Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab. Coordinated profiling of gene expression and cell lineage protein markers shows that S100A(hi)/HLA-DR(lo) classical monocytes and activated LAG-3(hi) T cells are hallmarks of progressive disease and highlights the abnormal MHC-II/LAG-3 interaction on myeloid and T cells, respectively. We also find skewed T cell receptor repertories in expanded effector CD8(+) clones, unmutated IGHG(+) B cell clones, and mutated B cell clones with stable somatic hypermutation frequency over time. In conclusion, our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19.
- Unterman, A.
- Sumida, T. S.
- Nouri, N.
- Yan, X.
- Zhao, A. Y.
- Gasque, V.
- Schupp, J. C.
- Asashima, H.
- Liu, Y.
- Cosme, C., Jr.
- Deng, W.
- Chen, M.
- Raredon, M. S. B.
- Hoehn, K. B.
- Wang, G.
- Wang, Z.
- DeIuliis, G.
- Ravindra, N. G.
- Li, N.
- Castaldi, C.
- Wong, P.
- Fournier, J.
- Bermejo, S.
- Sharma, L.
- Casanovas-Massana, A.
- Vogels, C. B. F.
- Wyllie, A. L.
- Grubaugh, N. D.
- Melillo, A.
- Meng, H.
- Stein, Y.
- Minasyan, M.
- Mohanty, S.
- Ruff, W. E.
- Cohen, I.
- Raddassi, K.
- Niklason, L. E.
- Ko, A. I.
- Montgomery, R. R.
- Farhadian, S. F.
- Iwasaki, A.
- Shaw, A. C.
- van Dijk, D.
- Zhao, H.
- Kleinstein, S. H.
- Hafler, D. A.
- Kaminski, N.
- Dela Cruz, C. S.
