{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T17:12:30Z","timestamp":1770397950128,"version":"3.49.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background &amp;amp; aims<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Aim of this study was to investigate the impact of the SARS-CoV-2 pandemic and severe COVID-19 on circulating IL-32 levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study design<\/jats:title>\n                    <jats:p>Observational retrospective biomarker study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients &amp;amp; methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pandemic-era blood plasma donors showed a +0.78 \u00b1 0.09 log\n                      <jats:sub>10<\/jats:sub>\n                      pg\/ml mean increase in IL-32 (pandemic-era 2.91 \u00b1 0.05 vs. pre-pandemic 2.14 \u00b1 0.07 log\n                      <jats:sub>10<\/jats:sub>\n                      pg\/ml, p&amp;lt;0.0001). COVID-19 patients exhibited a similar elevated IL-32 compared to unexposed controls (+0.29 \u00b1 0.11 log\n                      <jats:sub>10<\/jats:sub>\n                      pg\/ml, p=0.016; 2.43 \u00b1 0.08 hospital admission vs. pre-pandemic). Among patients, mean IL-32 was higher in first-wave patients (2.68 \u00b1 0.11 log\n                      <jats:sub>10<\/jats:sub>\n                      pg\/ml) than later waves (2.12 \u00b1 0.11 log\n                      <jats:sub>10<\/jats:sub>\n                      pg\/ml). In setting of severe COVID-19, IL-32 levels were associated with corticosteroids administration (estimate1.99 \u00b1 0.50; p&amp;lt;0.0001), whereas decreased during the later waves of infection (-0.56 \u00b1 0.16; p=0.0005) and with age (estimate -0.01 \u00b1 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\u2019 neutrophil-to-lymphocyte ratio (NLR) (estimate -0.23 \u00b1 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 \u00b1 0.12 log\n                      <jats:sub>10<\/jats:sub>\n                      pg\/ml, p=0.970; 2.55 \u00b1 0.15 hospital admission vs. follow-up 3\u201312 months 2.58 \u00b1 0.15 log\n                      <jats:sub>10<\/jats:sub>\n                      pg\/ml).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1739258","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T06:48:52Z","timestamp":1770360532000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of SARS-CoV-2 infection with long-lasting increase in circulating IL-32 levels"],"prefix":"10.3389","volume":"17","author":[{"given":"Lorenzo","family":"Miano","sequence":"first","affiliation":[{"name":"Universit\u00e0 degli Studi di Milano, Department of Pathophysiology and Transplantation","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Sinopoli","sequence":"additional","affiliation":[{"name":"Precision Medicine and Biological Resource Center, 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Carlo","family":"Valenti","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi di Milano, Department of Pathophysiology and Transplantation","place":["Milan, Italy"]},{"name":"Precision Medicine and Biological Resource Center, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.3390\/jcm9041225","article-title":"The COVID-19 pandemic: A comprehensive review of taxonomy, genetics, epidemiology, diagnosis, treatment, and control","volume":"9","author":"Helmy","year":"2020","journal-title":"J Clin Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0695-z","article-title":"The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it 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