A single-cell atlas of the peripheral immune response in patients with severe COVID-19
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Abstract
There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide 1. Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care 2. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines 3,4 that may be produced by a subset of inflammatory monocytes 5,6, lymphopenia 7,8 and T cell exhaustion 9,10. To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven patients hospitalized for COVID-19, four of whom had acute respiratory distress syndrome, and six healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19.
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Within the compendium, fourteen studies had control groups that included six or more samples.
“Within our compendium, we identified a total of fourteen studies with control groups that included six or more samples5,6,15,49–59.”
From Confronting false discoveries in single-cell differential expression (2021) · cites this paper as [50]
In ex vivo studies, NK cells from patients with COVID-19 displayed impaired cytotoxicity.
“In ex vivo studies, NK cells from patients with COVID-19 displayed impaired cytotoxicity (64, 65)”
From SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients (2021) · cites this paper as [65]
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- Authors
- Wilk, A. J., Rustagi, A., Zhao, N. Q., Roque, J., Martínez-Colón, G. J., McKechnie, J. L., Ivison, G. T., Ranganath, T., Vergara, R., Hollis, T., Simpson, L. J., Grant, P., Subramanian, A., Rogers, A. J., & Blish, C. A.
- Affiliations
- Stanford Medicine (US)
- Chan Zuckerberg Biohub San Francisco (US)
- Corresponding author
- Rogers, Angela J.
- Blish, Catherine A.
- ORCID
- Venue
- Nature Medicine
- Published
- 2020-06-08
- Volume
- 26
- Issue
- 7
- Pages
- 1070-1076
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC7382903
- OpenAlex
- W3034168389
- Cited by
- 1,493
- References
- 68
- Citations by year
- 2026: 58 · 2025: 90 · 2024: 173 · 2023: 216 · 2022: 348 · 2021: 420 · 2020: 185 · 2019: 1
- FWCI
- 38.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Medicine (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- PubMed Central (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (DP1 DA04608902)
- Burroughs Wellcome Fund (1016687)
- U.S. Department of Health & Human Services | National Institutes of Health (T32 GM007365-44, T32 AI007502-23, AI007290-35)
- Agency for Science, Technology and Research
- National Science Foundation (DGE-1656518)
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (K23 HL125663)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- severe COVID-19, SARS-CoV-2, peripheral immune response, peripheral blood mononuclear cells, acute respiratory distress syndrome, interferon-stimulated genes, inflammatory cytokines, monocytes, neutrophils, plasmablasts, lymphopenia, T cell exhaustion, immunopathology, mechanical ventilation
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