Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity

J Clin Invest. 2021 Mar 15;131(6):e144734. doi: 10.1172/JCI144734.


The immunopathology of coronavirus disease 2019 (COVID-19) remains enigmatic, causing immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSCs) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied the blood and airways of patients with COVID-19 across disease severities at multiple time points. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of patients with COVID-19 compared with healthy controls. M-MDSCs isolated from patients with COVID-19 suppressed T cell proliferation and IFN-γ production partly via an arginase 1-dependent (Arg-1-dependent) mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. Patients with COVID-19 had fewer T cells and downregulated expression of the CD3ζ chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expanded in the blood of patients with COVID-19, suppressed T cells, and were strongly associated with disease severity, indicating a role for M-MDSCs in the dysregulated COVID-19 immune response.

Keywords: COVID-19; Immunology; Innate immunity.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arginase / blood
  • COVID-19 / blood
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Humans
  • Influenza, Human / blood
  • Influenza, Human / immunology
  • Influenza, Human / pathology
  • Interferon-gamma / blood
  • Interleukin-6 / blood
  • Leukocyte Count
  • Male
  • Middle Aged
  • Myeloid-Derived Suppressor Cells / immunology*
  • Myeloid-Derived Suppressor Cells / pathology
  • Pandemics
  • Respiratory System / immunology
  • Respiratory System / pathology
  • SARS-CoV-2
  • Severity of Illness Index
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Young Adult


  • IL6 protein, human
  • Interleukin-6
  • Interferon-gamma
  • ARG1 protein, human
  • Arginase

Grants and funding

4 grants