{"doi":"10.1093/infdis/jiae031","title":"Interleukin-1 Receptor Antagonist Gene (<i>IL1RN</i>) Variants Modulate the Cytokine Release Syndrome and Mortality of COVID-19","abstract":"BACKGROUND: We examined effects of single-nucleotide variants (SNVs) of IL1RN, the gene encoding the anti-inflammatory interleukin 1 receptor antagonist (IL-1Ra), on the cytokine release syndrome (CRS) and mortality in patients with acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: IL1RN CTA haplotypes formed from 3 SNVs (rs419598, rs315952, rs9005) and the individual SNVs were assessed for association with laboratory markers of inflammation and mortality. We studied 2589 patients hospitalized with SARS-CoV-2 between March 2020 and March 2021. RESULTS: Mortality was 15.3% and lower in women than men (13.1% vs 17.3%, P = .0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra. Evaluation of the individual SNVs of the IL1RN, carriers of the rs419598 C/C SNV exhibited significantly reduced inflammatory biomarker levels and numerically lower mortality compared to the C/T-T/T genotype (10.0% vs 17.8%, P = .052) in men, with the most pronounced association observed in male patients ≤74 years old, whose mortality was reduced by 80% (3.1% vs 14.0%, P = .030). CONCLUSIONS: The IL1RN haplotype CTA and C/C variant of rs419598 are associated with attenuation of the CRS and decreased mortality in men with acute SARS-CoV-2 infection. The data suggest that the IL1RN pathway modulates the severity of coronavirus disease 2019 (COVID-19) via endogenous anti-inflammatory mechanisms.","journal":"The Journal of Infectious Diseases","year":2024,"id":442644,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9388,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":247803,"name":"Christopher M. Petrilli","orcid":"0000-0002-1424-401X","position":1,"is_corresponding":false},{"id":247795,"name":"Samrachana Adhikari","orcid":"0000-0001-9954-5999","position":2,"is_corresponding":false},{"id":810456,"name":"Eduardo Iturrate","orcid":"0000-0001-6434-2518","position":3,"is_corresponding":false},{"id":1168498,"name":"Xiyue Li","orcid":"0000-0001-7331-8544","position":4,"is_corresponding":false},{"id":429431,"name":"Stephanie Tuminello","orcid":null,"position":5,"is_corresponding":false},{"id":818919,"name":"Nan Hu","orcid":"0000-0002-3768-1554","position":6,"is_corresponding":false},{"id":21863,"name":"Aravinda Chakravarti","orcid":"0000-0002-4264-2285","position":7,"is_corresponding":false},{"id":218218,"name":"David B. Beck","orcid":"0000-0002-5884-6231","position":8,"is_corresponding":false},{"id":379126,"name":"Steven B. Abramson","orcid":"0000-0002-0668-6344","position":9,"is_corresponding":false},{"id":379120,"name":"Mukundan Attur","orcid":"0000-0001-7080-8118","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:01:20.107161Z","pmid":"38871359","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":[]}