title: Can a herd immunity strategy become a viable option against COVID-19? A model-based analysis on social acceptability and feasibility

text: This paper studies the social acceptability and feasibility of "herd immunity" strategies against coronavirus disease 2019 (COVID-19). To this end, we propose a control scheme that aims to develop herd immunity while satisfying the following two basic requirements for a viable policy option. The first requirement is social acceptability: the overall deaths should be minimized for social acceptance. The second is feasibility: the healthcare system should not be overwhelmed to avoid diverse adverse effects. Exploiting the fact that the severity of the disease increases considerably with age, the proposed control scheme protects high-risk individuals that mainly consist of the elderly. The protection of high-risk individuals reduces the average severity of the disease in the unprotected population, thereby substantially reducing mortality and avoiding the collapse of the healthcare system. Social acceptability (in terms of the resulting mortality) and feasibility (in terms of the healthcare system capacity) of the proposed herd immunity strategy are summarized into two respective, easily computable conditions by building on a simple susceptible--infected--recovered (SIR) model. For its parsimony, the proposed framework can provide a rule of thumb that applies to various populations for studying the viability of herd immunity strategies against COVID-19. For Japan, herd immunity may be developed by the considered control scheme if R0 [≤] 2.0 and the severity rates of the disease are 1/10 times smaller than the previously reported value, although as high mortality as seasonal influenza is expected.


title: A simplified model for the analysis of COVID-19 evolution during the lockdown period in Italy

text: A simplified model applied to COVID-19 cases detected and officially published by the italian government, seems to fit quite well the time evolution of the disease in Italy during the period feb-24th - may-19th 2020. The hypothesis behind the model is based on the fact that in the lockdown period the infection cannot be transmitted due to social isolation and, more generally, due to the strong protection measures in place during the observation period. In this case a compartment model is used and the interactions between the different compartments are simplified. The sample of cases detected is intended as a set of individuals susceptible to infection which, after being exposed and undergoing the infection, were isolated ('treated') in such a way they can no longer spread the infection. The values obtained are to be considered indicative as they depend not only on the quality of the data collected, but also on the qualitative approximation of the curves modeled to the data and on the number of available data. The same model has been applied both to the data relating to Italy and to some regions of Italy (Lombardia, Piemonte, Lazio, Campania, Calabria, Sicilia, Sardegna), generally finding a good response and indicatively interesting values.


title: Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies

text: The pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV-1) and COVID-19 coronavirus (SARS-CoV-2) have all emerged into the human population with devastating consequences. These viruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics to combat these highly pathogenic coronaviruses. Here, we describe the isolation and characterization of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs are capable of potently neutralizing MERS-CoV or SARS-CoV-1 S pseudotyped viruses. The crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs block receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S, and demonstrate that this cross-reactive VHH is capable of neutralizing SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.


title: Pulmonary Thromboembolic Disease in Patients with COVID-19 Undergoing Computed Tomography Pulmonary Angiography (CTPA): Incidence and Relationship with Pulmonary Parenchymal Abnormalities

text: Purpose This study aims to report the incidence, severity and extent of pulmonary thromboembolic disease (PTD) in patients with confirmed COVID-19 who have undergone CT pulmonary angiography (CTPA) in a tertiary centre. Materials and Methods This is a retrospective analysis of all patients undergoing CTPA between 23rd March 2020 and 19th April 2020 in a tertiary centre. The presence of PTD, location and involved pulmonary lobes were documented. The pattern and extent of pulmonary parenchymal abnormalities including the presence of fibrosis, lymph node enlargement and pleural effusion were evaluated by two experienced observers independently and consensus was achieved for the most disparate results. Inter-observer agreement was assessed using Kappa statistics. Student t-test, Chi square and Mann-Whitney U tests were used to compare imaging features between PTD and non-PTD sub-groups. Results During the study period, 2157 patients were confirmed with COVID-19, 297/2157 (13.8%) had CT imaging, 100/2157 (4.6%) were CTPA studies, 93 studies were analysed, excluding sub-optimal studies. Overall incidence of PTD was 41/93 (44%) with a third of patients showing segmental and subsegmental PTD (n=28/93, 30%,). D-dimer was elevated in 90/93 (96.8%) of cases. High Wells score did not differentiate between PE and non-PE groups (p=0.801). The inter-observer agreement was fair (Kappa=0.659) for parenchymal pattern and excellent (Kappa = 0.816) for severity. Lymph node enlargement was found in 34/93 of cases (36.6%) with 29/34 (85.3%) showing no additional source of infection. Fibrosis was seen in 16/93 (17.2%) of cases, mainly demonstrating fibrotic organising pneumonia. Conclusion There is a high incidence of PTD in COVID -19 patients undergoing CTPA, complicated by lack of a valid risk stratification tool. Our data indicates a much higher suspicion of PTD is needed in severe COVID-19 patients. The concomitant presence of fibrotic features on CT indicates the need for follow-up for evaluation of chronic pulmonary complications.


title: Proteotyping SARS-CoV-2 virus from nasopharyngeal swabs: a proof-of-concept focused on a 3 min mass spectrometry window

text: Rapid but yet sensitive, specific and high-throughput detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical samples is key to diagnose infected people and to better control the spread of the virus. Alternative methodologies to PCR and immunodiagnostic that would not require specific reagents are worth to investigate not only for fighting the COVID-19 pandemic, but also to detect other emergent pathogenic threats. Here, we propose the use of tandem mass spectrometry to detect SARS-CoV-2 marker peptides in nasopharyngeal swabs. We documented that the signal from the microbiota present in such samples is low and can be overlooked when interpreting shotgun proteomic data acquired on a restricted window of the peptidome landscape. Simili nasopharyngeal swabs spiked with different quantities of purified SARS-CoV-2 viral material were used to develop a nanoLC-MS/MS acquisition method, which was then successfully applied on COVID-19 clinical samples. We argue that peptides ADETQALPQR and GFYAQGSR from the nucleocapsid protein are of utmost interest as their signal is intense and their elution can be obtained within a 3 min window in the tested conditions. These results pave the way for the development of time-efficient viral diagnostic tests based on mass spectrometry.


title: The British Thoracic Society survey of rehabilitation to support recovery of the Post Covid -19 population.

text: Objectives Those discharged from hospital after treatment for Covid-19 are likely to have significant and ongoing symptoms, functional impairment and psychological disturbances. There is an immediate need to develop a safe and efficient discharge process and recovery programme. Pulmonary rehabilitation is well placed to deliver a rehabilitation programme for this group but will most likely need to be adapted for the post Covid-19 population. The purpose of this survey was to rapidly identify the components of a post-Covid-19 rehabilitation assessment and elements of a successful rehabilitation programme that would be required to deliver a comprehensive service for those post Covid-19 to inform service delivery. Design A survey comprising a series of closed questions and a free text comments box allowing for a qualitative analysis. Setting Online survey. Participants British Thoracic Society members and multi-professional clinicians, across specialities were invited to take part. Results 1031 participants responded from a broad range of specialities over 6 days. There was overwhelming support for early post discharge from hospital phase of the recovery programme to advise patients about the management of fatigue (95% agreed/ strongly agreed), breathlessness (94%), and mood disturbances (including symptoms of anxiety and depression) 92%. At the 6-8-week time point an assessment was considered important, focusing on the assessment of a broad range of possible symptoms and the need to potentially return to work. Recommendations for the intervention described a holistic programme focusing on symptom management, return of function and return to employment. The free text comments added depth to the survey and the need not to reinvent the wheel rather adapt well established (pulmonary rehabilitation) services to accommodate the needs of the post Covid-19 population. Conclusion The responses indicate the huge interest and the urgent need establish a programme to support and mitigate the long term impact of Covid-19.


title: Epidemiological and clinical characteristics in patients with SARS-CoV-2 antibody negative probable COVID-19 in Wuhan

text: Abstract Background Patients with suspected COVID-19 might be admitted to hospital. We aimed to describe the characteristic of SARS-CoV-2 antibody negative probable COVID-19 patients and give some suggestions to manage suspected COVID-19 patients. Methods We analyzed 616 confirmed COVID-19 patients and 35 SARS-CoV-2 antibody negative probable COVID-19 patients who were admitted in Wuhan Union Hospital from February 13, 2020 to February 16, 2020. Telephone interviews were conducted and medical records were reviewed for epidemiological, clinical, laboratory and radiographic data. Results Of the 35 SARS-CoV-2 antibody negative probable COVID-19 patients, all of them had tested at least 3 times of nucleic acid, 3 were believed to be non-SARS-CoV-2 infection. Compared with confirmed patients, antibody negative probable patients were younger (P=0.017), exhibited similar symptoms and chest CT images, had higher lymphocyte count (P=0.004) and albumin level (P<0.001), showed lower lactate dehydrogenase level (P=0.011) and erythrocyte sedimentation rate (P<0.001). During hospitalization, all the 35 patients had contacted with confirmed COVID-19 patients, but all used general face mask for protection and maintained a social distance of more than one meter from each other. All the isolation wards were kept ventilation and disinfected once a day. After discharged from hospital, all of them had negative nucleic acid tests and no one developed symptoms again. Conclusions The conditions of patients with AbN probable COVID-19 were less critical than those of patients with confirmed COVID-19. Room ventilation and daily disinfection, wearing face masks, and maintaining social distance might be helpful to prevent patients from hospital acquired COVID-19 infection.


title: Chasing the ghost of infection past: identifying thresholds of change during the COVID-19 infection in Spain

text: COVID-19 pandemic has spread worldwide rapidly from its first outbreak in China, with different impacts depending on the age and social structure of the populations, and the measures taken by each government. Within Europe, the first countries to be strongly affected have been Italy and Spain. In Spain, infection has expanded in highly populated areas, resulting in one of the largest nationwide bursts so far by early April. We analyze the evolution of the growth curve of the epidemic in both the whole of Spain and Madrid Autonomous Region (the second largest conurbation in Europe), based on the cumulative numbers of reported cases and deaths. We conducted segmented, linear regressions on log-transformed data to identify changes in the slope of these curves and/or sudden shifts in the number of cases (i.e. changes in the intercept) at fitted breaking points, and compared their results with a timeline including both key events of the epidemic and containment measures taken by the national and regional governments. Results were largely consistent in the four curves analyzed (reported infections and deaths for Spain and Madrid, respectively), showing two major shifts in slopes (growth rates) at 14-15 and 26-29 March that resulted in 37-65% reductions of slope, and originated in infection on 4-5 and 16-18 March (for case detections) and 14-23 February and 5-6 March (for deaths). Small upward shifts in the progress of the disease in Madrid were not associated with significant changes in the intercept of the curve, and seem related with unevenness in case reporting. These results evidence an early deceleration in the spread of COVID-19 coinciding with personal hygiene and social distancing recommendations, as well as the general awareness of the population; and a second, stronger decrease when harder isolation measures were enforced. The combination of both breakpoints seemingly led to the start of the contention of the disease outbreak by early April, the limit of our time series. This highlights the importance of adopting public health strategies that include disseminating basic knowledge on personal hygiene and reduced social contact at the onset of the epidemic, and the importance of early enforcement of hard contention measures for its subsequent contention.


COVID-19: Evacuations aériennes collectives de patients en syndrome de détresse respiratoire aigu


title: Database for drug metabolism and comparisons, NICEdrug.ch, aids discovery and design

text: The discovery of a drug requires over a decade of enormous research and financial investments—and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch database, which incorporates 250,000 bio-active molecules, and studied their metabolic targets, fate, and toxicity. NICEdrug.ch includes a unique fingerprint that identifies reactive similarities between drug-drug and drug-metabolite pairs. We use NICEdrug.ch to evaluate inhibition and toxicity by the anticancer drug 5-fluorouracil, and suggest avenues to alleviate its side effects. Clustering based on this fingerprint in statins identified drugs for repurposing. We propose shikimate 3-phosphate for targeting liver-stage malaria with minimal impact on the human host cell. Finally, NICEdrug.ch suggests over 1,300 drugs and food molecules to target COVID-19 and explains their inhibitory mechanisms. The NICEdrug.ch database is accessible online to systematically identify the reactivity of small molecules and druggable enzymes with practical applications in lead discovery and drug repurposing.


title: Larger viral genome size facilitates emergence of zoonotic diseases

text: Emergence of new viral diseases is linked to mutation or recombination events. The likelihood of cross-species transmission is related to phenotypic plasticity of a virus and its capacity to produce genetically variable progeny. Herein a model is described connecting the production of genetic variability with increasing genome size. Comparing all known zoonotic viral genome sizes to known non-zoonotic viral genome sizes demonstrates that zoonotic viruses have significantly larger genomes. These results support the notion that large viral genomes are important in producing new zoonotic disease, and suggest that genome size may be a useful surrogate in screening for potential zoonotic viruses.


title: The usefulness of SARS-CoV-2 test positive proportion as a surveillance tool

text: Comparison of COVID-19 case numbers over time and between locations is complicated by limits to virologic testing confirm SARS-CoV-2 infection, leading to under-reporting of incidence, and by variations in testing capacity between locations and over time. The proportion of tested individuals who have tested positive (test positive proportion, TPP) can potentially be used to qualitatively assess the testing capacity of a location; a high TPP could provide evidence that too few people are tested, leading to more under-reporting. In this study we propose a simple model for testing in a population experiencing an epidemic of COVID-19, and derive an expression for TPP in terms of well-defined parameters in the model, related to testing and presence of other pathogens causing COVID-19 like symptoms. We use simulations to show situations in which the TPP is higher or lower than we expect based on these parameters, and the effect of testing strategies on the TPP. In our simulations, we find in the absence of dramatic shifts of testing practices in time or between spatial locations, the TPP is positively correlated with the incidence of infection. As a corollary, the TPP can be used to distinguish between a decline in confirmed cases due to decline in incidence (in which case TPP should decline) and a decline in confirmed cases due to testing constraints (in which case TPP should remain constant). We show that the proportion of tested individuals who present COVID-19 like symptoms (test symptomatic proportion, TSP) encodes similar information to the TPP but has different relationships with the testing parameters, and can thus provide additional information regarding dynamic changes in TPP and incidence. Finally, we compare data on confirmed cases and TPP from US states. We conjecture why states may have higher or lower TPP than average. We suggest that collection of symptom status and age/risk category of tested individuals can aid interpretation of changes in TPP and increase the utility of TPP in assessing the state of the pandemic in different locations and times.


title: From the Common Cold to a Chaotic Contagion: the Potential for Coronaviruses To Cause Outbreaks of Severe Respiratory Disease Representing a Global Health Threat

text: Coronaviruses are a family of RNA viruses that typically cause mild respiratory disease in humans. However, over the past 20 years, three novel/variant coronaviruses have spilled over from animals into humans and have been associated with severe respiratory illness. In late 2002, severe acute respiratory syndrome (SARS) coronavirus (CoV) emerged in China and, over the following year, went on to cause approximately 8,100 cases and 774 deaths. A decade later, a cluster of severe pneumonia cases occurred on the Arabian Peninsula, marking the beginning of the Middle East respiratory syndrome (MERS)-CoV outbreak, which has resulted in nearly 2,500 confirmed cases and 850 deaths. Now in 2020, we are in the midst of a global pandemic caused by SARS-CoV-2, which, at the time of this writing, has claimed the lives of over 83,500 people and has been confirmed in over 1,500,000 cases. These outbreaks highlight the pathogenic potential of CoVs and the importance of infection prevention and diagnostic testing to reduce the spread of infectious diseases representing a global health threat.


Sensors: Sniffing out methanol/ Methanol erschnüffeln


title: Is One Diagnostic Test for COVID-19 Enough?

text: There is no doubt about the importance of diagnostic testing in an emergency;specifically, which range of tests is available, where and when they are dispensed, and who might be tested using laboratory-developed tests, or other diagnostic tests including experimental tests This includes testing for the SARS-CoV-2 virus that causes the COVID-19 disease Testing is essential to “flatten the curve”of the number of confirmed positive cases of the disease, in addition to handwashing, isolation, and social distancing, among other essential measures Is one diagnostic test enough to obtain the correct decision about a confirmed positive outcome?


title: S. Marinopoulos Un virus à deux têtes. Traversée en famille au temps du COVID-19

text: Unknown


title: A sweep of earth’s virome reveals host-guided viral protein structural mimicry; with implications for human disease

text: Viruses deploy an array of genetically encoded strategies to coopt host machinery and support viral replicative cycles. Molecular mimicry, manifested by structural similarity between viral and endogenous host proteins, allow viruses to harness or disrupt cellular functions including nucleic acid metabolism and modulation of immune responses. Here, we use protein structure similarity to scan for virally encoded structure mimics across thousands of catalogued viruses and hosts spanning broad ecological niches and taxonomic range, including bacteria, plants and fungi, invertebrates and vertebrates. Our survey identified over 6,000,000 instances of structural mimicry, the vast majority of which (>70%) cannot be discerned through protein sequence. The results point to molecular mimicry as a pervasive strategy employed by viruses and indicate that the protein structure space used by a given virus is dictated by the host proteome. Interrogation of proteins mimicked by human-infecting viruses points to broad diversification of cellular pathways targeted via structural mimicry, identifies biological processes that may underly autoimmune disorders, and reveals virally encoded mimics that may be leveraged to engineer synthetic metabolic circuits or may serve as targets for therapeutics. Moreover, the manner and degree to which viruses exploit molecular mimicry varies by genome size and nucleic acid type, with ssRNA viruses circumventing limitations of their small genomes by mimicking human proteins to a greater extent than their large dsDNA counterparts. Finally, we identified over 140 cellular proteins that are mimicked by CoV, providing clues about cellular processes driving the pathogenesis of the ongoing COVID-19 pandemic.


title: Assessing the impact of preventive mass vaccination campaigns on yellow fever outbreaks in Africa : a population-level self-controlled case-series study

text: Introduction: The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, by how much PMVCs decrease the risk of outbreak to occur has not yet been quantified. Methods: We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for, the SCCS method is an alternative to classical cohort or case-control study designs when the risk of residual confounding is high. The location and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the relative incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. Results: The study sample consisted of 33 African provinces. Among these, outbreaks occurred during the pre-PMVC period in 26 (78.8%) provinces versus 7 (21.2%) occurring in the post-PMVC period. This corresponded to a significantly reduced incidence rate ratio of 0.14 (95% Confidence interval 0.06 to 0.34) for the post-PMVC versus pre-PMVC period. This estimate was robust across a range of sensitivity analyses, while the results of the cohort-style analyses were highly sensitive to the choice of covariates included in the model. Based on the SCCS results, we estimated that PMVCs have reduced the number of outbreaks by 34% (22% to 45%) in Africa over the study period. Conclusion: Our estimates provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention.


title: The discovery of potential natural products for targeting SARS-CoV-2 spike protein by virtual screening

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into the cells through its spike proteins binding to human angiotensin-converting enzyme 2 (ACE2) protein and causes virus infection in host cells. Until now, there are no available antiviral drugs have been reported that can effectively block virus infection. The study aimed to discover the potential compounds to prevent viral spike proteins to bind to the human ACE2 proteins from Taiwan Database of Extracts and Compounds (TDEC) by structure-based virtual screening. In this study, to rapidly discover potential inhibitors against SARS-CoV-2 spike proteins, the molecular docking calculation was performed by AutoDock Vina program. Herein, we found that 39 potential compounds may have good binding affinities and can respectively bind to the viral receptor-binding domain (RBD) of spike protein in the prefusion conformation and spike-ACE2 complex protein in silico. Among those compounds, especially natural products thioflexibilolide A and candidine that were respectively isolated from the soft corals Sinularia flexibilis and Phaius mishmensis may have better binding affinity than others. This study provided the predictions that these compounds may have the potential to prevent SARS-CoV-2 spike protein from entry into cells.


title: Favipiravir and severe acute respiratory syndrome coronavirus 2 in hamster model

text: There is a need for safe and effective antiviral molecules with which to combat COVID-19 pandemics. Recently, in vitro inhibitory activity of favipiravir against SARS-CoV-2 was reported. Here, we used a Syrian hamster model to explore the pharmacokinetics of this molecule and its in vivo efficacy against SARS-CoV-2. Results revealed that high doses (700-1400mg/kg/day) significantly reduced virus replication in the lungs accompanied by clinical alleviation of the disease. However, these high doses were associated with significant toxicity in hamsters. Favipiravir pharmacokinetics displayed non-linear increase in plasma exposure between the doses and good lung penetration. Analysis of viral genomes in vivo showed that favipiravir induced a mutagenic effect. Whilst the plasma trough concentrations observed in this study were comparable with those previously found during human clinical trials, this potential toxicity requires further investigation to assess whether a tolerable dosing regimen can be found in humans that effectively reduces virus replication.


title: Managing Acute Portal Hypertensive Gastropathy Bleed During the Time of COVID-19 Pandemic: Novelty or Necessity?

text: Acute bleeding from portal hypertensive gastropathy (PHG) is an extremely rare event in the natural history of cirrhosis. The treatment recommendations include portal pressure reduction strategies including pharmacotherapy with vasoactive agents and beta-blockers and interventional strategies such as transjugular intrahepatic portosystemic shunt placement. In this report, we present the case of a patient with cirrhosis in whom acute PHG-related bleed was managed with endoscopic band ligation, a therapeutic modality which has not been described in current literature. Our decision to re-purpose a technique for variceal bleeding stems from the fact that during the ongoing COVID-19 pandemic, the technical assistance, resource availability, and sourcing of materials that were required for us to follow recommended management guidelines for acute PHG-related bleed was severely affected due to imposed lockdown between districts and states.


title: Antibody responses to SARS-CoV-2 in COVID-19 patients: the perspective application of serological tests in clinical practice

text: Background We aim to investigate the profile of acute antibody response in COVID-19 patients, and provide proposals for the usage of antibody test in clinical practice. Methods A multi-center cross-section study (285 patients) and a single-center follow-up study (63 patients) were performed to investigate the feature of acute antibody response to SARS-CoV-2. A cohort of 52 COVID-19 suspects and 64 close contacts were enrolled to evaluate the potentiality of the antibody test. Results The positive rate for IgG reached 100% around 20 days after symptoms onset. The median day of serocon-version for both lgG and IgM was 13 days after symptoms onset. Seroconversion of IgM occurred at the same time, or earlier, or later than that of IgG. IgG levels in 100% patients (19/19) entered a platform within 6 days after seroconversion. The criteria of IgG seroconversion and ≥ 4-fold increase in the IgG titers in sequential samples together diagnosed 82.9% (34/41) of the patients. Antibody test aided to confirm 4 patients with COVID-19 from 52 suspects who failed to be confirmed by RT-PCR and 7 patients from 148 close contacts with negative RT-PCR. Conclusion IgM and IgG should be detected simultaneously at the early phase of infection. The serological diagnosis criterion of seroconversion or ≥ 4-fold increase in the IgG titer is suitable for a majority of COVID-19 patients. Serologic test is helpful for the diagnosis of SARS-CoV-2 infection in suspects and close contacts.


title: How the COVID-19 pandemic is favoring the adoption of digital technologies in healthcare: a rapid literature review

text: Background. Healthcare is responding to the COVID-19 pandemic through the fast adoption of digital solutions and advanced technology tools. Many of the solutions implemented now could consolidate in the near future, contributing to the definition of new digital-based models of care. The aim of this study is to describe which digital solutions have been reported in the early scientific literature to respond and fight the COVID-19 pandemic. Methods. We conducted a rapid literature review searching PubMed and MedrXiv with terms considered adequate to find relevant literature on the use of digital technologies in response to COVID-19. Results. The search identified 52 articles, of which 38 full-text articles were assessed and 29 included in the review after screening. Of selected articles, most of them addressed the use of digital technologies for diagnosis, surveillance and prevention. We report that digital solutions and innovative technologies have mainly been proposed for the diagnosis of COVID-19. In particular, within the reviewed articles we identified numerous suggestions on the use of artificial intelligence-powered tools for the diagnosis and screening of COVID-19. Digital technologies are useful also for prevention and surveillance measures, for example through contact-tracing apps or monitoring of internet searches and social media usage. Discussion. It is worth taking advantage of the push given by the crisis, and mandatory to keep track of the digital solutions proposed today to implement tomorrow's best practices and models of care, and to be ready for any new moments of emergency.


title: A study’s got to know its limitations

text: Background All research has room for improvement, but authors do not always clearly acknowledge the limitations of their work. In this brief report, we sought to identify the prevalence of limitations statements in the medRxiv COVID-19 SARS-CoV-2 dataset. Methods We combined automated methods with manual review to analyse manuscripts for the presence, or absence, either of a defined limitations section in the text, or as part of the general discussion. Results We identified a structured limitations statement in 28% of the manuscripts, and overall 52% contained at least one mention of a study limitation. Over one-third of manuscripts contained none of the terms that might typically be associated with reporting of limitations. Overall our method performed with precision of 0.97 and recall of 0.91. Conclusion The presence or absence of limitations statements can be identified with reasonable confidence using automated tools. We suggest that it might be beneficial to require a defined, structured statement about study limitations, either as part of the submission process, or clearly delineated within the manuscript.


title: Modified Friedmann equations from DSR-GUP

text: Considering the modified entropy-area relation from DSR-GUP (Doubly special relativity-Generalized uncertainity principle), we obtain the modified Friedmann equations from the first law of thermodynamics at apparent horizon. Due to the importance of GUP at Planck scale, we investigate the Friedmann equations and show the maximum energy density \r{ho} at Planck scale. Since GUP implies a minimal length, we find a minimum apparent horizon which has a potential to remove the Big Bang singularity. Furthermore, we analyse the effects of DSR-GUP on deceleration parameter q for the equation of state p = {\omega}\r{ho} and the flat case. Finally, we check the validity of the generalized second law (GSL) of thermodynamics and show that it is valid all eras of the Universe for any spatial curvature.


title: Modeling the early phase of the Belgian COVID-19 epidemic using a stochastic compartmental model and studying its implied future trajectories

text: Following the onset of the ongoing COVID-19 pandemic throughout the world, a large fraction of the global population is or has been under strict measures of physical distancing and quarantine, with many countries being in partial or full lockdown. These measures are imposed in order to reduce the spread of the disease and to lift the pressure on healthcare systems. Estimating the impact of such interventions as well as monitoring the gradual relaxing of these stringent measures is quintessential to understand how resurgence of the COVID-19 epidemic can be controlled for in the future. In this paper we use a stochastic age-structured discrete time compartmental model to describe the transmission of COVID-19 in Belgium. Our model explicitly accounts for age-structure by integrating data on social contacts to (i) assess the impact of the lockdown as implemented on March 13, 2020 on the number of new hospitalizations in Belgium; (ii) conduct a scenario analysis estimating the impact of possible exit strategies on potential future COVID-19 waves. More specifically, the aforementioned model is fitted to hospital admission data, data on the daily number of COVID-19 deaths and serial serological survey data informing the (sero)prevalence of the disease in the population while relying on a Bayesian MCMC approach. Our age-structured stochastic model describes the observed outbreak data well, both in terms of hospitalizations as well as COVID-19 related deaths in the Belgian population. Despite an extensive exploration of various projections for the future course of the epidemic, based on the impact of adherence to measures of physical distancing and a potential increase in contacts as a result of the relaxation of the stringent lockdown measures, a lot of uncertainty remains about the evolution of the epidemic in the next months.


title: Intimate Partner Violence Victimization and Perpetration among U.S. Adults during COVID-19: A Brief Report

text: Importance: Anecdotal evidence such as increased calls to domestic violence (DV) hotlines across the globe suggest that there may be an increase of IPV prevalence in association with the COVID-19 outbreak; however, no study has investigated this phenomenon empirically. Objective: To evaluate the association between COVID-19 related conditions and recent use or experience of IPV (since the pandemic outbreak in the U.S). Design, Setting, and Participants: This cross-sectional study analyzed data collected online from a sample of noninstitutionalized adults (age 18+) in the U.S. (N=2,045). More than half of the sample self-identified as being in an intimate relationship at the time of the study. Main Outcomes and Measures: A four-item tool was used to assess IPV perpetration and victimization since the outbreak of COVID-19. The rapid tool inquired about two forms of IPV, psychological and physical. Participants self-reported demographic data and recent health histories, including COVID-19 tests results, related symptoms and degree of personal social distancing. We hypothesized that COVID-19 related factors would increase risks of IPV. Results: In this study, self-reported COVID-19 impacted respondents had an increased risk of IPV victimization and perpetration. Among those who reported having symptoms consistent with coronavirus, but were denied access to testing, psychological IPV victimization was 3 times greater than those who did not (Exp[B] =3.15, [1.19, 2.29] p <.05). For participants who reported testing positive to COVID-19, the odds of using psychological IPV (Exp[B] =3.24, [1.18, 8.89] p <.05) and physical IPV (Exp[B]=3.02, [1.12, 8.17] p <.05) against an intimate partner increased by more than 3 times. Conclusions and Relevance: Patient education and community outreach/health care system initiatives focused on IPV risk behaviors may help reduce the potential development of IPV. Continued surveillance is imperative to improve health and well-being along with effective intervention development and implementation.


docid: vkgnwxzc

title: Estimate the incubation period of coronavirus 2019 (COVID-19)

text: Motivation: Wuhan pneumonia is an acute infectious disease caused by the 2019 novel coronavirus (COVID-19). It is being treated as a Class A infectious disease though it was classified as Class B according to the Infectious Disease Prevention Act of China. Accurate estimation of the incubation period of the coronavirus is essential to the prevention and control. However, it remains unclear about its exact incubation period though it is believed that symptoms of COVID-19 can appear in as few as 2 days or as long as 14 or even more after exposure. The accurate incubation period calculation requires original chain-of-infection data that may not be fully available in the Wuhan regions. In this study, we aim to accurately calculate the incubation period of COVID-19 by taking advantage of the chain-of-infection data, which is well-documented and epidemiologically informative, outside the Wuhan regions. Methods: We acquired and collected officially reported COVID-19 data from 10 regions in China except for Hubei province. To achieve the accurate calculation of the incubation period, we only involved the officially confirmed cases with a clear history of exposure and time of onset. We excluded those without relevant epidemiological descriptions, working or living in Wuhan for a long time, or hard to determine the possible exposure time. We proposed a Monte Caro simulation approach to estimate the incubation of COVID-19 as well as employed nonparametric ways. We also employed manifold learning and related statistical analysis to decipher the incubation relationships between different age/gender groups. Result: The incubation period of COVID-19 did not follow general incubation distributions such as lognormal, Weibull, and Gamma distributions. We estimated that the mean and median of its incubation were 5.84 and 5.0 days via bootstrap and proposed Monte Carlo simulations. We found that the incubation periods of the groups with age>=40 years and age<40 years demonstrated a statistically significant difference. The former group had a longer incubation period and a larger variance than the latter. It further suggested that different quarantine time should be applied to the groups for their different incubation periods. Our machine learning analysis also showed that the two groups were linearly separable. incubation of COVID-19 along with previous statistical analysis. Our results further indicated that the incubation difference between males and females did not demonstrate a statistical significance.


Occupational health: the thin line protecting the front line


title: Seek COVER: Development and validation of a personalized risk calculator for COVID-19 outcomes in an international network

text: Abstract Importance COVID-19 is causing high mortality worldwide. Developing models to quantify the risk of poor outcomes in infected patients could help develop strategies to shield the most vulnerable during de-confinement. Objective To develop and externally validate COVID-19 Estimated Risk (COVER) scores that quantify a patient's risk of hospital admission (COVER-H), requiring intensive services (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis. Design Multinational, distributed network cohorts. Setting We analyzed a federated network of electronic medical records and administrative claims data from 13 data sources and 6 countries, mapped to a common data model. Participants Model development used a patient population consisting of >2 million patients with a general practice (GP), emergency room (ER), or outpatient (OP) visit with diagnosed influenza or flu-like symptoms any time prior to 2020. The model was validated on patients with a GP, ER, or OP visit in 2020 with a confirmed or suspected COVID-19 diagnosis across four databases from South Korea, Spain and the United States. Outcomes Age, sex, historical conditions, and drug use prior to index date were considered as candidate predictors. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death, and iii) death in the 30 days after index date. Results Overall, 43,061 COVID-19 patients were included for model validation, after initial model development and validation using 6,869,127 patients with influenza or flu-like symptoms. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, and kidney disease) which combined with age and sex could discriminate which patients would experience any of our three outcomes. The models achieved high performance in influenza. When transported to COVID-19 cohorts, the AUC ranges were, COVER-H: 0.73-0.81, COVER-I: 0.73-0.91, and COVER-F: 0.82-0.90. Calibration was overall acceptable, with overestimated risk in the most elderly and highest risk strata. Conclusions and relevance A 9-predictor model performs well for COVID-19 patients for predicting hospitalization, intensive services and death. The models could aid in providing reassurance for low risk patients and shield high risk patients from COVID-19 during de-confinement to reduce the virus' impact on morbidity and mortality.


title: Inferring transmission trees to guide targeting of interventions against visceral leishmaniasis and post-kala-azar dermal leishmaniasis

text: Understanding of spatiotemporal transmission of infectious diseases has improved significantly in recent years. Advances in Bayesian inference methods for individual-level geo-located epidemiological data have enabled reconstruction of transmission trees and quantification of disease spread in space and time, while accounting for uncertainty in missing data. However, these methods have rarely been applied to endemic diseases or ones in which asymptomatic infection plays a role, for which novel estimation methods are required. Here, we develop such methods to analyse longitudinal incidence data on visceral leishmaniasis (VL), and its sequela, post-kala-azar dermal leishmaniasis (PKDL), in a highly endemic community in Bangladesh. Incorporating recent data on infectiousness of VL and PKDL, we show that while VL cases drive transmission when incidence is high, the contribution of PKDL increases significantly as VL incidence declines (reaching 55% in this setting). Transmission is highly focal: >85% of mean distances from inferred infectors to their secondary VL cases were <300m, and estimated average times from infector onset to secondary case infection were <4 months for 90% of VL infectors, but up to 2.75yrs for PKDL infectors. Estimated numbers of secondary VL cases per VL and PKDL case varied from 0-6 and were strongly correlated with the infector's duration of symptoms. Counterfactual simulations suggest that prevention of PKDL could have reduced VL incidence by up to a quarter. These results highlight the need for prompt detection and treatment of PKDL to achieve VL elimination in the Indian subcontinent and provide quantitative estimates to guide spatiotemporally-targeted interventions against VL.


title: Incubation period and serial interval of Covid-19 in a chain of infections in Bahia Blanca (Argentina)

text: Objective: To estimate the incubation period and the serial interval of Covid-19 from a sample of symptomatic patients in Bahia Blanca city. Methods: We collected dates of illness onset for primary cases (infectors) and secondary cases (infectees) for the first 18 secondary patients infected with SARS-Cov-2 in Bahia Blanca (Argentina). We ranked the fiability of the data depending upon certainty about the identification of the infector and the date of exposition to infector. The sample has some missing values. In the case of incubation, as 3 patients were infected by other household members, we only have 15 observations with an observed date of exposition. For the estimation of serial interval, one patient became ill from close contact with an asymptomatic infectious. Also, estimations of both the incubation period and the serial interval were carried using the full sample and a subsample with higher certainty about the transmissor and date of exposition. By the time the dataset was prepared all infectors were recovered so estimations do need to take into account right censoring. Results: The mean incubation period for symptomatic patients is 7.9 days (95% CI: 4.6, 11.1) considering the sample of 15 cases patients and 7.5 days (95% CI: 4.1, 10.9) if the sample is restricted to the most certain cases (n=12). The median is 6.1 (95% CI: 4.1, 9.2) and 5.8 (95% CI: 3.6, 9.3) respectively. Moreover, 97.5% of symptomatic cases will develop symptoms after 13.6 days from exposition (95% CI 10.7, 16.5). The point estimation for the mean serial interval is 6.8 days (95% CI: 4.0-9.6). Considering only the most certain pairs, the mean serial interval is estimated at 5.5 days (95% CI: 2.8, 8.1). The estimated median serial intervals were 5.2 (95% CI: 3.0, 8.1) and 4.1 (95% CI: 2.0, 6.9) days respectively. Conclusions: Evidence from Bahia Blanca (Argentina) suggests that the median and mean serial interval of Covid-19 is shorter than the incubation period. This suggests that a pre-symptomatic transmission is not negligible. Comparisons with foreign estimates show that incubation period and serial interval could be longer in Bahia Blanca city than in other regions. That poses a signal of opportunity to attain more timely contact tracing and effective isolation.


title: Inflow restrictions can prevent epidemics when contact tracing efforts are effective but have limited capacity

text: When a region tries to prevent an outbreak of an epidemic, like that of COVID-19, two broad strategies are initially available: limiting the inflow of infected cases using travel restrictions and quarantines, and reducing transmissions from inflowing cases using contact tracing and community interventions. A large number of papers have used epidemiological models to argue that inflow restrictions are unlikely to be effective. We conduct a mathematical analysis using a simple epidemiological model and perform simulations that show this conclusion can change if we relax the assumption of unlimited capacity in containment efforts such as contact tracing. In particular, when contact tracing is effective, but the system is close to being overwhelmed, moderate travel restrictions can have very large effects on the probability of an epidemic.


title: Strong effect of socioeconomic levels on the spread and treatment of the 2019 novel coronavirus (COVID-19) in China

text: Background: Global response to the COVID-19 epidemic presents strengths and weaknesses in national and regional social governance capacities to address public health challenges. The emergence, detection, spread, treatment and containment of infectious diseases shows the considerable political and economic impacts in a highly interconnected world. We aimed to estimate the effects of socioeconomic levels on the spread and treatment of COVID-19 in China. Methods: We obtained daily COVID-19 cases at a city level in China. We used migration data from the major cities in Hubei Province, and macroeconomic data at city and province levels. We obtained social management measures in response to COVID-19 outbreak. We assessed the association between measures, migration and COVID-19 spread, and the association between socioeconomic levels and COVID-19 treatment capacity. Findings: On January 1, 2020, COVID-19 spread that affected by management measures and migration started across China. After Wuhan lockdown, the case number reached peak in 12 days, and COVID-19 outbreak was basically contained in China in four weeks due to intensive measures. Guangdong, Jiangsu and Zhejiang Provinces showed the most excellent COVID-19 treatment capacities. Socioeconomic levels in these provinces ranked top in China. Guangdong achieved the largest decline in severe case rate by 22.1%. Jiangsu had the lowest average rate of severe cases (1.7%) and zero death. Among the regions with top case number, Zhejiang showed the highest rate of cured cases on confirmed cases (96.3%), the lowest average rate of severe cases (7.7%), and one death. The COVID-19 treatment capacities were strongly affected by regional economics and measures on control, detection and treatment. Interpretation: Socioeconomic levels had strong effect on the spread and treatment of COVID-19 in China. Further investigations are needed on the effectiveness of Chinese measures and the effects of socioeconomic levels on COVID-19 treatment outside China. Fund Guangdong Natural Science Foundation


title: The advantages of the simplest pandemic models

text: As a pandemic of coronavirus spreads across the globe, people debate policies to mitigate its severity. Many complex, highly detailed models have been developed to help policy setters make better decisions. However, the basis of these models is unlikely to be understood by non-experts. We describe the advantages of simple models for covid-19. We say a model is simple if its only parameter is the rate of contact between people in the population. This contact rate can vary over time, depending on choices by policy setters. Such models can be understood by a broad audience, and thus can be helpful in explaining the policy decisions to the public. They can be used to evaluate the outcomes of different policy strategies. However, simple models have a disadvantage when dealing with inhomogeneous populations. To augment the power of a simple model to evaluate complicated situations, we add what we call satellite equations that do not change the original model. For example, with the help of a satellite equation, one could know what his/her chance is of remaining uninfected through the end of epidemic. Satellite equations can model the effect of the epidemic on high-risk individuals, or death rates, or on nursing homes, and other isolated populations. To compare simple models with complex models, we introduce our slightly complex Model J. We find the conclusions of simple and complex models can be quite similar. But, for each added complexity, a modeler may have to choose additional parameter values describing who will infect whom under what conditions, choices for which there is often little rationale but that can have a big impact on predictions. Our simulations suggest that the added complexity offers little predictive advantage.


docid: dcifzudk

title: The current clinically relevant findings on COVID-19 pandemic

text: The emergence of a novel coronavirus and coronavirus disease 2019 (COVID-19) represents a challenge to global healthcare. In the past 20 years, this is the third coronavirus that jumped the species barrier and infected humans. It is highly contagious but associated with low pathogenicity. First identified in Wuhan, China, a city of over 11 million, the disease has since spread to every continent except Antarctica. About 15% to 20% of all cases may be called severe, and it is believed many cases are asymptomatic. The average age of a person with COVID has been reported as 49 years. Worse outcomes are associated with geriatric populations and those with un-derlying diseases such as cardiovascular, respiratory disorders, and/or diabetes. The coronavirus, like other coronaviruses, is highly contagious and has a latency period of about 14 days. Most patients present with fever and a dry cough, but fever may be absent. Differential diagnosis can be challenging since influenza may present with similar symptoms. Chest radiography or computed to-mography may be used to find evidence of secondary pneumonia. Nosocomial infection is of concern, and it has been reported that 3.8% of all cases with COVID-19 in that country involve healthcare workers in China. Most patients have mild disease, and supportive care suffices. A variety of repurposed and investigational drugs are being evaluated. There are currently no antiviral therapies or vaccines, even if many therapies are proposed. Hand hygiene, social distancing, and scientifically sound information are the best strategies at the moment to combat this epidemic.


The impact of COVID-19 non-pharmaceutical interventions on the future dynamics of endemic infections


title: Calibrating an Epidemic Compartment Model to Seroprevalence Survey Data

text: To date, the Covid-19 epidemic has produced tremendous cost and harm. However, to date, many epidemic models are not calibrated to seroprevalence survey(s). This paper calibrates a relatively simple, SIR plus confirmed cases ("SIRX") model against seroprevalence survey data released by the State of New York. The intention of this paper is to demonstrate a potentially new technique of calibration for epidemic models used by scientists, public health officials and governments. The technique can then be incorporated in other more complex models. Open source code is included to assist model developers.


title: Using Digital Surveillance Tools for Near Real-Time Mapping of the Risk of International Infectious Disease Spread: Ebola as a Case Study

text: In our increasingly interconnected world, it is crucial to understand the risk of an outbreak originating in one country or region and spreading to the rest of the world. Digital disease surveillance tools such as ProMED and HealthMap have the potential to serve as important early warning systems as well as complement the field surveillance during an ongoing outbreak. Here we present a flexible statistical model that uses data produced from digital surveillance tools (ProMED and HealthMap) to forecast short term incidence trends in a spatially explicit manner. The model was applied to data collected by ProMED and HealthMap during the 2013-2016 West African Ebola epidemic. The model was able to predict each instance of international spread 1 to 4 weeks in advance. Our study highlights the potential and limitations of using publicly available digital surveillance data for assessing outbreak dynamics in real-time.


title: Prevalence and phenology of mycorrhizal colonization across populations of Lycopodiella inundata

text: Mycorrhizal fungi are critical components of terrestrial habitats and agroecosystems. Recently, Mucoromycotina fine root endophyte (MucFRE) fungi were found to engage in nutritional mutualism with the rare plant Lycopodiella inundata (‘marsh clubmoss’), one of the earliest vascular plant lineages known to associate with MucFRE. The extent to which this mutualism plays a role in resilient plant populations can only be understood by examining its occurrence rate and phenological patterns. To test for prevalence and seasonality in colonization, we examined 1,297 individual L. inundata roots collected during spring and autumn 2019 from 11 semi-natural heathlands in Britain and the Netherlands. We quantified presence/absence of MucFRE-like hyphae and vesicles and explored possible relationships between temperature and precipitation in the months immediately before sampling. MucFRE-like hyphae were the dominant mycorrhizal fungi observed in all of the examined heathlands. However, we found significant differences in colonization between the two seasons at every site. Overall, 14% of L. inundata roots were colonised in spring (2.4% with vesicles) compared with 86% in autumn (7.6% with vesicles). Colonization levels between populations were also significantly different, and correlated with temperature and precipitation, suggesting some local environments may be more conducive to hyphal growth. These marked seasonal differences in host-plant colonization suggest that results about mycorrhizal status - typically drawn from single time point collections - should be carefully interpreted. Our findings are directly relevant to habitat restoration, species conservation plans, agricultural bio-inoculation nutrient enhancement treatments, microbial diversity and functional studies of host plants and symbionts.


title: Joint Detection of Serum IgM/IgG Antibody is An Important Key to Clinical Diagnosis of SARS-COV-2 Infection

text: Background: This study was aimed to investigate the application of SARS- COV-2 IgM and IgG antibodies in diagnosis of COVID-19 infection. Method: This study enrolled a total of 178 patients at Huangshi Central Hospital from January to February, 2020. Among them, 68 patients were SARS-COV-2 infected confirmed with nucleic acid test (NAT) and CT imaging. 9 patients were in the suspected group (NAT negative) with fever and other respiratory symptoms. 101 patients were in the control group with other diseases and negative to SARS-COV-2 infection. After serum samples were collected, SARS-COV-2 IgG and IgM antibodies were tested by chemiluminescence immunoassay (CLIA) for all patients. Results: The specificity of serum IgM and IgG antibodies to SARS-COV-2 were 99.01% (100/101) and 96.04% (97/101) respectively, and the sensitivity were 88.24% (60/68) and 97.06% (66/68) respectively. The combined detection rate of SARS-COV-2 IgM and IgG antibodies were 98.53% (67/68). Conclusion: Combined detection of serum SARS-COV-2 IgM and IgG antibodies had better sensitivity compared with single IgM or IgG test, which can be used as an important diagnostic tool for SARS-COV-2 infection and a screening tool of potential SARS-COV-2 carriers in clinics, hospitals and accredited scientific laboratory.


Houston we have a problem: coronavirus!


title: For-profit nursing homes and the risk of COVID-19 outbreaks and resident deaths in Ontario, Canada

text: Background: Nursing homes have become the epicentre of the coronavirus disease 2019 (COVID-19) pandemic in Canada. Previous research demonstrates that for-profit nursing homes deliver inferior care across a variety of outcome and process measures, raising the question of whether for-profit homes have had worse COVID-19 outcomes than non-profit homes. Methods: We conducted a retrospective cohort study of all nursing homes in Ontario, Canada from March 29-May 20, 2020 using a COVID-19 outbreak database maintained by the Ontario Ministry of Long-Term Care. We used hierarchical logistic and count-based methods to model the associations between nursing home profit status (for-profit, non-profit or municipal) and nursing home COVID-19 outbreaks, COVID-19 outbreak sizes, and COVID-19 resident deaths. Results: The analysis included all 623 Ontario nursing homes, of which 360 (57.7%) were for-profit, 162 (26.0%) were non-profit, and 101 (16.2%) were municipal homes. There were 190 (30.5%) COVID-19 nursing home outbreaks involving 5218 residents (mean of 27.5 +/- 41.3 residents per home), resulting in 1452 deaths (mean of 7.6 +/- 12.7 residents per home) with an overall case fatality rate of 27.8%. The odds of a COVID-19 outbreak was associated with the incidence of COVID-19 in the health region surrounding a nursing home (adjusted odds ratio [aOR], 1.94; 95% confidence interval [CI] 1.23-3.09) and number of beds (aOR, 1.40; 95% CI 1.20-1.63), but not profit status. For-profit status was associated with both the size of a nursing home outbreak (adjusted risk ratio [aRR], 1.96; 95% CI 1.26-3.05) and the number of resident deaths (aRR, 1.78; 95% CI 1.03-3.07), compared to non-profit homes. These associations were mediated by a higher prevalence of older nursing home design standards in for-profit homes. Interpretation: For-profit status is associated with the size of a COVID-19 nursing home outbreak and the number of resident deaths, but not the likelihood of outbreaks. Differences between for profit and non-profit homes are largely explained by older design standards, which should be a focus of infection control efforts and future policy.


title: Asymptomatic infection and herd immunity of COVID-19 in Wuhan and Japan

text: Background: The COVID-19 outbreak has shown two inconsistent phenomena: its reproduction number is almost two; and it shows earlier and lower peaks for new cases and the total number of patients. Object: To resolve this inconsistency, we constructed a mathematical model to explain these phenomena. Method: To outbreak data from Wuhan, China and Japan, we applied a susceptible-infected-recovery model with the proportion of asymptomatic patients among infected people (q) as a key parameter for estimation, along with the basic reproduction number (R0). Results: The first outbreak peak was recorded in Japan on April 3 for those infected on March 29. Their R0 and q were estimated respectively as 3.19 and 99.32% in Wuhan. In Japan, these were estimated around the peak as 2.96 and 99.99%. Discussion and Conclusion: By introducing a very high proportion of asymptomatic cases, the two inconsistent phenomena might be resolved. Especially in Japan, the asymptomatic cases were 60 times higher than those of China.


title: Bio-JOIE: Joint Representation Learning of Biological Knowledge Bases

text: The widespread of Coronavirus has led to a worldwide pandemic with a high mortality rate. Currently, the knowledge accumulated from different studies about this virus is very limited. Leveraging a wide-range of biological knowledge, such as gene on-tology and protein-protein interaction (PPI) networks from other closely related species presents a vital approach to infer the molecular impact of a new species. In this paper, we propose the transferred multi-relational embedding model Bio-JOIE to capture the knowledge of gene ontology and PPI networks, which demonstrates superb capability in modeling the SARS-CoV-2-human protein interactions. Bio-JOIE jointly trains two model components. The knowledge model encodes the relational facts from the protein and GO domains into separated embedding spaces, using a hierarchy-aware encoding technique employed for the GO terms. On top of that, the transfer model learns a non-linear transformation to transfer the knowledge of PPIs and gene ontology annotations across their embedding spaces. By leveraging only structured knowledge, Bio-JOIE significantly outperforms existing state-of-the-art methods in PPI type prediction on multiple species. Furthermore, we also demonstrate the potential of leveraging the learned representations on clustering proteins with enzymatic function into enzyme commission families. Finally, we show that Bio-JOIE can accurately identify PPIs between the SARS-CoV-2 proteins and human proteins, providing valuable insights for advancing research on this new disease.


title: Two alternative scenarios for easing COVID-19 lockdown measures: one reasonable and one catastrophic

text: We consider two sub-populations consisting of individuals below or above 40 years of age, which will be referred to as "young" and "older". A person infected with SARS-CoV-2, following an incubation period, will become either sick (with COVID-19) or will be asymptomatic; the latter will recover, whereas a sick person will either recover or will be hospitalized where they will either die or recover. We assume that the interaction between a person who is infected and a person with the capacity to be infected is described by the usual mechanism of the standard epidemiological models. We first show that by choosing appropriately the parameters of the mathematical equations describing the dynamics of the above sub-populations in data stemming from Greece, one can obtain a reasonable match of the existing data for the time evolution of the total number of deaths and infections for both subpopulations during the current state of lockdown. Then, we consider two possible alternatives: first, we keep the two parameters describing the interactions of older-older and older-young as they are now, but we increase the value of the parameter describing the interaction of young-young; this means that we allow the lockdown measures to be eased only in the young sub-population. Second, we increase the values of all the three above parameters, which means we ease the lockdown measures in both sub-populations. In the first case, the number of deaths remains relatively small, whereas in the second case the situation, upon sufficient increase of the number of contacts, may become catastrophic potentially leading to a dramatic loss of lives.


title: UV-C irradiation is highly effective in inactivating and inhibiting SARS-CoV-2 replication

text: The potential virucidal effects of UV-C irradiation on SARS-CoV-2 were experimentally evaluated for different illumination doses and virus concentrations (1000, 5, 0.05 MOI). Both virus inactivation and replication inhibition were investigated as a function of these parameters. At a virus density comparable to that observed in SARS-CoV-2 infection, an UV-C dose of just 3.7 mJ/cm2 was sufficient to achieve a 3-log inactivation, and complete inhibition of all viral concentrations was observed with 16.9 mJ/cm2. These results could explain the epidemiological trends of COVID-19 and are important for the development of novel sterilizing methods to contain SARS-CoV-2 infection.


title: Immunization by replication-competent controlled herpesvirus vectors

text: Replication-competent controlled virus vectors were derived from virulent HSV-1 wildtype strain 17syn+ by placing one or two replication-essential genes under the stringent control of a gene switch that is co-activated by heat and an antiprogestin. Upon activation of the gene switch, the vectors replicate in infected cells with an efficacy that approaches that of the wildtype virus from which they were derived. Essentially no replication occurs in the absence of activation. When administered to mice, localized application of a transient heat treatment in the presence of systemic antiprogestin results in efficient but limited virus replication at the site of administration. The immunogenicity of these viral vectors was tested in a mouse footpad lethal challenge model. Unactivated viral vectors - which may be regarded as equivalents of inactivated vaccines - induced detectable protection against lethality caused by wildtype virus challenge. Single activation of the viral vectors at the site of administration (rear footpads) greatly enhanced protective immune responses, and second immunization resulted in complete protection. Once activated vectors also induced far better neutralizing antibody and HSV-1-specific T cells responses than unactivated vectors. To find out whether the immunogenicity of a heterologous antigen was also enhanced in the context of efficient transient vector replication, a virus vector constitutively expressing an equine influenza virus hemagglutinin was constructed. Immunization of mice with this recombinant induced detectable antibody-mediated neutralization of equine influenza virus as well as a hemagglutinin-specific T cell response. Single activation of viral replication resulted in a several-fold enhancement of this immune response. IMPORTANCE We hypothesized that vigorous replication of a pathogen may be critical for eliciting the most potent and balanced immune response against it. Hence, attenuation/inactivation (as in conventional vaccines) should be avoided. Instead, necessary safety should be provided by placing replication of the pathogen under stringent control and of activating time-limited replication of the pathogen strictly in an administration region in which pathology cannot develop. Immunization will then occur in the context of highly efficient pathogen replication and uncompromised safety. We found that localized activation in mice of efficient but limited replication of a replication-competent controlled herpesvirus vector resulted in a greatly enhanced immune response to the virus or an expressed heterologous antigen. This finding supports the above hypothesis as well as suggests that the vectors may be promising novel agents worth exploring for the prevention/mitigation of infectious diseases for which efficient vaccination is lacking, in particular in immunocompromised patients.


docid: vxbvdcvq

title: Development of internal sound sensor using stethoscope and its applications for machine monitoring

text: Abstract With the development of Internet of Things (IoT), predictive maintenance (PdM) for smart manufacturing receives attentions recently. For the monitoring of machines with rotary components, sound and vibration emitted from the machines have been utilized as the meaningful information. However, sound sensors are susceptible to external noise and the costs for signal conditioning should be considered. In this paper, a stethoscope is utilized as an internal sound sensor which are capable of noise reduction and affordable as IoT solutions. After the stethoscope was assembled with a microphone, a frequency range for measurement was identified as 0~255Hz using the swept-sine technique. Two stethoscope sensors were attached to an industrial robot, and the capability of noise reduction is verified by similarity of Short-Time Fourier Transform (STFT) spectrograms from sounds with and without existence of factory noise. Next, impact tests were performed to detect collision when the robot was stationary, and collisions by human hand during robot operation were detected from STFT spectrogram analysis. Finally, the Convolutional Neural Network (CNN) model from the spectrograms was established to estimate a rotating joint axis during operation, showing 91% and 90.83% accuracy for each stethoscope, respectively.


title: A Rapid COVID-19 RT-PCR Detection Assay for Low Resource Settings

text: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay is the gold standard recommended to test for acute SARS-CoV-2 infection. It has been used by the Centers for Disease Control and Prevention (CDC) and several other companies in their Emergency Use Authorization (EUA) assays. RT-qPCR requires expensive equipment such as RNA isolation instruments and real-time PCR thermal cyclers, which are not available in many low resource settings and developing countries. As a pandemic, COVID-19 has quickly spread to the rest of the world. Many underdeveloped and developing counties do not have the means for fast and accurate COVID-19 detection to control this outbreak. Using COVID-19 positive clinical specimens, we demonstrated that RT-PCR assays can be performed in as little as 12 minutes using untreated samples, heat-inactivated samples, or extracted RNA templates. Rapid RT-PCR was achieved using thin-walled PCR tubes and a setup including sous vide immersion heaters/circulators. Our data suggest that rapid RT-PCR can be implemented for sensitive and specific molecular diagnosis of COVID-19 in situations where sophisticated laboratory instruments are not available.


Breaking News: Has the Emergency Department Ever Been More Boring — or Terrifying?


title: The possible immunological pathways for the variable immunopathogenesis of COVID—19 infections among healthy adults, elderly and children

text: Novel Coronavirus, COVID-19 discovered in December, 2019 in Wuhan, China started a world-wide epidemic. It is not clear till now what is the pathogenesis of this virus infection in human or the exact strategies of host immune response in combating this novel threat to human beings. However, morbidity and mortality of COVID-19 infections vary widely from asymptomatic, mild to deadly critical. Strangely, children were found to be protected from severe or deadly critical infections, while elderly and immunocompromised adults are most affected badly by this virus. It is necessary to disclose the possible viral and host interactions that lead to such variable morbid effects among patients of COVID-19 infections.


title: Modeling COVID-19 dynamics in Illinois under non-pharmaceutical interventions

text: We present modeling of the COVID-19 epidemic in Illinois, USA, capturing the implementation of a Stay-at-Home order and scenarios for its eventual release. We use a non-Markovian age-of-infection model that is capable of handling long and variable time delays without changing its model topology. Bayesian estimation of model parameters is carried out using Markov Chain Monte Carlo (MCMC) methods. This framework allows us to treat all available input information, including both the previously published parameters of the epidemic and available local data, in a uniform manner. To accurately model deaths as well as demand on the healthcare system, we calibrate our predictions to total and in-hospital deaths as well as hospital and ICU bed occupancy by COVID-19 patients. We apply this model not only to the state as a whole but also its sub-regions in order to account for the wide disparities in population size and density. Without prior information on non-pharmaceutical interventions (NPIs), the model independently reproduces a mitigation trend closely matching mobility data reported by Google and Unacast. Forward predictions of the model provide robust estimates of the peak position and severity and also enable forecasting the regional-dependent results of releasing Stay-at-Home orders. The resulting highly constrained narrative of the epidemic is able to provide estimates of its unseen progression and inform scenarios for sustainable monitoring and control of the epidemic.


title: Children’s Hospital Los Angeles COVID-19 Analysis Research Database (CARD) - A Resource for Rapid SARS-CoV-2 Genome Identification Using Interactive Online Phylogenetic Tools

text: Effective response to the Coronavirus Disease 2019 (COVID-19) pandemic requires genomic resources and bioinformatics tools for genomic epidemiology and surveillance studies that involve characterizing full-length viral genomes, identifying origins of infections, determining the relatedness of viral infections, performing phylogenetic analyses, and monitoring the continuous evolution of the SARS-CoV-2 viral genomes. The Children’s Hospital, Los Angeles (CHLA) COVID-19 Analysis Research Database (CARD) (https://covid19.cpmbiodev.net/) is a comprehensive genomic resource that provides access to full-length SARS-CoV-2 viral genomes and associated meta-data for over 30,000 (as of May 20, 2020) isolates collected from global sequencing repositories and the sequencing performed at the Center for Personalized Medicine (CPM) at CHLA. Reference phylogenetic trees of global and USA viral isolates were constructed and are periodically updated using selected high quality SARS-CoV-2 genome sequences. These provide the baseline and analytical context for identifying the origin of a viral infection, as well as the relatedness of SARS-CoV-2 genomes of interest. A web-based and interactive Phylogenetic Tree Browser supports flexible tree manipulation and advanced analysis based on keyword search while highlighting time series animation, as well as subtree export for graphical representation or offline exploration. A Virus Genome Tracker accepts complete or partial SARS-CoV-2 genome sequence, compares it against all available sequences in the database (>30,000 at time of writing), detects and annotates the variants, and places the new viral isolate within the global or USA phylogenetic contexts based upon variant profiles and haplotype comparisons, in a few seconds. The generated analysis can potentially aid in genomic surveillance to trace the transmission of any new infection. Using CHLA CARD, we demonstrate the identification of a candidate outbreak point where 13 of 31 CHLA internal isolates may have originated. We also discovered multiple indels of unknown clinical significance in the orf3a gene, and revealed a number of USA-specific variants and haplotypes.


title: Possibilities of "Crushing" the Transmission Curve of COVID-19 in Latin America - We Still Have Time

text: Latin America is suppose to have significant advantages over other developing regions, such as Asia and Africa, given the time where the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), causing the Coronavirus Diseases 2019 (COVID-19), arrived, mainly from Europe This occurred on February 26, 2020 Then, multiple previous measures were taken in order to prevent and mitigate the impact of pandemic in the region In the current mini-review update we discuss the possibilities of "crushing" the transmission curve of COVID-19 in the region after two months of the arrival of this emerging coronavirus


title: A Susceptible-Infected-Removed (SIR) model of COVID-19 epidemic trend in Malaysia under Movement Control Order (MCO) using a data fitting approach

text: Background: In this work, we presented a Susceptible-Infected-Removed (SIR) epidemiological model of COVID-19 epidemic in Malaysia post- and pre-Movement Control Order (MCO). The proposed SIR model was fitted to confirmed COVID-19 cases from the official press statements to closely reflect the observed epidemic trend in Malaysia. The proposed model is aimed to provide an accurate predictive information for decision makers in assessing the public health and social measures related to COVID-19 epidemic. Methods: The SIR model was fitted to the data by minimizing a weighted loss function; the sum of the residual sum of squares (RSS) of infected, removed and total cases. Optimized beta ({beta}), gamma ({gamma}) parameter values and the starting value of susceptible individuals (N) were obtained. Results: The SIR model post-MCO indicates the peak of infection on 10 April 2020, less than 100 active cases by 8 July 2020, less than 10 active cases by 29 August 2020, and close to zero daily new case by 22 July 2020, with a total of 6562 infected cases. In the absence of MCO, the model predicts the peak of infection on 1 May 2020, less than 100 active cases by 14 February 2021, less than 10 active cases by 26 April 2021 and close to zero daily new case by 6 October 2020, with a total of 1.6 million infected cases. Conclusion: The results suggest that the present MCO has significantly reduced the number of susceptible population and the total number of infected cases. The method to fit the SIR model used in this study was found to be accurate in reflecting the observed data. The method can be used to predict the epidemic trend of COVID-19 in other countries.


title: Hydroxychloroquine serum concentrations in non-critical care patients infected with SARS CoV 2

text: Hydroxychloroquine(HCQ) has been widely used to treat SARS-CoV-2 infection however HCQ pharmacokinetics in this condition have not been studied in non-critical care patient groups. Here we report the serum concentrations of HCQ in a small cohort of patients treated with HCQ as part of the RECOVERY trial.


title: An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 and multiple endemic, epidemic and bat coronavirus

text: Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2. Herein, we show that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV 2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to another nucleoside analog inhibitor. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (b-D-N4-hydroxycytidine-5’-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis. The potency of NHC/EIDD-2801 against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.


title: DeepRC: Immune repertoire classification with attention-based deep massive multiple instance learning

text: High-throughput immunosequencing allows re-constructing the immune repertoire of an individual, which is an exceptional opportunity for new immunotherapies, immunodiagnostics, and vaccine design. Such immune repertoires are shaped by past and current immune events, for example infection and disease, and thus record an individual’s state of health. Consequently, immune repertoire sequencing data may enable the prediction of health and disease using machine learning. However, finding the connections between an individual’s repertoire and the individual’s disease class, with potentially hundreds of thousands to millions of short sequences per individual, poses a difficult and unique challenge for machine learning methods. In this work, we present our method DeepRC that combines a Deep Learning architecture with attention-based multiple instance learning. To validate that DeepRC accurately predicts an individual’s disease class based on its immune repertoire and determines the associated class-specific sequence motifs, we applied DeepRC in four large-scale experiments encompassing ground-truth simulated as well as real-world virus infection data. We demonstrate that DeepRC out-performs all tested methods with respect to predictive performance and enables the extraction of those sequence motifs that are connected to a given disease class.


title: On Global Power Differentials, Moral Realism, and the Rise of China: A Review Essay

text: This review essay examines the recent theoretical contribution of Yan Xuetong—China’s most cited political scientist—on ‘Moral Realism’ as it is presented in his latest magnum opus: ‘Leadership and the Rise of Great Powers.’ The essay evaluates the theoretical foundations of Yan’s treatise as well as its application on China’s domestic politics and foreign policy. Lastly the essay juxtaposes Yan’s theoretical take on moral realism, which draws extensively from the Chinese pre-Qin classics, to ideas deriving from Thucydides and the Greek classics. This comparative analysis between the western and eastern strategic logic attests to the existence of a universal cannon of strategy which puts a premium on ‘the first image’ of analysis—that of political leadership—and acknowledges the consequentiality of utilitarian morality in global politics within the structural restrictions of the international system.


title: The combined effect of indoor air quality and soffieconomic factors on health in Northeast China

text: Research has increasingly demonstrated that complex relationships exist between residential indoor air quality, health and soffieconomic factors. However, few studies have provided a comprehensive understanding of these relationships. The purpose of this paper, therefore, was to use structural equation modeling to identify the combined effect of residential indoor air quality and soffieconomic factors on occupants' health, based on field measurement data in Northeast China. The results showed that soffieconomic status had a direct impact on the occupants' health with the path coefficient of 0.413, whereas the effect from indoor air quality was 0.105. Soffieconomic status posed the direct effect on indoor air quality with path coefficients of 0.381. The weights of PM2.5, CO2, TVOC (Total Volatile Organic Compounds), and formaldehyde concentration to the indoor air quality were 0.813, 0.385, 0.218, and 0.142, respectively. Relative contributions of Income level, education level, and occupation prestige to soffieconomic status were 0.595, 0.551, and 0.508, respectively. Relationships between indoor air quality, soffieconomic factors and health were further confirmed based on multiple group analysis. The study defines and quantifies complex relationships between residential indoor air quality, soffieconomic status and health, which will help improve knowledge of the impacts of the residential indoor environment on health.


title: COVID-19-induced acute respiratory failure: an exacerbation of organ-specific autoimmunity?

text: Background: Understanding the pathophysiology of respiratory failure (ARDS) in coronavirus disease 2019 (COVID-19) patients is of utmost importance for the development of therapeutic strategies and identification of risk factors. Since we observed clinical and histopathological similarities between COVID-19 and lung manifestations of connective tissue disease (CTD-ILD) in our clinical practice, aim of the present study is to analyze a possible role of autoimmunity in SARS-CoV-2-associated respiratory failure. Methods: In this prospective, single-center trial, we enrolled 22 consecutive patients with RT-PCR-confirmed SARS-CoV-2 infection hospitalized in March and April, 2020. We performed high-resolution computed tomography (HR-CT) and full laboratory testing including autoantibody (AAB) screening (anti-ANA, SS-B/La, Scl-70, Jo-1, CENP-B, PM-Scl). Transbronchial biopsies as well as post mortem tissue samples were obtained from 3 and 2 cases, respectively, and subsequent histopathologic analysis with special emphasis on characterization of interstitial lung disease was performed. Results: Twelve of 22 patients (54.5%) were male and median age was 69.0 (range: 28-88). 11 (50.0%) patients had to be undergo intensive care unit (ICU) treatment. Intubation with ventilation was required in 10/22 cases (46%). Median follow-up was 26 days. Clinical and serological parameters were comparable to previous reports. Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of CTD-ILD. AAB titers [≥]1:100 were detected in 10/11 (91.9%) COVID-19 patients who required ICU treatment, but in 4/11 (36.4%) patients with mild clinical course (p=0.024). Patients with AABs tended to require invasive ventilation and showed significantly more severe complications (64.3% vs. 12.5%, p=0.031). Overall COVID-19-related mortality was 18.2% among hospitalized patients at our institution. Conclusion: Our findings point out serological, radiological and histomorphological similarities between COVID-19-associated ARDS and acute exacerbation of CTD-ILD. While the exact mechanism is still unknown, we postulate that SARS-CoV-2 infection might trigger or simulate a form of organ-specific autoimmunity in predisposed patients. The detection of autoantibodies might identify patients who profit from immunosuppressive therapy to prevent the development of respiratory failure.


title: Predicting mammalian hosts in which novel coronaviruses can be generated

text: Novel pathogenic coronaviruses – including SARS-CoV and SARS-CoV-2 – arise by homologous recombination in a host cell1,2. This process requires a single host to be infected with more than one type of coronavirus, which recombine to form novel strains of virus with unique combinations of genetic material. Identifying possible sources of novel coronaviruses requires identifying hosts (termed recombination hosts) of more than one coronavirus type, in which recombination might occur. However, the majority of coronavirus-host interactions remain unknown, and therefore the vast majority of recombination hosts for coronaviruses cannot be identified. Here we show that there are 11.5-fold more coronavirus-host associations, and over 30-fold more potential SARS-CoV-2 recombination hosts, than have been observed to date. We show there are over 40-fold more host species with four or more different subgenera of coronaviruses. This underestimation of both number and novel coronavirus generation in wild and domesticated animals. Our results list specific high-risk hosts in which our model predicts homologous recombination could occur, our model identifies both wild and domesticated mammals including known important and understudied species. We recommend these species for coronavirus surveillance, as well as enforced separation in livestock markets and agriculture.


title: Immune defects and cardiovascular risk in X chromosome monosomy mosaicism mediated by loss of chromosome Y. A risk factor for SARS-CoV-2 vulnerability in elderly men?

text: The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) has an estimated overall case fatality ratio of 1.38% in China, being 53% higher in males and increasing exponentially with age. Mosaicism for X chromosome monosomy (XCM) shows a similar increase in aging population mostly driven by loss of chromosome Y in males (LOY), and is associated with a raise in all-cause mortality. Using comparative transcriptomic data, we have defined that XCM/LOY is associated with abnormal peripheral blood cell counts with decreased progenitor cells and multiple biomarkers of immune system dysfunction, pro-coagulation activity and increased cardiovascular risk. Several differentially down-regulated genes in XCM/LOY individuals are involved in the initial immune response to SARS-CoV-2 (OR of enrichment=7.23, p=1.5x10-7), mainly interferon-induced genes that code for inhibitors of viral processes. Thus, our data suggest that XCM mosaicism underlies at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential relevance for modulating prognosis and therapeutic response, we propose that evaluation of LOY and XCM by currently established methods should be implemented as biomarkers in infected patients, including currently ongoing clinical trials with different medications and vaccines for COVID-19. Testing for LOY/XCM at large scale among elderly people may also be helpful to identify still unexposed people who may be especially vulnerable to severe Covid-19 disease.


title: Development of a Coronavirus Disease 2019 Nonhuman Primate Model Using Airborne Exposure

text: Airborne transmission is predicted to be a prevalent route of human exposure with SARS-CoV-2. Aside from African green monkeys, nonhuman primate models that replicate airborne transmission of SARS-CoV-2 have not been investigated. A comprehensive and comparative evaluation of COVID-19 in African green monkeys, rhesus macaques, and cynomolgus macaques following airborne exposure to SARS-CoV-2 was performed to define parameters critical to disease progression and the extent to which they correlate with human COVID-19. Respiratory abnormalities and viral shedding were noted for all animals, indicating successful infection. Cynomolgus macaques developed fever, and thrombocytopenia was measured for African green monkeys and rhesus macaques. Type II pneumocyte hyperplasia and alveolar fibrosis were more frequently observed in lung tissue from cynomolgus macaques and African green monkeys. The data indicate that, in addition to African green monkeys, macaques can be successfully infected by airborne SARS-CoV-2, providing viable macaque natural transmission models for medical countermeasure evaluation. One Sentence Summary Nonhuman primates develop COVID-19 following airborne virus exposure.


title: Covid-19 testing strategies and lockdowns: the European closed curves, analysed by ``skew-normal'' distributions, the forecasts for the UK, Sweden, and the USA, and the ongoing outbreak in Brazil.

text: As the number of Covid-19 infections worldwide overtakes 6 millions of Total Confirmed Cases (TCC), the data reveal almost closed outbreaks in many European countries. Using the European data as a basis for our analysis, we study the spreading rate of Covid-19 and model the Daily Confirmed Cases and Deaths per Million (DCCpM and DDpM) curves by using ``skew-normal'' probability density functions. The use of these asymmetrical distributions allows to get a more realistic prediction of the end of the disease in each country and to evaluate the effectiveness of the local authorities strategies in facing the European outbreak. The initial stage of the Brazilian disease is compared with the early phase of the European one. This is done by using the weekly spreading rate of Covid-19. For Sweden, UK, and USA, we shall give a forecast for the end of pandemic and for Brazil the prediction of the peak of DDpM. We also discuss additional factors that could play an important role in the fight against Covid-19, such as the fast response of the local authorities, the testing strategies, the number of beds in the intensive care units, and, last but not least, the measures of isolation adopted. The Brazilian mitigation measures can be placed between the strict lockdown of many European countries and the Swedish approach, but clearly much comparable to the European ones (in particular to the Netherlands). Methods. For Brazil, the weekly spreading rates of Covid-19, as more people are getting infected, was used to compare the outbreak in these countries with the ones of the European countries when they were at the same stage of infection. In the early stage of the disease, normal distributions have been used to obtain what we call a dynamic prediction of the peaks. After reaching the peak of daily infections and/or deaths, skew-normal distributions are required to correctly fit the asymmetrical DCCpM and DDpM curves and get a realistic forecast of the pandemic end. Findings. The European data analysis shows that the spreading rate of Covid-19 increased similarly for all countries in its initial stage, but it changed as the number of TCCpM in each country grew. This was caused by the different timely action of the authorities in adopting isolation measures and/or massive testing strategies. The early stage of the outbreak in the USA and Brazil shows for their $boldsymbol{alpha}$ factor (DCCpM) a behaviour similar to Italy and Sweden, respectively. For the $boldsymbol{beta}$ factor (DDpM), the American spreading is similar to the one of Switzerland, whereas the Brazilian factor is greater than the ones of Portugal, Germany, and Austria (which showed, in terms of TDpM, the best results in Europe) but, at the moment, it is lower than the other European countries. Interpretation. The fitting skew parameters used to model the DCCpM and DDpM curves allow a more realistic prediction of the end of the pandemic and give us the possibility to compare the mitigation measures adopted by the local authorities by analysing their respective skew normal parameters (mean, mode, standard deviation, and skewness). In Europe, Sweden and the UK show the greatest asymmetries, a kind of marathon instead of the sprint of other European countries (as observed by Swedish authorities). This also happens for the USA. The Brazilian weekly spreading rate for deaths is lower than most of the European countries at the same stage of the outbreak.


title: Higher Body Mass Index is an Important Risk factor in COVID-19 patients: A Systematic Review

text: Background: Globally, both obesity and underweight are severe health risks for various diseases. The current study systematically examines the emerging evidence to identify an association between Body Mass Index (BMI) and COVID-19 disease outcome. Methods: Online literature databases (e.g., Google Scholar, PubMed, MEDLINE, EMBASE, Scopus, Medrixv and BioRixv) were screened following standard search strategy having the appropriate keyword such as Obesity, Underweight, BMI, Body Mass Index, 2019-nCov, COVID-19, novel coronavirus, coronavirus disease. Studies published till 20th April 2020 were included without language restriction. These studies include case reports, case series, cohort, and any other which reported BMI, overweight/obesity or underweight, and its complication with COVID-19 disease. Findings: Obesity plays a significant part in the pathogenesis of COVID-19 patients, though the role of BMI in the COVID-19 pandemic must not be ignored. Interpretation: Consequences of inflammation of adipose tissue has been reported as a leading cause of insulin resistance and hypertension due to metabolic dysfunction. The results of the current study show that BMI plays a significant role in COVID-19 severity in all ages, especially the elderly population. A panel should review COVID-19 patients with higher BMI and other co-morbidities, and they should be given increased vigilance, testing priority, and therapy. Further, the COVID-19 patients whose illness entered 7-10 days, age >50 yrs, and elevated CRP levels should have additional medical considerations. Recommendation: Population and patients with high BMI have moderate to high risk of medical complications with COVID-19, and hence their health status should be monitored more frequently. Keywords: Age, BMI, COVID-19, Obesity.


docid: gajnivfe

title: Elizabeth Conner Internet Guide to Travel Health

text: Unknown