Elevated plasma sTIM-3 levels in patients with severe COVID-19

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.
Capsule summaryOur study evaluating plasma leukocyte activation markers during hospitalization for COVID-19 disease indicate neutrophil and T cell activation, with signs of T cell exhaustion, associated with severe outcome.