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Nature medicine
07, 2020;26 (7): 1070-1076.

A single-cell atlas of the peripheral immune response in patients with severe COVID-19.

Aaron J Wilk, Arjun Rustagi, Nancy Q Zhao, Jonasel Roque, Giovanny J Martínez-Colón, Julia L McKechnie, Geoffrey T Ivison, Thanmayi Ranganath, Rosemary Vergara, Taylor Hollis, Laura J Simpson, Philip Grant, Aruna Subramanian, Angela J Rogers, Catherine A Blish
Author Information
  1. Aaron J Wilk: Stanford Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA, USA. ORCID
  2. Arjun Rustagi: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. ORCID
  3. Nancy Q Zhao: Stanford Immunology Program, Stanford University School of Medicine, Stanford, CA, USA. ORCID
  4. Jonasel Roque: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  5. Giovanny J Martínez-Colón: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  6. Julia L McKechnie: Stanford Immunology Program, Stanford University School of Medicine, Stanford, CA, USA.
  7. Geoffrey T Ivison: Stanford Immunology Program, Stanford University School of Medicine, Stanford, CA, USA. ORCID
  8. Thanmayi Ranganath: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. ORCID
  9. Rosemary Vergara: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  10. Taylor Hollis: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  11. Laura J Simpson: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  12. Philip Grant: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  13. Aruna Subramanian: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  14. Angela J Rogers: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. ajrogers@stanford.edu. ORCID
  15. Catherine A Blish: Stanford Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA, USA. cblish@stanford.edu. ORCID
PMID: 32514174 DOI: 10.1038/s41591-020-0944-y

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. Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines that may be produced by a subset of inflammatory monocytes, lymphopenia and T cell exhaustion. 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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Grants

  1. DGE-1656518/National Science Foundation (NSF)
  2. DP1 DA04608902/U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
  3. T32 GM007365/NIGMS NIH HHS
  4. DP1 DA046089/NIDA NIH HHS
  5. R25 GM086262/NIGMS NIH HHS
  6. AI007290-35/U.S. Department of Health & Human Services | National Institutes of Health (NIH)
  7. 1016687/Burroughs Wellcome Fund (BWF)
  8. T32 AI007502/NIAID NIH HHS
  9. T32 AI007290/NIAID NIH HHS
  10. T32 GM007365-44/U.S. Department of Health & Human Services | National Institutes of Health (NIH)
  11. K23 HL125663/NHLBI NIH HHS
  12. T32 AI007502-23/U.S. Department of Health & Human Services | National Institutes of Health (NIH)
  13. /Wellcome Trust

MeSH Term

Adult
Aged
Aged, 80 and over
Betacoronavirus
COVID-19
Case-Control Studies
Coronavirus Infections
Cytokines
Female
Gene Expression Profiling
Humans
Immunity, Cellular
Killer Cells, Natural
Leukocytes, Mononuclear
Male
Middle Aged
Pandemics
Pneumonia, Viral
RNA-Seq
SARS-CoV-2
Sequence Analysis, RNA
Severity of Illness Index
Single-Cell Analysis
T-Lymphocytes
Young Adult

Chemicals

Cytokines
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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