{"entity": "publication", "iuid": "80ced4ca3b5941f092f5450858912ad4", "timestamp": "2026-09-30T22:59:24.319Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/80ced4ca3b5941f092f5450858912ad4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/80ced4ca3b5941f092f5450858912ad4"}}, "title": "OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2.", "authors": [{"family": "DeDiego", "given": "Marta L", "initials": "ML"}, {"family": "L\u00f3pez-Fern\u00e1ndez-Sobrino", "given": "Ra\u00fal", "initials": "R"}, {"family": "Pedragosa", "given": "Jordi", "initials": "J"}, {"family": "L\u00f3pez-Garc\u00eda", "given": "Dar\u00edo", "initials": "D"}, {"family": "Nogales", "given": "Aitor", "initials": "A"}, {"family": "Durb\u00e1n", "given": "Jordi", "initials": "J"}, {"family": "Cardona", "given": "Fernando", "initials": "F"}, {"family": "Lluci\u00e0-Carol", "given": "Laia", "initials": "L"}, {"family": "Rivero", "given": "Vanessa", "initials": "V"}, {"family": "Vazquez-Utrilla", "given": "Paula", "initials": "P"}, {"family": "Sanchez-Grande", "given": "Laura Palomo", "initials": "LP"}, {"family": "Cobo", "given": "Miriam", "initials": "M"}, {"family": "Lloret", "given": "Lara", "initials": "L"}, {"family": "M\u00e1rquez-Kisinousky", "given": "Leonardo", "initials": "L"}, {"family": "Ruiz-Ja\u00e9n", "given": "Francisca", "initials": "F"}, {"family": "Lozano", "given": "Francisco", "initials": "F"}, {"family": "Sibila", "given": "Oriol", "initials": "O"}, {"family": "Faner", "given": "Rosa", "initials": "R"}, {"family": "Castro", "given": "Pedro", "initials": "P"}, {"family": "Domingo", "given": "Carlos", "initials": "C"}, {"family": "Robles", "given": "Ver\u00f3nica", "initials": "V"}, {"family": "Bedini", "given": "Josep L", "initials": "JL"}, {"family": "Rico", "given": "Ver\u00f3nica", "initials": "V"}, {"family": "Aguero", "given": "Daiana", "initials": "D"}, {"family": "Soriano", "given": "Alex", "initials": "A"}, {"family": "Nalda", "given": "Andrea Mart\u00edn", "initials": "AM"}, {"family": "Mart\u00ednez", "given": "Alba Parra", "initials": "AP"}, {"family": "Colobran", "given": "Roger", "initials": "R"}, {"family": "Soler-Palac\u00edn", "given": "Pere", "initials": "P"}, {"family": "Serra-Llovich", "given": "Alexandre", "initials": "A"}, {"family": "Dietl", "given": "Beatriz", "initials": "B"}, {"family": "Arranz", "given": "M Jes\u00fas", "initials": "MJ"}, {"family": "Dalmau", "given": "David", "initials": "D"}, {"family": "Signes-Costa", "given": "Jaime", "initials": "J"}, {"family": "Gil-Carbonell", "given": "Joan", "initials": "J"}, {"family": "Todol\u00ed", "given": "Jos\u00e9", "initials": "J"}, {"family": "Mart\u00ednez", "given": "Jacobo", "initials": "J"}, {"family": "Rojo", "given": "Silvia", "initials": "S"}, {"family": "Fiz-L\u00f3pez", "given": "Aida", "initials": "A"}, {"family": "Arribas", "given": "Elisa", "initials": "E"}, {"family": "Cal-Sabater", "given": "Paloma", "initials": "P"}, {"family": "Bernado", "given": "David", "initials": "D"}, {"family": "Vogel", "given": "Marina", "initials": "M"}, {"family": "Wiemann", "given": "Stefan", "initials": "S"}, {"family": "Abolhassani", "given": "Hassan", "initials": "H"}, {"family": "Pan-Hammarstr\u00f6m", "given": "Qiang", "initials": "Q"}, {"family": "Pujol", "given": "Aurora", "initials": "A"}, {"family": "COVID Human Genetic Effort", "given": "", "initials": ""}, {"family": "Su", "given": "Helen C", "initials": "HC"}, {"family": "Lee", "given": "Danyel", "initials": "D"}, {"family": "Zhang", "given": "Shen-Ying", "initials": "SY"}, {"family": "Casanova", "given": "Jean-Laurent", "initials": "JL"}, {"family": "Fern\u00e1ndez-Cadenas", "given": "Israel", "initials": "I"}, {"family": "P\u00e9rez-Tur", "given": "Jordi", "initials": "J"}, {"family": "Planas", "given": "Anna M", "initials": "AM"}], "type": "journal article", "published": "2025-12-19", "journal": {"title": "iScience", "issn": "2589-0042", "volume": "28", "issue": "12", "pages": "113966", "issn-l": null}, "abstract": "Recessive deficiency in 2',5'-oligoadenylate synthetase (OAS) or RNase L can cause systemic inflammation in children with SARS-CoV-2 infection, but its role in adult respiratory disease is unclear. We analyzed rare OAS1/OAS3 variants and the common OAS1 rs10774671 polymorphism in 342 COVID-19 patients, assessing enzymatic activity, RNase L activation, viral replication, and inflammation in cell systems and Oas3-deficient mice. Rare heterozygous variants showed impaired RNase L activation but were not enriched in pneumonia cases. In contrast, the rs10774671 A/A genotype (OAS1-p42 isoform) was associated with severe disease (OR = 2.28; 95% CI = 1.13-4.58; p = 0.0107) and reduced viral control despite intact RNase L activation. OAS3 and OAS1-p46 isoform limited viral replication and inflammatory responses, whereas Oas3-deficient mice showed increased cytokines. These findings suggest that common OAS1 variation influences COVID-19 severity, while rare OAS variants may affect inflammation regulation rather than respiratory pathology.", "doi": "10.1016/j.isci.2025.113966", "pmid": "41438061", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12719101"}, {"db": "pii", "key": "S2589-0042(25)02227-8"}], "notes": [], "created": "2026-09-23T13:25:15.628Z", "modified": "2026-09-23T13:25:15.657Z"}