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-a2 and IFN-w, whereas two neutralized IFN-w only. No patient neutralized IFN-b. 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.
Original language | English |
---|---|
Article number | eabp8966 |
Journal | Science immunology |
Volume | 8 |
Issue number | 90 |
DOIs | |
Publication status | Published - Dec 2023 |
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In: Science immunology, Vol. 8, No. 90, eabp8966, 12.2023.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
AU - COVID HGE consortium
AU - French COVID Study Group
AU - Consortium
AU - Bastard, Paul
AU - Vazquez, Sara E.
AU - Liu, Jamin
AU - Laurie, Matthew T.
AU - Wang, Chung Yu
AU - Gervais, Adrian
AU - Voyer, Tom Le
AU - Bizien, Lucy
AU - Zamecnik, Colin
AU - Philippot, Quentin
AU - Rosain, Jérémie
AU - Catherinot, Emilie
AU - Willmore, Andrew
AU - Mitchell, Anthea M.
AU - Bair, Rebecca
AU - Garçon, Pierre
AU - Kenney, Heather
AU - Fekkar, Arnaud
AU - Salagianni, Maria
AU - Poulakou, Garyphallia
AU - Siouti, Eleni
AU - Sahanic, Sabina
AU - Tancevski, Ivan
AU - Weiss, Günter
AU - Nagl, Laurenz
AU - Manry, Jérémy
AU - Duvlis, Sotirija
AU - Arroyo-Sánchez, Daniel
AU - Artal, Estela Paz
AU - Rubio, Luis
AU - Perani, Cristiano
AU - Bezzi, Michela
AU - Sottini, Alessandra
AU - Quaresima, Virginia
AU - Roussel, Lucie
AU - Vinh, Donald C.
AU - Reyes, Luis Felipe
AU - Garzaro, Margaux
AU - Hatipoglu, Nevin
AU - Boutboul, David
AU - Tandjaoui-Lambiotte, Yacine
AU - Borghesi, Alessandro
AU - Aliberti, Anna
AU - Cassaniti, Irene
AU - Venet, Fabienne
AU - Monneret, Guillaume
AU - Halwani, Rabih
AU - Sharif-Askari, Narjes Saheb
AU - Danielson, Jeffrey
AU - van de Beek, Diederik
N1 - Funding Information: 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). Publisher Copyright: Copyright © 2023 The Authors, some rights reserved.
PY - 2023/12
Y1 - 2023/12
N2 - 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-a2 and IFN-w, whereas two neutralized IFN-w only. No patient neutralized IFN-b. 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.
AB - 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-a2 and IFN-w, whereas two neutralized IFN-w only. No patient neutralized IFN-b. 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.
UR - http://www.scopus.com/inward/record.url?scp=85181178475&partnerID=8YFLogxK
U2 - https://doi.org/10.1126/sciimmunol.abp8966
DO - https://doi.org/10.1126/sciimmunol.abp8966
M3 - Article
C2 - 35857576
SN - 2470-9468
VL - 8
JO - Science immunology
JF - Science immunology
IS - 90
M1 - eabp8966
ER -