| Title: |
Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs |
| Authors: |
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 |
| Contributors: |
Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163); Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Rockefeller University New York; University of California San Francisco (UC San Francisco); University of California (UC); Chan Zuckerberg BioHub San Francisco, CA; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Hôpital Foch Suresnes; Grand Hôpital de l'Est Francilien (GHEF); CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); 4th Department of Internal Medicine; “Attikon” University Hospital; Innsbruck Medical University = Medizinische Universität Innsbruck (IMU); Goce Delchev University (UGD); Pathogenesis and Control of Chronic and Emerging Infections (PCCEI); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Établissement Français du Sang Montpellier (EFS - Montpellier); Établissement Français du Sang La Plaine Saint-Denis (EFS)-Établissement Français du Sang La Plaine Saint-Denis (EFS)-Université de Montpellier (UM); Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier); Génétique Evolutive Humaine - Human Evolutionary Genetics; Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute; The Rockefeller University; the St. Giles Foundation; the NIH (R01AI088364 and R01AI163029); the National Center for Advancing Translational Sciences (NCATS); NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866); a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University; the Fisher Center for Alzheimer’s Research Foundation; the Meyer Foundation; the JPB Foundation; the program “Investissement d’Avenir” launched by the French Government and implemented by the Agence Nationale de la Recherche (ANR) with references ANR-21-RHUS-08 and ANR-10-IAHU-01; the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM; EQU201903007798); the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), ANR AABIFNCOV (ANR-20-CO11-0001), and ANR GenMISC (ANR-21-COVR-0039) projects; the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 824110 (EASI-genomics); the Square Foundation; Grandir–Fonds de solidarité pour l’enfance; the Fondation du Souffle; the SCOR Corporate Foundation for Science; the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19); Institut National de la Santé et de la Recherche Médicale (INSERM); REACTing-INSERM; and the University of Paris. C.R.-G., R.P.D., and C.F. were funded by Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, UE), the Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC19/43), Grupo DISA (OA18/017), Fundación MAPFRE Guanarteme (OA21/131), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). E.A. is supported by the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574) and the European Commission’s Horizon 2020 research and innovation programme (CURE, grant no. 767015; IMMUNAID, grant no. 779295). L.R. and L.F.P.N. were supported by Singapore National Medical Research Council COVID-19 Research Fund (COVID19RF-001, COVID19RF-007, COVID19RF-0008, and COVID19RF-060) and A*STAR COVID-19 Research funding (H/20/04/g1/006). The UCSF COMET Consortium is supported by the Clinical and Translational Science Institute University of California, San Francisco and the NIH (U19AI077439). A.A., G.R.-B., and X.S. are funded by the 202115-31 project, funded by La Marató de TV3. L.D.N. was supported by the intramural Research Program of the NIAID, NIH. J.L.D. is supported by the Chan Zuckerberg Biohub. We acknowledge the support of the Chao Family Comprehensive Cancer Center Experimental Tissue Shared Resource, supported by the National Cancer Institute of the NIH under award number P30CA062203. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. P.B. was supported by the FRM (EA20170638020). P.B. and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller).; ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021); ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020); ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020); ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021); ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010); European Project: 824110,H2020-INFRAIA-2018-2020,H2020-INFRAIA-2018-1,EASI-Genomics(2019); European Project: 767015,H2020-FETOPEN-2016-2017,H2020-FETOPEN-1-2016-2017,CURE(2017); European Project: 779295,H2020-SC1-2016-2017,H2020-SC1-2017-Single-Stage-RTD,ImmunAID(2018) |
| Source: |
ISSN: 2470-9468 ; Science Immunology ; https://hal.sorbonne-universite.fr/hal-03948899 ; Science Immunology, 2022, 8 (90), eabp8966. ⟨10.1126/sciimmunol.abp8966⟩. |
| Publisher Information: |
CCSD; American Association for the Advancement of Science (AAAS) |
| Publication Year: |
2022 |
| Collection: |
Institut Pasteur: HAL |
| Subject Terms: |
MESH: COVID-19 Vaccines; MESH: COVID-19; MESH: Humans; MESH: Interferon Type 1; MESH: RNA; Messenger; MESH: SARS-CoV-2; MESH: Vaccination; MESH: Vaccines; [SDV.IMM]Life Sciences [q-bio]/Immunology |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/35857576; info:eu-repo/grantAgreement//824110/EU/European Advanced infraStructure for Innovative Genomics/EASI-Genomics; info:eu-repo/grantAgreement//767015/EU/Constructing a ‘Eubiosis Reinstatement Therapy’ for Asthma/CURE; info:eu-repo/grantAgreement//779295/EU/Immunome project consortium for AutoInflammatory Disorders/ImmunAID; PUBMED: 35857576; PUBMEDCENTRAL: PMC9210448; WOS: 000933997900001 |
| DOI: |
10.1126/sciimmunol.abp8966 |
| Availability: |
https://hal.sorbonne-universite.fr/hal-03948899; https://hal.sorbonne-universite.fr/hal-03948899v1/document; https://hal.sorbonne-universite.fr/hal-03948899v1/file/sciimmunol.abp8966.pdf; https://doi.org/10.1126/sciimmunol.abp8966 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.CEF648B8 |
| Database: |
BASE |