Elevated plasma sTIM-3 levels in severe Covid-19 patients

Ueland, Thor; Heggelund, Lars; Lind, Andreas; Holten, Aleksander R.; Tonby, Kristian; Michelsen, Annika E.; Jenum, Synne; Jørgensen, Marthe J.; Barratt-Due, Andreas; Skeie, Linda G.; Nordøy, Ingvild; Aanensen Fraz, Mai Sasaki; Quist-Paulsen E, Else; Pischke, Søren E.; Johal, Simreen K.; Hesstvedt, Liv; Bogen, Mette; Fevang, Børre; Halvorsen, Bente; Müller, Fredrik; Bekken, Gry Kloumann; Mollnes, Tom E.; Dudman, Susanne; Aukrust, Pål; Dyrhol-Riise, Anne M.; Holter, Jan C.

Background The pathogenesis of COVID-19 is still incompletely understood, but seems to involve immune activation and immune dysregulation. Objective We examined parameters of activation of different leukocyte subsets in COVID-19 infected patients in relation to disease severity. Methods We analyzed plasma levels of myeloperoxidase (MPO, neutrophil activation), soluble (s) CD25 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 two additional times during the first 10 days in relation to the need for ICU treatment. Results Our major findings were: (i) Severe clinical outcome (ICU) was associated with high plasma levels sTIM-3 and MPO suggesting activated and potentially exhausted T cells and activated neutrophils, respectively. (ii) In contrast, sCD14 and sCD163 showed no association with need for ICU treatment. (iii) sCD25, sTIM-3 and MPO were inversely correlated with the degree of respiratory failure as assessed by P/F ratio and 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.