{"doi":"10.1084/jem.20211211","title":"Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs","abstract":"IFN-I and IFN-III immunity in the nasal mucosa is poorly characterized during SARS-CoV-2 infection. We analyze the nasal IFN-I/III signature, namely the expression of ISGF-3-dependent IFN-stimulated genes, in mildly symptomatic COVID-19 patients and show its correlation with serum IFN-α2 levels, which peak at symptom onset and return to baseline from day 10 onward. Moreover, the nasal IFN-I/III signature correlates with the nasopharyngeal viral load and is associated with the presence of infectious viruses. By contrast, we observe low nasal IFN-I/III scores despite high nasal viral loads in a subset of critically ill COVID-19 patients, which correlates with the presence of autoantibodies (auto-Abs) against IFN-I in both blood and nasopharyngeal mucosa. In addition, functional assays in a reconstituted human airway epithelium model of SARS-CoV-2 infection confirm the role of such auto-Abs in abrogating the antiviral effects of IFN-I, but not those of IFN-III. Thus, IFN-I auto-Abs may compromise not only systemic but also local antiviral IFN-I immunity at the early stages of SARS-CoV-2 infection.","journal":"The Journal of Experimental Medicine","year":2021,"id":148344,"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":129,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9663,"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":630979,"name":"Marine Mommert","orcid":"0000-0001-5624-7756","position":1,"is_corresponding":false},{"id":630980,"name":"William Mouton","orcid":"0000-0002-8455-0952","position":2,"is_corresponding":false},{"id":553952,"name":"Andrés Pizzorno","orcid":"0000-0002-0918-6804","position":3,"is_corresponding":false},{"id":630981,"name":"Karen Brengel‐Pesce","orcid":"0000-0001-8795-0647","position":4,"is_corresponding":false},{"id":630982,"name":"Mehdi Mezidi","orcid":"0000-0002-8715-8323","position":5,"is_corresponding":false},{"id":630983,"name":"Marine Villard","orcid":"0000-0002-3905-8993","position":6,"is_corresponding":false},{"id":345142,"name":"Bruno Lina","orcid":"0000-0002-8959-2123","position":7,"is_corresponding":false},{"id":630984,"name":"Jean‐Christophe Richard","orcid":"0000-0003-1503-3035","position":8,"is_corresponding":false},{"id":630985,"name":"Jean‐Baptiste Fassier","orcid":"0000-0003-3885-4987","position":9,"is_corresponding":false},{"id":630986,"name":"Valérie Cheynet","orcid":"0000-0001-6168-1821","position":10,"is_corresponding":false},{"id":630987,"name":"Blandine Padey","orcid":"0000-0002-2159-6507","position":11,"is_corresponding":false},{"id":630988,"name":"Victoria Dulière","orcid":"0000-0003-2153-0927","position":12,"is_corresponding":false},{"id":630989,"name":"Thomas Julien","orcid":"0000-0002-8607-2827","position":13,"is_corresponding":false},{"id":481115,"name":"Stéphane Paul","orcid":"0000-0002-8830-4273","position":14,"is_corresponding":false},{"id":104138,"name":"Paul Bastard","orcid":"0000-0002-5926-8437","position":15,"is_corresponding":false},{"id":104157,"name":"Alexandre Bélot","orcid":"0000-0003-4902-5332","position":16,"is_corresponding":false},{"id":630990,"name":"Antonin Bal","orcid":"0000-0002-0261-2495","position":17,"is_corresponding":false},{"id":57373,"name":"Jean-Laurent Casanova","orcid":"0000-0002-7782-4169","position":18,"is_corresponding":false},{"id":553961,"name":"Manuel Rosa‐Calatrava","orcid":"0000-0002-7559-9527","position":19,"is_corresponding":false},{"id":630991,"name":"Florence Morfin","orcid":"0000-0002-1962-808X","position":20,"is_corresponding":false},{"id":287595,"name":"Thierry Walzer","orcid":"0000-0002-0857-8179","position":21,"is_corresponding":false},{"id":104154,"name":"Sophie Trouillet‐Assant","orcid":"0000-0001-6439-4705","position":22,"is_corresponding":false},{"id":630978,"name":"Jonathan Lopez","orcid":"0000-0003-3768-2378","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T23:42:41.063423Z","pmid":"34357402","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":[]}