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Hyperinflammatory State and Low T1 Adaptive Immune Response in Severe and Critical Acute COVID-19 Patients

Authors :
Mercedes Garcia-Gasalla
María Berman-Riu
Jaime Pons
Adrián Rodríguez
Amanda Iglesias
Natalia Martínez-Pomar
Isabel Llompart-Alabern
Melchor Riera
Adrián Ferré Beltrán
Albert Figueras-Castilla
Javier Murillas
Joana M. Ferrer
Source :
Frontiers in Medicine, Vol 9 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

BackgroundA better understanding of COVID-19 immunopathology is needed to identify the most vulnerable patients and improve treatment options.ObjectiveWe aimed to identify immune system cell populations, cytokines, and inflammatory markers related to severity in COVID-19.Methods139 hospitalized patients with COVID-19−58 mild/moderate and 81 severe/critical—and 74 recovered patients were included in a prospective longitudinal study. Clinical data and blood samples were obtained on admission for laboratory markers, cytokines, and lymphocyte subsets study. In the recovered patients, lymphocyte subsets were analyzed 8–12 weeks after discharge.ResultsA National Early Warning Score 2 >2 (OR:41.4; CI:10.38–167.0), ferritin >583 pg/mL (OR:16.3; CI: 3.88–69.9), neutrophil/lymphocyte ratio >3 (OR: 3.5; CI: 1.08–12.0), sIL-2rα (sCD25) >512 pg/mL (OR: 3.3; CI: 1.48–7.9), IL-1Ra >94 pg/mL (OR: 3.2; IC: 1.4–7.3), and IL-18 >125 pg/mL (OR: 2.4; CI: 1.1–5.0) were associated with severe/critical COVID-19 in the multivariate models used. Lower absolute values of CD3, CD4, CD8, and CD19 lymphocytes together with higher frequencies of NK cells, a CD4 and CD8 activated (CD38+HLA-DR+) memory T cell and effector memory CD45RA+ (EMRA) phenotype, and lower T regulatory cell frequencies were found in severe/critical patients relative to mild/moderate and recovered COVID-19 patients. A significant reduction in Th1, Tfh1, and Tc1 with higher Th2, Tfh2, Tc2, and plasma cell frequencies was found in the most severe cases.ConclusionA characteristic hyperinflammatory state with significantly elevated neutrophil/lymphocyte ratio and ferritin, IL-1Ra, sIL-2rα, and IL-18 levels together with a “low T1 lymphocyte signature” was found in severe/critical COVID-19 patients.

Details

Language :
English
ISSN :
2296858X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
Frontiers in Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.43cadb821502443bbbdbe4a144f4711c
Document Type :
article
Full Text :
https://doi.org/10.3389/fmed.2022.828678