Binding kinetics study of SARS-CoV-2 main protease and potential inhibitors via molecular dynamics simulations.

The pandemic COVID-19 was induced by the novel coronavirus SARS-CoV-2. The virus main protease (Mpro) cleaves the coronavirus polyprotein translated from the viral RNA in the host cells. Because of its crucial role in virus replication, Mpro is a potential drug target for COVID-19 treatment. Herein, we study the interactions between Mpro and three HIV-1 protease (HIV-1 PR) inhibitors, Lopinavir (LPV), Saquinavir (SQV), Ritonavir (RIT), and an inhibitor PF-07321332, by conventional and replica exchange molecular dynamics (MD) simulations. The association/dissociation rates and the affinities of the inhibitors were estimated. The three HIV-1 PR inhibitors exhibit low affinities, while PF-07321332 has the highest affinity among these four simulated inhibitors. Based on cluster analysis, the HIV-1 PR inhibitors bind to Mpro at multiple sites, while PF-07321332 specifically binds to the catalytically activated site of Mpro. The stable and specific binding is because PF-07321332 forms multiple H-bonds to His163 and Glu166 simultaneously. The simulations suggested PF-07321332 could serve as an effective inhibitor with high affinity and shed light on the strategy of drug design and drug repositioning.

Airborne antibiotic resistome and human health risk in railway stations during COVID-19 pandemic.

Antimicrobial resistance is recognized as one of the greatest public health concerns. It is becoming an increasingly threat during the COVID-19 pandemic due to increasing usage of antimicrobials, such as antibiotics and disinfectants, in healthcare facilities or public spaces. To explore the characteristics of airborne antibiotic resistome in public transport systems, we assessed distribution and health risks of airborne antibiotic resistome and microbiome in railway stations before and after the pandemic outbreak by culture-independent and culture-dependent metagenomic analysis. Results showed that the diversity of airborne antibiotic resistance genes (ARGs) decreased following the pandemic, while the relative abundance of core ARGs increased. A total of 159 horizontally acquired ARGs, predominantly confering resistance to macrolides and aminoglycosides, were identified in the airborne bacteria and dust samples. Meanwhile, the abundance of horizontally acquired ARGs hosted by pathogens increased during the pandemic. A bloom of clinically important antibiotic (tigecycline and meropenem) resistant bacteria was found following the pandemic outbreak. 251 high-quality metagenome-assembled genomes (MAGs) were recovered from 27 metagenomes, and 86 genera and 125 species were classified. Relative abundance of ARG-carrying MAGs, taxonomically assigned to genus of Bacillus, Pseudomonas, Acinetobacter, and Staphylococcus, was found increased during the pandemic. Bayesian source tracking estimated that human skin and anthropogenic activities were presumptive resistome sources for the public transit air. Moreover, risk assessment based on resistome and microbiome data revealed elevated airborne health risks during the pandemic.

Wastewater monitoring of COVID-19: a perspective from Scotland.

Scotland introduced wastewater monitoring for COVID-19 early in the pandemic. From May 2020, samples have been taken and analysed using quantitative polymerase chain reaction (qPCR). The programme was expanded to over 100 sites accounting for around 80% of the population. Data are presented publicly via a dashboard and regular reports are produced for both the public and health professionals. Wastewater-based epidemiology (WBE) offers opportunities and challenges. It offers an objective means of measuring COVID-19 prevalence and can be more practical or timely than other methods of mass testing. However, it also has substantial variability impacted by multiple environmental factors. Methods for data collection and analysis have developed significantly through the pandemic, reflecting the evolving situation and policy direction. We discuss the Scottish experience of wastewater monitoring for COVID-19, with a focus on the analysis of data. This includes our approach to flow normalisation, our experience of variability in measurements and anomalous values, and the visualisation and presentation of data to stakeholders. Summarising the Scottish methodology as of March 2022, we also discuss how wastewater data were used for informing policy and public health actions. We draw lessons from our experience and consider future directions for WBE in Scotland.

T cell repertoire profiling in allografts and native tissues in recipients with COVID-19 after solid organ transplantation: Insight into T cell-mediated allograft protection from viral infection.

Introduction: The effects of the SARS-CoV-2 virus on the body, and why the effects are more severe in certain patients, remain incompletely understood. One population of special interest is transplant recipients because of their immunosuppressed state. Understanding the pathophysiology of graft dysfunction in transplant patients with the COVID-19 viral syndrome is important for prognosticating the risk to the graft as well as understanding how best to prevent and, if necessary, treat graft injury in these patients. Methods: We analyzed multiple types of solid organ transplant recipients (liver, kidney, heart or lung) at our institution who died from SARS-CoV-2 and underwent autopsy (n = 6) or whose grafts were biopsied during active SARS-CoV-2 infection (n = 8). Their serum inflammatory markers were examined together with the histological appearance, viral load, and TCR repertoire of their graft tissue and, for autopsy patients, several native tissues. Results: Histology and clinical lab results revealed a systemic inflammatory pattern that included elevated inflammatory markers and diffuse tissue damage regardless of graft rejection. Virus was detected throughout all tissues, although most abundant in lungs. The TCR repertoire was broadly similar throughout the tissues of each individual, with greater sharing of dominant clones associated with more rapid disease course. There was no difference in viral load or clonal distribution of overall, COVID-associated, or putative SARS-CoV-2-specific TCRs between allograft and native tissue. We further demonstrated that SARSCoV-2-specific TCR sequences in transplant patients lack a donor HLArestricted pattern, regardless of distribution in allograft or native tissues,suggesting that recognition of viral antigens on infiltrating recipient cells can effectively trigger host T cell anti-viral responses in both the host and graft. Discussion: Our findings suggest a systemic immune response to the SARS-CoV-2 virus in solid organ transplant patients that is not associated with rejection and consistent with a largely destructive effect of recipient HLA-restricted T cell clones that affects donor and native organs similarly.

SARS-CoV-2 RNA levels in Scotland's wastewater.

Nationwide, wastewater-based monitoring was newly established in Scotland to track the levels of SARS-CoV-2 viral RNA shed into the sewage network, during the COVID-19 pandemic. We present a curated, reference dataset produced by this national programme, from May 2020 to February 2022. Viral levels were analysed by RT-qPCR assays of the N1 gene, on RNA extracted from wastewater sampled at 162 locations. Locations were sampled up to four times per week, typically once or twice per week, and in response to local needs. We report sampling site locations with geographical coordinates, the total population in the catchment for each site, and the information necessary for data normalisation, such as the incoming wastewater flow values and ammonia concentration, when these were available. The methodology for viral quantification and data analysis is briefly described, with links to detailed protocols online. These wastewater data are contributing to estimates of disease prevalence and the viral reproduction number (R) in Scotland and in the UK.

Sustainable Development of Corporate Governance in the Hospitality and Tourism Industry: The Evolution and the Future

This study provides a systematic review of the content of the hospitality and tourism literature on corporate governance. The purpose of this study is to identify gaps in the existing research and practice context and to provide guidance for future research. Based on 174 peer-reviewed articles published since 2000, this paper employs a content analysis approach to identify eight major themes explored by scholars. The study found that most previous research on corporate governance mechanisms in tourism was conducted in developed regions and mostly used quantitative research methods. Shareholder governance, board governance, executive compensation incentives, social responsibility governance, reputation themes and corporate governance provisions received more academic attention than the themes of organizational structure governance and information disclosure. The systematic review in this paper helps to consolidate the existing literature and make recommendations to promote the field of corporate governance research in the hospitality and tourism industry and to provide a reference for the industry.

Analysis of the Mental Health Status of University students after the COVID-19 Epidemic (preprint)

Objective The aim of this study was to investigate the mental health status and sleep quality of university students after local outbreak of COVID-19, and to help them understand the psychological stress reaction and provide base for their mental health education. Methods A cross-sectional survey was conducted on the mental health status of university students in a Wuhan-based university. Results A total of 897 university students were enrolled in the study. Compared with the epidemic period, university students' mental health status and sleep quality has a great deal of difference in the aspects of gender, grade, discipline and specialty, physical exercise, as well as with their family relationships and so on. 64.26% students would like to talk to their peers or close friends, while only 2.71% would like to call a caring hotline or seek help from a psychologist. Conclusion After the local outbreak of COVID-19 in Wuhan was contained, the mental health status and sleep quality of more than half of the students improved. However, priority attention and care should be given to female students, senior students, those undertaking literature and history majors and those dissatisfied with family relationships.

Administration of Parenteral Vitamin C in Patients With Severe Infection: Protocol for a Systematic Review and Meta-analysis.

BACKGROUND: Severe infections are characterized by inflammation and oxidative damage. Ascorbic acid (vitamin C) administration may attenuate oxidative damage and, in turn, reduce vascular endothelial injury in pulmonary and systemic vasculature. OBJECTIVE: We aim to describe a protocol for a living systematic review that will evaluate the effectiveness and safety of parenteral vitamin C administration in adults with severe infections, including those with COVID-19. METHODS: We searched Ovid MEDLINE, Embase, CINAHL, the Centers for Disease Control and Prevention COVID-19 database, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to March 30, 2021, for randomized controlled trials evaluating parenteral vitamin C versus no parenteral vitamin C in hospitalized adults with severe infection. Eligible studies will include at least 1 arm involving any dose of parenteral vitamin C alone or in combination with other cointerventions and at least 1 arm not involving parenteral vitamin C. The primary outcomes of interest will include in-hospital, 30-day, and 90-day mortality. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation via a modified Risk of Bias 2.0 tool will be conducted independently and in pairs. We will perform random effects modeling for meta-analyses, in which study weights will be generated by using the inverse variance method. We will assess certainty in effect estimates by using the Grading of Recommendations Assessment, Development and Evaluation methodology. Meta-analyses will be updated iteratively as new trial evidence becomes available. RESULTS: Among the 1386 citations identified as of March 30, 2021, a total of 17 eligible randomized controlled trials have been identified as of September 2021. We are in the process of updating the search strategy and associated data analyses. CONCLUSIONS: The results will be of importance to critical care physicians and hospitalists who manage severe infection and COVID-19 in daily practice, and they may directly inform international clinical guidance. Although our systematic review will incorporate the most recent trial evidence, ongoing trials may change our confidence in the estimates of effects, thereby necessitating iterative updates in the form of a living review. TRIAL REGISTRATION: PROSPERO CRD42020209187; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=209187. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/33989.

Understanding and managing uncertainty and variability for wastewater monitoring beyond the pandemic: Lessons learned from the United Kingdom national COVID-19 surveillance programmes.

The COVID-19 pandemic has put unprecedented pressure on public health resources around the world. From adversity, opportunities have arisen to measure the state and dynamics of human disease at a scale not seen before. In the United Kingdom, the evidence that wastewater could be used to monitor the SARS-CoV-2 virus prompted the development of National wastewater surveillance programmes. The scale and pace of this work has proven to be unique in monitoring of virus dynamics at a national level, demonstrating the importance of wastewater-based epidemiology (WBE) for public health protection. Beyond COVID-19, it can provide additional value for monitoring and informing on a range of biological and chemical markers of human health. A discussion of measurement uncertainty associated with surveillance of wastewater, focusing on lessons-learned from the UK programmes monitoring COVID-19 is presented, showing that sources of uncertainty impacting measurement quality and interpretation of data for public health decision-making, are varied and complex. While some factors remain poorly understood, we present approaches taken by the UK programmes to manage and mitigate the more tractable sources of uncertainty. This work provides a platform to integrate uncertainty management into WBE activities as part of global One Health initiatives beyond the pandemic.

Clinical features, treatments and outcomes of severe and critical severe patients infected with COVID-19: A system review and meta-analysis (preprint)

Backgrounds: The outbreak of COVID-19 caused by a novel coronavirus, SARS-CoV-2, has been listed as a public health emergency of international concern by WHO. Most COVID-19 patients presented with a mild infection, but many challenges exist in therapy of severe and critical severe patients. This paper systematically reviewed clinical features, treatments and outcomes of severe and critical severe patients infected COVID-19. Methods: The clinical, laboratory, imaging features, treatment and outcomes of COVID-19 were collected. The data were analyzed by using STATA 15 statistical software to estimate the prevalence and 95% CI in severe and critical severe patients with COVID-19. A random or fixed effect model was used to estimate the prevalence and 95% CI. Results: After screening, 8 studies including a total of 275 patients were included in this meta-analysis. The percentage of severe and critical severe patients in confirmed COVID-19 cases was 25% (95% CI 16-36%). Fever, cough, dyspnea, lymphopenia and bilateral distribution of patchy shadows were the most prevalent findings in these patients. Utilization rate of antiviral drugs, corticosteroid, non-invasive ventilation, invasive mechanical ventilation was high in therapy strategies. The most prevalent complications were ARDS, shock, and acute cardiac injury. Discussion: Severe and critical severe COVID-19 patients usually had complications even a fatal outcome. As vaccines and anti-coronaviral drugs are under development, the principles of treatment for these patients should be focused on improving oxygenation, lung protective and function support of multiple organs.

Expert consensus on emergency surgery management for traumatic orthopedics under prevention and control of novel coronavirus pneumonia / 中华创伤杂志

Since December 2019, novel coronavirus pneumonia (NCP) has been reported in Wuhan, Hubei Province, and spreads rapidly to all through Hubei Province and even to the whole country. The virus is 2019 novel coronavirus (2019-nCoV), never been seen previously in human, but all the population is generally susceptible. The virus spreads through many ways and is highly infectious, which brings great difficulties to the prevention and control of NCP. Based on the needs of orthopedic trauma patients for emergency surgery and review of the latest NCP diagnosis and treatment strategy and the latest principles and principles of evidence-based medicine in traumatic orthopedics, the authors put forward this expert consensus to systematically standardize the clinical pathway and protective measures of emergency surgery for orthopedic trauma patients during prevention and control of NCP and provide reference for the emergency surgical treatment of orthopedic trauma patients in hospitals at all levels.

Study on SARS-COV-2 transmission and the effects of control measures in China (preprint)

Objective To reconstruct the transmission trajectory of SARS-COV-2 and analyze the effects of control measures in China. Methods Python 3.7.1 was used to write a SEIR class to model the epidemic procedure and a back propagation class to estimate the initial true infected number. The epidemic area in China was divided into three parts, Wuhan city, Hubei province (except Wuhan) and China (except Hubei) based on the different transmission pattern. A limitation factor for the medical resource was imposed to model the infected but not quarantined. Credible data source from Baidu Qianxi were used to assess the number of infected cases migrated from Wuhan to other areas. Results Basic reproduction number, R0, was 3.6 in the very early stage. The true infected number was 4508 in our model in Wuhan before January 22, 2020. By January 22 2020, it was estimated that 1764 infected cases migrated from Wuhan to other cities in Hubei province. Effective reproductive number, R, gradually decreased from 3.6 (Wuhan, stage 1), 3.4 (Hubei except Wuhan, stage 1) and 3.3 (China except Hubei, stage 1) to 0.67 (Wuhan, stage 4), 0.83 (Hubei except Wuhan, stage 2) and 0.63 (China except Hubei, stage 2), respectively. Especially after January 23, 2020 when Wuhan City was closed, the infected number showed a turning point in Wuhan. By early April, there would be 42073, 21342 and 13384 infected cases in Wuhan, Hubei (except Wuhan) and China (except Hubei) respectively, and there would be 2179, 633 and 107 death in Wuhan, Hubei (except Wuhan) and China (except Hubei) respectively. Conclusion A series of control measures in China have effectively prevented the spread of COVID-19, and the epidemic will end in early April.