mobile application (Aarogya Setu).


title: Is it safe to use a single ventilator for two or more patients?

text: In the context of SARS-CoV-2 pandemic, the mechanical ventilation is essential. Given its limited availability due to high cost, increased by a global demand, sharing a single mechanical ventilator with 2 or more patients with has been advocated. We have designed an experimental model for ventilating 2 test lungs with a single equipment, in order to measure these possible asymmetries during ventilation in parallel circuits with different compliances. This report attempts a first approach to the risks in ventilating 2 patients with single equipment, since there are differences in volumes which are not monitored by the ventilator, with the consequent risks of distension or alveolar collapse if used in real patients with different thoracopulmonary mechanics.


title: Self-reported food choices before and during COVID-19 lockdown

text: Stressful situations can cause changes in individual food choices, most notably, choices of highly rewarding foods that are high in fat or sugar. Few studies have examined how a population's food choices change during a country-wide stress-inducing event such as the beginning of the COVID-19 stay-at-home orders in the United States. Food data from a digital behavior change weight loss program, which includes an interface for logging meals, were analyzed to assess self-reported food choices from March 5-March 11 ("pre-COVID") and during the first week of the COVID-19 lockdown (March 12-March 18; "during-COVID"). The final sample consisted of 381,564 participants: 318,076 (83.4%) females, the majority who were aged 45-65 years (45.2%). Results indicate that self-reported servings of fresh fruit and vegetable intake decreased from pre- to during-COVID, while intake of red meat and starchy vegetables increased. More men than women increased their intake of red meat and processed meat. There was less overall change in fruit and vegetable consumption in participants aged 66 and older, compared to younger participants (aged 18-35). The percentage of older participants who reported lean meat and starchy vegetable intake increased, but these groups had a negligible change in younger subjects. More subjects aged 18-35 years reduced their intake of caffeine, desserts, lean meat and salads compared to older participants. No changes were observed in terms of snack or alcoholic beverage intake logged. In conclusion, this study of 381,564 US participants revealed that intake of particular food groups were altered during the first weeks of COVID lockdown.


title: Current Status of Prescriptive Authority by Pharmacists in the United States

text: Introduction: While pharmacists in other countries have broad independent prescribing privileges, pharmacists in the United States are making progress. Pharmacist prescriptive authority in the U.S. occurs on a continuum with four identified models: patient-specific collaborative prescribing through collaborative practice agreements (CPAs), population-specific prescribing through CPAs, statewide protocols, and class-specific prescribing. States have implemented pharmacist prescriptive authority across this spectrum. As approximately 90% of Americans reside within two miles of a community pharmacy, prescriptive authority of pharmacists leads to improved public health access points and outcomes. Objective: This paper is intended to provide insight into the current landscape of pharmacist prescriptive authority in the United States through 2019 in order to provide historical context and identify opportunities for state policy considerations. This was done through a review of published literature, national professional association resources, individual state pharmacy practice acts, and state legislation and regulations. Conclusion: Significant variability regarding what medications pharmacists can prescribe exists per state statutes. According to data collected from the National Alliance of State Pharmacy Associations (NASPA), 147 bills related to pharmacist provider status were introduced in 39 states during the 2019 legislative session. The interest in pharmacist prescribing stems from current and future challenges within the U.S. health care system: access to care, cost of care, and the anticipated shortage of physicians. The challenge to standardize prescriptive authority across states presents a unique opportunity for future considerations. This article is protected by copyright. All rights reserved.


title: Emerging details about covid-19 and chronology of the pandemic in turkey/ Covid-19 hakkında ortaya çıkan bilgiler ve türkiye'de pandeminin kronolojisi

text: Coronaviruses are found in all mammalian and avian species. Due to its mild infection on upper respiratory tract, this virus was not considered as a serious human pathogen until the outbreaks of SARS-CoV and MERS-CoV in 2002 and 2012, respectively. Recently the third and the biggest outbreak of coronavirus “COVID-19” or “SARS-CoV-2” has erupted and the world is now in a struggle to combat this disease. Although everything has not yet been fully clarified about this new type of virus, the data obtained from the studies conducted so far provides guidance on how to deal with SARS-CoV-2. In this context, this review provides information about pathogenesis, clinical symptoms, presence in animals, potential transmission routes of SARS-CoV-2 as well as the detection methods used in the world and Turkey.


Plastic Surgeons in the middle of the Coronavirus Disease 2019 Pandemic Storm in Italy


title: Testing an ‘ungrading’ approach

text: As the threat of COVID-19, the disease caused by the novel coronavirus, became apparent in early March, US universities and colleges rushed to implement contingency plans that protected their students and staff but also ensured that learning continued In addition to extending spring break and moving courses to an online-only format, schools such as the University of California, Berkeley, and the University of North Carolina at Chapel Hill gave students the option of switching from letter grades to pass-fail in their major courses This move took pressure off both students and professors during a difficult time “When we think about what our students really need—how do we get through this, how do we focus on the essentials—for some institutions, grades took a big back seat,” says Karen Cangialosi, a professor of biology at Keene State College Cangialosi thinks that prioritization says something about the importance of grades in general Are


title: Identifying Infection Sources and Regions in Large Networks

text: Identifying the infection sources in a network, including the index cases that introduce a contagious disease into a population network, the servers that inject a computer virus into a computer network, or the individuals who started a rumor in a social network, plays a critical role in limiting the damage caused by the infection through timely quarantine of the sources. We consider the problem of estimating the infection sources and the infection regions (subsets of nodes infected by each source) in a network, based only on knowledge of which nodes are infected and their connections, and when the number of sources is unknown a priori. We derive estimators for the infection sources and their infection regions based on approximations of the infection sequences count. We prove that if there are at most two infection sources in a geometric tree, our estimator identifies the true source or sources with probability going to one as the number of infected nodes increases. When there are more than two infection sources, and when the maximum possible number of infection sources is known, we propose an algorithm with quadratic complexity to estimate the actual number and identities of the infection sources. Simulations on various kinds of networks, including tree networks, small-world networks and real world power grid networks, and tests on two real data sets are provided to verify the performance of our estimators.


title: The effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on death and severity of disease in patients with coronavirus disease 2019 (COVID-19): A meta-analysis

text: Background: Effect of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on outcomes in patients with coronavirus disease 2019 (COVID-19) is uncertain. Available evidence is limited to a few retrospective observational studies with small number of patients. Methods: We did a meta-analysis to assess the effect of ACEi/ARB in patients with COVID-19 on severity of disease, risk for hospitalisation, and death compared to those not on ACEi/ARB. We searched the Cochrane library, PubMed, Embase, ClinicalTrial.gov and medRxiv for studies published until 21.04.2020. Inclusion criteria included all studies with patients with confirmed COVID-19 either taking, or not taking, ACEi/ARB. Depending on degree of heterogeneity, fixed or random effect model was selected to calculate effect size (Odds ratio). Findings: Five studies were eligible for meta-analysis. These included 308 patients on ACEi/ARB, and 1172 not on ACEi/ARB. Compared to patients with COVID-19 not on ACEi/ARB, there was a statistically significant 44% reduction in odds of developing severe disease (OR: 0.56; 95% CI: 0.34-1.89, I2=68.15), and 62% reduction in odds of death (OR: 0.38; 95% CI: 0.19-0.74, I2=0.000) in those on ACEi/ARB. There was a non-significant 19% (OR 0.81; 95% CI: 0.42-1.55, I2: 0.000) reduction in odds of hospitalisation among those on ACEi/ARB. Interpretation: It is safe to use ACEi/ARB in patients with COVID-19 requiring these medications for associated comorbidities. Although limited by confounding factors typical of a meta-analysis of retrospective observational studies, our data suggests that use of these medications may reduce risk of developing severe disease and death. Funding Source: None


title: COVID-19 severity is associated with immunopathology and multi-organ damage

text: COVID-19 is characterised by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand how host responses contribute to COVID-19 pathophysiology, we used a multi-omics approach to identify molecular markers in peripheral blood and plasma samples that distinguish COVID-19 patients experiencing a range of disease severities. A large number of expressed genes, proteins, metabolites and extracellular RNAs (exRNAs) were identified that exhibited strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients, indicative of multi-organ damage. The continuous activation of IFN-I signalling and neutrophils, as well as a high level of inflammatory cytokines, were observed in severe disease patients. In contrast, COVID-19 in mild patients was characterised by robust T cell responses. Finally, we show that some of expressed genes, proteins and exRNAs can be used as biomarkers to predict the clinical outcomes of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19 and will help guide future studies in this area.


title: Mental health status of the general population, healthcare professionals, and university students during 2019 coronavirus disease outbreak in Jordan: a cross-sectional study

text: Background: The emergence of COVID-19 global pandemic coupled with high transmission rate and mortality has created an unprecedented state of emergency worldwide. This global situation may have a negative impact on the psychological well-being of individuals which in turn impacts individuals performance. Methods: A cross-sectional study using an online survey was conducted in Jordan between 22nd and 28th of March 2020 to explore the mental health status (depression and anxiety) of the general population, healthcare professionals, and university students during the COVID-19 outbreak. The Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to assess depression and anxiety among the study participants. Logistic regression analysis was used to identify predictors of depression and anxiety. Results: The prevalence of depression and anxiety among the entire study participants was 23.8% and 13.1%, respectively. Anxiety was most prevalent across university students 21.5%, followed by healthcare professionals 11.3%, and general population 8.8%. Females among healthcare professionals and university students, divorced healthcare professionals, pulmonologists, and university students with history of chronic disease were at higher risk of developing depression. Females, divorced participants among the general population, and university students with history of chronic disease and those with high income ([≥]1500 JD) were at higher risk of developing anxiety. Conclusions: During outbreaks, individuals are put under extreme stressful condition resulting in higher risk of developing anxiety and depression particularly for students and healthcare professionals. Policymakers and mental healthcare providers are advised to provide further mental support to these vulnerable groups during this pandemic.


title: Length of Mucin-Like Domains Enhance Cell-Ebola Virus Adhesion by Increasing Binding Probability

text: The Ebola virus (EBOV) hijacks normal physiological processes by apoptotic mimicry in order to be taken up by the cell it infects. The initial adhesion of the virus to the cell is based on the interaction between T-cell immunoglobulin and mucin domain protein, TIM, on the cell-surface and phosphatidylserine (PS) on the viral outer surface. Therefore, it is important to understand the interaction between EBOV/PS and TIM, with selective blocking of the interaction as a potential therapy. Recent experimental studies have shown that for TIM-dependent EBOV entry, a Mucin-like Domain (MLD) with a length of at least 120 amino acids is required, possibly due to the increase of area of the PS-coated surface sampled. We examine this hypothesis by modeling the process of TIM-PS adhesion using a coarse-grained molecular model. We find that the strength of bound PS−TIM pairs is essentially independent of TIM length. TIMs with longer MLDs have higher average binding strengths because of an increase in the probability of binding between EBOV and TIM proteins. Similarly, we find that for larger persistence length (less flexible) the average binding force decreases, again because of a reduction in the probability of binding. Statement of Significance This work studies the mechanism of TIM-dependent adhesion of the Ebola virus to a cell. Through coarse grained modeling we show that longer TIM stalks adhere more easily as they can sample a larger area, thus offering a mechanistic interpretation of an experimental finding. Better mechanistic understanding can lead to therapeutic ideas for blocking adhesion.


title: Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM

text: The recent outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid international spread pose a global health emergency. The trimeric spike (S) glycoprotein interacts with its receptor human ACE2 to mediate viral entry into host-cells. Here we present cryo-EM structures of an uncharacterized tightly closed SARS-CoV-2 S-trimer and the ACE2-bound-S-trimer at 2.7-Å and 3.8-Å-resolution, respectively. The tightly closed S-trimer with inactivated fusion peptide may represent the ground prefusion state. ACE2 binding to the up receptor-binding domain (RBD) within S-trimer triggers continuous swing-motions of ACE2-RBD, resulting in conformational dynamics of S1 subunits. Noteworthy, SARS-CoV-2 S-trimer appears much more sensitive to ACE2-receptor than SARS-CoV S-trimer in terms of receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and residue Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2, and provided structural basis of the spike D614G-mutation induced enhanced infectivity. Our findings offer a thorough picture on the mechanism of ACE2-induced conformational transitions of S-trimer from ground prefusion state towards postfusion state, thereby providing important information for development of vaccines and therapeutics aimed to block receptor binding.


title: Profiling pre-symptomatic and asymptomatic cases with confirmed SARS-CoV-2 infection in Mexico City

text: IMPORTANCE: Asymptomatic SARS-CoV-2 infections are potential sources for transmission; characterization of these cases has not been conducted in most low/middle income countries, including Mexico. OBJECTIVE: To profile pre-symptomatic/asymptomatic SARS-CoV-2 infections in Mexico City, its associated comorbidities and outcomes. DESIGN: Prospective observational study SETTING: Subjects assessed by convenience sampling within the National Epidemiological Surveillance System in Mexico City. PARTICIPANTS: Subjects with and without respiratory and non-respiratory symptoms (RS, NRS, respectively) assessed for SARS-CoV-2 using real time RT-PCR from nasopharyngeal swabs. OUTCOMES: Severe COVID-19, intensive care unit admission, 30-day mortality and their outcomes in cases RS or NRS and asymptomatic cases. RESULTS: Amongst 60121 cases with confirmed SARS-CoV-2 infection as of July 1st, 2020, we identified 5982 cases without RS (9.9%) and 2452 who were asymptomatic at first evaluation (4.1%). Compared to cases with RS, NRS and asymptomatic cases were younger and had lower rates of comorbidities. Cases with NRS had higher rates of severe COVID-19 outcomes including hospitalization, ICU admission, and intubation (p<0.001). Mortality was higher for cases with NRS (HR 3.13, 95%CI 1.80-5.45) or RS (HR 7.58, 95%CI 4.56-12.58) compared to asymptomatic cases, adjusted for age, sex and comorbidities. Predictors for mortality in cases without RS included older age, previous exposure to suspected viral infection cases, comorbidities, presence of NRS and vomiting. For asymptomatic SARS-Co-V-2 infections, chronic kidney disease, previous exposure with suspected infection cases and older age were predictors for lethality. CONCLUSIONS AND RELEVANCE: Definition of pre-symptomatic/asymptomatic cases has relevant implications for SARS-CoV-2 infection outcomes. Older age and comorbidity impact on the probability of developing severe complications for cases who were asymptomatic or had only NRS at evaluation and were sent for domiciliary treatment. Extending testing for detection of asymptomatic cases must be considered in Mexico to better understand the impact of the pandemic.


Mental Health Care Measures in Response to the 2019 Novel Coronavirus Outbreak in Korea


title: COVID-19 in Multiple Sclerosis Patients and Risk Factors for Severe Infection

text: Importance: Multiple sclerosis patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, no study has identified clinical characteristics of multiple sclerosis associated with worse COVID-19 outcomes. Objective: To evaluate the clinical characteristics of multiple sclerosis, including staging, degree of disability, and disease-modifying therapy use that are associated with worse outcomes from COVID-19. Design: Prospective cohort study looking at the outcomes of multiple sclerosis patients with COVID-19 between March 1st and May 18th, 2020. Setting: This is a multicenter study of three distinct hospital systems within the U.S. Participants: The study included 40 consecutive patients with nasopharyngeal/oropharyngeal PCR-confirmed COVID-19 infection. Exposures: Multiple sclerosis staging, severe disability (based on baseline-extended disability status scale equal to or greater than 6.0) and disease-modifying therapy. Main Outcomes and Measure: Severity of COVID-19 infection was based on hospital course, where a mild course was defined as the patient not requiring hospital admission, moderate severity was defined as the patient requiring hospital admission to the general floor only, and most severe was defined as requiring intensive care unit admission and/or death. Results: For the 40 patients, the median age was 52(45.5-61) years, 16/40(40%) were male, and 21/40(52.5%) were African American. 19/40(47.5%) had mild courses, 15/40(37.5%) had moderate courses, and 6/40(15%) had severe courses. Patients with moderate and severe courses were significantly older than those with a mild course (57[50-63] years old and 66[58.8-69.5] years old vs 48[40-51.5] years old, P=0.0121, P=0.0373). There was differing prevalence of progressive multiple sclerosis staging in those with more severe courses (severe:2/6[33.3%]primary-progressing and 0/6[0%]secondary-progressing, moderate:1/14[7.14%] and 5/14[35.7%] vs mild:0/19[0%] and 1/19[5.26%], P=0.0075, 1 unknown). Significant disability was found in 1/19(5.26%) mild course-patients, but was in 9/15(60%, P=0.00435) of moderate course-patients and 2/6(33.3%, P=0.200) of severe course-patients. Disease-modifying therapy prevalence did not differ among courses (mild:17/19[89.5%], moderate:12/15[80%] and severe:3/6[50%], P=0.123). Conclusions and Relevance: Multiple sclerosis patients with more severe COVID-19 courses tended to be older, were more likely to suffer from progressive staging, and had a higher degree of disability. However, disease-modifying therapy use was not different among courses.


title: Deep sequencing of B cell receptor repertoires from COVID-19 patients reveals strong convergent immune signatures

text: Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 19 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients and may be a positive indicator of disease outcome. Clonal expansion of the B cell memory response is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 777 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralising antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand and predict positive patient responses.


title: Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype

text: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. Studies on SARS-CoV-2 are being carried out at an unprecedented rate to tackle this threat. Genomics studies, in particular, are indispensable to elucidate the dynamic nature of the RNA genome of SARS-CoV-2. RNA viruses are marked by their unique ability to undergo high rates of mutation in their genome, much more frequently than their hosts, which diversifies their strengths qualifying them to elude host immune response and amplify drug resistance. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. In addition to multiple point mutations, we found a remarkable similarity between relatively common mutations of 36-nucleotide deletion in ORF8 of SARS-CoV-2. Our results corroborate with the earlier reported 29-nucleotide deletion in SARS, which was frequent during the early stage of human-to-human transmission. The results will be useful to understand the biology of SARS-CoV-2 and itsattenuation for vaccine development.


title: Blood Supply Milestones in the Netherlands in the First Weeks of COVID-19

text: Abstract ?It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity ? Dickens On March 12th, the Dutch government announced its first measures to combat COVID-19 in the Netherlands through implementation of strict social distancing (e g closing of public venues and employees working from home) as part of maximum control measures, lasting until April 6th 1 For Sanquin, the national blood establishment solely responsible for the blood supply in the Netherlands, it was vital the organization continue to operate The leadership knew that as outbreaks may adversely impact blood supply and its related activities, steps would be needed to assess, plan, and respond appropriately in a time like this 2 Thus, the employees directly involved in the supply chain, from collection to distribution, remained hard at work


Canada’s Covid-19 response: navigating national and global solidarity


title: Covid-19, an emerging coronavirus infection: Current scenario and recent developments - An overview

text: During December 2019, a novel coronavirus virus (2019-nCov) emerged in China, which posed an International Public Health Emergency in a couple of weeks, and very recently attained the position of a very high-risk category by World Health Organization (WHO). This virus was named the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses (ICTV), and the disease referred to as Coronavirus Disease-19 (COVID-19). Till March 8, 2020, the virus has claimed the lives of nearly 3,600 humans out a total of approximately 110,000 confirmed cases affected by this infection. The present editorial is a brief overview highlighting the most salient features and facts with regards to COVID-19, an emerging coronavirus infection, its causative virus (SARS-CoV-2), the current worldwide scenario, recent developments and currently ongoing progresses to contain and control this disease which have now spread to more than 100 countries across the globe. Of note, worldwide researchers and various health agencies are all together doing their best to halt the spread of this virus and avoid any possible pandemic situation to be faced, which otherwise would threaten the lives of millions of human beings.


title: COVID-19 Myocarditis and Severity Factors： An Adult Cohort Study

text: Background Notwithstanding the clinical hallmarks of COVID-19 patients were reported, several critical issues still remain mysterious, i.e., prognostic factors for COVID-19 including extrinsic factors as viral load of SARS-CoV-2 and intrinsic factors as individual's health conditions; myocarditis incidence rate and hallmarks. Methods Demographic, epidemiologic, radiologic and laboratory data were collected by medical record reviews of adult hospitalized patients diagnosed as COVID-19. Cycle threshold (Ct) value data of real-time PCR (RT-PCR) were collected. The time duration was from 21 January to 2 March, 2020. Pulmonary inflammation index (PII) values were used for chest CT findings. Multivariate logistic regression analysis was used to identify independent severity risk factors. RESULTS In total, 84 hospitalized adult patients diagnosed as COVID-19 were included, including 20 severe and 64 nonsevere cases. The viral load of the severe group was significantly higher than that of the non-severe group, regardless of the Ct values for N or ORF1ab gene of virus (all p<0.05).Typical CT abnormalities was more likely existing in the severe group than in the nonsevere group in patchy shadows or ground glass opacities, consolidation, and interlobular septal thickening (all p<0.05). In addition, the PII values in the severe group was significantly higher than that in the nonsevere group (52.5 [42.5-62.5] vs 20 [5.0-31.6]; p<0.001). Amongst 84 patients, 13 patients (15.48%) were noted with abnormal electrocardiograms (ECGs) and serum myocardial enzyme levels; whereas 4 (4.8%) were clinically diagnosed as SARS-CoV-2 myocarditis. Multivariable logistic regress analysis distinguished three key independent risk factors for the severity of COVID-19, including age [OR 2.350; 95% CI (1.206 to 4.580); p=0.012], Ct value [OR 0.158; 95% CI (0.025 to 0.987); p=0.048] and PII [OR 1.912; 95% CI (1.187 to 3.079); p=0.008]. Interpretation Three key-independent risk factors of COVID-19 were identified, including age, PII, and Ct value. The Ct value is closely correlated with the severity of COVID-19, and may act as a predictor of clinical severity of COVID-19 in the early stage. SARS-CoV-2 myocarditis should be highlighted despite a relatively low incidence rate (4.8%). The oxygen pressure and blood oxygen saturation should not be neglected as closely linked with the altitude of epidemic regions.


title: Scalable Analysis of Authentic Viral Envelopes on FRONTERA

text: Enveloped viruses infect host cells via fusion of their viral envelope with the plasma membrane. Upon cell entry, viruses gain access to all the macromolecular machinery necessary to replicate, assemble, and bud their progeny from the infected cell. By employing molecular dynamics simulations to characterize the dynamical and chemical-physical properties of viral envelopes, researchers can gain insights into key determinants of viral infection and propagation. Here, the Frontera supercomputer is leveraged for large-scale analysis of authentic viral envelopes, whose lipid compositions are complex and realistic. VMD with support for MPI is employed on the massive parallel computer to overcome previous computational limitations and enable investigation into virus biology at an unprecedented scale. The modeling and analysis techniques applied to authentic viral envelopes at two levels of particle resolution are broadly applicable to the study of other viruses, including the novel coronavirus that causes COVID-19. A framework for carrying out scalable analysis of multi-million particle MD simulation trajectories on Frontera is presented, expanding the the utility of the machine in humanity’s ongoing fight against infectious disease.


title: Weak chatter detection in milling based on sparse dictionary

text: Abstract As one of the most unfavorable factors in milling, chatter will lead to poor surface quality, low production efficiency and tool life reduction. Chatter detection, especially weak chatter detection, is an effective way to ensure stable cutting. In this work, the milling dynamic responses based weak chatter detection method is put forward using sparse dictionary. Based on the milling dynamic equations, chatter frequencies are calculated and verified, which are the bases for chatter detection. With the calculated chatter frequencies, the sparse dictionary matrix can be constructed and the orthogonal matching pursuit (OMP) algorithm is adopted for chatter frequencies reconstruction. The proposed method can extract weak chatter frequencies accurately. Experimental results shows that the proposed method can be successful in weak chatter identification.


title: Single source of pangolin CoVs with a near identical Spike RBD to SARS-CoV-2

text: Multiple publications have independently described pangolin CoV genomes from the same batch of smuggled pangolins confiscated in Guangdong province in March, 2019. We analyzed the three metagenomic datasets that sampled this batch of pangolins and found that the two complete pangolin CoV genomes, GD_1 by Xiao et al. Nature and MP789 by Liu et al. PLoS Pathogens, were both built primarily using the 2019 dataset first described by Liu et al. Viruses. Other publications, such as Zhang et al. Current Biology and Lam et al. Nature, have also relied on this same dataset by Liu et al. Viruses for their assembly of pangolin CoV sequences and comparisons to SARS-CoV-2. To our knowledge, all of the published pangolin CoV genome sequences that share a nearly identical Spike receptor binding domain with SARS-CoV-2 originate from this single batch of smuggled pangolins. This raises the question of whether pangolins are truly reservoirs or hosts of SARS-CoV-2-related coronaviruses in the wild, or whether the pangolins may have contracted the CoV from another host species during trafficking. Our observations highlight the importance of requiring authors to publish their complete genome assembly pipeline and all contributing raw sequence data, particularly those supporting epidemiological investigations, in order to empower peer review and independent analysis of the sequence data.


title: Effects of physical activity and exercise on well-being in the context of the Covid-19 pandemic

text: Background: A disease discovered in China, COVID-19, was characterized by the World Health Organization (WHO) as a pandemic in March 2020. Many countries in the world implemented social isolation as a strategy to contain the virus transmission. The same physical distancing which protects society from COVID-19 from spreading may have an impact on the mental health and well-being of the population This study aims to shed some light on this phenomenon by assessing the relationship between physical activity and SWB among individuals in the social isolation period of COVID-19. Methods: Data were collected in Brazil between March 31st and April 2nd, 2020. All volunteers agreed to participate by digitally checking the option of agreement right after reading the Consent Terms. The inclusion criteria were participants over 18 years old who had been in social isolation for at least one week and agreed to the Consent Terms. Three instruments were used: a questionnaire was built for this study which aimed to assess the participants' exercise routine. The second instrument called Psychosocial Aspects, Well-being and Exercise in Confinement (PAWEC) was also created by these researchers and aimed to assess the relationship between well-being and physical activity during the social isolation period. And the third measure was the Brazilian Portuguese-adapted version of the Positive and Negative Affect Schedule (PANAS). Findings: A total of 592 participants reported being in social isolation for an average of 14.4 (SD=3.3) days. The amount of participants who reported strength training as exercise increased from 31 (5.2%) before isolation to 82 (13.9%) during quarantine. The study shows that well-being related to the practice of physical activity during quarantine is linked to an established routine of physical activity prior to the social isolation period. Interpretation: People who already practiced physical activity feel more motivated to continue practicing during this period and this causes the appearance of positive affects, unlike people who are only now starting to exercise; according to the study, negative aspects can occur for those who are only just starting. In a period of social isolation, it is important that the practice of physical activity is closer to previous habits, also finding that an obligation to exercise during this period when this was not a reality for the person can contribute to an increase in malaise.


title: Rigidity, normal modes and flexible motion of a SARS-CoV-2 (COVID-19) protease structure

text: The rigidity and flexibility of two recently reported crystal structures (PDB entries 6Y2E and 6LU7) of a protease from the SARS-CoV-2 virus, the infectious agent of the COVID-19 respiratory disease, has been investigated using pebble-game rigidity analysis, elastic network model normal mode analysis, and all-atom geometric simulations. This computational investigation of the viral protease follows protocols that have been effective in studying other homodimeric enzymes. The protease is predicted to display flexible motions in vivo which directly affect the geometry of a known inhibitor binding site and which open new potential binding sites elsewhere in the structure. A database of generated PDB files representing natural flexible variations on the crystal structures has been produced and made available for download from an institutional data archive. This information may inform structure-based drug design and fragment screening efforts aimed at identifying specific antiviral therapies for the treatment of COVID-19.


title: Low and high infection dose transmission of SARS-CoV-2 in the first COVID-19 clusters in Northern Germany

text: Objectives: We used viral genomics to deeply analyze the first SARS-CoV-2 infection clusters in the metropolitan region of Hamburg, Germany. Epidemiological analysis and contact tracing together with a thorough investigation of virus variant patterns revealed low and high infection dose transmissions to be involved in transmission events. Methods: Infection control measures were applied to follow up contract tracing. Metagenomic RNA- and SARS-CoV-2 amplicon sequencing was performed from 25 clinical samples for sequence analysis and variant calling. Results: The index patient acquired SARS-CoV-2 in Italy and after his return to Hamburg transmitted it to 2 out of 132 contacts. Virus genomics and variant pattern clearly confirms the initial local cluster. We identify frequent single nucleotide polymorphisms at positions 241, 3037, 14408, 23403 and 28881 previously described in Italian sequences and now considered as one major genotype in Europe. While the index patient showed a single nucleotide polymorphism only one variant was transmitted to the recipients. Different to the initial cluster, we observed in household clusters occurring at the time in Hamburg also intra-host viral species transmission events. Conclusions: SARS-CoV-2 variant tracing highlights both, low infection dose transmissions suggestive of fomites as route of infection in the initial cluster and high and low infection dose transmissions in family clusters indicative of fomites and droplets as infection routes. This suggests (1) single viral particle infection can be sufficient to initiate SARS-CoV-2 infection and (2) household/family members are exposed to high virus loads and therefore have a high risk to acquire SARS-CoV-2.


title: Integrated technology platform for accelerated discovery of antiviral antibody therapeutics

text: The emergence and reemergence of highly virulent viral pathogens with pandemic potential has created an urgent need for accelerated discovery of antiviral therapeutics. Antiviral human monoclonal (mAbs) are promising drug candidates to prevent or treat severe viral diseases, but the long timelines needed for discovery limits their rapid deployment and use. Here, we report the development of an integrated sequence of technologies incorporating advances in single-cell mRNA sequence analysis, bioinformatics, synthetic biology, and high-throughput functional analysis that allowed us to discover highly potent antiviral human mAbs and validate their activity in vivo at an unprecedented scale, speed, and efficiency. In a 78-day study, modeling deployment of a rapid response platform to an outbreak, we isolated >100 individual Zika virus (ZIKV) specific human mAbs, assessed their function, identified 29 broadly-neutralizing mAbs, and verified therapeutic potency of lead candidates with antibody-encoding mRNA formulation and/or IgG protein delivery in mice and nonhuman primates. Our work provides a roadmap for the rapid antibody discovery programs against viral pathogens of global concern.


title: Survey of Insomnia and Related Social Psychological Factors Among Medical Staff Involved in the 2019 Novel Coronavirus Disease Outbreak

text: OBJECTIVE: The outbreak of the 2019 novel coronavirus disease (COVID-19) not only caused particularly large public health problems, but also caused great psychological distress, especially for medical staff. We aimed to investigate the prevalence rate of insomnia and to confirm the related social psychological factors among medical staff in hospitals during the COVID-19 outbreak. METHOD: Medical staff members in China were recruited, including frontline medical workers. The questionnaire, administered through the WeChat program, obtained demographic data and asked self-design questions related to the COVID-19 outbreak, insomnia/depressive/anxiety symptoms, and stress-related symptoms. We used a logistic regression analysis to examine the associations between sociodemographic factors and insomnia symptoms. RESULT: There were a total of 1,563 participants in our study. Five-hundred-and-sixty-four (36.1%) participants had insomnia symptoms according to the Insomnia Severity Index (ISI) (total score ≥ 8). A multiple binary logistic regression model revealed that insomnia symptoms were associated with an education level of high school or below (OR = 2.69, p = 0.042, 95% CI = 1.0–7.0), being a doctor (OR = 0.44, p = 0.007, 95% CI = 0.2–0.8), currently working in an isolation unit (OR = 1.71, p = 0.038, 95% CI = 1.0–2.8), is worried about being infected (OR = 2.30, p < 0.001, 95% CI = 1.6–3.4), perceived lack of helpfulness in terms of psychological support from news or social media with regard to COVID-19 (OR = 2.10, p = 0.001, 95% CI = 1.3–3.3), and having very strong uncertainty regarding effective disease control (OR = 3.30, p = 0.013, 95% CI = 1.3–8.5). CONCLUSION: Our study found that more than one-third of the medical staff suffered insomnia symptoms during the COVID-19 outbreak. The related factors included education level, an isolation environment, psychological worries about the COVID-19 outbreak, and being a doctor. Interventions for insomnia among medical staff are needed considering the various sociopsychological factors at play in this situation.


title: Anomaly detection in milling tools using acoustic signals and generative adversarial networks

text: Abstract Acoustic monitoring presents itself as a flexible but under-reported method of tool condition monitoring in milling operations. This paper demonstrates the power of the monitoring paradigm by presenting a method of characterizing milling tool conditions by detecting anomalies in the time-frequency domain of the tools’ acoustic spectrum during cutting operations. This is done by training a generative adversarial neural network on only a single, readily obtained class of acoustic data and then inverting the generator to perform anomaly detection. Anomalous and non-anomalous data are shown to be nearly linearly separable using the proposed method, resulting in 90.56% tool condition classification accuracy and a 24.49% improvement over classification without the method.


title: The December 2019 New Corona Virus (SARS-CoV-2) Outbreak: A Behavioral Infectious Disease Policy Model

text: It is critical to understand the impact of distinct policy interventions to the ongoing December 2019 coronavirus (SARS-CoV-2) pandemic. We develop a flexible behavioral, dynamic, and sectorial epidemic policy model comprising both endogenous virus transmission and public health and citizen responses. Applicable to the full epidemic cycle including resurgence, the model allows exploring the multivariate impact of distinct policy interventions, including general and targeted testing and social contact reduction efforts. Calibrating the model to the early SARS-CoV-2 outbreak at the level of continents, we demonstrate how early, rapid, and extensive buildup of testing and social contact reduction efforts interplay to suppress the outbreak. Next, applying the model within hypothetical contexts we demonstrate how: i) sociodemographic variation in vulnerability to the virus affects overall reported and actual outbreak patterns; ii) feasible timing of deconfinement depends on earlier responses to the outbreak; and, iii) targeted approaches help suppress resurgent outbreaks and their various impacts. Finally, given the importance of broad support of outbreak control efforts, across public health experts, policymakers, volunteers, media, and citizens, we make the model also accessible in the form of a free web-based management flight simulator.


title: Performance of Abbott ID NOW COVID-19 rapid nucleic acid amplification test in nasopharyngeal swabs transported in viral media and dry nasal swabs, in a New York City academic institution

text: The recent emergence of the SARS-CoV-2 pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real time RT-PCR platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. Both platforms demonstrate comparable performance; however, the run times for each assay are 3.5 hours and 45 minutes, respectively. In search for a platform with shorter turnaround time, we sought to evaluate the recently released Abbott ID NOW COVID-19 assay which is capable of producing positive results in as little as 5 minutes. We present here the results of comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID NOW. Regardless of method of collection and sample type, Abbott ID NOW COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs.


The Caribbean and Covid-19: not a health crisis, but a looming economic one


title: Grappling with our therapeutic relationship and professional self-doubt during COVID-19: will we use video therapy again?

text: The social restrictions during the COVID-19 crisis led to many therapists providing therapy remotely, despite some therapists’ concerns regarding its efficacy, technical challenges and their ability to build a strong therapeutic relationship online. This survey study reports on the experiences of 141 therapists who transitioned to providing video therapy during the pandemic. Aspects of the therapeutic relationship (e.g. working alliance, real relationship), experienced anxiety and professional self-doubt, attitudes towards and intention of video therapy use in the future were assessed. Although therapists reported some anxiety and self-doubt, most felt that online sessions had a sufficient working alliance and a strong real relationship. Therapists with more online therapy experience, lower levels of self-doubt and anxiety, and those who experienced a strong online real relationship during the pandemic, or thought their patients viewed it positively, tended to be more accepting of video therapy. Therapists were largely undecided as to whether they planned to use video therapy in the future; however, those with prior video therapy experience were more likely to endorse future utilization. Training is needed, especially for therapists with less online therapy experience, in order to foster a better experience and to support effective use of online therapy in the future.