Longitudinal blood and tissue single cell transcriptomics of humans challenged with SARS-CoV-2 reveals innate and adaptive immune dynamics

Le résumé fourni par la source

Despite the rapid development and rollout of first-generation vaccines, COVID-19 remains an ongoing global health concern. Whilst single cell transcriptional studies have provided deep biological insights, limited longitudinal sampling has made temporal inferences difficult. The Human COVID-19 Challenge Study offers a unique opportunity to study these cellular dynamics, from pre-infection to recovery, in a controlled and safe environment. Matched nasopharyngeal swabs and peripheral blood samples were collected at 6-7 timepoints (pre-infection to 28 days post-infection) from 16 healthy seronegative individuals inoculated intranasally with pre-alpha SARS-CoV-2. Samples (n=184) were processed for single cell- and CITE-sequencing. Preliminary analyses revealed dozens of highly dynamic cellular response states in epithelial, nasal resident and circulating immune cells associated with specific infection time points. Several ciliated anti-viral responses were identified in the nose, including a novel acute phase and professional antigen presentation response activated immediately after infection. Whilst a global nasopharyngeal immune infiltration was observed in all patients, a greater and more rapid response occurred within the transient, and to a lesser extent aborted, infections compared to sustained ones. Unexpectedly, the first interferon response was detected in the blood, preceding that of the nasopharynx. Overall, our results so far have started to pull apart the temporal and highly dynamic SARS-CoV-2 specific responses, both locally and systemically, identifying several molecular and cellular features contributing towards protection.

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