Identification of SARS-CoV-2-specific immune alterations in acutely ill patients

J Clin Invest. 2021 Apr 15;131(8):e145853. doi: 10.1172/JCI145853.


Dysregulated immune profiles have been described in symptomatic patients infected with SARS-CoV-2. Whether the reported immune alterations are specific to SARS-CoV-2 infection or also triggered by other acute illnesses remains unclear. We performed flow cytometry analysis on fresh peripheral blood from a consecutive cohort of (a) patients hospitalized with acute SARS-CoV-2 infection, (b) patients of comparable age and sex hospitalized for another acute disease (SARS-CoV-2 negative), and (c) healthy controls. Using both data-driven and hypothesis-driven analyses, we found several dysregulations in immune cell subsets (e.g., decreased proportion of T cells) that were similarly associated with acute SARS-CoV-2 infection and non-COVID-19-related acute illnesses. In contrast, we identified specific differences in myeloid and lymphocyte subsets that were associated with SARS-CoV-2 status (e.g., elevated proportion of ICAM-1+ mature/activated neutrophils, ALCAM+ monocytes, and CD38+CD8+ T cells). A subset of SARS-CoV-2-specific immune alterations correlated with disease severity, disease outcome at 30 days, and mortality. Our data provide an understanding of the immune dysregulation specifically associated with SARS-CoV-2 infection among acute care hospitalized patients. Our study lays the foundation for the development of specific biomarkers to stratify SARS-CoV-2-positive patients at risk of unfavorable outcomes and to uncover candidate molecules to investigate from a therapeutic perspective.

Keywords: Adaptive immunity; COVID-19; Innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • B-Lymphocyte Subsets / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 / epidemiology
  • COVID-19 / immunology*
  • COVID-19 / mortality
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Hospitalization
  • Humans
  • Leukocytes / classification*
  • Leukocytes / immunology*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Models, Immunological
  • Monocytes / immunology
  • Multivariate Analysis
  • Neutrophils / immunology
  • Pandemics
  • Prognosis
  • Prospective Studies
  • Quebec / epidemiology
  • Risk Factors
  • SARS-CoV-2* / immunology
  • Severity of Illness Index