Elevated plasma sTIM-3 levels in patients with severe COVID-19
Ueland, Thor; Heggelund, Lars; Lind, Andreas; Holten, Aleksander Rygh; Tonby, Kristian; Michelsen, Annika; Jenum, Synne; Jørgensen, Marthe Jøntvedt; Barratt-Due, Andreas; Skeie, Linda Gail; Nordøy, Ingvild; Aanensen Fraz, Mai Sasaki; Paulsen, Else Quist; Pischke, Soeren; Johal, Simreen Kaur; Hesstvedt, Liv; Bogen, Mette; Fevang, Børre; Halvorsen, Bente; Müller, Fredrik; Bekken, Gry Kloumann; Mollnes, Tom Eirik; Dudman, Susanne Gjeruldsen; Aukrust, Pål; Dyrhol-Riise, Anne Ma; Holter, Jan Cato
Peer reviewed, Journal article
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Original versionJournal of Allergy and Clinical Immunology. 2020, 1-7. 10.1016/j.jaci.2020.09.007
Background The pathogenesis of coronavirus disease 2019 (COVID-19) is still incompletely understood, but it seems to involve immune activation and immune dysregulation. Objective We examined the parameters of activation of different leukocyte subsets in COVID-19–infected patients in relation to disease severity. Methods We analyzed plasma levels of myeloperoxidase (a marker of neutrophil activation), soluble (s) CD25 (sCD25) and soluble T-cell immunoglobulin mucin domain-3 (sTIM-3) (markers of T-cell activation and exhaustion), and sCD14 and sCD163 (markers of monocyte/macrophage activation) in 39 COVID-19–infected patients at hospital admission and 2 additional times during the first 10 days in relation to their need for intensive care unit (ICU) treatment. Results Our major findings were as follows: (1) severe clinical outcome (ICU treatment) was associated with high plasma levels of sTIM-3 and myeloperoxidase, suggesting activated and potentially exhausted T cells and activated neutrophils, respectively; (2) in contrast, sCD14 and sCD163 showed no association with need for ICU treatment; and (3) levels of sCD25, sTIM-3, and myeloperoxidase were inversely correlated with degree of respiratory failure, as assessed by the ratio of Pao2 to fraction of inspired oxygen, and were positively correlated with the cardiac marker N-terminal pro-B–type natriuretic peptide. Conclusion Our findings suggest that neutrophil activation and, in particular, activated T cells may play an important role in the pathogenesis of COVID-19 infection, suggesting that T-cell–targeted treatment options and downregulation of neutrophil activation could be of importance in this disorder.