Single-Cell Omics Reveals Dyssynchrony of the Innate and Adaptive Immune System in Progressive COVID-19
Tomokazu S. Sumida,
Amy Y. Zhao,
Micha Sam Brickman Raredon,
Chantal B.F. Vogels,
Anne L Wyllie,
Nathan D. Grubaugh,
The Yale IMPACT research team,
Laura E Niklason,
Albert I. Ko,
Ruth R. Montgomery,
Shelli F. Farhadian,
Albert C Shaw,
David van Dijk,
David A. Hafler,
Charles S. Dela Cruz
Posted 17 Jul 2020
medRxiv DOI: 10.1101/2020.07.16.20153437
Posted 17 Jul 2020
A dysregulated immune response against the SARS-CoV-2 virus plays a critical role in severe COVID-19. However, the molecular and cellular mechanisms by which the virus causes lethal immunopathology are poorly understood. Here, we utilize multi-omics single-cell analysis to probe dynamic immune responses in patients with stable or progressive manifestations of COVID-19, and assess the effects of tocilizumab, an anti-IL-6 receptor monoclonal antibody. Coordinated profiling of gene expression and cell lineage protein markers reveals a prominent type-1 interferon response across all immune cells, especially in progressive patients. An anti-inflammatory innate immune response and a pre-exhaustion phenotype in activated T cells are hallmarks of progressive disease. Skewed T cell receptor repertoires in CD8 T cells and uniquely enriched V(D)J sequences are also identified in COVID-19 patients. B cell repertoire and somatic hypermutation analysis are consistent with a primary immune response, with possible contribution from memory B cells. Our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19, which may contribute to delayed virus clearance and has implications for therapeutic intervention.
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