{"doi":"10.1126/sciimmunol.abl4340","title":"Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths","abstract":"Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.","journal":"Science Immunology","year":2021,"id":145196,"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":634,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":615375,"name":"Adrian Gervais","orcid":"0000-0002-1083-5787","position":1,"is_corresponding":false},{"id":104488,"name":"Tom Le Voyer","orcid":"0000-0002-0630-8626","position":2,"is_corresponding":false},{"id":104146,"name":"Jérémie Rosain","orcid":"0000-0002-2822-161X","position":3,"is_corresponding":false},{"id":104145,"name":"Quentin Philippot","orcid":"0000-0003-3429-9605","position":4,"is_corresponding":false},{"id":104148,"name":"Jérémy Manry","orcid":"0000-0001-5998-2051","position":5,"is_corresponding":false},{"id":104141,"name":"Eleftherios Michailidis","orcid":"0000-0002-9907-4346","position":6,"is_corresponding":false},{"id":104142,"name":"Hans-Heinrich Hoffmann","orcid":"0000-0003-0554-0244","position":7,"is_corresponding":false},{"id":615376,"name":"Shohei Eto","orcid":"0000-0002-2885-7490","position":8,"is_corresponding":false},{"id":615377,"name":"Marina García-Prat","orcid":"0000-0001-5387-1908","position":9,"is_corresponding":false},{"id":104153,"name":"Lucy Bizien","orcid":"0000-0001-9163-9122","position":10,"is_corresponding":false},{"id":615378,"name":"Alba Parra-Martínez","orcid":"0000-0002-9564-8912","position":11,"is_corresponding":false},{"id":104165,"name":"Rui Yang","orcid":"0000-0003-4427-2158","position":12,"is_corresponding":false},{"id":104150,"name":"Liis Haljasmägi","orcid":"0000-0001-7162-9808","position":13,"is_corresponding":false},{"id":104177,"name":"Mélanie Migaud","orcid":"0000-0003-3062-1214","position":14,"is_corresponding":false},{"id":615379,"name":"Karita Särekannu","orcid":"0000-0002-5984-668X","position":15,"is_corresponding":false},{"id":615380,"name":"Julia Maslovskaja","orcid":"0000-0002-6836-9520","position":16,"is_corresponding":false},{"id":535486,"name":"Nicolas de Prost","orcid":"0000-0002-4833-4320","position":17,"is_corresponding":false},{"id":104160,"name":"Yacine Tandjaoui-Lambiotte","orcid":"0000-0003-1123-4788","position":18,"is_corresponding":false},{"id":615381,"name":"Charles‐Édouard Luyt","orcid":"0000-0001-7424-2705","position":19,"is_corresponding":false},{"id":285927,"name":"Blanca Amador-Borrero","orcid":"0000-0001-6170-8721","position":20,"is_corresponding":false},{"id":615382,"name":"Alexandre Gaudet","orcid":"0000-0003-3787-8135","position":21,"is_corresponding":false},{"id":616937,"name":"Julien Poissy","orcid":null,"position":22,"is_corresponding":false},{"id":615383,"name":"Pascal Morel","orcid":"0000-0002-8916-7717","position":23,"is_corresponding":false},{"id":615384,"name":"Pascale Richard","orcid":"0000-0003-1864-3824","position":24,"is_corresponding":false},{"id":615385,"name":"Fabrice Cognasse","orcid":"0000-0001-8041-928X","position":25,"is_corresponding":false},{"id":83795,"name":"Jesús Troya","orcid":"0000-0001-7323-114X","position":26,"is_corresponding":false},{"id":104154,"name":"Sophie Trouillet‐Assant","orcid":"0000-0001-6439-4705","position":27,"is_corresponding":false},{"id":104157,"name":"Alexandre Bélot","orcid":"0000-0003-4902-5332","position":28,"is_corresponding":false},{"id":615386,"name":"Kahina Saker","orcid":"0000-0001-8825-5400","position":29,"is_corresponding":false},{"id":616938,"name":"Pierre Garçon","orcid":null,"position":30,"is_corresponding":false},{"id":615387,"name":"Jacques G. Rivière","orcid":"0000-0003-1055-2063","position":31,"is_corresponding":false},{"id":615388,"name":"Jean‐Christophe Lagier","orcid":"0000-0003-0771-8245","position":32,"is_corresponding":false},{"id":615389,"name":"Stéphanie Gentile","orcid":"0000-0003-3858-9503","position":33,"is_corresponding":false},{"id":104139,"name":"Lindsey B. Rosen","orcid":"0000-0001-5894-3878","position":34,"is_corresponding":false},{"id":104149,"name":"Elana Shaw","orcid":"0000-0001-9265-8026","position":35,"is_corresponding":false},{"id":57372,"name":"Tomohiro Morio","orcid":"0000-0002-9259-1025","position":36,"is_corresponding":false},{"id":615390,"name":"Junko Tanaka","orcid":"0000-0002-5669-4051","position":37,"is_corresponding":false},{"id":83488,"name":"David Dalmau","orcid":"0000-0003-1936-478X","position":38,"is_corresponding":false},{"id":260723,"name":"Pierre‐Louis Tharaux","orcid":"0000-0002-6062-5905","position":39,"is_corresponding":false},{"id":615391,"name":"D. Sène","orcid":"0000-0001-8640-4580","position":40,"is_corresponding":false},{"id":615392,"name":"Alain Stépanian","orcid":"0000-0002-2942-0901","position":41,"is_corresponding":false},{"id":615393,"name":"Bruno Mégarbane","orcid":"0000-0002-2522-2764","position":42,"is_corresponding":false},{"id":615394,"name":"Vasiliki Triantafyllia","orcid":"0000-0001-5832-4014","position":43,"is_corresponding":false},{"id":615395,"name":"Arnaud Fekkar","orcid":"0000-0001-9954-075X","position":44,"is_corresponding":false},{"id":6311,"name":"James R. Heath","orcid":"0000-0001-5356-4385","position":45,"is_corresponding":false},{"id":241312,"name":"José Luis Franco","orcid":"0000-0001-5664-6415","position":46,"is_corresponding":false},{"id":615396,"name":"Juan‐Manuel Anaya","orcid":"0000-0002-6444-1249","position":47,"is_corresponding":false},{"id":84251,"name":"Jordi Solé‐Violán","orcid":"0000-0002-0483-4470","position":48,"is_corresponding":false},{"id":104205,"name":"Luisa Imberti","orcid":"0000-0002-2075-8391","position":49,"is_corresponding":false},{"id":104195,"name":"Andrea Biondi","orcid":"0000-0002-6757-6173","position":50,"is_corresponding":false},{"id":104198,"name":"Paolo Bonfanti","orcid":"0000-0001-7289-8823","position":51,"is_corresponding":false},{"id":104210,"name":"Riccardo Castagnoli","orcid":"0000-0003-0029-9383","position":52,"is_corresponding":false},{"id":104168,"name":"Ottavia M. Delmonte","orcid":"0000-0002-4772-0799","position":53,"is_corresponding":false},{"id":104143,"name":"Yu Zhang","orcid":"0000-0002-6904-0372","position":54,"is_corresponding":false},{"id":241321,"name":"Andrew L. Snow","orcid":"0000-0002-8728-6691","position":55,"is_corresponding":false},{"id":104227,"name":"Steven M. Holland","orcid":"0000-0003-3207-5464","position":56,"is_corresponding":false},{"id":241302,"name":"Catherine M. Biggs","orcid":"0000-0002-4363-2660","position":57,"is_corresponding":false},{"id":104461,"name":"Marcela Moncada‐Vélez","orcid":"0000-0002-3073-5345","position":58,"is_corresponding":false},{"id":104468,"name":"Andrés A. Arias","orcid":"0000-0002-9478-8403","position":59,"is_corresponding":false},{"id":104152,"name":"Lazaro Lorenzo","orcid":"0000-0001-6648-8684","position":60,"is_corresponding":false},{"id":273551,"name":"Soraya Boucherit","orcid":"0000-0002-8819-7594","position":61,"is_corresponding":false},{"id":311248,"name":"Boubacar Coulibaly","orcid":"0000-0002-4777-6741","position":62,"is_corresponding":false},{"id":615397,"name":"Dany Anglicheau","orcid":"0000-0001-5793-6174","position":63,"is_corresponding":false},{"id":241318,"name":"Anna M. Planas","orcid":"0000-0002-6147-1880","position":64,"is_corresponding":false},{"id":104186,"name":"Filomeen Haerynck","orcid":"0000-0001-9161-7361","position":65,"is_corresponding":false},{"id":615398,"name":"Sotiriјa Duvlis","orcid":"0000-0001-8587-7386","position":66,"is_corresponding":false},{"id":2900,"name":"Robert L. Nussbaum","orcid":"0000-0003-3445-8880","position":67,"is_corresponding":false},{"id":104513,"name":"Tayfun Özçelık","orcid":"0000-0001-5937-1082","position":68,"is_corresponding":false},{"id":104511,"name":"Sevgi Keleş","orcid":"0000-0001-7344-8947","position":69,"is_corresponding":false},{"id":615399,"name":"Ahmed Aziz Bousfiha","orcid":"0000-0002-5011-9873","position":70,"is_corresponding":false},{"id":615400,"name":"Jalila El Bakkouri","orcid":"0000-0003-2303-3369","position":71,"is_corresponding":false},{"id":615401,"name":"Carolina Ramı́rez-Santana","orcid":"0000-0003-2137-4899","position":72,"is_corresponding":false},{"id":481115,"name":"Stéphane Paul","orcid":"0000-0002-8830-4273","position":73,"is_corresponding":false},{"id":14420,"name":"Qiang Pan‐Hammarström","orcid":"0000-0003-1990-8804","position":74,"is_corresponding":false},{"id":281914,"name":"Lennart Hammarström","orcid":"0000-0002-8635-9609","position":75,"is_corresponding":false},{"id":615402,"name":"Annabelle Dupont","orcid":"0000-0002-1554-9931","position":76,"is_corresponding":false},{"id":585381,"name":"Alina Kurolap","orcid":"0000-0002-7005-3621","position":77,"is_corresponding":false},{"id":228215,"name":"Christine N. Metz","orcid":"0000-0002-1013-1691","position":78,"is_corresponding":false},{"id":104170,"name":"Alessandro Aiuti","orcid":"0000-0002-5398-1717","position":79,"is_corresponding":false},{"id":104171,"name":"Giorgio Casari","orcid":"0000-0002-0115-8980","position":80,"is_corresponding":false},{"id":104172,"name":"Vito Lampasona","orcid":"0000-0001-5162-8445","position":81,"is_corresponding":false},{"id":104174,"name":"Fabio Ciceri","orcid":"0000-0003-0873-0123","position":82,"is_corresponding":false},{"id":615403,"name":"Lucila Akune Barreiros","orcid":"0000-0002-9818-2345","position":83,"is_corresponding":false},{"id":615404,"name":"Elena Domínguez‐Garrido","orcid":"0000-0002-2066-0511","position":84,"is_corresponding":false},{"id":616939,"name":"Mateus Vidigal","orcid":null,"position":85,"is_corresponding":false},{"id":615405,"name":"Mayana Zatz","orcid":"0000-0003-3970-8025","position":86,"is_corresponding":false},{"id":104182,"name":"Diederik van de Beek","orcid":"0000-0002-4571-044X","position":87,"is_corresponding":false},{"id":615406,"name":"Sabina Sahanic","orcid":"0000-0002-0583-9310","position":88,"is_corresponding":false},{"id":615407,"name":"Ivan Tancevski","orcid":"0000-0001-5116-8960","position":89,"is_corresponding":false},{"id":615408,"name":"Yuriy Stepanovskyy","orcid":"0000-0001-6339-5490","position":90,"is_corresponding":false},{"id":615409,"name":"Oksana Boyarchuk","orcid":"0000-0002-1234-0040","position":91,"is_corresponding":false},{"id":615410,"name":"Yoko Nukui","orcid":"0000-0002-6123-5212","position":92,"is_corresponding":false},{"id":615411,"name":"Miyuki Tsumura","orcid":"0000-0002-8272-9588","position":93,"is_corresponding":false},{"id":615412,"name":"Loreto Vidaur","orcid":"0000-0002-6720-4900","position":94,"is_corresponding":false},{"id":104185,"name":"Stuart G. Tangye","orcid":"0000-0002-5360-5180","position":95,"is_corresponding":false},{"id":615413,"name":"Sonia Burrel","orcid":"0000-0002-7783-2601","position":96,"is_corresponding":false},{"id":104180,"name":"Darragh Duffy","orcid":"0000-0002-8875-2308","position":97,"is_corresponding":false},{"id":104181,"name":"Lluís Quintana‐Murci","orcid":"0000-0003-2429-6320","position":98,"is_corresponding":false},{"id":615414,"name":"Adam Klocperk","orcid":"0000-0002-1526-4557","position":99,"is_corresponding":false},{"id":104138,"name":"Paul Bastard","orcid":"0000-0002-5926-8437","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:41:52.374756Z","pmid":"34413139","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":[]}