{"authors":[{"id":"orcid_______::9aa24ccecd0e40f3160ffa7333ea7348","fullName":"Miano, Lorenzo","name":"Lorenzo","surname":"Miano","rank":1,"pid":{"id":{"scheme":"orcid","value":"0009-0000-6552-2027"},"provenance":null}},{"id":null,"fullName":"Sinopoli, Elena","name":"Elena","surname":"Sinopoli","rank":2,"pid":null},{"id":null,"fullName":"Cherubini, Alessandro","name":"Alessandro","surname":"Cherubini","rank":3,"pid":null},{"id":null,"fullName":"Suffritti, Chiara","name":"Chiara","surname":"Suffritti","rank":4,"pid":null},{"id":null,"fullName":"Pelusi, Serena","name":"Serena","surname":"Pelusi","rank":5,"pid":null},{"id":null,"fullName":"Rahmeh, Fatima","name":"Fatima","surname":"Rahmeh","rank":6,"pid":null},{"id":null,"fullName":"Lamorte, Giuseppe Enzo","name":"Giuseppe Enzo","surname":"Lamorte","rank":7,"pid":null},{"id":null,"fullName":"Peyvandi, Flora","name":"Flora","surname":"Peyvandi","rank":8,"pid":{"id":{"scheme":"orcid_pending","value":"0000-0001-7423-9864"},"provenance":null}},{"id":"orcid_______::541c2fc9043a973af1a0da9fcbba6e77","fullName":"Blasi, Francesco","name":"Francesco","surname":"Blasi","rank":9,"pid":{"id":{"scheme":"orcid","value":"0000-0002-2285-9970"},"provenance":null}},{"id":null,"fullName":"Grasselli, Giacomo","name":"Giacomo","surname":"Grasselli","rank":10,"pid":{"id":{"scheme":"orcid_pending","value":"0000-0002-1735-1400"},"provenance":null}},{"id":"orcid_______::ed2656b37a9378818301c40ccc10162e","fullName":"Bandera, Alessandra","name":"Alessandra","surname":"Bandera","rank":11,"pid":{"id":{"scheme":"orcid","value":"0000-0001-9440-4601"},"provenance":null}},{"id":null,"fullName":"Gualtierotti, Roberta","name":"Roberta","surname":"Gualtierotti","rank":12,"pid":{"id":{"scheme":"orcid_pending","value":"0000-0001-6465-7624"},"provenance":null}},{"id":null,"fullName":"Prati, Daniele","name":"Daniele","surname":"Prati","rank":13,"pid":null},{"id":null,"fullName":"Valenti, Luca Vittorio Carlo","name":"Luca Vittorio Carlo","surname":"Valenti","rank":14,"pid":{"id":{"scheme":"orcid_pending","value":"0000-0001-8909-0345"},"provenance":null}}],"openAccessColor":"gold","publiclyFunded":false,"eoscIfGuidelines":null,"type":"publication","language":{"code":"und","label":"Undetermined"},"countries":[{"code":"IT","label":"Italy","provenance":null}],"subjects":[{"subject":{"scheme":"keyword","value":"Male"},"provenance":null},{"subject":{"scheme":"keyword","value":"Adult"},"provenance":null},{"subject":{"scheme":"FOS","value":"0303 health sciences"},"provenance":null},{"subject":{"scheme":"keyword","value":"SARS-CoV-2"},"provenance":null},{"subject":{"scheme":"keyword","value":"Interleukins"},"provenance":null},{"subject":{"scheme":"keyword","value":"COVID-19"},"provenance":null},{"subject":{"scheme":"keyword","value":"Middle Aged"},"provenance":null},{"subject":{"scheme":"FOS","value":"03 medical and health sciences"},"provenance":null},{"subject":{"scheme":"keyword","value":"COVID-19; cytokine storm; IL-32; inflammation; long-covid"},"provenance":null},{"subject":{"scheme":"keyword","value":"Humans"},"provenance":null},{"subject":{"scheme":"keyword","value":"Female"},"provenance":null},{"subject":{"scheme":"keyword","value":"Biomarkers"},"provenance":null},{"subject":{"scheme":"keyword","value":"Original Research"},"provenance":null},{"subject":{"scheme":"keyword","value":"Retrospective Studies"},"provenance":null},{"subject":{"scheme":"keyword","value":"Aged"},"provenance":null}],"mainTitle":"Association of SARS-CoV-2 infection with long-lasting increase in circulating IL-32 levels","subTitle":null,"descriptions":["<jats:sec>                     <jats:title>Background &amp;amp; aims</jats:title>                     <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>                   </jats:sec>                   <jats:sec>                     <jats:title>Aim</jats:title>                     <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>                   </jats:sec>                   <jats:sec>                     <jats:title>Study design</jats:title>                     <jats:p>Observational retrospective biomarker study.</jats:p>                   </jats:sec>                   <jats:sec>                     <jats:title>Patients &amp;amp; methods</jats:title>                     <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>                   </jats:sec>                   <jats:sec>                     <jats:title>Results</jats:title>                     <jats:p>                       Pandemic-era blood plasma donors showed a +0.78 ± 0.09 log                       <jats:sub>10</jats:sub>                       pg/ml mean increase in IL-32 (pandemic-era 2.91 ± 0.05 vs. pre-pandemic 2.14 ± 0.07 log                       <jats:sub>10</jats:sub>                       pg/ml, p&amp;lt;0.0001). COVID-19 patients exhibited a similar elevated IL-32 compared to unexposed controls (+0.29 ± 0.11 log                       <jats:sub>10</jats:sub>                       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                       <jats:sub>10</jats:sub>                       pg/ml) than later waves (2.12 ± 0.11 log                       <jats:sub>10</jats:sub>                       pg/ml). In setting of severe COVID-19, IL-32 levels were associated with corticosteroids administration (estimate1.99 ± 0.50; p&amp;lt;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                       <jats:sub>10</jats:sub>                       pg/ml, p=0.970; 2.55 ± 0.15 hospital admission vs. follow-up 3–12 months 2.58 ± 0.15 log                       <jats:sub>10</jats:sub>                       pg/ml).                     </jats:p>                   </jats:sec>                   <jats:sec>                     <jats:title>Conclusions</jats:title>                     <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>                   </jats:sec>"],"publicationDate":"2026-02-06","publisher":"Frontiers Media SA","embargoEndDate":null,"sources":["Crossref","Front Immunol"],"formats":["application/pdf"],"contributors":null,"coverages":null,"bestAccessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/"},"container":{"name":"Frontiers in 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