Innate immune response in COVID-19 pneumonia during the pandemic: a prospective cohort study.
- 1Fourth (4th) Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Rimini 1, Athens, Greece.
- 2Hellenic Institute for the Study of Sepsis, Laodikeias 17, Athens, Greece.
Abstract
Background
Dysregulated innate immunity contributes to COVID-19 severity, but its evolution over the periods of the pandemic is undefined. The aim of the study was to compare ex vivo innate immune responses in COVID-19 and non-COVID-19 community-acquired pneumonia (CAP) and assess associations with pandemic period, severe respiratory failure (SRF), mortality, and circulating microRNA patterns.Methods
In this prospective cohort study conducted at 2 tertiary hospitals in Athens, Greece, 102 hospitalized patients with COVID-19 pneumonia and 28 with non-COVID-19 community-acquired pneumonia were enrolled. Peripheral blood mononuclear cells were isolated during the first 24 hours before any immune intervention other than dexamethasone and stimulated for cytokine production. SRF was defined as a PaO₂/FiO₂ ratio <150 mmHg necessitating invasive or non-invasive ventilation. Exploratory serum microRNA sequencing was performed in a small subset.Results
On Day 1, release of TNFα and IL-6 was higher by the PBMCs of patients with COVID-19 pneumonia than non-COVID-19 CAP; the opposite was found for IL-1RA. Patients infected by the Omicron variant had higher production of TNFα and lower of IL-6. Using multivariate logistic regression analysis, it was confirmed that over-time decrease of the production of IL-6 by the PBMCs of patients with COVID-19 was a risk factor for progression into SRF and 28-day mortality.Conclusion
COVID-19 pneumonia and non-COVID-19 CAP exhibited distinct patterns of ex vivo PBMC responsiveness, characterized by higher TNF-α and IL-6 production in COVID-19. Functional cytokine responses also varied across pandemic periods.
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BibTeX
@article{chachali2026innate,
title = {{Innate immune response in COVID-19 pneumonia during the pandemic: a prospective cohort study.}},
author = {Stavroula-Porfyria Chachali and Spyros Foutadakis and Nikolaos Antonakos and Konstantinos Leventogiannis and Panagiotis Koufargyris and Evangelos J Giamarellos-Bourboulis},
journal = {Annals of intensive care},
year = {2026},
month = oct,
doi = {10.1016/j.aicoj.2026.100182},
url = {https://europepmc.org/article/MED/42903821},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Innate immune response in COVID-19 pneumonia during the pandemic: a prospective cohort study.
AU - Stavroula-Porfyria Chachali
AU - Spyros Foutadakis
AU - Nikolaos Antonakos
AU - Konstantinos Leventogiannis
AU - Panagiotis Koufargyris
AU - Evangelos J Giamarellos-Bourboulis
PY - 2026
DA - 2026/10/09
JO - Annals of intensive care
DO - 10.1016/j.aicoj.2026.100182
UR - https://europepmc.org/article/MED/42903821
AB - Background Dysregulated innate immunity contributes to COVID-19 severity, but its evolution over the periods of the pandemic is undefined. The aim of the study was to compare ex vivo innate immune responses in COVID-19 and non-COVID-19 community-acquired pneumonia (CAP) and assess associations with pandemic period, severe respiratory failure (SRF), mortality, and circulating microRNA patterns.Methods In this prospective cohort study conducted at 2 tertiary hospitals in Athens, Greece, 102 hospitalized patients with COVID-19 pneumonia and 28 with non-COVID-19 community-acquired pneumonia were enrolled. Peripheral blood mononuclear cells were isolated during the first 24 hours before any immune intervention other than dexamethasone and stimulated for cytokine production. SRF was defined as a PaO₂/FiO₂ ratio <150 mmHg necessitating invasive or non-invasive ventilation. Exploratory serum microRNA sequencing was performed in a small subset.Results On Day 1, release of TNFα and IL-6 was higher by the PBMCs of patients with COVID-19 pneumonia than non-COVID-19 CAP; the opposite was found for IL-1RA. Patients infected by the Omicron variant had higher production of TNFα and lower of IL-6. Using multivariate logistic regression analysis, it was confirmed that over-time decrease of the production of IL-6 by the PBMCs of patients with COVID-19 was a risk factor for progression into SRF and 28-day mortality.Conclusion COVID-19 pneumonia and non-COVID-19 CAP exhibited distinct patterns of ex vivo PBMC responsiveness, characterized by higher TNF-α and IL-6 production in COVID-19. Functional cytokine responses also varied across pandemic periods.
SN - 2110-5820
ER -