AUTHOR=Garcia-Gasalla Mercedes , Berman-Riu María , Pons Jaime , Rodríguez Adrián , Iglesias Amanda , Martínez-Pomar Natalia , Llompart-Alabern Isabel , Riera Melchor , Ferré Beltrán Adrián , Figueras-Castilla Albert , Murillas Javier , Ferrer Joana M. TITLE=Hyperinflammatory State and Low T1 Adaptive Immune Response in Severe and Critical Acute COVID-19 Patients JOURNAL=Frontiers in Medicine VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.828678 DOI=10.3389/fmed.2022.828678 ISSN=2296-858X ABSTRACT=Background

A better understanding of COVID-19 immunopathology is needed to identify the most vulnerable patients and improve treatment options.

Objective

We aimed to identify immune system cell populations, cytokines, and inflammatory markers related to severity in COVID-19.

Methods

139 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.

Results

A 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.

Conclusion

A 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.