Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
Life-threatening "breakthrough" 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-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. 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.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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Enthalten in: |
Science immunology - 8(2023), 90 vom: 22. Dez., Seite eabp8966 |
Sprache: |
Englisch |
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Links: |
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Themen: |
COVID-19 Vaccines |
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Anmerkungen: |
Date Completed 25.12.2023 Date Revised 25.12.2023 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1126/sciimmunol.abp8966 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM343776448 |
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520 | |a Life-threatening "breakthrough" 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-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. 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 | ||
650 | 4 | |a Journal Article | |
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650 | 7 | |a Vaccines |2 NLM | |
650 | 7 | |a Interferon Type I |2 NLM | |
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