Single-Cell Omics Reveals Dyssynchrony of the Innate and Adaptive Immune System in Progressive COVID-19
By
Avraham Unterman,
Tomokazu S. Sumida,
Nima Nouri,
Xiting Yan,
Amy Y. Zhao,
Victor Gasque,
Jonas Christian Schupp,
Hiromitsu Asashima,
Yunqing Liu,
Carlos Cosme,
Wenxuan Deng,
Ming Chen,
Micha Sam Brickman Raredon,
Kenneth Hoehn,
Guilin Wang,
Zuoheng Wang,
Giuseppe Deiuliis,
Neal G. Ravindra,
Ningshan Li,
Christopher Castaldi,
Patrick Wong,
John Fournier,
Santos Bermejo,
Lokesh Sharma,
Arnau Cassanovas-Massana,
Chantal B.F. Vogels,
Anne L. Wyllie,
Nathan D. Grubaugh,
Anthony Melillo,
Hailong Meng,
Maksym Minasyan,
The Yale IMPACT research team,
Laura E Niklason,
Albert Ko,
Ruth R. Montgomery,
Shelli F. Farhadian,
Akiko Iwasaki,
Albert C Shaw,
David van Dijk,
Hongyu Zhao,
Steven H. Kleinstein,
David A. Hafler,
Naftali Kaminski,
Charles S. Dela Cruz
Posted 17 Jul 2020
medRxiv DOI: 10.1101/2020.07.16.20153437
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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