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

Bastard, Paul and Vazquez, Sara and Liu, Jamin and Laurie, Matthew T and Wang, Chung Yu and Gervais, Adrian and Le Voyer, Tom and Bizien, Lucy and Zamecnik, Colin and Philippot, Quentin and Rosain, Jérémie and Catherinot, Emilie and Willmore, Andrew and Mitchell, Anthea M and Bair, Rebecca and Garçon, Pierre and Kenney, Heather and Fekkar, Arnaud and Salagianni, Maria and Poulakou, Garyphallia and Siouti, Eleni and Sahanic, Sabina and Tancevski, Ivan and Weiss, Günter and Nagl, Laurenz and Manry, Jérémy and Duvlis, Sotirija and Arroyo-Sánchez, Daniel and Paz Artal, Estela and Rubio, Luis and Perani, Cristiano and Bezzi, Michela and Sottini, Alessandra and Quaresima, Virginia and Roussel, Lucie and Vinh, Donald C and Reyes, Luis Felipe and Garzaro, Margaux and Hatipoglu, Nevin and Boutboul, David and Tandjaoui-Lambiotte, Yacine and Borghesi, Alessandro and Aliberti, Anna and Cassaniti, Irene and Venet, Fabienne and Monneret, Guillaume and Halwani, Rabih and Sharif-Askari, Narjes Saheb and Danielson, Jeffrey and Burrel, Sonia and Morbieu, Caroline and Stepanovskyy, Yurii and Bondarenko, Anastasia and Volokha, Alla and Boyarchuk, Oksana and Gagro, Alenka and Neuville, Mathilde and Neven, Bénédicte and Keles, Sevgi and Hernu, Romain and Bal, Antonin and Novelli, Antonio and Novelli, Giuseppe and Saker, Kahina and Ailioaie, Oana and Antolí, Arnau and Jeziorski, Eric and Rocamora-Blanch, Gemma and Teixeira, Carla and Delaunay, Clarisse and Lhuillier, Marine and Le Turnier, Paul and Zhang, Yu and Mahevas, Matthieu and Pan-Hammarström, Qiang and Abolhassani, Hassan and Bompoil, Thierry and Dorgham, Karim and Gorochov, Guy and Laouenan, Cédric and Rodríguez-Gallego, Carlos and Ng, Lisa F P and Renia, Laurent and Pujol, Aurora and Belot, Alexandre and Raffi, François and Allende, Luis M and Martinez-Picado, Javier and Ozcelik, Tayfun and Keles, Sevgi and Imberti, Luisa and Notarangelo, Luigi D and Troya, Jesus and Solanich, Xavier and Zhang, Shen-Ying and Puel, Anne and Wilson, Michael R and Trouillet-Assant, Sophie and Abel, Laurent and Jouanguy, Emmanuelle and Ye, Chun Jimmie and Cobat, Aurélie and Thompson, Leslie M and Andreakos, Evangelos and Zhang, Qian and Anderson, Mark S and Casanova, Jean-Laurent and DeRisi, Joseph L (2022) Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs. Science immunology. eabp8966. ISSN 2470-9468

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Life-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-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. 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.

Item Type: Article
Subjects: Medical and Health Sciences > Basic medicine
Divisions: Faculty of Medical Science
Depositing User: Sotirija Duvlis
Date Deposited: 20 Jun 2023 12:33
Last Modified: 20 Jun 2023 12:33

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