Author: Falck-Jones, S.; Vangeti, S.; Yu, M.; Falck-Jones, R.; Cagigi, A.; Badolati, I.; Osterberg, B.; Lautenbach, M. J.; Ahlberg, E.; Lin, A.; Szurgot, I.; Lenart, K.; Hellgren, F.; Salde, J.; Albert, J.; Johansson, N.; Bell, M.; Lore, K.; Farnert, A.; Smed-Sorensen, A.
Title: Functional myeloid-derived suppressor cells expand in blood but not airways of COVID-19 patients and predict disease severity Cord-id: 8tb8qpvm Document date: 2020_9_9
ID: 8tb8qpvm
Snippet: The immunopathology of COVID-19 remains enigmatic, exhibiting immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSC) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied blood and airways of COVID-19 patients across disease severity at multiple timepoints. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of COVID-19 patients co
Document: The immunopathology of COVID-19 remains enigmatic, exhibiting immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSC) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied blood and airways of COVID-19 patients across disease severity at multiple timepoints. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of COVID-19 patients compared to controls. M-MDSCs isolated from COVID-19 patients suppressed T cell proliferation and IFN{gamma} production partly via an arginase-1 (Arg-1) dependent mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. COVID-19 patients had fewer T cells, and displayed downregulated expression of the CD3{zeta} chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expand in blood of COVID-19 patients, suppress T cells and strongly associate with disease severity, suggesting a role for M-MDSCs in the dysregulated COVID-19 immune response.
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