Project description:The European project ORCHESTRA intends to create a new pan-European cohort to rapidly advance the knowledge of the effects and treatment of COVID-19. Establishing processes that facilitate the merging of heterogeneous clusters of retrospective data was an essential challenge. In addition, data from new ORCHESTRA prospective studies have to be compatible with earlier collected information to be efficiently combined. In this article, we describe how we utilized and contributed to existing standard terminologies to create consistent semantic representation of over 2500 COVID-19-related variables taken from three ORCHESTRA studies. The goal is to enable the semantic interoperability of data within the existing project studies and to create a common basis of standardized elements available for the design of new COVID-19 studies. We also identified 743 variables that were commonly used in two of the three prospective ORCHESTRA studies and can therefore be directly combined for analysis purposes. Additionally, we actively contributed to global interoperability by submitting new concept requests to the terminology Standards Development Organizations.
Project description:Rapid identification and investigation of healthcare-associated infections (HCAIs) is important for suppression of SARS-CoV-2, but the infection source for hospital onset COVID-19 infections (HOCIs) cannot always be readily identified based only on epidemiological data. Viral sequencing data provides additional information regarding potential transmission clusters, but the low mutation rate of SARS-CoV-2 can make interpretation using standard phylogenetic methods difficult. We developed a novel statistical method and sequence reporting tool (SRT) that combines epidemiological and sequence data in order to provide a rapid assessment of the probability of HCAI among HOCI cases (defined as first positive test >48 hr following admission) and to identify infections that could plausibly constitute outbreak events. The method is designed for prospective use, but was validated using retrospective datasets from hospitals in Glasgow and Sheffield collected February-May 2020. We analysed data from 326 HOCIs. Among HOCIs with time from admission ≥8 days, the SRT algorithm identified close sequence matches from the same ward for 160/244 (65.6%) and in the remainder 68/84 (81.0%) had at least one similar sequence elsewhere in the hospital, resulting in high estimated probabilities of within-ward and within-hospital transmission. For HOCIs with time from admission 3-7 days, the SRT probability of healthcare acquisition was >0.5 in 33/82 (40.2%). The methodology developed can provide rapid feedback on HOCIs that could be useful for infection prevention and control teams, and warrants further prospective evaluation. The integration of epidemiological and sequence data is important given the low mutation rate of SARS-CoV-2 and its variable incubation period. COG-UK HOCI funded by COG-UK consortium, supported by funding from UK Research and Innovation, National Institute of Health Research and Wellcome Sanger Institute.
Project description:The purpose of this experiment was to investigate the transcriptional differences between mice infected with icSARS CoV, SARS MA15 wild type or SARS BatSRBD viruses. Overview of Experiment: Groups of 20 week old C57BL6 mice were infected with icSARS CoV, Wild Type SARS MA15 or SARS BatSRBD mutant viruses. Infections were done at 10^4 PFU or 10^5 PFU or time-matched mock infected. Time points were 1, 2, 4 and 7 d.p.i. There were 3-5 animals/dose/time point. Lung samples were collected for virus load, transcriptional and proteomics analysis. Weight loss and animal survival were also monitored.
Project description:BackgroundThe emergence of novel variants of concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demands fast and reliable detection of such variants in local populations.MethodsHere we present a cost-efficient and fast workflow combining a prescreening of SARS-CoV-2-positive samples using reverse transcription polymerase chain reaction melting curve analysis with multiplexed IP-RP-HPLC-based single nucleotide primer extensions.ResultsThe entire workflow from positive SARS-CoV-2 testing to base-specific identification of variants requires about 24 hours.ConclusionsWe applied the sensitive method to monitor local variant of concern outbreaks in SARS-CoV-2-positive samples collected in a confined region of Germany.
Project description:The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on long term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We here have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma and Epsilon, at picomolar ranges of IC50 in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by co-treatment in K18-hACE2-transgenic mice, accompanying with a significant prevention of virus-associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggests that C6G25S provides an alternative and effective approach to combating the COVID-19 pandemic.
Project description:Recently, in China, in 2019, a new type of disease has arisen caused by a new strain of coronavirus, the SARS-CoV-2 virus, considered extremely worrying due to its high infectivity power and the easy ability to spread geographically. For patients in general, the clinical features resulting from respiratory syndromes can trigger an asymptomatic condition. However, 25 % of patients infected by SARS-CoV-2 can progress to severity. Pregnant women are an unknown field in this complex process, and although they have symptoms similar to non-pregnant women, some points should be considered, such as complications during pregnancy and postpartum. Thus, the aim of this study was to understand the consequences of pregnancy and fetal development, caused by infections by the SARS-CoV, MERS-CoV and SARS-CoV-2 viruses. Among the aforementioned infections, MERS-CoV seems to be the most dangerous for newborns, inducing high blood pressure, pre-eclampsia, pneumonia, acute renal failure, and multiple organ failure in mother. This also causes a higher occurrence of emergency cesarean deliveries and premature births, in addition, some deaths of mothers and fetuses were recorded. Meanwhile, SARS-CoV and SARS-CoV-2 appear to have less severe symptoms. Furthermore, although a study found the ACE2 receptor, used by SARS-CoV-2, widely distributed in specific cell types of the maternal-fetal interface, there is no evidence of vertical transmission for any of the coronaviruses. Thus, the limited reported obstetric cases alert to the need for advanced life support for pregnant women infected with coronaviruses and to the need for further investigation for application in clinical practice.
Project description:The COVID-19 pandemic has affected more than 38 million people world-wide by person to person transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therapeutic and preventative strategies for SARS-CoV-2 remains a significant challenge. Within the past several months, effective treatment options have emerged and now include repurposed antivirals, corticosteroids and virus-specific antibodies. The latter has included convalescence plasma and monoclonal antibodies. Complete viral eradication will be achieved through an effective, safe and preventative vaccine. To now provide a comprehensive summary for each of the pharmacotherapeutics and preventative strategies being offered or soon to be developed for SARS-CoV-2.