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 - Dalgard, Clifton L.
N1 - 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 - 10.1126/sciimmunol.abp8966
DO - 10.1126/sciimmunol.abp8966
M3 - Article
C2 - 35857576
AN - SCOPUS:85181178475
SN - 2470-9468
VL - 8
JO - Science Immunology
JF - Science Immunology
IS - 90
M1 - eabp8966
ER -