Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
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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, 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 | Achille, Cristian | Aiuti, Alessandro | Al-Muhsen, Saleh | Al-Mulla, Fahd | Angelini, Micol | Arias, Andrés, A | Aytekin, Gokhan | Baldanti, Fausto | Feldman, Hagit, Baris | Bergami, Federica | Biggs, Catherine, M | Bogunovic, Dusan | Bolze, Alexandre | Bondarenko, Anastasiia | Bousfiha, Ahmed, A | Brodin, Petter | Bryceson, Yenan | Bustamante, Carlos, D | Butte, Manish, J | Casari, Giorgio | Christodoulou, John | Condino-Neto, Antonio | Constantinescu, Stefan, N | Conti, Francesca | Cooper, Megan, A | Dalgard, Clifton, L | Desai, Murkesh | Drolet, Beth, A | El Baghdadi, Jamila | Ergun, Recai | Ergun, Dilek | Espinosa-Padilla, Sara | Fellay, Jacques | Flores, Carlos | Franco, José, Luis | Froidure, Antoine | Ghirardello, Stefano | Gregersen, Peter, K | Grimbacher, Bodo | Haerynck, Filomeen | Hagin, David | Hammarström, Lennart | Heath, James, R | Henrickson, Sarah, E | Hsieh, Elena, W Y | Husebye, Eystein | Imai, Kohsuke | Itan, Yuval | Jarvis, Erich, D | Kanat, Fikret | Karamitros, Timokratis | Kisand, Kai | Kopcha, Vasyl | Korda, Mykhaylo | Ku, Cheng-Lung | Lau, Yu-Lung | Ling, Yun | Lucas, Carrie, L | Maniatis, Tom | Mansouri, Davood | Maródi, László | Meyts, Isabelle | Milner, Joshua, D | Mironska, Kristina | Mogensen, Trine, H | Mojoli, Francesco | Morandeira, Francisco | Morio, Tomohiro | O'Farrelly, Cliona | Okada, Satoshi | Okamoto, Keisuke | Pagani, Michele | Pape, Jean, W | de Diego, Rebeca, Perez | Perlin, David, S | Pesole, Graziano | Pession, Andrea | Piralla, Antonio | Planas, Anna, M | Prando, Carolina | Quintana-Murci, Lluis | Ramaswamy, Sathishkumar | Resnick, Igor | Rigo-Bonnin, Raúl | Sancho-Shimizu, Vanessa | Sediva, Anna | Seppänen, Mikko, R J | Shahrooei, Mohammed | Shcherbina, Anna | Slaby, Ondrej | Snow, Andrew, L | Soler-Palacín, Pere | Spaan, András, N | Tangye, Stuart, G | Abou Tayoun, Ahmad | Tulek, Baykal | Turvey, Stuart, E | Uddin, K, M Furkan | Uddin, Mohammed | Clément, Bénédicte | Abe-Jones, Yumiko | Asthana, Saurabh | Bhide, Sharvari | Calfee, Carolyn, S | Carrillo, Sidney, A | Chak, Suzanna | Collins, Zachary | Erle, David, J | Fragiadakis, Gabriela, K | Ghale, Rajani | Hendrickson, Carolyn, M | Jauregui, Alejandra | Kangelaris, Kirsten, N | Krummel, Matthew, F | Langelier, Charles, R | Lea, Tasha | Lee, Deanna | Leligdowicz, Aleksandra | Leroux, Carolyn | Lota, Raphael | Matthay, Michael | Nguyen, Viet | Patel, Ravi | Pierce, Logan | Prasad, Priya | Rao, Arjun, Arkal | Rashid, Ahmad | Rodriguez, Nicklaus | Samad, Bushra | Shaw, Cole | Sigman, Austin | Tang, Kevin | Altamirano, Luz, Torres | Ward, Alyssa | Woodruff, Prescott, G | Allavena, Clotilde | Andrejak, Claire | Angoulvant, François | Azoulay, Cecile | Bachelet, Delphine | Bartoli, Marie | Basmaci, Romain | Behilill, Sylvie | Beluze, Marine | Benech, Nicolas | Benkerrou, Dehbia | Bhavsar, Krishna | Bitker, Laurent | Bouadma, Lila | Bouscambert, Maude | Paz, Pauline, Caraux | Cervantes-Gonzalez, Minerva | Chair, Anissa | Chirouze, Catherine | Coelho, Alexandra | Cordel, Hugues | Couffignal, Camille | Couffin-Cadiergues, Sandrine | D’ortenzio, Eric | de Montmollin, Etienne | Debard, Alexa | Debray, Marie-Pierre | Deplanque, Dominique | Descamps, Diane | Desvallée, Mathilde | Diallo, Alpha | Diehl, Jean-Luc | Diouf, Alphonsine | Dorival, Céline | Dubos, François | Duval, Xavier | Eloy, Philippine | Enouf, Vincent | Epaulard, Olivier | Esperou, Hélène | Esposito-Farese, Marina | Etienne, Manuel | Garot, Denis | Gault, Nathalie | Gaymard, Alexandre | Ghosn, Jade | Gigante, Tristan | Gilg, Morgane | Goehringer, François | Guedj, Jérémie | Hoctin, Alexandre | Hoffmann, Isabelle | Houas, Ikram | Hulot, Jean-Sébastien | Jaafoura, Salma | Kafif, Ouifiya | Kaguelidou, Florentia | Kali, Sabrina | Kerroumi, Younes | Khalil, Antoine | Khan, Coralie | Kimmoun, Antoine | Laine, Fabrice | Laouénan, Cédric | Laribi, Samira | Le, Minh | Le Bris, Cyril | Le Gac, Sylvie | Le Hingrat, Quentin | Le Mestre, Soizic | Le Nagard, Hervé | Lemaignen, Adrien | Lemee, Véronique | Lescure, François-Xavier | Letrou, Sophie | Levy, Yves | Lina, Bruno | Lingas, Guillaume | Lucet, Jean, Christophe | Machado, Moïse | Malvy, Denis | Mambert, Marina | Manuel, Aldric | Mentré, France | Meziane, Amina | Mouquet, Hugo | Mullaert, Jimmy | Neant, Nadège | Nguyen, Duc | Noret, Marion | Papadopoulos, Aurélie | Paul, Christelle | Peiffer-Smadja, Nathan | Peigne, Vincent | Petrov-Sanchez, Ventzislava | Peytavin, Gilles | Pham, Huong | Picone, Olivier | Piquard, Valentine | Poissy, Julien | Puéchal, Oriane | Rosa-Calatrava, Manuel | Rossignol, Bénédicte | Rossignol, Patrick | Roy, Carine | Schneider, Marion | Su, Richa | Tardivon, Coralie | Tellier, Marie-Capucine | Téoulé, François | Terrier, Olivier | Timsit, Jean-François | Tual, Christelle | Tubiana, Sarah | van der Werf, Sylvie | Vanel, Noémie | Veislinger, Aurélie | Visseaux, Benoit | Wiedemann, Aurélie | Yazdanpanah, Yazdan
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CCSD ; American Association for the Advancement of Science (AAAS) -
International audience.
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.
