Distinct soluble immune checkpoint profiles characterize COVID-19 severity, mortality and SARS-CoV-2 variant infections.

Autor:	Paranga TG; Department of Infectious Diseases (Internal Medicine II), Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.; St. Parascheva Clinical Hospital for Infectious Diseases, Iasi, Romania., Pavel-Tanasa M; Department of Immunology, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.; Laboratory of Immunology, St. Spiridon County Clinical Emergency Hospital, Iasi, Romania., Constantinescu D; Department of Immunology, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.; Laboratory of Immunology, St. Spiridon County Clinical Emergency Hospital, Iasi, Romania., Iftimi E; Department of Immunology, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania., Plesca CE; Department of Infectious Diseases (Internal Medicine II), Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.; St. Parascheva Clinical Hospital for Infectious Diseases, Iasi, Romania., Miftode IL; Department of Infectious Diseases (Internal Medicine II), Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.; St. Parascheva Clinical Hospital for Infectious Diseases, Iasi, Romania., Cianga P; Department of Immunology, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.; Laboratory of Immunology, St. Spiridon County Clinical Emergency Hospital, Iasi, Romania., Miftode E; Department of Infectious Diseases (Internal Medicine II), Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.; St. Parascheva Clinical Hospital for Infectious Diseases, Iasi, Romania.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Sep 23; Vol. 15, pp. 1464480. Date of Electronic Publication: 2024 Sep 23 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1464480
Abstrakt:	Introduction: Over the past four years, the COVID-19 pandemic has posed serious global health challenges. The severe form of disease and death resulted from the failure of immune regulatory mechanisms, closely highlighted by the dual proinflammatory cytokine and soluble immune checkpoint (sICP) storm. Identifying the individual factors impacting on disease severity, evolution and outcome, as well as any additional interconnections, have become of high scientific interest. Methods: In this study, we evaluated a novel panel composed of ten sICPs for the predictive values of COVID-19 disease severity, mortality and Delta vs. Omicron variant infections in relation to hyperinflammatory biomarkers. The serum levels of sICPs from confirmed SARS-CoV-2 infected patients at hospital admission were determined by Luminex, and artificial neural network analysis was applied for defining the distinct patterns of molecular associations with each form of disease: mild, moderate, and severe. Results: Notably, distinct sICP profiles characterized various stages of disease and Delta infections: while sCD40 played a central role in all defined diagrams, the differences emerged from the distribution levels of four molecules recently found and relatively less investigated (sCD30, s4-1BB, sTIM-1, sB7-H3), and their associations with various hematological and biochemical inflammatory biomarkers. The artificial neural network analysis revealed the prominent role of serum sTIM-1 and Galectin-9 levels at hospital admission in discriminating between survivors and non-survivors, as well as the role of specific anti-interleukin therapy (Tocilizumab, Anakinra) in improving survival for patients with initially high sTIM-1 levels. Furthermore, strong associations between sCD40 and Galectin-9 with suPAR defined the Omicron variant infections, while the positive match of sCD40 with sTREM-1 serum levels characterized the Delta-infected patients. Conclusions: Of importance, this study provides a comprehensive analysis of circulatory immune factors governing the COVID-19 pathology, and identifies key roles of sCD40, sTIM-1, and Galectin-9 in predicting mortality. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Paranga, Pavel-Tanasa, Constantinescu, Iftimi, Plesca, Miftode, Cianga and Miftode.)
Databáze:	MEDLINE
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