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Elevated plasma sTIM-3 levels in patients with severe COVID-19 - 09/01/21

Doi : 10.1016/j.jaci.2020.09.007 
Thor Ueland, PhD a, b, c, , Lars Heggelund, MD, PhD d, e, Andreas Lind, MD, PhD f, Aleksander R. Holten, MD, PhD g, Kristian Tonby, MD, PhD h, Annika E. Michelsen, PhD a, b, Synne Jenum, MD, PhD h, Marthe J. Jørgensen, PhD b, h, Andreas Barratt-Due, MD, PhD g, Linda G. Skeie, RN h, Ingvild Nordøy, MD, PhD a, l, Mai Sasaki Aanensen Fraz, MD a, Else Quist-Paulsen E, MD, PhD b, f, Søren E. Pischke, MD, PhD g, j, Simreen K. Johal, MD f, Liv Hesstvedt, MD, PhD h, Mette Bogen, MSc k, Børre Fevang, MD, PhD a, i, Bente Halvorsen, PhD a, b, Fredrik Müller, MD, PhD b, f, Gry Kloumann Bekken, MD, PhD e, Tom E. Mollnes, MD, PhD c, j, l, m, Susanne Dudman, MD, PhD b, f, Pål Aukrust, MD, PhD a, b, c, i, Anne M. Dyrhol-Riise, MD, PhD b, h, Jan C. Holter, MD, PhD b, f
a Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway 
b Institute of Clinical Medicine, University of Oslo, Oslo, Norway 
c Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway 
d Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway 
e Department of Internal Medicine, Drammen Hospital, Drammen, Norway 
f Department of Microbiology, Oslo University Hospital, Oslo, Norway 
g Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway 
h Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway 
i Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway 
j Department of Immunology, University of Oslo, Oslo, Norway 
k Department of Laboratory Medicine, Vestre Viken Hospital Trust, Drammen, Norway 
l Research Laboratory, Nordland Hospital, Bodø, Norway 
m Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway 

Corresponding author: Thor Ueland, PhD, Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, PB 4950 Nydalen, 0424 Oslo, Norway.Research Institute of Internal MedicineOslo University HospitalRikshospitaletPB 4950 NydalenOslo0424Norway

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Abstract

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.

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Key words : COVID-19, outcome, T cell, TIM-3, neutrophil

Abbreviations used : COVID-19, eGFR, Fio2, hsCRP, ICU, NT-proBNP, OUH, P/F ratio, s, sTIM-3


Plan


 This project has received a private donation from Vivaldi Invest A/S, which is owned by Jon Stephenson von Tetzchner, and has also received funding from COVID-19 Emergency Call for Proposals: Collaborative and Knowledge-building Projects for the Fight Against Coronavirus Disease (COVID-19) from the Research Council of Norway (grant no. 312780).
 Disclosure of potential conflict of interest T. E. Mollnes is a medical advisor for Ra Pharmaceutical, which produces complement inhibitors. The rest of the authors declare that they have no relevant conflicts of interest.


© 2020  Publié par Elsevier Masson SAS.
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Vol 147 - N° 1

P. 92-98 - janvier 2021 Retour au numéro
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