COVID-profiler: a webserver for the analysis of SARS-CoV-2 sequencing data.

BACKGROUND: SARS-CoV-2 virus sequencing has been applied to track the COVID-19 pandemic spread and assist the development of PCR-based diagnostics, serological assays, and vaccines. With sequencing becoming routine globally, bioinformatic tools are needed to assist in the robust processing of resulting genomic data. RESULTS: We developed a web-based bioinformatic pipeline ("COVID-Profiler") that inputs raw or assembled sequencing data, displays raw alignments for quality control, annotates mutations found and performs phylogenetic analysis. The pipeline software can be applied to other (re-) emerging pathogens. CONCLUSIONS: The webserver is available at http://genomics.lshtm.ac.uk/ . The source code is available at https://github.com/jodyphelan/covid-profiler .

The effect of immunosuppressants on the prognosis of SARS-CoV-2 infection.

BACKGROUND: Immunosuppression may worsen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a nationwide cohort study of the effect of exposure to immunosuppressants on the prognosis of SARS-CoV-2 infection in Denmark. METHODS: We identified all SARS-CoV-2 test-positive patients from February 2020 to October 2020 and linked healthcare data from nationwide registers, including prescriptions for the exposure (immunosuppressant drugs). We estimated relative risks of hospital admission, intensive care unit (ICU) admission and death (each studied independently up to 30 days from testing) with a log-linear binomial regression adjusted for confounders using a propensity score-based matching weights model. RESULTS: A composite immunosuppressant exposure was associated with a significantly increased risk of death (adjusted relative risk 1.56 (95% CI 1.10-2.22)). The increased risk of death was mainly driven by exposure to systemic glucocorticoids (adjusted relative risk 2.38 (95% CI 1.72-3.30)), which were also associated with an increased risk of hospital admission (adjusted relative risk 1.34 (95% CI 1.10-1.62)), but not of ICU admission (adjusted relative risk 1.76 (95% CI 0.93-3.35)); these risks were greater for high cumulative doses of glucocorticoids than for moderate doses. Exposure to selective immunosuppressants, tumour necrosis factor inhibitors or interleukin inhibitors was not associated with an increased risk of hospitalisation, ICU admission or death, nor was exposure to calcineurin inhibitors, other immunosuppressants, hydroxychloroquine or chloroquine. CONCLUSIONS: Exposure to glucocorticoids was associated with increased risks of hospital admission and death. Further investigation is needed to determine the optimal management of coronavirus disease 2019 (COVID-19) in patients with pre-morbid glucocorticoid usage, specifically whether these patients require altered doses of glucocorticoids.

An integrated in silico immuno-genetic analytical platform provides insights into COVID-19 serological and vaccine targets.

During COVID-19, diagnostic serological tools and vaccines have been developed. To inform control activities in a post-vaccine surveillance setting, we have developed an online "immuno-analytics" resource that combines epitope, sequence, protein and SARS-CoV-2 mutation analysis. SARS-CoV-2 spike and nucleocapsid proteins are both vaccine and serological diagnostic targets. Using the tool, the nucleocapsid protein appears to be a sub-optimal target for use in serological platforms. Spike D614G (and nsp12 L314P) mutations were most frequent (> 86%), whilst spike A222V/L18F have recently increased. Also, Orf3a proteins may be a suitable target for serology. The tool can accessed from: http://genomics.lshtm.ac.uk/immuno (online); https://github.com/dan-ward-bio/COVID-immunoanalytics (source code).