1. Elevated plasma sTIM-3 levels in patients with severe COVID-19
- Author
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Thor Ueland, Tom Eirik Mollnes, Annika E. Michelsen, Bente Halvorsen, Anne Ma Dyrhol-Riise, Linda Gail Skeie, Andreas Lind, Aleksander Rygh Holten, Marthe Jøntvedt Jørgensen, Else Quist-Paulsen E, Ingvild Nordøy, Kristian Tonby, Synne Jenum, Pål Aukrust, Jan Cato Holter, Simreen K. Johal, Liv Hesstvedt, Mette Bogen, Søren Erik Pischke, Børre Fevang, Gry Kloumann Bekken, Susanne Gjeruldsen Dudman, Andreas Barratt-Due, Mai Sasaki Aanensen Fraz, Lars Heggelund, and Fredrik Müller
- Subjects
0301 basic medicine ,Male ,Time Factors ,T-Lymphocytes ,Lipopolysaccharide Receptors ,medicine.disease_cause ,Lymphocyte Activation ,Severity of Illness Index ,Pathogenesis ,0302 clinical medicine ,Natriuretic peptide ,MPO, Myeoloperoxidase ,Medicine ,Immunology and Allergy ,030212 general & internal medicine ,IL-2 receptor ,hsCRP, high-sensitivity C-reactive protein ,Hepatitis A Virus Cellular Receptor 2 ,biology ,NT-proBNP, N-terminal pro-B-type natriuretic peptide ,eGFR, estimated glomerular filtration rate ,CV, cardiovascular ,neutrophil ,ARDS, Acute Respiratory Distress Syndrome ,Middle Aged ,ICU, intensive care unit ,VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710 ,medicine.anatomical_structure ,Myeloperoxidase ,outcome ,Female ,Antibody ,P/F ratio, arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FIO2) ,medicine.drug_class ,T cell ,TIM-3 ,Immunology ,Antigens, Differentiation, Myelomonocytic ,Receptors, Cell Surface ,Article ,03 medical and health sciences ,Antigens, CD ,Humans ,sTIM-3, T-cell immunoglobulin mucin-3 ,Aged ,business.industry ,SARS-CoV-2 ,Monocyte ,Interleukin-2 Receptor alpha Subunit ,COVID-19 ,VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710 ,Immune dysregulation ,IL, interleukin ,030104 developmental biology ,biology.protein ,business - Abstract
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.
- Published
- 2020