Single-cell multi-omics analysis of the immune response in COVID-19

By Emily Stephenson, G. Reynolds, R. Botting, F. Calero-Nieto, Martin T. Morgan, Z. Tuong, K. Bach, W. Sungnak, Kaylee B. Worlock, Masahiro Yoshida and 166 more. Nature Medicine, 2021

626 citations recorded by the source corpus.

Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy. Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Subfields: Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2ce658859be554a62ffa24bedf3d17f1b7e8073a

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In Molecular Biology

Citations in the corpus

Multiple early factors anticipate post-acute COVID-19 sequelae (2022, positive): “Additional CD8 + T cells derived from healthy samples were extracted from published datasets based on previous cell type annotation (Ren et al., 2021; Stephenson et al., 2021).”
Best practices for single-cell analysis across modalities (2023, background): “Incomplete AIRs with cells assigned to only a VJ or VDJ chain are regularly detected and represent valid cells, but cannot be used for all downstream processes that expect complete AIRs.”