biostudies-literatureLopez JSquare FoundationClaude Bernard Lyon 1 UniversityFrench Foundation for Medical ResearchNCATS NIH HHSAgence Nationale de la RechercheHoward Hughes Medical InstituteGeorge Mason UniversityFondation des Hospices Civils de LyonNational Institutes of HealthJPB FoundationSt. Giles FoundationREACTingSCOR Corporate Foundation for ScienceIntegrative Biology of Emerging Infectious Diseases Laboratory of ExcellenceCentre National de la Recherche ScientifiqueFisher Center for Alzheimer's Research FoundationNIH HHSNational Center for Advancing Translational SciencesInstitut MérieuxGrandir - Fonds de solidarité pour l'enfanceGrandir - Fonds de solidarité pour l’enfanceNIAID NIH HHSInstitut National de la Santé et de la Recherche MédicaleFisher Center for Alzheimer’s Research FoundationEmergent VenturesInstitut National du CancerÉcole normale supérieure de LyonFondation ARCFondation ARC (équipe labellisée)Meyer FoundationRockefeller UniversityHospices Civils de LyonUniversity of Parise20211211https://www.ebi.ac.uk/biostudies/studies/S-EPMC8352718biostudies-literatureUnknown218(10)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 rThe Journal of experimental medicineEarly nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs.PMC8352718ANR-20-C11-0001ANRS-COV05R01AI088364R01 AI088364ANR-10-LABX-62-IBEIDUL1 TR001866ANR-20-COVI-0003EQU201903007798ANR-10-IAHU-01Padey BRosa-Calatrava MBal ABastard PMorfin FDuliere VCheynet VPaul SCasanova JLMezidi MRichard JCWalzer TPizzorno ABrengel-Pesce KLopez JBelot AMommert MTrouillet-Assant SJulien TLina BFassier JBMouton WVillard MfalseEarly nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs.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 r2021-01-01T00:00:00Z2021 Oct2026-05-31T18:02:45.822Z2025-04-05T22:20:51.669ZS-EPMC83527183435740210.1084/jem.20211211