Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity.
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.
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D000328:Adult D000368:Aged D000369:Aged, 80 and over D001119:Arginase D000086382:COVID-19 D016022:Case-Control Studies D015331:Cohort Studies D005260:Female D006801:Humans D007251:Influenza, Human D007371:Interferon-gamma D015850:Interleukin-6 D007958:Leukocyte Count D008297:Male D008875:Middle Aged D000072737:Myeloid-Derived Suppressor Cells D058873:Pandemics D012137:Respiratory System D000086402:SARS-CoV-2 D012720:Severity of Illness Index D013601:T-Lymphocytes D055815:Young Adult
COVID-19 Immunology Innate immunity