Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity
Sara Falck-Jones, … , Anna Färnert, Anna Smed-Sörensen
Sara Falck-Jones, … , Anna Färnert, Anna Smed-Sörensen
Published January 25, 2021
Citation Information: J Clin Invest. 2021;131(6):e144734. https://doi.org/10.1172/JCI144734.
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Research Article Immunology

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

Abstract

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.

Authors

Sara Falck-Jones, Sindhu Vangeti, Meng Yu, Ryan Falck-Jones, Alberto Cagigi, Isabella Badolati, Björn Österberg, Maximilian Julius Lautenbach, Eric Åhlberg, Ang Lin, Rico Lepzien, Inga Szurgot, Klara Lenart, Fredrika Hellgren, Holden Maecker, Jörgen Sälde, Jan Albert, Niclas Johansson, Max Bell, Karin Loré, Anna Färnert, Anna Smed-Sörensen

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Figure 6

M-MDSC frequency predicts disease severity and is associated with male sex and age.

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M-MDSC frequency predicts disease severity and is associated with male s...
(A) Criteria for inclusion in the ordinal logistic regression model. Only patients with symptoms for up to 2 weeks, not yet admitted to the ICU, and in the pre-peak or peak phase were included in the analysis. (B) Proportional odds logistic regression showing the capacity of M-MDSC frequency to predict the peak disease severity score. Crude and adjusted (Adj.) ORs are presented. (C) Overview of the 41 patients included in the ordinal logistic regression model. Circles represent the samples included in the analysis, and colors represent the daily disease severity. Patients were separated on the basis of peak disease severity. (D) Peak M-MDSC frequency in men and women with COVID-19 compared using a Wilcoxon-Mann-Whitney U test.***P < 0.001. Circles are color-coded by disease severity. Men: mild, n = 7; moderate, n = 40; severe, n = 47; and fatal, n = 9. Women: mild, n = 12; moderate, n = 13; severe, n = 9; and fatal, n = 3. (E) Spearman’s correlation between age and peak M-MDSC frequency (n = 140).