{"doi":"10.1002/iid3.712","title":"Exploratory analysis of interleukin‐38 in hospitalized COVID‐19 patients","abstract":"INTRODUCTION: A major contributor to coronavirus disease 2019 (COVID-19) progression and severity is a dysregulated innate and adaptive immune response. Interleukin-38 (IL-38) is an IL-1 family member with broad anti-inflammatory properties, but thus far little is known about its role in viral infections. Recent studies have shown inconsistent results, as one study finding an increase in circulating IL-38 in COVID-19 patients in comparison to healthy controls, whereas two other studies report no differences in IL-38 concentrations. METHODS: Here, we present an exploratory, retrospective cohort study of circulating IL-38 concentrations in hospitalized COVID-19 patients admitted to two Dutch hospitals (discovery n = 148 and validation n = 184) and age- and sex-matched healthy subjects. Plasma IL-38 concentrations were measured by enzyme-linked immunosorbent assay, disease-related proteins by proximity extension assay, and clinical data were retrieved from hospital records. RESULTS: IL-38 concentrations were stable during hospitalization and similar to those of healthy control subjects. IL-38 was not associated with rates of intensive care unit admission or mortality. Only in men in the discovery cohort, IL-38 concentrations were positively correlated with hospitalization duration. A positive correlation between IL-38 and the inflammatory biomarker d-dimer was observed in men of the validation cohort. In women of the validation cohort, IL-38 concentrations correlated negatively with thrombocyte numbers. Furthermore, plasma IL-38 concentrations in the validation cohort correlated positively with TNF, TNFRSF9, IL-10Ra, neurotrophil 3, polymeric immunoglobulin receptor, CHL1, CD244, superoxide dismutase 2, and fatty acid binding protein 2, and negatively with SERPINA12 and cartilage oligomeric matrix protein. CONCLUSIONS: These data indicate that IL-38 is not associated with disease outcomes in hospitalized COVID-19 patients. However, moderate correlations between IL-38 concentrations and biomarkers of disease were identified in one of two cohorts. While we demonstrate that IL-38 concentrations are not indicative of COVID-19 severity, its anti-inflammatory effects may reduce COVID-19 severity and should be experimentally investigated.","journal":"Immunity Inflammation and Disease","year":2022,"id":295999,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":651061,"name":"Lisa U. Teufel","orcid":"0000-0003-4287-5908","position":1,"is_corresponding":false},{"id":982747,"name":"Aline H. de Nooijer","orcid":null,"position":2,"is_corresponding":false},{"id":982197,"name":"Adriaan J. van Gammeren","orcid":"0000-0002-6975-2476","position":3,"is_corresponding":false},{"id":982748,"name":"Antonius A.M. Ermens","orcid":null,"position":4,"is_corresponding":false},{"id":982749,"name":"Ildikó O. Gaál","orcid":null,"position":5,"is_corresponding":false},{"id":667506,"name":"Tania O. Crișan","orcid":"0000-0002-3282-5627","position":6,"is_corresponding":false},{"id":225204,"name":"Frank L. van de Veerdonk","orcid":"0000-0002-1121-4894","position":7,"is_corresponding":false},{"id":104377,"name":"Mihai G. Netea","orcid":"0000-0003-2421-6052","position":8,"is_corresponding":false},{"id":235545,"name":"Charles A. Dinarello","orcid":"0000-0002-5073-8316","position":9,"is_corresponding":false},{"id":104383,"name":"Leo A. B. Joosten","orcid":"0000-0001-6166-9830","position":10,"is_corresponding":false},{"id":648638,"name":"Rob J.W. Arts","orcid":"0000-0002-6649-7190","position":11,"is_corresponding":false},{"id":481608,"name":"Dennis M. de Graaf","orcid":"0000-0002-9198-7159","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T00:31:12.531553Z","pmid":"36301025","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}