학술논문
Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
Document Type
article
Author
Bastard, Paul; Vazquez, Sara; Liu, Jamin; Laurie, Matthew T; Wang, Chung Yu; Gervais, Adrian; Le Voyer, Tom; Bizien, Lucy; Zamecnik, Colin; Philippot, Quentin; Rosain, Jérémie; Catherinot, Emilie; Willmore, Andrew; Mitchell, Anthea M; Bair, Rebecca; Garçon, Pierre; Kenney, Heather; Fekkar, Arnaud; Salagianni, Maria; Poulakou, Garyphallia; Siouti, Eleni; Sahanic, Sabina; Tancevski, Ivan; Weiss, Günter; Nagl, Laurenz; Manry, Jérémy; Duvlis, Sotirija; Arroyo-Sánchez, Daniel; Paz Artal, Estela; Rubio, Luis; Perani, Cristiano; Bezzi, Michela; Sottini, Alessandra; Quaresima, Virginia; Roussel, Lucie; Vinh, Donald C; Reyes, Luis Felipe; Garzaro, Margaux; Hatipoglu, Nevin; Boutboul, David; Tandjaoui-Lambiotte, Yacine; Borghesi, Alessandro; Aliberti, Anna; Cassaniti, Irene; Venet, Fabienne; Monneret, Guillaume; Halwani, Rabih; Sharif-Askari, Narjes Saheb; Danielson, Jeffrey; Burrel, Sonia; Morbieu, Caroline; Stepanovskyy, Yurii; Bondarenko, Anastasia; Volokha, Alla; Boyarchuk, Oksana; Gagro, Alenka; Neuville, Mathilde; Neven, Bénédicte; Keles, Sevgi; Hernu, Romain; Bal, Antonin; Novelli, Antonio; Novelli, Giuseppe; Saker, Kahina; Ailioaie, Oana; Antolí, Arnau; Jeziorski, Eric; Rocamora-Blanch, Gemma; Teixeira, Carla; Delaunay, Clarisse; Lhuillier, Marine; Le Turnier, Paul; Zhang, Yu; Mahevas, Matthieu; Pan-Hammarström, Qiang; Abolhassani, Hassan; Bompoil, Thierry; Dorgham, Karim; Gorochov, Guy; Laouenan, Cédric; Rodríguez-Gallego, Carlos; Ng, Lisa FP; Renia, Laurent; Pujol, Aurora; Belot, Alexandre; Raffi, François; Allende, Luis M; Martinez-Picado, Javier; Ozcelik, Tayfun; Imberti, Luisa; Notarangelo, Luigi D; Troya, Jesus; Solanich, Xavier; Zhang, Shen-Ying; Puel, Anne; Wilson, Michael R; Trouillet-Assant, Sophie; Abel, Laurent; Jouanguy, Emmanuelle
Source
Science Immunology. 7(74)
Subject
Language
Abstract
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.