{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:00:01Z","timestamp":1793761201853,"version":"4.6.1"},"reference-count":58,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"90","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2023,12,22]]},"abstract":"<jats:p>Life-threatening \u201cbreakthrough\u201d cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Ab 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 Ab response to the vaccine. Among them, 10 (24%) had auto-Abs neutralizing type I IFNs (aged 43 to 86 years). Eight of these 10 patients had auto-Abs neutralizing both IFN-\u03b12 and IFN-\u03c9, whereas two neutralized IFN-\u03c9 only. No patient neutralized IFN-\u03b2. Seven neutralized type I IFNs at 10 ng\/ml and three at 100 pg\/ml only. Seven patients neutralized SARS-CoV-2 D614G and Delta efficiently, whereas one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only type I IFNs at 100 pg\/ml neutralized both D614G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating Abs capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a notable proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.<\/jats:p>","DOI":"10.1126\/sciimmunol.abp8966","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T13:59:01Z","timestamp":1655215141000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":60,"title":["Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5926-8437","authenticated-orcid":true,"given":"Paul","family":"Bastard","sequence":"first","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France."},{"name":"Imagine Institute, University of Paris Cit\u00e9, Paris, France."},{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA."},{"name":"Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0601-7001","authenticated-orcid":true,"given":"Sara E.","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA 94143, USA."},{"name":"Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA."},{"name":"Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6386-3709","authenticated-orcid":true,"given":"Jamin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA."},{"name":"University of California, Berkeley\u2013University of California, San Francisco Graduate Program in Bioengineering, University of California, San Francisco, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3526-7368","authenticated-orcid":true,"given":"Matthew T.","family":"Laurie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1083-5787","authenticated-orcid":true,"given":"Adrian","family":"Gervais","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France."},{"name":"Imagine Institute, University of Paris Cit\u00e9, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0630-8626","authenticated-orcid":true,"given":"Tom","family":"Le Voyer","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France."},{"name":"Imagine Institute, University of Paris Cit\u00e9, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9163-9122","authenticated-orcid":true,"given":"Lucy","family":"Bizien","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France."},{"name":"Imagine Institute, University of Paris Cit\u00e9, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9477-1388","authenticated-orcid":true,"given":"Colin","family":"Zamecnik","sequence":"additional","affiliation":[{"name":"Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Philippot","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France."},{"name":"Imagine Institute, University of Paris Cit\u00e9, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2822-161X","authenticated-orcid":true,"given":"J\u00e9r\u00e9mie","family":"Rosain","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France."},{"name":"Imagine Institute, University of Paris Cit\u00e9, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Catherinot","sequence":"additional","affiliation":[{"name":"Pneumology Department, Foch Hospital, Suresne, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Willmore","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, 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