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

• Autor(es): Bastard, Paul ; Vazquez, Sara E. ; 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 F. P. ; 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 ; Ye, Chun Jimmie ; Cobat, Aurélie ; Thompson, Leslie M. ; Andreakos, Evangelos ; Zhang, Qian ; Anderson, Mark S. ; Casanova, Jean-Laurent ; DeRisi, Joseph L.
• Data: 2023
• Identificador Persistente: http://hdl.handle.net/10400.16/3012
• Origem: Repositório Científico da Unidade Local de Saúde de Santo António (ULSSA)
• Tipo de Documento: Artigo científico
• Idioma: Inglês
• Contribuidor(es): Repositório Científico da Unidade Local de Saúde de Santo António

Descrição

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.