{"doi":"10.1126/scitranslmed.adq1789","title":"Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19","abstract":"Preexisting anti-interferon-α (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, to quantify and profile the isotypes of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-IFN-α antibodies in longitudinal samples collected over 20 months from the airways and blood of 129 donors spanning mild to severe COVID-19. We found that nasal IgA1 anti-IFN-α autoantibodies were induced after infection onset in more than 70% of mild and moderate COVID-19 cases and were associated with robust anti-SARS-CoV-2 immunity, fewer symptoms, and efficient recovery. Nasal anti-IFN-α autoantibodies followed the peak of host IFN-α production and waned with disease recovery, revealing a regulated balance between IFN-α and anti-IFN-α response. In contrast, systemic IgG1 anti-IFN-α autoantibodies appeared later and were detected only in a subset of patients with elevated systemic inflammation and worsening symptoms. These data reveal a protective role for nasal anti-IFN-α in the immunopathology of COVID-19 and suggest that anti-IFN-α autoantibodies may serve a homeostatic function to regulate host IFN-α after viral infection in the respiratory mucosa.","journal":"Science Translational Medicine","year":2024,"id":433382,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9693,"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":246064,"name":"Astrid Kosters","orcid":"0000-0002-4771-5236","position":1,"is_corresponding":false},{"id":677874,"name":"Devon J. 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Giacalone","orcid":"0000-0002-3496-7776","position":11,"is_corresponding":false},{"id":393272,"name":"Rabindra Tirouvanziam","orcid":"0000-0003-3526-9985","position":12,"is_corresponding":false},{"id":108278,"name":"Richard P. Ramonell","orcid":"0000-0002-2385-0636","position":13,"is_corresponding":false},{"id":108297,"name":"Scott A. Jenks","orcid":"0000-0001-7485-8331","position":14,"is_corresponding":false},{"id":108304,"name":"Igñacio Sanz","orcid":"0000-0003-4182-587X","position":15,"is_corresponding":false},{"id":108303,"name":"F. Eun‐Hyung Lee","orcid":"0000-0002-6133-5942","position":16,"is_corresponding":false},{"id":71692,"name":"Nadia R. Roan","orcid":"0000-0002-5464-1976","position":17,"is_corresponding":false},{"id":75994,"name":"Sulggi A. 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