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 4

Levels of cytokines in blood and NPA from HCs, COVID-19 patients, and influenza patients.

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Levels of cytokines in blood and NPA from HCs, COVID-19 patients, and in...
(A–C) Arg-1 was measured in (A) plasma, (B) NPAs, and (C) plasma across COVID-19 disease severities. HCs (blue points): n = 5 (blood), n = 5 (NPAs). Influenza patients (open circles): n = 6 (blood), n = 3 (NPAs). Patients with COVID-19 (solid circles): n = 93 (blood), n = 13 (NPAs). Patients with COVID-19 (color-coded by peak disease severity): mild, n = 8; moderate, n = 41; severe, n = 36; and fatal, n = 8. (D–F) IL-6 was measured in (D) plasma, (E) NPAs, and (F) plasma across COVID-19 disease severities. HCs (blue): n = 11 (blood), n = 3 (NPAs). Patients with influenza (open circles): n = 37 (blood), n = 24 (NPAs). Patients with COVID-19 (solid circles): n = 133 (blood), n = 7 (NPAs). Patients with COVID-19: mild, n = 14; moderate, n = 56; severe,n = 52; and fatal, n = 11. (G) Comparison of GM-CSF levels in plasma from HCs and patients. HCs (blue): n = 9. Patients with influenza (open circles): n = 13. Patients with COVID-19 (solid circles, color-coded by peak disease severity): mild, n = 12; moderate, n = 38; severe, n = 48; and fatal, n = 8. (H) IL-1β and (I) IL-10 levels in plasma from patients with moderate-to-severe disease or a fatal outcome. COVID-19 patients: moderate, n = 3; severe, n = 44; and fatal, n = 9. *P ≤ 0.05, **P < 0.01, and ***P < 0.001. (A–I) Medians were compared using the nonparametric Kruskal-Wallis test. Post-hoc testing was carried out while controlling the FDR (A–C) or using Dunn’s multiple-comparison test (D–I). In strip charts, the group medians are presented as horizontal lines and individual patients as jitter points.