title: Exploring active compounds of Da-Yuan-Yin in treatment of COVID-19 based on network pharmacology and molecular docking method/ 基于网络药理学和分子对接法探寻达原饮治疗新型冠状病毒肺炎（COVID-19）活性化合物的研究

text: Objective: To explore the active compound of Da-Yuan-Yin for treatment of coronavirus disease 2019 (COVID-19). Methods: Based on traditional Chinese medicine system pharmacology platform (TCMSP), the chemical composition and targets of Arecae Semen, Magnoliae Officinalis Cortex, Tsaoko Fructus, Anemarrhenae Rhizoma, Paeoniae Radix Alba, Scutellariae Radix, and Glycyrrhizae Radix et Rhizoma were screened. The targets of corresponding gene were searched through UniProt, GeneCards databases, and then Cytoscape3.2.1 was used to build compound-targets (genes) networks. The enrichment of gene ontology (GO) function analysis by DAVID and the pathway enrichment analysis by Kyoto Encyclopedia of Genes and Genomes (KEGG) were carried out, the mechanism of its action was predicted. Results: The compound-target network contained 141 compounds and 267 corresponding targets, and the key targets involved PTGS2, HSP90AA1, ESR1, AR, NOS2, etc. The function enrichment analysis of GO was 522 (P < 0.05), of which there were 421 biological processes (BP) items, and 38 related items of cell composition (CC),and 63 molecular function (MF) items. There were 25 signal pathways (P < 0.05) in the KEGG pathway enrichment screening, involving small cell lung cancer, non-small cell lung cancer and T cell receptor signaling pathways, etc. The results of molecular docking showed that the affinity of quercetin, kaempferol, baicalin and other core compounds was similar to recommended drugs recommended in the treatment of COVID-19. Conclusion: The active compounds in Da-Yuan-Yin may regulate multiple signaling pathways by binding angiotensin converting enzyme II (ACE2) and acting on targets such as PTGS2, HSP90AA1 and ESR1 to inhibit COVID-19.


title: The organizational principles of de-differentiated topographic maps

text: Topographic maps are a fundamental feature of cortex architecture in the mammalian brain. One common theory is that the de-differentiation of topographic maps links to impairments in everyday behavior due to less precise functional map readouts. Here, we tested this theory by characterizing de-differentiated topographic maps in primary somatosensory cortex (SI) of younger and older adults by means of ultra-high resolution functional magnetic resonance imaging together with perceptual finger individuation and hand dexterity. Older adults’ SI maps showed similar amplitude, size, and levels of stimulus-related noise than younger adults’ SI maps, but presented with less representational similarity between distant fingers. Larger population receptive field sizes in older adults’ maps did not correlate with behavior, whereas reduced cortical distances related to better hand dexterity. Our data uncover the drawbacks of a simple de-differentiation model of topographic map function, and motivate the introduction of a feature-based model of cortical reorganization.


title: Chronology

text: Unknown


title: Famotidine Use is Associated with Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Retrospective Cohort Study

text: Background: The SARS-CoV-2 pandemic has resulted in enormous morbidity and mortality worldwide, yet no medications to date are proven to improve clinical outcomes in hospitalized COVID-19 patients. Famotidine is commonly used for gastric acid suppression but also has recently gained attention as an antiviral that may inhibit SARS-CoV-2 replication. Objective: To determine whether famotidine use is associated with improved clinical outcomes in patients with COVID-19 initially hospitalized to a non-intensive care setting. Design: Retrospective cohort study. Setting: Inpatients at a single academic medical center. Participants: Consecutive hospitalized patients with COVID-19 infection from February 25 to April 13, 2020. Measurements: Famotidine use (exposure); intubation or death (primary outcome) Results: 1,620 hospitalized patients with COVID-19 were analyzed including 84 (5.1%) who received famotidine within 24 hours of hospital admission. There were no differences between famotidine users and non-users in age, body mass index, or comorbidities including diabetes or hypertension. 340 (21%) patients met the study composite outcome of death or intubation. Use of famotidine was associated with reduced risk for death or intubation (adjusted hazard ratio (aHR) 0.40, 95% CI 0.20-0.81) and also with reduced risk for death alone (aHR 0.29, 95% CI 0.11-0.78). Proton pump inhibitors, which also suppress gastric acid, were not associated with reduced risk for death or intubation. In patients without COVID-19 hospitalized during the same time period, no association was observed between use of famotidine and death or intubation. Limitations: Retrospective analysis; non-randomized exposure. Conclusion: Famotidine use is associated with reduced risk of intubation or death in hospitalized COVID-19 patients. Randomized controlled trials are warranted to determine whether famotidine therapy improves outcomes in hospitalized COVID-19 patients.


title: Investigation of ACE2 N-terminal fragments binding to SARS-CoV-2 Spike RBD

text: Coronavirus disease 19 (COVID-19) is an emerging global health crisis. With over 7 million confirmed cases to date, this pandemic continues to expand, spurring research to discover vaccines and therapies. SARS-CoV-2 is the novel coronavirus responsible for this disease. It initiates entry into human cells by binding to angiotensin-converting enzyme 2 (ACE2) via the receptor binding domain (RBD) of its spike protein (S). Disrupting the SARS-CoV-2-RBD binding to ACE2 with designer drugs has the potential to inhibit the virus from entering human cells, presenting a new modality for therapeutic intervention. Peptide-based binders are an attractive solution to inhibit the RBD-ACE2 interaction by adequately covering the extended protein contact interface. Using molecular dynamics simulations based on the recently solved cryo-EM structure of ACE2 in complex with SARS-CoV-2-RBD, we observed that the ACE2 peptidase domain (PD) α1 helix is important for binding SARS-CoV-2-RBD. Using automated fast-flow peptide synthesis, we chemically synthesized a 23-mer peptide fragment of the ACE2 PD α1 helix (SBP1) composed entirely of proteinogenic amino acids. Chemical synthesis of SBP1 was complete in 1.5 hours, and after work up and isolation >20 milligrams of pure material was obtained. Bio-layer interferometry (BLI) revealed that SBP1 associates with micromolar affinity to insect-derived SARS-CoV-2-RBD protein obtained from Sino Biological. Association of SBP1 was not observed to an appreciable extent to HEK cell-expressed SARS-CoV-2-RBD proteins and insect-derived variants acquired from other vendors. Moreover, competitive BLI assays showed SBP1 does not outcompete ACE2 binding to Sino Biological insect-derived SARS-CoV-2-RBD. Further investigations are ongoing to gain insight into the molecular and structural determinants of the variable binding behavior to different SARS-CoV-2-RBD protein variants.


title: Investigating SARS-CoV-2 surface and air contamination in an acute healthcare setting during the peak of the COVID-19 pandemic in London

text: Objectives: To evaluate SARS-CoV-2 surface and air contamination during the peak of the COVID-19 pandemic in London. Design: Prospective cross-sectional observational study. Setting: An acute NHS healthcare provider. Participants: All inpatient wards were fully occupied by patients with COVID-19 at the time of sampling. Interventions: Air and surface samples were collected from a range of clinical areas and a public area of the hospital. An active air sampler was used to collect three or four 1.0 m3 air samples in each area. Surface samples were collected by swabbing approximately 25 cm2 of items in the immediate vicinity of each air sample. SARS-CoV-2 was detected by RT-qPCR and viral culture using Vero E6 and Caco2 cells; additionally the limit of detection for culturing SARS-CoV-2 dried onto surfaces was determined. Main outcome measures: SARS-CoV-2 detected by PCR or culture. Results: Viral RNA was detected on 114/218 (52.3%) of surface and 14/31 (38.7%) air samples but no virus was cultured. The proportion of surface samples contaminated with viral RNA varied by item sampled and by clinical area. Viral RNA was detected on surfaces and in air in public areas of the hospital but was more likely to be found in areas immediately occupied by COVID-19 patients (67/105 (63.8%) in areas immediately occupied by COVID-19 patients vs. 29/64 (45.3%) in other areas (odds ratio 0.5, 95% confidence interval 0.2-0.9, p=0.025, Fishers exact test). The PCR Ct value for all surface and air samples (>30) indicated a viral load that would not be culturable. Conclusions: Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from surface and air contamination in managing COVID-19, and the need for effective use of PPE, social distancing, and hand/surface hygiene.


Even with COVID-19 neurosurgeons should still perform necessary urgent/emergent neurosurgery to avoid major permanent neurological deficits


title: Prevention of pathogen transmission during ultrasound use in the Intensive Care Unit: Recommendations from the College of Intensive Care Medicine Ultrasound Special Interest Group (USIG)

text: ICU ultrasonography constitutes important part of modern car patient care. Current standards and practice of infection control and prevention are inadequate. This purpose of this document is to adapt and expand the 2017 Australasian Society for Ultrasound in Medicine (ASUM) and the Australasian College for Infection Prevention Control (ACIPC) guidelines on minimum standards for reprocessing/cleaning of ultrasound transducers to the specifics of intensive care medicine and provide advice to the ICU practitioners and health care administrators. It considers the medical, administrative, financial and practical controversies surrounding implementation, and addresses emerging issues of care for patients with confirmed or suspected Corona Virus Disease 2019 (COVID-19).


title: Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection

text: Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy's and St Thomas' Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection that causes low disease severity and the circulating seasonal coronaviruses that are associated with common colds. This study has important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection.


Reply: Introducing special cutaneous “sign” tribute to healthcare workers managing new coronavirus disease (Covid −19)


title: Agent-Based Simulation for Evaluation of Contact-Tracing Policies Against the Spread of SARS-CoV-2

text: The decline of active COVID-19 cases in many countries in the world has proved that lockdown policies are indeed a very effective measure to stop the exponential spread of the virus. Still, the danger of a second wave of infections is omnipresent and it is clear, that every policy of the lockdown has to be carefully evaluated and possibly replaced by a different, less restrictive policy, before it can be lifted. Tracing of contacts and consequential tracing and breaking of infection-chains is a promising and comparably straightforward strategy to help containing the disease, although its precise impact on the epidemic is unknown. In order to quantify the benefits of tracing and similar policies we developed an agent-based model that not only validly depicts the spread of the disease, but allows for exploratory analysis of containment policies. We will describe our model and perform case studies in which we use the model to quantify impact of contact tracing in different characteristics and draw valuable conclusions about contact tracing policies in general.


title: The prevalence of antibodies to SARS-CoV-2 in asymptomatic healthcare workers with intensive exposure to COVID-19

text: The prevalence of asymptomatic SARS-CoV-2 infection in healthcare workers with intensive exposure to COVID-19 is unclear. In this study, we investigated the seroprevalence of SARS-CoV-2 in 797 asymptomatic healthcare workers with intensive exposure to COVID-19 patients in Wuhan, China. Positive IgG was detected from 35 asymptomatic healthcare workers, and the prevalence of antibodies to SARS-CoV-2 in asymptomatic healthcare workers was 4.39% (35/797). None of them developed COVID-19 until May 15. 33 of them have performed at least one chest CT scan showing no viral pneumonia features, and 16 have finished at least one-time SARS-CoV-2 RNA detection with negative results. When contacting with the patients, 15 of them dressed with full personal protective equipment (PPE), and 16 worn N95 mask and gown. To the best of our knowledge, this is the first investigation reported that the seroprevalence of SARS-CoV-2 was 4.39% in asymptomatic healthcare workers with applied PPE in a high epidemic area, which may provide useful information of estimating asymptomatic infection rate in general population.


title: Reagents hold up European COVID-19 tests

text: Politicians in the UK and the Netherlands claim that delays in the rollout of COVID-19 testing are because of a shortage of reagents—typically enzymes and buffers—used in antigen tests to determine the presence of the coronavirus that causes COVID-19 Politicians in the Netherlands have accused Roche of withholding the latest chemical formula for a buffer used in its polymerase chain reaction–based COVID-19 tests And Dutch media outlets say Roche is keeping reagents for its tests within its home country of Switzerland The company tells C&EN that it is doing all it can to provide COVID-19 test kits, as well as the required reagents, in Europe and beyond In the UK, “a critical constraint on the ability to rapidly increase testing capacity is the availability of the chemical reagents,” UK government minister Michael Gove told journalists March 31 UK politicians are under scrutiny because the country’s testing lags Germany’s as well


title: Detection of 2019 novel coronavirus in semen and testicular biopsy specimen of COVID-19 patients

text: Background: As of March 11, 2020, the COVID-19 outbreak was declared as a pandemic. Expending our understanding of the transmission routes of the viral infection is crucial in controlling the outbreak. It is unclear whether the 2019 novel coronavirus (2019-nCoV) can directly infect the testes or male genital tract and be sexually transmitted from males. Methods: From January 31 to March 14, 2020, 12 patients in recovery and one patient died of COVID-19 were included in this descriptive study. The clinical characteristics, laboratory findings, chest CT scans and outcome data were recorded. To examine whether there is sexual transmission from male, we employed realtime polymerase chain reaction testing (RT-PCR) to detect 2019-nCov in semen or testicular biopsy specimen. Findings: The age range of the 12 patients in recovery was 22-38 years. None of the patients developed severe COVID-19 pneumonia. As of March 14, 2020, ten patients discharged from the hospital while the rest 2 had developed into recovery stage. All of the patients in recovery tested negative for 2019-nCoV RNA in semen samples. Another died patient was 67 years old, who died in March 10, 2020 and tissue sample via testicular biopsy was tested negative for viral RNA. Conclusion: No positive RT-PCR result was found in the semen or testicular biopsy specimen. The results from this study show no evidence of sexual transmission of 2019-nCov from males.


docid: byigkblc

title: Assessment of SARS-CoV-2 Specific CD4(+) and CD8 (+) T Cell Responses Using MHC Class I and II Tetramers

text: The success of SARS-CoV-2 (CoV-2) vaccines is measured by their ability to mount immune memory responses that are long-lasting. To achieve this goal, it is important to identify surrogates of immune protection, namely, CoV-2 MHC Class I and II immunodominant pieces/epitopes and methodologies to measure them. Here, we present results of flow cytometry-based MHC Class I and II QuickSwitch™ platforms for assessing SARS-CoV-2 peptide binding affinities to various human alleles as well as the H-2 Kb mouse allele. Multiple SARS-CoV-2 potential MHC binders were screened and validated by QuickSwitch testing. While several predicted peptides with acceptable theoretical Kd showed poor MHC occupancies, fourteen MHC class II and a few MHC class I peptides showed promiscuity in that they bind with multiple MHC molecule types. With the peptide exchange generated MHC tetramers, scientists can assess CD4+ and CD8+ immune responses to these different MHC/peptide complexes. Results obtained with several SARS-CoV-2 MHC class I and II peptides are included and discussed.


title: Epidemiology of sleep disorders during COVID-19 pandemic: A systematic scoping review protocol

text: Background: The coronavirus disease (COVID-19) is impacting human health globally. In addition to physical health problems, a growing burden of mental health problems has become a global concern amid this pandemic. Sleep disorders are major mental health problems associated with increased psychosocial stressors; however, no research synthesis is available on the epidemiology of sleep disorders. In this systematic scoping review, we aim to assess the current evidence on the epidemiological burden, associated factors, and interventions from the existing literature on sleep disorders. Methods: We will search seven major health databases and additional sources to identify, evaluate, and synthesize empirical studies on the prevalence and correlates of sleep disorders and available interventions addressing the same. We will use the Joanna Briggs Institute Methodology for Scoping Review and report the findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. Conclusion: This review will identify the epidemiological burden of and interventions for sleep disorders. The findings of this review will be widely communicated with the research and professional community to facilitate future research and practice.


title: COVID-19 FATALITY RISK: WHY IS AUSTRALIA LOWER THAN SOUTH KOREA?

text: Background: As the Covid-19 virus epidemic spreads, it is important to establish reliable estimates of fatality hazard rates. Australia and South Korea are ideal candidates for detailed consideration. Both have completed the first wave of the epidemic, they have extensive Covid-19 testing and tracking programs so that confirmed case load data are reliable, and neither country has had any significant case load stress in their hospital systems. Methods: For each country, mortality hazard models were estimated using a parameterized distributed lag model where the number of daily deaths was dependent on the number of confirmed cases in each of the preceding six weeks. Age cohort CFRs were also examined. Findings: We observed major difference in the mortality rates when comparing South Korea to Australia in both the simple age adjusted fatality rates and in the disease hazard curve. On a like-for-like basis, the CFR for South Korea appears to be close to double the Australian rate (aggregate; 2.4% vs 1.4%). Interpretation: Neither differences in the time pattern of the peaking of the case load of confirmed cases, nor differences in the size of age cohorts of confirmed cases explain the difference in mortality observed. We discuss possible explanations that point the way for further investigation. Funding: nil.


title: Asymptomatic carriage rates and case-fatality of SARS-CoV-2 infection in residents and staff in Irish nursing homes

text: Background: SARS-CoV-2 has disproportionately affected nursing home (NH) residents. In Ireland, the first NH case of COVID-19 occurred on 16/03/2020. A national point-prevalence testing program of all NH residents and staff took place from 18/04/2020-05/05/2020. Aims: To examine characteristics of NHs across three Community Health Organisations (CHOs) in Ireland, proportions with COVID-19 outbreaks, staff and resident, symptom-profile and resident case-fatality. Methods: Forty-five NHs surveyed across three CHOs requesting details on occupancy, size, COVID-19 outbreak, timing of outbreak, total symptomatic/asymptomatic cases, and outcomes for residents from 29/02/2020-22/05/2020. Results: Surveys were returned from (62.2%, 28/45) of NHs (2043 residents, 2303 beds). Three-quarters (21/28) had COVID-19 outbreaks (1741 residents, 1972 beds). Median time from first case of COVID-19 in Ireland to first case in these NHs was 27.0 days. Resident COVID-19 incidence was (43.9%, 764/1741): laboratory-confirmed (40.1%, 710/1741) with (27.2%, 193/710 asymptomatic), and clinically-suspected (3.1%, 54/1741). Resident case-fatality was (27.6%, 211/764) for combined laboratory-confirmed/clinically-suspected COVID-19. Similar proportions of residents in NH with an early outbreak (<28days) versus a later outbreak developed confirmed/suspected COVID-19. A lower proportion of residents in NHs with early outbreaks had recovered compared to those with late outbreaks (37.4% vs 61.7%; X2=56.9, p<0.001). Among 675 NH staff across twenty-four sites who had confirmed/suspected COVID-19 (23.6%, 159/675) were asymptomatic. There was a significant correlation between the proportion of staff with symptomatic COVID-19 and resident numbers with confirmed/suspected COVID-19 (Spearmans rho=0.81, p<0.001). Conclusion: This study demonstrates COVID-19 impact on NH residents and staff. High infection rates lead to challenges in care provision.


A GP, a virus and a patient: the story of incertitude


title: A spatial model to optimise predictions of COVID-19 incidence risk in Belgium using symptoms as reported in a large-scale online survey

text: Although COVID-19 has been spreading throughout Belgium since February, 2020, its spatial dynamics in Belgium remain poorly understood, due to the limited testing of suspected cases. We analyse data of COVID-19 symptoms, as self-reported in a weekly online survey, which is open to all Belgian citizens. We predict symptoms' incidence using binomial models for spatially discrete data, and we introduce these as a covariate in the spatial analysis of COVID-19 incidence, as reported by the Belgian government during the days following a survey round. The symptoms' incidence predictions explain a significant proportion of the variation in the relative risks based on the confirmed cases, and exceedance probability maps of the symptoms' incidence and the confirmed cases' relative risks pinpoint the same high-risk region. We conclude that these results can be used to develop public monitoring tools in scenarios with limited lab testing capacity, and to supplement test-based information otherwise.


title: Characteristics and predictors of hospitalization and death in the first 9,519 cases with a positive RT-PCR test for SARS-CoV-2 in Denmark: A nationwide cohort

text: Objective To provide population-level knowledge on individuals at high risk of severe and fatal coronavirus disease 2019 (COVID-19) in order to inform targeted protection strategies in the general population and appropriate triage of hospital contacts. Design, Setting, and Participants Nationwide population-based cohort of all 228.677 consecutive Danish individuals tested (positive or negative) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA from the identification of the first COVID-19 case on February 27th, 2020 until April 30th, 2020. Main Outcomes and Measures We examined characteristics and predictors of inpatient hospitalization versus community-management, and death versus survival, adjusted for age-, sex- and number of comorbidities. Results We identified 9,519 SARS-CoV-2 PCR-positive cases of whom 78% were community-managed, 22% were hospitalized (3.2% at an intensive care unit) and 5.5% had died within 30 days. Median age varied from 45 years (interquartile range (IQR) 31-57) among community-managed cases to 82 years (IQR 75-89) among those who died. Age was a strong predictor of fatal disease (odds ratio (OR) 14 for 70-79-year old, OR 26 for 80-89-year old, and OR 82 for cases older than 90 years, when compared to 50-59-year old and adjusted for sex and number of comorbidities). Similarly, the number of comorbidities was strongly associated with fatal disease (OR 5.2, for cases with [≥]4 comorbidities versus no comorbidities), and 82% of fatal cases had at least 2 comorbidities. A wide range of major chronic diseases were associated with hospitalization with ORs ranging from 1.3-1.4 (e.g. stroke, ischemic heart disease) to 2.2-2.7 (e.g. heart failure, hospital-diagnosed kidney disease, chronic liver disease). Similarly, chronic diseases were associated with mortality with ORs ranging from 1.2-1.3 (e.g. ischemic heart disease, hypertension) to 2.4-2.7 (e.g. major psychiatric disorder, organ transplantation). In the absence of comorbidities, mortality was relatively low (5% or less) in persons aged up to 80 years. Conclusions and Relevance In this first nationwide population-based study, increasing age and number of comorbidities were strongly associated with hospitalization requirement and death in COVID-19. In the absence of comorbidities, the mortality was, however, lowest until the age of 80 years. These results may help in accurate identification, triage and protection of high-risk groups in general populations, i.e. when reopening societies.


title: Dynamics of viral index infections in novel hosts

text: Whether a pathogen entering a new host species results in a single infection or in onward transmission, and potentially an outbreak, depends upon the progression of infection in the index case. Although index infections are rarely observable in nature, experimental inoculations of pathogens into novel host species have a long history in biomedical research. This provides a rich and largely unexploited data source for meta-analyses to identify the host and pathogen determinants of variability in infection outcomes. Here, we analysed the progressions of 514 experimental cross-species inoculations of rabies virus, a widespread zoonotic pathogen which in nature exhibits both dead end infections and varying levels of sustained transmission in novel hosts. Inoculations originating from bats rather than carnivores, and from warmer to cooler-bodied species caused infections with shorter incubation periods that were associated with diminished virus excretion. Inoculations between distantly related hosts tended to result in shorter clinical disease periods, which will also impede transmission. All effects were modulated by infection dose and together suggest that increased virulence as host species become more dissimilar is the limiting factor preventing onward transmission. These results explain observed constraints on rabies virus host shifts, allow us to evaluate the risk of novel reservoirs establishing, and give mechanistic insights into why host shifts are less likely between genetically distant species. More generally, our study highlights meta-analyses of experimental infections as a tractable approach to quantify the complex interactions between virus, reservoir, and novel host that shape the outcome of cross-species transmission. Significance statement Emerging disease epidemics often result from a pathogen establishing transmission in a novel host species. However, most cross-species transmissions fail to establish in the newly infected species for reasons that remain poorly understood. Examining cross-species inoculations involving rabies, a widespread viral zoonosis, we show that mismatches in virulence, which are predictable from host and viral factors, make sustained transmission in the novel host less likely. In particular, disease progression was accelerated and virus excretion decreased when the reservoir and novel host were physiologically or genetically more dissimilar. These mechanistic insights help to explain and predict host shift events and highlight meta-analyses of existing experimental inoculation data as a powerful and generalisable approach for understanding the dynamics of index infections in novel species.


title: Age Alone is not Adequate to Determine Health-care Resource Allocation During the COVID-19 Pandemic

text: BACKGROUND: The Canadian Geriatrics Society (CGS) fosters the health and well-being of older Canadians and older adults worldwide. Although severe COVID-19 illness and significant mortality occur across the lifespan, the fatality rate increases with age, especially for people over 65 years of age. The dichotomization of COVID-19 patients by age has been proposed as a way to decide who will receive intensive care admission when critical care unit beds or ventilators are limited. We provide perspectives and evidence why alternative approaches should be used. METHODS: Practitioners and researchers in geriatric medicine and gerontology have led in the development of alternative approaches to using chronological age as the sole criterion for allocating medical resources. Evidence and ethical based recommendations are provided. RESULTS: Age alone should not drive decisions for health-care resource allocation during the COVID-19 pandemic. Decisions on health-care resource allocation should take into consideration the preferences of the patient and their goals of care, as well as patient factors like the Clinical Frailty Scale score based on their status two weeks before the onset of symptoms. CONCLUSIONS: Age alone does not accurately capture the variability of functional capacities and physiological reserve seen in older adults. A threshold of 5 or greater on the Clinical Frailty Scale is recommended if this scale is utilized in helping to decide on access to limited health-care resources such as admission to a critical care unit and/or intubation during the COVID-19 pandemic.


docid: jcqhxzih

title: Risk of drug-induced Long QT Syndrome associated with the use of repurposed COVID-19 drugs: a systematic review

text: Background: The World Health Organization first declared SARS-CoV-2 (COVID-19) a pandemic on March 11, 2020. There are currently no vaccines or therapeutic agents proven efficacious to treat COVID-19. So, whether existing approved drugs could be repurposed and used off-label for the treatment of novel COVID-19 disease is being explored. Methods: A thorough literature search was performed to gather information on the pharmacological properties and toxicity of 6 drugs (azithromycin, chloroquine, favipiravir, hydroxychloroquine, lopinavir/ritonavir, remdesivir) proposed to be repurposed to treat COVID-19. Researchers emphasized affinity of these drugs to block the rapid component of the delayed rectifier cardiac potassium current (IKr) encoded by the human ether-a-go-go gene (hERG), their propensity to prolong cardiac repolarization (QT interval) and cause torsade de pointes (TdP). Risk of drug-induced Long QT Syndrome (LQTS) for these drugs was quantified by comparing six indices used to assess such risk and by querying the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System database with specific key words. Data are also provided to compare the level of risk for drug-induced LQTS by these drugs to 23 other, well-recognized, torsadogenic compounds. Results: Estimators of LQTS risk levels indicated a very-high or high risk for all COVID-19 repurposed drugs except for azithromycin, although cases of TdP have been reported following the administration of this drug. There was an excellent agreement among the various indices used to assess risk of drug-induced LQTS for the six repurposed drugs and the 23 torsadogenic compounds. Conclusion: The risk-benefit assessment for the use of repurposed drugs to treat COVID-19 is complicated since benefits are currently anticipated, not proven. Mandatory monitoring of the QT interval shall be performed as such monitoring is possible for hospitalized patients or by the use of biodevices for outpatients initiated on these drugs.


docid: ewagtpoh

title: periscope: sub-genomic RNA identification in SARS-CoV-2 ARTIC Network Nanopore Sequencing Data

text: We have developed periscope, a tool for the detection and quantification of sub-genomic RNA in ARTIC network protocol generated Nanopore SARS-CoV-2 sequence data. We applied periscope to 1155 SARS-CoV-2 sequences from Sheffield, UK. Using a simple local alignment to detect reads which contain the leader sequence we were able to identify and quantify reads arising from canonical and non-canonical sub-genomic RNA. We were able to detect all canonical sub-genomic RNAs at expected abundances, with the exception of ORF10, suggesting that this is not a functional ORF. A number of recurrent non-canonical sub-genomic RNAs are detected. We show that the results are reproducible using technical replicates and determine the optimum number of reads for sub-genomic RNA analysis. Finally variants found in genomic RNA are transmitted to sub-genomic RNAs with high fidelity in most cases. This tool can be applied to tens of thousands of sequences worldwide to provide the most comprehensive analysis of SARS-CoV-2 sub-genomic RNA to date.


title: Anosmia and ageusia are emerging as symptoms in patients with COVID-19: What does the current evidence say?

text: There have been several reports noting anosmia and ageusia as possible symptoms of COVID-19. This is of particular interest in oncology since patients receiving some cancer treatments such as chemotherapy or immune therapy often experience similar symptoms as side-effects. The purpose of this report was to summarise the evidence on the existence of anosmia and ageusia an emerging COVID-19 symptoms in order to better inform both oncology patients and clinicians. Currently, there is no published evidence or case reports noting anosmia or ageusia as symptoms of COVID-19. Nevertheless, experts in rhinology have suggested that the onset of such symptoms could either act as a trigger for testing for the disease where possible, or could be a new criterion to self-isolate. Whilst more data is currently needed to strengthen our knowledge of the symptoms of COVID-19, oncology patients who are concerned about anosmia or ageusia in the context of their systemic anti-cancer therapy should contact their acute oncology support line for advice.


Prepare for a pandemic


title: Networks of information token recurrences derived from genomic sequences may reveal hidden patterns in epidemic outbreaks: A case study of the 2019-nCoV coronavirus.

text: Profiling the genetic evolution and dynamic spreading of viruses is a crucial task when responding to epidemic outbreaks. We aim to devise novel ways to model, visualise and analyse the temporal dynamics of epidemic outbreaks in order to help researchers and other people involved in crisis response to make well-informed and targeted decisions about from which geographical locations and time periods more genetic samples may be required to fully understand the outbreak. Our approach relies on the application of Transcendental Information Cascades to a set of temporally ordered nucleotide sequences and we apply it to real-world data that was collected during the currently ongoing outbreak of the novel 2019-nCoV coronavirus. We assess information-theoretic and network-theoretic measures that characterise the resulting complex network and suggest touching points and temporal pathways that are of interest for deeper investigation by geneticists and epidemiologists.


docid: flfnpzsd

title: Treatment to prevent the development of severe COVID-19

text: The respiratory virus infection COVID-19 caused by the new coronavirus SARS-CoV2 has been reported in China since December 2019 It has been reported that COVID-19 tends to be more severe in the elderly and in patients with underlying diseases including diabetes, heart disease, and chronic lung disease In severe cases, patients require intensive cares including mechanical ventilation in the ICUs So far, no biomarker that predicts the severity, or no therapeutic strategies to prevent the development of severe diseases has been established Pathology of severe COVID-19 has two aspects: viral overgrowth and excess pulmonary inflammation For the former, clinical trials using existing drugs such as remdesivir (nucleic acid drug), lopinavir/ritonavir combination drug (protease inhibitor), favipravir (polymerase inhibitor), and interferon (antiviral drugs) are being conducted in patients with severe COVID-19 in China Furthermore the interest has been focused on immune globulin preparations enriched with pathogen-specific antibodies collected from the plasma of recovered patients For the latter, clinical studies using tocilizumab (IL-6 receptor antibody) and ACE2 protein have been conducted with the purpose of reducing excessive inflammation of the lung In addition, single cell analysis of immune cells and comprehensive repertoire analysis of TCR/BCR using patient blood are in progress overseas, which are useful to elucidate the mechanism of the severe disease progression and identify the useful biomarkers for it


title: Predictive value of sudden olfactory loss in the diagnosis of COVID-19

text: Introduction: Recent reports suggest that sudden smell loss might be a symptom of SARS-CoV-2 infection. The aim of this study was to investigate the frequency of olfactory loss in an out-patient population who presented to a coronavirus testing center during a 2-week period and to evaluate the diagnostic value of the symptom sudden smell loss for screening procedures. Methods: In this cross-sectional controlled cohort study, 500 patients who presented with symptoms of a common cold to a corona testing center and fulfilled corona testing criteria, completed a standardized diagnostic questionnaire which included the patients main symptoms, time course and an additional self-assessment of the patients current smell, taste function and nasal breathing compared to the level before onset of symptoms. Results: Out of the 500 patients, 69 presented with olfactory loss. Twenty-two of them subsequently tested positive for SARS-CoV-2. Only twelve out of the patients without olfactory loss tested positive, resulting in a frequency of 64.7% for the symptom sudden smell loss in COVID-19 patients. Compared to COVID-19 patients without smell loss, they were significantly younger and less severely affected. Changes in nasal airflow were significantly more pronounced in SARS-CoV-2 negative patients with olfactory complaints compared to the patients with smell loss who were tested positive for SARS-CoV-2. By excluding patients with a blocked nose, the symptom sudden smell loss can be attested a high specificity (97%) and a sensitivity of 65% with a PPV of 63% and NPV of 97% for COVID-19. Conclusion: Considering the high frequency of smell loss in non-hospitalized COVID-19 patients, acute olfactory impairment should be included in the WHO symptoms list and should be recognized as an early symptom of the disease. In contrast to other acute viral smell impairment, COVID-19 associated smell loss seems to be only rarely accompanied by a severely blocked nose.


title: Outdoor Air Pollutant Concentration and COVID-19 Infection in Wuhan, China

text: COVID-19 infection, first reported in Wuhan, China in December 2019, has become a global pandemic, causing significantly high infections and mortalities in Italy, the UK, the US, and other parts of the world. Based on the statistics reported by John Hopkins University, 4.7M people worldwide and 84,054 people in China have been confirmed positive and infected with COVID-19, as of 18 May 2020. Motivated by the previous studies which show that the exposures to air pollutants may increase the risk of influenza infection, our study examines if such exposures will also affect Covid-19 infection. To the best of our understanding, we are the first group in the world to rigorously explore the effects of outdoor air pollutant concentrations, meteorological conditions and their interactions, and lockdown interventions, on Covid-19 infection in China. Since the number of confirmed cases is likely to be under-reported due to the lack of testing capacity, the change in confirmed case definition, and the undiscovered and unreported asymptotic cases, we use the rate of change in the daily number of confirmed infection cases instead as our dependent variable. Even if the number of reported infections is under-reported, the rate of change will still accurately reflect the relative change in infection, provided that the trend of under-reporting remains the same. In addition, the rate of change in daily infection cases can be distorted by the government imposed public health interventions, including the lockdown policy, inter-city and intra-city mobility, and the change in testing capacity and case definition. Hence, the effects of the lockdown policy and the inter-city and intra-city mobility, and the change in testing capacity and case definition are all taken into account in our statistical modelling. Furthermore, we adopt the generalized linear regression models covering both the Negative Binomial Regression and the Poisson Regression. These two regression models, when combined with different time-lags (to reflect the COVID-19 incubation period and delay due to official confirmation) in air pollutant exposure (PM2.5), are used to fit the COVID-19 infection model. Our statistical study has shown that higher PM2.5 concentration is significantly correlated with a higher rate of change in the daily number of confirmed infection cases in Wuhan, China (p < 0.05). We also determine that a higher dew point interacting with a higher PM2.5 concentration is correlated with a higher rate of change in the daily number of confirmed infection cases, while a higher UV index and a higher PM2.5 concentration are correlated with a lower rate of change. Furthermore, we find that PM2.5 concentration eight days ago has the strongest predictive power for COVID-19 Infection. Our study bears significance to the understanding of the effect of air pollutant (PM2.5) on COVID-19 infection, the interaction effects of both the air pollutant concentration (PM2.5) and the meteorological conditions on the rate of change in infection, as well as the insights into whether lockdown should have an effect on COVID-19 infection.


title: Comparative transcriptome analyses reveal genes associated with SARS-CoV-2 infection of human lung epithelial cells

text: Understanding the molecular mechanism of SARS-CoV-2 infection (the cause of COVID-19) is a scientific priority for 2020. Various research groups are working toward development of vaccines and drugs, and many have published genomic and transcriptomic data related to this viral infection. The power inherent in publicly available data can be demonstrated via comparative transcriptome analyses. In the current study, we collected high-throughput gene expression data related to human lung epithelial cells infected with SARS-CoV-2 or other respiratory viruses (SARS, H1N1, rhinovirus, avian influenza, and Dhori) and compared the effect of these viruses on the human transcriptome. The analyses identified fifteen genes specifically expressed in cells transfected with SARS-CoV-2; these included CSF2 (colony-stimulating factor 2) and S100A8 and S100A9 (calcium-binding proteins), all of which are involved in lung/respiratory disorders. The analyses showed that genes involved in the Type1 interferon signaling pathway and the apoptosis process are commonly altered by infection of SARS-CoV-2 and influenza viruses. Furthermore, results of protein-protein interaction analyses were consistent with a functional role of CSF2 in COVID-19 disease. In conclusion, our analysis has revealed cellular genes associated with SARS-CoV-2 infection of the human lung epithelium; these are potential therapeutic targets.


title: Antibody surveys suggesting vast undercount of coronavirus infections may be unreliable

text: Surveying large swaths of the public for antibodies to the new coronavirus promises to show how widespread undiagnosed infections are, how deadly the virus really is, and whether enough of the population has become immune for social distancing measures to be eased But the first batch of results has generated more controversy than clarity The survey results, from Germany, the Netherlands, and several locations in the United States, find that anywhere from 2% to 30% of certain populations have already been infected with the virus The numbers imply that confirmed COVID-19 cases are an even smaller fraction of the true number of people infected than many had estimated and that the vast majority of infections are mild But many scientists question the accuracy of the antibody tests and complain that several of the research groups announced their findings in the press rather than in preprints or published papers, where their data could be scrutinized Critics are also wary because some of the researchers are on record advocating for an early end to lockdowns and other control measures, and claim the new prevalence figures support that call


title: Closed environments facilitate secondary transmission of coronavirus disease 2019 (COVID-19)

text: Objective: To identify common features of cases with novel coronavirus disease (COVID-19) so as to better understand what factors promote secondary transmission including superspreading events. Methods: A total of 110 cases were examined among eleven clusters and sporadic cases, and investigated who acquired infection from whom. The clusters included four in Tokyo and one each in Aichi, Fukuoka, Hokkaido, Ishikawa, Kanagawa and Wakayama prefectures. The number of secondary cases generated by each primary case was calculated using contact tracing data. Results: Of the 110 cases examined, 27 (24.6%) were primary cases who generated secondary cases. The odds that a primary case transmitted COVID-19 in a closed environment was 18.7 times greater compared to an open-air environment (95% confidence interval [CI]: 6.0, 57.9). Conclusions: It is plausible that closed environments contribute to secondary transmission of COVID-19 and promote superspreading events. Our findings are also consistent with the declining incidence of COVID-19 cases in China, as gathering in closed environments was prohibited in the wake of the rapid spread of the disease.


title: Evaluation of the Practicability of a Finger-Stick Whole-Blood SARS-Cov-2 Self-Test Adapted for the General Population.

text: Background COVID-19 (COronaVIrus Disease 2019) is an infectious respiratory disease caused by the novel SARS-CoV-2 virus. Rapid Diagnostic Tests (RDTs) have been developed to detect specific antibodies, IgG and IgM, to SARS-CoV-2 virus in human whole blood and easily usable by the general population are needed in order to alleviate the lockdown that many countries have initiated in response to the growing COVID-19 pandemic. A real-life study has been conducted in order to evaluate the performance of the COVID-PRESTO RDT and the results have been submitted for publication and are currently under review. Even if this test showed very high sensitivity and specificity in a laboratory setting when used by trained professionals, it needs to be further evaluated for practicability when used by common folk in order to be approved by health authorities for in-home use Methods 142 participants were recruited between March 2020 and April 2020 among non-medical populations in central France (nuclear plants workers, individuals attending the Orleans University Hospital vaccination clinic and Orleans University Hospital non-medical staff). Instructions for use with or without a tutorial video was made available to the volunteers. Two separate objectives were pursued: evaluation of the capability of participants to obtain an interpretable result, and evaluation of the users ability to read the results. Results 88.4 % of the test users judged the instruction for use leaflet to be clear and understandable. 99.3 % of the users obtained a valid results and according to the supervisors 92.7% of the tests were properly performed by the user. Overall, 95% of the users gave positive feedback toward the COVID PRESTO as a potential self-test. No influence of age and education was observed. Conclusion COVID-PRESTO was successfully used by an overwhelming majority of participants and its utilization was judged very satisfactory, therefore showing a promising potential as a self-test to be used by the general population. This RDT can become an easy-to-use tool to help know whether individuals are protected or not, particularly in the perspective of a second wave or a mass vaccination program.


title: Appendix 3 Interviews with Ian Burton and Ken Hewitt

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title: Covid-19 and dysregulated cerebral perfusion: observations with multimodal MRI

text: The pathogenesis of encephalopathy-associated Covid-19 is still unclear. Multimodal brain MRI in 25 Covid-19 patients with neurological symptoms revealed angiographic and brain perfusion changes suggesting an under-recognized dysregulated brain perfusion not identified by morphological neuroimaging alone. Endothelial dysfunction, a key pathomechanism of dysregulated brain perfusion, may contribute to central-nervous-system disturbances in Covid-19.


title: COVID-19 - ESSKA guidelines and recommendations for resuming elective surgery

text: The roadmap to elective surgery resumption after this COVID-19 pandemic should be progressive and cautious. The aim of this paper was to give recommendations and guidelines for resuming elective orthopedic surgery in the safest environment possible. Elective surgery should be performed in COVID-free facilities and hospital stay should be as short as possible. For matters of safety, patients considered first for surgery should be carefully selected according to COVID infection status/exposure, age, ASA physical status classification system / risk factors, socio-professional situation and surgical indication. A strategy for resuming elective surgery in four phases is proposed. Preoperative testing for COVID-19 infection is highly recommended. In any cases, COVID symptoms including fever and increased temperature should be constantly monitored until the day of surgery. Elective surgery should be postponed at the slightest suspicion of a COVID-19 infection. In case of surgery, adapted personal protective equipment in terms of gowns, gloves, masks and eye protection is highly recommended and described.


title: MosMedData: Chest CT Scans with COVID-19 Related Findings

text: This dataset contains anonymised human lung computed tomography (CT) scans with COVID-19 related findings, as well as without such findings. A small subset of studies has been annotated with binary pixel masks depicting regions of interests (ground-glass opacifications and consolidations). CT scans were obtained between 1st of March, 2020 and 25th of April, 2020, and provided by municipal hospitals in Moscow, Russia. Permanent link: https://mosmed.ai/datasets/covid19_1110. This dataset is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0) License.


docid: qcirvcbf

title: High sensitivity CDC EUA SARS-CoV-2 kit-based End Point-PCR assay.

text: SARS-CoV-2 diagnosis is based on RT-qPCR protocols that limited testing to facilities with Real Time PCR devices and probes supply. Here we described and adapted version of the RT-qPCR CDC protocol where N1, N2 and N3 primers are used for end point PCR and amplicons are visualized on agarose gel with a limit of detection up to 20 viral RNA copies/uL. This protocol would allow to extend SARS-CoV-2 diagnosis to basic molecular biology laboratories with a great impact on surveillance programs at developing countries.


title: COVID-19 SCREENING AND MONITORING OF ASYMPTOMATIC HEALTH WORKERS WITH A RAPID SEROLOGICAL TEST

text: Background Health workers are at high risk for SARS-CoV-2 infection and, if asymptomatic, for transmitting the virus on to fragile cancer patients. Materials and method We monitored health care workers (HCW) of our Cancer Institute with the rapid serological test Viva-DiagTM analyzing COVID-19 associated-IgG/IgM. Test were performed at time 0 and after 14 days; Rt-PCR and CLIA assays were also perfoRmed in positive Viva-DiagTM cases. 606 and 393 HCW had blood sample taken at time 0 and 14, respectively. Results Overall, 9 HCW (1.5%) resulted not-negative at Viva-DiagTM and one of them was confirmed positive for SARS-COV2 infection at RT-PCR oropharingeal swab. At time 0, all 9 cases showed some IgM expression and only one IgG; after 14 days IgM persisted in all cases while IgG became evident in 4 ones. A parallel CLIA test was performed in 23 quaratined subjetcs and in all Viva-Diag not negative cases. CLIA confirmed a positive level of IgM in 5/13 positive Viva-Diag cases; conversely, IgG was confirmed positive at CLIA in 4/5 cases positive at Viva-Diag. These results pose the question of different performances of the two tests. Conclusions Our study suggest that Viva-Diag assay can be of help in individualizing SARS_COV2 infected people fisrt of all in cohorts of subjetcs with high prevalence. Different performances of serological colorimetric and CLIA tools remain to be ascertained.


title: Moderna provides cursory glance at first COVID-19 vaccine data

text: Preliminary data from a small study of an experimental COVID-19 vaccine developed by Moderna suggest that the vaccine is safe and can spur the immune system to produce antibodies that neutralize SARS-CoV-2, the coronavirus that causes the disease It’s the first time that results from any COVID-19 vaccine study in humans have been announced The news, disclosed May 18, quickly swept the globe and was widely credited as a catalyst for a rise in the stock market Moderna’s stock soared more than 20%, putting the company’s value at nearly $30 billion—versus about $6 5 billion at the start of the year The biotech firm said it would raise $1 25 billion in a public stock offering and put the money toward manufacturing its COVID-19 vaccines But scientists hoping to parse the news themselves are out of luck “I was disappointed that they didn’t disclose any data It is hard to interpret their[truncated]


title: Diabetes is associated with increased risk for in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis comprising 18,506 patients

text: Background: Infectious diseases are more frequent and can be associated with worse outcomes in patients with diabetes. Our aim was to systematically review and synthesize with a meta-analysis the available observational studies reporting the effect of diabetes in mortality among hospitalized patients with COVID-19. Methods: Medline, Embase, Google Scholar, and medRxiv databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. In-hospital mortality was defined as the endpoint. Sensitivity, subgroup, and meta-regression analyses were performed. Results: 18,506 patients were included in this meta-analysis (3,713 diabetics and 14,793 non-diabetics). Patients with diabetes were associated with a higher risk of death compared to patients without diabetes (OR: 1.65; 95% CI: 1.35, 1.96; I2 77.4%). The heterogeneity was high. A study level meta-regression analysis was performed for all the important covariates and no significant interactions were found between the covariates and the outcome of mortality. Conclusion: This meta-analysis shows that that the likelihood of death is 65% higher in diabetic hospitalized patients with COVID-19 compared to non-diabetics. Further studies are needed to assess whether this association is independent or not, as well as to investigate to role of glucose control prior or during the disease.


title: SARS-CoV-2 amino acid substitutions widely spread in the human population are mainly located in highly conserved segments of the structural proteins

text: The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic offers a unique opportunity to study the introduction and evolution of a pathogen into a completely naïve human population. We identified and analysed the amino acid mutations that gained prominence worldwide in the early months of the pandemic. Eight mutations have been identified along the viral genome, mostly located in conserved segments of the structural proteins and showing low variability among coronavirus, which indicated that they might have a functional impact. At the moment of writing this paper, these mutations present a varied success in the SARS-CoV-2 virus population; ranging from a change in the spike protein that becomes absolutely prevalent, two mutations in the nucleocapsid protein showing frequencies around 25%, to a mutation in the matrix protein that nearly fades out after reaching a frequency of 20%.


title: From crisis to catastrophe: The death and viral legacies of austere neoliberalism in Europe?

text: The COVID-19 pandemic is a global event, but what became apparent almost immediately was that while the virus seems indiscriminate, vulnerability and the capacity to mitigate its impact are not spread equally, either between or within countries. Years of austere neoliberalism in Europe have exacerbated inequality and precarity, acting as a ‘pre-existing condition’ onto which the virus has now landed. The question we ask is: when the pandemic subsides, can the underlying conditions of contemporary neoliberalism remain? And what may replace it?


title: Benefits of bioradar sleep monitoring in self-isolation

text: In the context of the COVID-19 pandemic and the need to maintain self-isolation, the vast majority of outpatient services are closed, and the inpatient clinics have limited the workload admitting almost only urgent cases. Outpatients, including ones with various sleep disorders, are left without access to the specialized examinations. This will lead to the late diagnosis and untimely therapy prescriptions. In such conditions, it is relevant to take into account new instrumental diagnostic methods that could be used by the patient themselves to register their vital parameters at home. The obtained data can be transmitted via the Internet to the attending physician for further analysis followed by prescriptions when required. One of these methods is bioradiolocation, which allows noncontact recording of breathing patterns, heart rate and movement of a person during sleep, as well as detection of various sleep disorders and determination of sleep stages. This method is easy to use, and can be recommended for home-screening by patients. Sleep has a significant immunomodulating function, and sleep assessment is important in both patients at risk and afflicted with novel coronavirus infection. Thus, the use of bioradiolocation method at home for non-contact sleep monitoring may be relevant in case of closure of outpatient facilities and will provide the doctor with objective data on sleep patterns and patterns of breathing, motor activity, the presence and amount of respiratory disturbances during sleep.


title: Evaluation of symptomatic patient saliva as a sample type for the Abbott ID NOW COVID-19 assay

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has presented significant challenges for laboratories including supply chain limitations with restricted access to reagents and sample collection materials (i.e. swabs, viral transport media (VTM)) for patients testing. Therefore, saliva has been evaluated as an alternative specimen for COVID-19 diagnosis. comparable performance between dry nasal swabs (NS) and nasopharyngeal swabs (NPS) collected in VTM has been observed with the ID NOW for SARS-CoV-2; the majority of false-negative results occur with higher cycle number (CN) or cycle threshold (Ct) values suggesting low viral load in these specimens. We performed clinical validation of saliva specimens on the ID NOW molecular platform to detect SARS-CoV-2. Saliva was compared to nasopharyngeal swabs tested on the ID NOW and the Cepheid molecular assay. We also performed stability studies of saliva samples over 5 days. A total of 96 saliva samples and 64 paired NPS were analyzed. We observed 78% (18/23) positive percent agreement (PPA) and 100% (44/44) negative percent agreement (NPA) between matched saliva and nasopharyngeal specimens performed on ID NOW. We found 83% (19/23) PPA and 100% NPA (25/25) between saliva run on the ID NOW and Cepheid assay. Six saliva specimens positive for SARS-CoV-2 were continuously positive for five days when stored at room temperature. Therefore, we propose further investigation of saliva as an alternative sample type for testing symptomatic patients with ID NOW as a promising method to address COVID-19 testing.


title: The Prevalence of ocular manifestations and ocular samples polymerase chain reaction positivity in patients with COVID 19 - a systematic review and meta-analysis

text: Objective: To estimate the prevalence of ocular manifestations and ocular samples polymerase chain reaction (PCR) positivity among COVID 19 patients. Methods: A systematic literature review was performed using search engines (PubMed, Google Scholar, Medrixv and BioRixv) with keywords SARS CoV 2, novel coronavirus, COVID 19, ocular manifestations, conjunctival congestion, Ocular detection, Polymerase chain reaction, and conjunctivitis. The measure of heterogeneity was evaluated with the I2 statistic. The pooled proportion of patients presenting with symptoms and ocular samples PCR positivity was estimated. Results: A total of 20 studies (14 studies and 6 case reports) were included in the systematic review and 14 studies were included in the metaanalysis. The pooled prevalence of conjunctivitis was 5.17% (95% CI: 2.90 to 8.04). Conjunctivitis was reported as an initial symptom of the disease in 0.858 % (95% CI: 0.31 to 1.67). Common associated features include itching, chemosis, epiphora. Seven patients (29 %) with conjunctivitis showed positive results in ocular samples, whereas 13 patients (54%) showed positive only in their nasopharyngeal samples (NPs) or sputum samples and 4 patients (16 %) were negative for both NPs and Sputum as well as ocular samples. The pooled prevalence of ocular PCR positivity was 2.90 % (95% CI: 1.77 to 4.46) vs. NPs 89.8% (95% CI: 78.80 to 79.0). Conclusion: The prevalence of conjunctivitis and ocular samples PCR positivity among COVID 19 patients was low indicating that the eye is a less affected organ. However, conjunctivitis may present as the first symptom of the disease making the patient seek medical care at the earliest.


docid: nnkholfe

title: A quantitative framework to define the end of an outbreak: application to Ebola Virus Disease

text: Declaring the end of an outbreak is an important step in controlling infectious disease outbreaks. An objective estimation of the probability of cases arising in the future is important to reduce the risk of post-declaration flare-ups. We developed a simulation-based model to quantify that probability. We tested it on simulated Ebola Virus Disease (EVD) data and found this probability was most sensitive to the instantaneous reproduction number, the reporting rate, and the delay between symptom onset and recovery or death of the last detected case. For EVD, our results suggest that the current WHO criterion of 42 days since the outcome of the last detected case is too short and very sensitive to underreporting. The 90 days of enhanced surveillance period after the end-of-outbreak declaration is therefore crucial to capture potential flare-ups of cases. Hence, we suggest a shift to a preliminary end-of-outbreak declaration after 63 days from the symptom onset day of the last detected case. This should be followed by a 90-day enhanced surveillance, after which the official end-of-outbreak can be declared. This corresponds to less than 5% probability of flare ups in most of the scenarios examined. Our quantitative framework could be adapted to define end-of-outbreak criteria for other infectious diseases.


title: Simple model for Covid-19 epidemics - back-casting in China and forecasting in the US

text: In our previous work, we analyze, in near-real time, evolution of Covid-19 epidemic in China for the first 22 days of reliable data (up to February 6, 2020). In this work, we used the data for the whole 87 days (up to March 13, 2020) in China and the US data available till March 31 (day 70) for systematic evaluation of the logistic model to predict epidemic growth. We sequentially estimated sets of model parameters (maximum number of cases K, growth rate r, and half-time t0) and the epidemic "end time" t95 (defined as the time when the number of cases, predicted or actual, reached 95% of the maximum). The estimates of these parameters were done for sequences of reported cases growing daily (back-casting for China and forecasting for the US). In both countries, the estimates of K grew very much in time during the exponential and nearly exponential phases making longer term forecasting not reliable. For the US, the current estimate of the maximum number of cases K is about 265,000 but it is very likely that it will grow in the future. However, running estimates of the "end time" t95 were in a much smaller interval for China (60 - 70 days vs. the actual value of 67). For the US, the values estimated from the data sequences going back two weeks from now range from 70 to 80 days. If the behavior of the US epidemic is similar to the previous Chinese development, the number of reported cases could reach a maximum around April 10 to 14.


title: Global genetic diversity patterns and transmissions of SARS-CoV-2

text: Background: Since it was firstly discovered in China, the SARS-CoV-2 epidemic has caused a substantial health emergency and economic stress in the world. However, the global genetic diversity and transmissions are still unclear. Methods: 3050 SARS-CoV-2 genome sequences were retrieved from GIASID database. After aligned by MAFFT, the mutation patterns were identified by phylogenetic tree analysis. Results: We detected 17 high frequency (>6%) mutations in the 3050 sequences. Based on these mutations, we classed the SARS-CoV-2 into four main groups and 10 subgroups. We found that group A was mainly presented in Asia, group B was primarily detected in North America, group C was prevailingly appeared in Asia and Oceania and group D was principally emerged in Europe and Africa. Additionally, the distribution of these groups was different in age, but was similar in gender. Group A, group B1 and group C2 were declined over time, inversely, group B2, group C3 and group D were rising. At last, we found two apparent expansion stages (late Jan-2020 and late Feb-2020 to early Mar-2020, respectively). Notably, most of groups are quickly expanding, especially group D. Conclusions: We classed the SARS-CoV-2 into four main groups and 10 subgroups based on different mutation patterns at first time. The distribution of the 10 subgroups was different in geography, time and age, but not in gender. Most of groups are rapidly expanding, especially group D. Therefore, we should attach importance to these genetic diversity patterns of SARS-CoV-2 and take more targeted measures to constrain its spread.


Early minimal lesions of COVID-19 pneumonia with interstitial lung abnormality: A case description


title: Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxychloroquine and azithromycin in Lebanon.

text: Background: We share our experience in COVID-19 pneumonia management at Saint George Hospital University Medical Center (SGHUMC) in Lebanon. In the absence of a standard of care, early diagnosis and opt-in therapy with Hydroxychloroquine and Azithromycin were offered. Methods: We reviewed records of COVID-19 pneumonia patients from March 16-April 26 2020. Based on NEWS score, we stratified patients as A: low B: medium, and C: high clinical severity and obtained pharmacotherapy data. Chest-CT-severity-score (CTSS) was used. We defined clinical cure as resolution of symptoms and biomarkers and virologic cure as a PCR above 35 cycles(Ct). Results: We recorded 21 COVID-19 pneumonia patients of whom 19 opted for treatment. Clinical symptoms and laboratory markers at presentation did not significantly correlate with severity. Lower initial viral load significantly correlated with lower levels of clinical and radiological severity (p=0.038). Virologic cure, Ct>35, by day 10, was only 33% in high severity significantly less than categories A and B. We observed 100% clinical cure at day 10 in Category-A, 67% in B, and 33% in C(p<0.05). Patients with the lowest severity had the fastest virologic cure in a mean of 5.8 days from diagnosis, shortest hospitalization and earlier radiological improvement(p<0.005). Ultimately, 18 patients were discharged home in good condition and one remains in the ICU. Conclusion: Viral dynamics matter in COVID-19 pneumonia. An early control of replication may be crucial in averting complications. Early administration of Hydroxychloroquine and Azithromycin potentially explains our 94.7% success rate in treating a fairly complex cohort of COVID-19 pneumonia.


title: Limited Role for Antibiotics in COVID-19: Scarce Evidence of Bacterial Coinfection

text: Background: There is currently a paucity of data describing bacterial coinfections, related antibiotic prescribing patterns, and the potential role of antimicrobial stewardship in the care of patients infected with SARS-CoV-2. Methods: This prospective, observational study was conducted from March 10, 2020 to April 21, 2020 in admitted patients with confirmed COVID-19. Patients were included if [≥] 18 years old and admitted to the hospital for further treatment. Data was collected via chart review from the enterprise electronic health record database. Data collected include factors driving antibiotic choice, indication, and duration of therapy as well as microbiological data. Findings: Antibiotics were initiated on admission in 87/147 (59%) patients. Of these, 85/87 (98%) prescriptions were empiric. The most common indication for empiric antibiotics was concern for community-acquired pneumonia (76/85, 89%) with the most prescribed antibiotics being ceftriaxone and azithromycin. The median duration of antibiotic therapy was two days (interquartile range 1-5). No patients had a community-acquired bacterial respiratory coinfection, but 10/147 (7%) of patients were found to have concurrent bacterial infections from a non-respiratory source, and one patient was diagnosed with active pulmonary tuberculosis at the time of admission for COVID-19. Interpretation: Bacterial coinfection in patients with COVID-19 was infrequent. Antibiotics are likely unnecessary in patients with mild symptoms. There is little role for broad-spectrum antibiotics to empirically treat multidrug resistant organisms in patients with COVID-19, regardless of disease severity. Antimicrobial stewardship remains important in patients infected with SARS-CoV-2.


‘What is anthropology good for?’ Anthropologists working in public health interstices


title: The COVID-19 Pandemic Predominantly Hits Poor Neighborhoods, or does it? Evidence from Germany

text: Background Reports from the UK and the USA suggest that COVID-19 predominantly affects poorer individuals and neighbourhoods. This article paints a more complex picture by distinguishing between a first and second phase of the pandemic. The initial spread of infections and its correlation with socio-economic factors largely depends on how the virus first entered a country. The second phase of the pandemic begins when individuals start taking precautionary measures and governments implement lockdowns. In this phase the further spread of the virus depends on the ability of individuals to socially distance themselves, which is to some extent socially stratified. Methods We analyze the geographical distribution of known cases per capita across 401 local districts in Germany, once for infections in the initial phase and for new infections during the second phase. Results In Germany, the virus first entered via individuals returning from skiing in the Alps and other international travel. In this first phase we find a positive association between the wealth of a district and infection rates and a negative association with indicators of social deprivation. During the second phase, richer districts and districts with a higher share of university-educated employees record fewer new infections, whilst the initial safety advantage of more socially deprived districts disappears. Conclusion The social stratification of Covid-19 changes substantively across the two phases of the pandemic in Germany. Only in the second phase does socio-economic advantage turn into a safety advantage. Thus, suggestions that the pandemic predominantly hits the poor needs to be qualified.


title: Why don't some coronavirus patients sense their alarmingly low oxygen levels?

text: Many doctors now recognize clotting as a major feature of severe COVID-19 On 20 April, she posted a preprint detailing her hospital’s experience with 27 COVID-19 patients Is home monitoring “going to prevent all bad outcomes in COVID?


How COVID-19 Disrupts—and Enhances—My Clinical Work


title: Renin-angiotensin-aldosterone system inhibitors and mortality in patients with hypertension hospitalized for COVID-19: a systematic review and meta-analysis

text: Objective: The association between renin-angiotensin-aldosterone (RAAS) inhibitors and Coronavirus diseases 2019 (COVID-19) mortality is unclear. We aimed to explore the association of RAAS inhibitors, including angiotensin-converting inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) with COVID-19 mortality in patients with hypertension. Methods: MEDLINE, SCOPUS, OVID, and Cochrane Library were searched for the period of January 1, 2020 to May 20, 2020. Studies reporting the association of RAAS inhibitors (ACEi and ARBs) and mortality in patients with hypertension, hospitalized for COVID-19 were extracted. Two reviewers independently extracted appropriate data of interest and assessed the risk of bias. All analyses were performed using random-effects models on log-transformed risk ratio estimates, and heterogeneity was quantified. Results: Data were collected on 2,065,805 individuals (mean age, 58.73 years; 53.4% male). Patients with hypertension taking RAAS inhibitors were 35% less likely to die from COVID-19 compared to patients with hypertension not taking RAAS inhibitors (pooled RR= 0.65, 95% Confidence Intervals (CI): 0.45-0.94). To explore the association of COVID-19 and specific classes of RAAS inhibitors, we conducted a subgroup analysis of ARBs and ACEi separately from studies that provided them. Pooled risk ratio estimates from ARBs and ACEi showed a lower but not significant risk of death from COVID-19 (RR=0.93, 95% CI: 0.70-1.22) and ACEi (RR=0.65, 95% CI: 0.32-1.30). Conclusions: In this meta-analysis, it was discovered that taking RAAS inhibitors, significantly decreased the risk of COVID-19 mortality in patients with hypertension. This indicates a potential protective role that RAAS-inhibitors may have in COVID-19 patients with hypertension.


A primary care approach to the COVID-19 pandemic: clinical features and natural history of 2,073 suspected cases in the Corona Sao Caetano programme, Sao Paulo, Brazil


title: Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key determinants

text: Background Long-term shedding of viral RNA in COVID-19 prevents timely discharge from the hospital or de-escalation of infection prevention and control practices. Key questions are the duration and determinants of infectious virus shedding. We assessed these questions using virus cultures of respiratory tract samples from hospitalized COVID-19 patients as a proxy for infectious virus shedding. Methods Clinical and virological data were obtained from 129 hospitalized COVID-19 patients (89 intensive care, 40 medium care). Generalized estimating equations were used to identify if viral RNA load, detection of viral subgenomic RNA, serum neutralizing antibody response, duration of symptoms, or immunocompromised status were predictive for a positive virus culture. Findings Infectious virus shedding was detected in 23 of the 129 patients (17,8%). The median duration of shedding was 8 days post onset of symptoms (IQR 5-11) and the probability of detecting infectious virus dropped below 5% after 15,2 days post onset of symptoms (95% confidence interval (CI) 13,4-17,2). Multivariate analyses identified viral loads above 7 log10 RNA copies/mL (odds ratio [OR]; CI 14,7 (3,57-58,1; p<0,001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0,01 (CI 0,003-0,08; p<0,001) was independently associated with non-infectious SARS-CoV-2. Interpretation Infection prevention and control guidelines should take into account that patients with severe or critical COVID-19 may shed infectious virus for longer periods of time compared to what has been reported for in patients with mild COVID-19. Infectious virus shedding drops to undetectable levels below a viral RNA load threshold and once serum neutralizing antibodies are present, which warrants the use of quantitative viral RNA load assays and serological assays in test-based strategies to discontinue or de-escalate infection prevention and control precautions.


title: ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity

text: The susceptibility of different populations to the SARS-CoV-2 infection is not yet understood. A deeper analysis of the genomes of individuals from different populations might explain their risk for infection. In this study, a combined analysis of ACE2 coding variants in different populations and computational chemistry calculations are conducted in order to probe the potential effects of ACE2 coding variants on SARS-CoV-2/ACE2 binding affinity. Our study reveals novel interaction data on the variants and SARS-CoV-2. We could show that ACE2-K26R; which is more frequent in the Ashkenazi Jewish population decrease the electrostatic attraction between SARS-CoV-2 and ACE2. On the contrary, ACE2-I468V, R219C, K341R, D206G, G211R were found to increase the electrostatic attraction and increase the binding to SARS-CoV-2; ordered by the strength of binding from weakest to strongest. I468V, R219C, K341R, D206G and G211R were more frequent in East Asian, South Asian, African and African American, European and European and South Asian populations, respectively. SARS-CoV-2/ACE2 interface in the WT protein and corresponding variants is showed to be a dominated by van der Waals (vdW) interactions. All the mutations except K341R induce an increase in the vdW attractions between the ACE2 and the SARS-CoV-2. The largest increase of is observed for the R219C mutant.


title: Towards the Target: Tilorone, Quinacrine and Pyronaridine Bind to Ebola Virus Glycoprotein

text: Pyronaridine, tilorone and quinacrine were recently identified by a machine learning model and demonstrated in vitro and in vivo activity against Ebola virus (EBOV) and represent viable candidates for drug repurposing. These drugs were docked into the crystal structure of the ebola glycoprotein and then experimentally validated in vitro to generate Kd values for tilorone (0.73 μM) pyronaridine (7.34 μM), and quinacrine (7.55 μM). These are more potent than the previously reported toremifene (16 μM).


title: Development of a Predictive Score for COVID-19 Diagnosis based on Demographics and Symptoms in Patients Attended at a Dedicated Screening Unit

text: Background: The diagnosis of COVID-19 based on clinical evaluation is difficult because symptoms often overlap with other respiratory diseases. A clinical score predictive of COVID-19 based on readily assessed variables may be useful in settings with restricted or no access to molecular diagnostic tests. Methods: A score based on demographics and symptoms was developed in a cross-sectional study including patients attended in a dedicated COVID-19 screening unit. A backward stepwise logistic regression model was constructed and values for each variable were assigned according to their {beta} coefficient values in the final model. Receiver operating characteristic (ROC) curve was constructed and its area under the curve (AUC) was calculated. Results: A total of 464 patients were included: 98 (21.1%) COVID-19 and 366 (78.9%) non-COVID-19 patients. The score included variables independently associated with COVID-19 in the final model: age equal or above 60 years (2 points), fever (2), dyspnea (1), fatigue (1 point) and coryza (-1). Score values were significantly higher in COVID-19 than non-COVID-19 patients: median (Interquartile Range), 3 (2-4), and 1 (0-2), respectively; P<0.001. The score had an AUC of 0.80 (95% Confidence Interval [CI], 0.76-0.86). The specificity of scores equal or greater than 4 and 5 points were 90.4 (95%CI, 87.0-93.3) and 96.2 (95%CI, 93.7-97.9), respectively. Conclusions: This preliminary score based on patients symptoms is a feasible tool that may be useful in setting with restricted or no access to molecular tests in a pandemic period, owing to the high specificity. Further studies are required to validate the score in other populations.


title: A Fundamental Inconsistency in the SIR Model Structure and Proposed Remedies

text: The susceptible-infectious-removed (SIR) compartmental model structure and its variants are a fundamental modeling tool in epidemiology. As typically used, however, this tool may introduce an inconsistency by assuming that the rate of depletion of a compartment is proportional to the content of that compartment. As mentioned in the seminal SIR work of Kermack and McKendrick, this is an assumption of mathematical convenience rather than realism. As such, it leads to underprediction of the infectious compartment peaks by a factor of about two, a problem of particular importance when dealing with availability of resources during an epidemic. To remedy this problem, we develop the dSIR model structure, comprising a single delay differential equation and associated delay algebraic equations. We show that SIR and dSIR fully agree in assessing stability and long-term values of a population through an epidemic, but differ considerably in the exponential rates of ascent and descent as well as peak values during the epidemic. The novel Pade-SIR structure is also introduced as a approximation of dSIR by ordinary differential equations. We rigorously analyze the properties of these models and present a number of illustrative simulations, particularly in view of the recent coronavirus epidemic. Suggestions for further study are made.


title: Assessing the plausibility of subcritical transmission of 2019-nCoV in the United States

text: Abstract: The 2019-nCoV outbreak has raised concern of global spread. While person-to-person transmission within the Wuhan district has led to a large outbreak, the transmission potential outside of the region remains unclear. Here we present a simple approach for determining whether the upper limit of the confidence interval for the reproduction number exceeds one for transmission in the United States, which would allow endemic transmission. As of February 7, 2020, the number of cases in the United states support subcritical transmission, rather than ongoing transmission. However, this conclusion can change if pre-symptomatic cases resulting from human-to-human transmission have not yet been identified.


title: Coronavirus Research Trends: A 50–Year Bibliometric Assessment

text: Coronaviruses (CoVs) are a large family of viruses and are endemic in humans and animals, causing respiratory and intestinal infections. Coronavirus has become a challenge in China region due to its recent outbreak at the start of the year 2020. The current outbreak of coronavirus disease (COVID) has resulted in many fatalities and has forced the people of Wuhan Province in China to remain confined in their homes. Two other two forms of CoV were epidemic in 2003 when Severe Acute Respiratory Syndrome (SARS-CoV) spread in Hong Kong and Middle East Respiratory Syndrome (MERS-CoV) spread in the Middle East region. This bibliometric study is an attempt to trace the trends of research associated with “Coronavirus” for a period of 50 years using the SCOPUS database. The study was carried out using the keyword Coronavirus and analyzed for annual growth, productive countries, institutes, authors, journals, highly cited papers, and research focus using keywords. There were two peaks when a large number of publications appeared. Most of the research publications were from the USA (31.67%), and the University of Hong Kong was the most productive institute. The Journal of Virology has published the most number of articles on CoV.


title: Mapping RNA dependent RNA polymerase activity and immune gene expression using PRO-seq

text: Positive strand, single strand RNA viruses ((+)ssRNA viruses) are viruses with an RNA genome that have broad impacts on a wide range of hosts, including SARS-CoV-2 human respiratory infections. Their replication and gene expression are driven by RNA dependent RNA polymerases (RdRp). Detecting active RNA synthesis by RdRp is critical for assessing the infectivity and pathogenicity of (+)ssRNA viruses. Current approaches rely on viral RNA detection, which cannot distinguish viral titer from RdRp activity. Precision Run-On sequencing (PRO-seq) is a nuclear run-on based nascent RNA sequencing method, widely used to map eukaryotic RNA polymerases by using labeled nucleotide analogues. Here we provide evidence that PRO-seq also detects RdRp activity and can serve as a highly sensitive RdRp mapping method. Coupled to PRO-seq in human blood samples, we propose to use PRO-seq as a single package method to detect (+)ssRNA virus RdRp activity and its interaction with host immune response through transcriptome-wide profiling of leukocyte gene expressions at once.


title: Tablet Based Limited Echocardiogram to Reduce Sonographer Scan and Decontamination Time During The COVID-19 Pandemic

text: Background Limited assessments with handheld ultrasound have found meaningful clinical use in the care of acutely ill patients. However, there are limited data on incorporating handheld based limited echocardiograms into the echocardiogram laboratory. The purpose of this study is to assess the efficacy of a limited handheld tablet echocardiogram as an alternate to traditional echocardiography during the COVID-19 pandemic as a means to limit exposure while providing essential clinical information. Methods Ninety consecutive inpatients with known or suspected COVID-19 infection were scanned according to laboratory COVID-19 guidelines using a limited 11-20 clip protocol on a tablet sonograph. The primary assessment was length of study time. Comparison data was drawn from comprehensive echocardiograms ordered on intensive care patients not under COVID-19 precautions. Results Over a 36 day time period there were a total of 91 requests deemed to be appropriate for echocardiography on COVID-19 positive or suspected patients (average age: 67, 64% male, body mass index 32kg/m2). Of these, ninety (99%) were performed on a handheld device and all were deemed diagnostic and provided sufficient information for the clinical care team. Sonographer scan time decreased from an average of 24±6.8min on a traditional platform to 5.4±1.9min on a tablet. Conclusions Limited handheld echocardiography can be successfully implemented in the echocardiography laboratory for screening of COVID related cardiac conditions. The protocol performed with handheld tablet ultrasound provides adequate diagnostic information of major cardiac complications of COVID-19 infection while decreasing sonographer contact and simplifying decontamination.


Objectives The prevalence of antibodies to SARS-CoV-2 among blood donors in China remains unknown. To reveal the missing information, we investigated the seroprevalence of SARS-CoV-2 antibodies among blood donors in the cities of Wuhan, Shenzhen, and Shijiazhuang of China. Design Cross-sectional study Setting Three blood centers, located in the central, south and north China, respectively, recruiting from January to April 2020. Participants 38,144 healthy blood donors donated in Wuhan, Shenzhen and Shijiazhuang were enrolled, who were all met the criteria for blood donation during the COVID-19 pandemic in China. Main outcome measures Specific antibodies against SARS-CoV-2 including total antibody (TAb), IgG antibody against receptor-binding domain of spike protein (IgG-RBD) and nucleoprotein (IgG-N), and IgM. Pseudotype lentivirus-based neutralization test was performed on all TAb-positive samples. In addition, anonymous personal demographic information, including gender, age, ethnicity, occupation and educational level, and blood type were collected. Results A total of 519 samples from 410 donors were confirmed by neutralization tests. The SARS-CoV-2 seroprevalence among blood donors was 2.29% (407/17,794, 95%CI: 2.08% to 2.52%) in Wuhan, 0.029% (2/6,810, 95%CI: 0.0081% to 0.11%) in Shenzhen, and 0.0074% (1/13,540, 95%CI: 0.0013% to 0.042%) in Shijiazhuang, respectively. The earliest emergence of SARS-CoV-2 seropositivity in blood donors was identified on January 20, 2020 in Wuhan. The weekly prevalence of SARS-CoV-2 antibodies in Wuhan's blood donors changed dynamically and were 0.08% (95%CI: 0.02% to 0.28%) during January 15 to 22 (before city lockdown), 3.08% (95%CI: 2.67% to 3.55%) during January 23 to April 7 (city quarantine period) and 2.33% (95%CI: 2.06% to 2.63%) during April 8 to 30 (after lockdown easing). Female and older-age were identified to be independent risk factors for SARS-CoV-2 seropositivity among donors in Wuhan. Conclusions The prevalence of antibodies to SARS-CoV-2 among blood donors in China was low, even in Wuhan city. According to our data, the earliest emergence of SARS-CoV-2 in Wuhan's donors should not earlier than January, 2020. As most of the population of China remained uninfected during the early wave of COVID-19 pandemic, effective public health measures are still certainly required to block viral spread before a vaccine is widely available.


docid: mhawyect

title: SilentMutations (SIM): a tool for analyzing long-range RNA-RNA interactions in viral genomes and structural RNAs

text: Background A single nucleotide change or mutation in the coding region can alter the amino acid sequence of a protein. In consequence, natural or artificial sequence changes in viral RNAs may have various effects not only on protein stability, function and structure but also on viral replication. In the last decade, several tools have been developed to predict the effect of mutations in structural RNA genomes. Some tools employ multiple point mutations and are also taking coding regions into account. However, none of these tools was designed to specifically simulate the effect of mutations on viral long-range interactions. Results Here, we developed SilentMutations (SIM), an easy-to-use tool to analyze the effect of multiple point mutations on the secondary structures of two interacting viral RNAs. The tool can simulate destructive and compensatory mutants of two interacting single-stranded RNAs. This will facilitate a fast and accurate assessment of key regions, possibly involved in functional long-range RNA-RNA interactions and finally help virologists to design appropriate experiments. SIM only needs two interacting single-stranded RNA regions as input. The output is a plain text file containing the most promising mutants and a graphical representation of all interactions. Conclusion We applied our tool on two experimentally validated influenza A virus and hepatitis C virus interactions and we were able to predict potential double mutants for in vitro validation experiments. Availability The source code and documentation of SIM are freely available at github.com/desiro/SilentMutations


title: Street-level bureaucrats under COVID-19: Police officers’ responses in constrained settings

text: The COVID-19 poses unprecedented challenges for Street Level Bureaucrats (SLB). Whereas there are discussions about the pandemic impacts on health care workers, less is known about how it affects police officer’s responses. Drawing upon an inductive qualitative research that follows the ethnographic sensibility inspired approach on a major Brazilian police force, we argue that conflicts concerning political, occupational culture, and material dimensions can negatively affect police officers’ responses in financially and institutionally constrained settings. By unveiling how the identified conflicts can jeopardize the efforts to prevent the spread of COVID-19 and suggesting that the usual discretion of street-level bureaucrats can be both a blessing and a curse, our work informs existing SLB literature and sheds light on practical issues that police officers in constrained settings face when dealing with the pandemic.


docid: nkwnexqp

title: Answers to Study Questions

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title: Associations between immune-suppressive and stimulating drugs and novel COVID-19—a systematic review of current evidence

text: BACKGROUND: Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19. METHODS: Using Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factorα (TNFα) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig. RESULTS: 89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNFα blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19. CONCLUSION: The COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNFα agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications.


title: An exact method for quantifying the reliability of end-of-epidemic declarations in real time

text: We derive and validate a novel and analytic method for estimating the probability that an epidemic has been eliminated (i.e. that no future local cases will emerge) in real time. When this probability crosses 0.95 an outbreak can be declared over with 95% confidence. Our method is easy to compute, only requires knowledge of the incidence curve and the serial interval distribution, and evaluates the statistical lifetime of the outbreak of interest. Using this approach, we rigorously show how the time-varying under-reporting of infected cases will artificially inflate the inferred probability of elimination and hence lead to early (false- positive) end-of-epidemic declarations. Contrastingly, we prove that incorrectly identifying imported cases as local will deceptively decrease this probability, resulting in late (false-negative) declarations. Failing to sustain intensive surveillance during the later phases of an epidemic can therefore substantially mislead policymakers on when it is safe to remove travel bans or relax quarantine and social distancing advisories. World Health Organisation guidelines recommend fixed (though disease-specific) waiting times for end-of-epidemic declarations that cannot accommodate these variations. Consequently, there is an unequivocal need for more active and specialised metrics for reliably identifying the conclusion of an epidemic.