Journal Article

Association of SARS-CoV-2 infection with long-lasting increase in circulating IL-32 levels

Suffritti, Chiara, Gualtierotti, Roberta, Pelusi, Serena, Peyvandi, Flora, Bandera, Alessandra, Lamorte, Giuseppe Enzo, Miano, Lorenzo, Sinopoli, Elena, Rahmeh, Fatima, Prati, Daniele, Cherubini, Alessandro, Valenti, Luca Vittorio Carlo, Blasi, Francesco, Grasselli, Giacomo

2026

Overview

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has a wide spectrum of clinical presentations ranging from asymptomatic viral replication to hyper-inflammatory syndrome and respiratory failure and can trigger immune disorders and long-COVID. Interleukin-32 (IL-32) is a pro-inflammatory cytokine induced during viral infections and chronic pulmonary disease. Aim of this study was to investigate the impact of the SARS-CoV-2 pandemic and severe COVID-19 on circulating IL-32 levels. Observational retrospective biomarker study. We analyzed 949 healthy blood donors (pre-pandemic and pandemic-era) and 212 patients hospitalized due to severe COVID-19 during the first five infection waves. IL-32 levels were measured by ELISA. Pandemic-era blood plasma donors showed a +0.78 ± 0.09 log pg/ml mean increase in IL-32 (pandemic-era 2.91 ± 0.05 vs. pre-pandemic 2.14 ± 0.07 log pg/ml, p<0.0001). COVID-19 patients exhibited a similar elevated IL-32 compared to unexposed controls (+0.29 ± 0.11 log pg/ml, p=0.016; 2.43 ± 0.08 hospital admission vs. pre-pandemic). Among patients, mean IL-32 was higher in first-wave patients (2.68 ± 0.11 log pg/ml) than later waves (2.12 ± 0.11 log pg/ml). In setting of severe COVID-19, IL-32 levels were associated with corticosteroids administration (estimate1.99 ± 0.50; p<0.0001), whereas decreased during the later waves of infection (-0.56 ± 0.16; p=0.0005) and with age (estimate -0.01 ± 0.01; p=0.020). No links were found with sex, Intensive care unit admission, comorbidities, or mortality. A subset of the COVID patient cohort was tested for pro-inflammatory biomarkers: IL-32 displayed an inverse correlation with patients' neutrophil-to-lymphocyte ratio (NLR) (estimate -0.23 ± 0.81; p=0.005) and not with IL-6 and biomarkers of endothelial dysfunction (n=42, p=NS). In patients with available follow-up (n=96), IL-32 remained stable up to one-year post-discharge (+0.03 ± 0.12 log pg/ml, p=0.970; 2.55 ± 0.15 hospital admission vs. follow-up 3-12 months 2.58 ± 0.15 log pg/ml). IL-32 levels increased following COVID-19, especially during the initial severe wave, and correlated with some markers of inflammation. IL-32 remained elevated up to one-year post-discharge, suggesting ongoing inflammation and supporting its potential as a biomarker for long-term sequelae.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adult / Aged / Antihypertensives / Biomarkers / Biomarkers - blood / Blood & organ donations / Blood donors / Body mass index / Cardiovascular disease / Chronic obstructive pulmonary disease / Comorbidity / Complications / Coronaviruses / Corticosteroids / COVID-19 / COVID-19 - blood / COVID-19 - epidemiology / COVID-19 - immunology / Cytokine storm / Diabetes / Female / Hospitalization / Humans / Hypertension / IL-32 / Inflammation / Intensive care / Interleukins - blood / Kinases / Leukocytes (neutrophilic) / Liver diseases / long-covid / Lung diseases / Lymphocytes / Male / Metabolism / Middle Aged / Neutrophils / Original Research / Pandemics / Patients / Pneumonia / Retrospective Studies / SARS-CoV-2 - immunology / Severe acute respiratory syndrome coronavirus 2 / Steroids / Viral infections