Project description:SARS-CoV-2 consensus sequences from the national surveillance in Denmark - Samples sequenced in 2024 and onwards and older sequences submitted in 2024
Project description:Rapid dissemination of SARS-CoV-2 sequencing data to public repositories has enabled widespread study of viral genomes, but studies of longitudinal specimens from infected persons are relatively limited. Analysis of longitudinal specimens enables understanding of how host immune pressures drive viral evolution in vivo. Here we performed sequencing of 49 longitudinal SARS-CoV-2-positive samples from 20 patients in Washington State collected between March and September of 2020. Viral loads declined over time with an average increase in RT-PCR cycle threshold (Ct) of 0.87 per day. We found that there was negligible change in SARS-CoV-2 consensus sequences over time, but identified a number of nonsynonymous variants at low frequencies across the genome. We observed enrichment for a relatively small number of these variants, all of which are now seen in consensus genomes across the globe at low prevalence. In one patient, we saw rapid emergence of various low-level deletion variants at the N-terminal domain of the spike glycoprotein, some of which have previously been shown to be associated with reduced neutralization potency from sera. In a subset of samples that were sequenced using metagenomic methods, differential gene expression analysis showed a downregulation of cytoskeletal genes that was consistent with a loss of ciliated epithelium during infection and recovery. We also identified co-occurrence of bacterial species in samples from multiple hospitalized individuals. These results demonstrate that the intrahost genetic composition of SARS-CoV-2 is dynamic during the course of COVID-19, and highlight the need for continued surveillance and deep sequencing of minor variants.
Project description:Healthcare workers were recruited at St Bartholomew’s Hospital, London, UK in the week of lockdown in the United Kingdom (between 23rd and 31st March 2020). Participants underwent weekly evaluation using a questionnaire and biological sample collection (including serological assays) for up to 16 weeks when attending for work and self-declared as fit to attend work at each visit, with further follow up samples collected at 24 weeks. Blood RNA sequencing data was to be used to identify host-response biomarkers of early SARS-CoV-2 infection, to evaluate existing blood transcriptomic signatures of viral infection, and to describe the underlying biology during SARS-CoV-2 infection. This submission includes a total of 172 blood RNA samples from 99 participants. Of these, 114 samples (including 16 convalescent samples collected 6 months after infection) were obtained from 41 SARS-CoV-2 cases, with the remaining 58 from uninfected controls. Participants with available blood RNA samples who had PCR-confirmed SARS-CoV-2 infection during follow-up were included as ‘cases’. Those without evidence of SARS-CoV-2 infection on nasopharyngeal swabs and who remained seronegative by both Euroimmun anti S1 spike protein and Roche anti nucleocapsid protein throughout follow-up were included as uninfected controls. ‘Cases’ include all available RNA samples, including convalescent samples at week 24 of follow-up for a subset of participants. For uninfected controls, we included baseline samples only. Sample class denotes weekly interval to positive SARS-CoV-2 PCR; non-infected controls (NIC); convalescent samples (Conv)_.
