Browsing by Author "Vazquez, S. E."

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    Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
    (American Association for the Advancement of Science (AAAS), 2022-06-14) Bastard, P.; Vazquez, S. E.; Liu, J.; Laurie, M. T.; Wang, C. Y.; Gervais, A.; Voyer, T. L.; Bizien, L.; Zamecnik, C.; Philippot, Q.; Rosain, J.; Catherinot, E.; Willmore, A.; Mitchell, A. M.; Bair, R.; Garçon, P.; Kenney, H.; Fekkar, A.; Salagianni, M.; Poulakou, G.; Siouti, E.; Sahanic, S.; Tancevski, I.; Weiss, G.; Nagl, L; Manry, J.; Duvlis, S.; Arroyo-Sánchez, D.; Artal, E. P.; Rubio, L.; Perani, C.; Bezzi, M.; Sottini, A.; Quaresima, V.; Roussel, L.; Vinh, D. C.; Reyes, L. F.; Garzaro, M.; Hatipoglu, N.; Boutboul, D.; Tandjaoui-Lambiotte, Y.; Borghesi, A.; Aliberti, A.; Cassaniti, I.; Venet, F.; Monneret, G.; Halwani, R.; Sharif-Askari, N. S.; Danielson, J.; Burrel, S.; Morbieu, C.; Stepanovskyy, Y.; Bondarenko, A.; Volokha, A.; Boyarchuk, O.; Gagro, A.; Neuville, M.; Neven, B.; Keles, S.; Hernu, R.; Bal, A.; Novelli, A.; Novelli, G.; Saker, K.; Ailioaie, O.; Antolí, A.; Jeziorski, E.; Rocamora-Blanch, G.; Teixeira, C.; Delaunay, C.; Lhuillier, M.; Turnier, P. L.; Zhang, Y.; Mahevas, M.; Pan-Hammarström, Q.; Abolhassani, H.; Bompoil, T.; Dorgham, K.; Consortium, C.; Group, F.; Consortium, C.; Gorochov, G.; Laouenan, C.; Rodríguez-Gallego, C.; Ng, L. F. P.; Renia, L.; Pujol, A.; Belot, A.; Raffi, F.; Allende, L. M.; Martinez-Picado, J.; Özçelik, Tayfun; Imberti, L.; Notarangelo, L. D.; Troya, J.; Solanich, X.; Zhang, S.; Puel, A.; Wilson, M. R.; Trouillet-Assant, S.; Abel, L.; Jouanguy, E.; Ye, C. J.; Cobat, A.; Thompson, L. M.; Andreakos, E.; Zhang, Q.; Anderson, M. S.; Casanova, J.; DeRisi, J. L.
    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.