Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

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dc.contributor.authorBastard, Paul
dc.contributor.authorVazquez, Sara
dc.contributor.authorLiu, Jamin
dc.contributor.authorLaurie, Matthew T.
dc.contributor.authorWang, Chung Yu
dc.contributor.authorGervais, Adrian
dc.contributor.authorLe Voyer, Tom
dc.date.accessioned2024-02-23T14:26:09Z
dc.date.available2024-02-23T14:26:09Z
dc.date.issued2022
dc.departmentNEÜen_US
dc.description.abstractLife-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.en_US
dc.identifier.doi10.1126/sciimmunol.abp8966
dc.identifier.issn2470-9468
dc.identifier.issue74en_US
dc.identifier.pmid35857576en_US
dc.identifier.scopus2-s2.0-85181178475en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1126/sciimmunol.abp8966
dc.identifier.urihttps://hdl.handle.net/20.500.12452/14073
dc.identifier.volume7en_US
dc.identifier.wosWOS:000933997900001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmer Assoc Advancement Scienceen_US
dc.relation.ispartofScience Immunologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject[Keyword Not Available]en_US
dc.titleVaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNsen_US
dc.typeArticleen_US

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