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

被引：42

作者：

Bastard, Paul ^{[1
,2
,3
,4
]}

Vazquez, Sara ^{[5
,6
,7
]}

Liu, Jamin ^{[8
,9
]}

Laurie, Matthew T. ^{[8
]}

Wang, Chung Yu ^{[10
]}

Gervais, Adrian ^{[1
,2
]}

Le Voyer, Tom ^{[1
,2
]}

Bizien, Lucy ^{[1
,2
]}

Zamecnik, Colin ^{[11
]}

Philippot, Quentin ^{[1
,2
]}

Rosain, Jeremie ^{[1
,2
]}

Catherinot, Emilie ^{[12
]}

Willmore, Andrew ^{[10
]}

Mitchell, Anthea M. ^{[10
]}

Bair, Rebecca ^{[11
]}

Garcon, Pierre ^{[13
]}

Kenney, Heather ^{[14
]}

Fekkar, Arnaud ^{[1
,2
,15
]}

Salagianni, Maria ^{[16
]}

Poulakou, Garyphallia ^{[17
]}

Siouti, Eleni ^{[16
]}

Sahanic, Sabina ^{[18
]}

Tancevski, Ivan ^{[18
]}

Weiss, Gunter ^{[18
]}

Nagl, Laurenz ^{[19
]}

Manry, Jeremy ^{[1
,2
]}

Duvlis, Sotirija ^{[20
,21
]}

Arroyo-Sanchez, Daniel ^{[22
,23
]}

Paz Artal, Estela ^{[22
,23
]}

Rubio, Luis ^{[8
]}

Perani, Cristiano ^{[24
]}

Bezzi, Michela ^{[25
]}

Sottini, Alessandra ^{[26
]}

Quaresima, Virginia ^{[26
]}

Roussel, Lucie ^{[27
,28
]}

Vinh, Donald C. ^{[27
,28
]}

Felipe Reyes, Luis ^{[29
,30
]}

Garzaro, Margaux ^{[31
]}

Hatipoglu, Nevin ^{[32
]}

Boutboul, David ^{[33
]}

Tandjaoui-Lambiotte, Yacine ^{[34
,35
,36
]}

Borghesi, Alessandro ^{[37
]}

Aliberti, Anna ^{[38
]}

Cassaniti, Irene ^{[39
]}

Venet, Fabienne ^{[40
,41
,42
]}

Monneret, Guillaume ^{[40
,41
]}

Halwani, Rabih ^{[43
,44
]}

Sharif-Askari, Narjes Saheb ^{[43
]}

Danielson, Jeffrey ^{[14
]}

Burrel, Sonia ^{[45
]}

机构：

[1] Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM U1163, Paris, France

[2] Univ Paris Cite, Imagine Inst, Paris, France

[3] Rockefeller Univ, St Giles Lab Human Genet Infect Dis, Rockefeller Branch, 1230 York Ave, New York, NY 10021 USA

[4] Necker Hosp Sick Children, AP HP, Dept Pediat, Paris, France

[5] Univ Calif San Francisco, Med Scientist Training Program, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Tetrad Grad Program, San Francisco, CA 94143 USA

[7] Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94143 USA

[8] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA

[9] Univ Calif Berkeley, Univ Calif San Francisco, San Francisco Grad Program Bioengn, San Francisco, CA USA

[10] Chan Zuckerberg Biohub, San Francisco, CA 94158 USA

[11] Univ Calif San Francisco, Dept Neurol, Weill Inst Neurosci, San Francisco, CA USA

[12] Foch Hosp, Pneumol Dept, Suresne, France

[13] Grand Hop Est Francilien Site Marne La Vallee, Intens Care Unit, Jossigny, France

[14] NIAID, Lab Clin Immunol & Microbiol, NIH, Div Intramural Res, Bethesda, MD USA

[15] Grp Hosp Pitie Salpetriere, AP HP, Serv Parasitol Mycol, Paris, France

[16] Biomed Res Fdn Acad Athens, Ctr Clin Expt Surg & Translat Res, Lab Immunobiol, Athens, Greece

[17] Natl & Kapodistrian Univ Athens, Sotiria Gen Hosp Chest Dis, Med Sch, Dept Internal Med 3, Athens, Greece

[18] Med Univ Innsbruck, Dept Internal Med 2, Innsbruck, Austria

[19] Med Univ Innsbruck, Dept Internal Med 5, Innsbruck, Austria

[20] Univ Goce Delchev, Fac Med Sci, Stip, North Macedonia

[21] Inst Publ Hlth Republ North Macedonia, Stip, North Macedonia

[22] Univ Complutense Madrid, Inst Invest Sanitaria Hosp 12 Octubre Imas12, Dept Immunol, CIBERINFEC,Sch Med, Madrid, Spain

[23] Univ Complutense Madrid, Dept Immunol Ophthalmol & ENT, Sch Med, CIBERINFEC, Madrid, Spain

[24] ASST Spedali Civili Brescia, Emergency Room, Brescia, Italy

[25] ASST Spedali Civili, Covid Unit, Brescia, Italy

[26] ASST Spedali Civili Brescia, CREA Lab, Diagnost Dept, Brescia, Italy

[27] McGill Univ, Dept Med, Div Infect Dis, Hlth Ctr, Montreal, PQ, Canada

[28] McGill Univ, Infect Dis Susceptibil Program, Res Inst, Hlth Ctr, Montreal, PQ, Canada

[29] Univ La Sabana, Dept Microbiol, Chia, Colombia

[30] Clin Univ La Sabana, Dept Crit Care Med, Chia, Colombia

[31] Necker Hosp Sick Children, AP HP, Dept Infect Dis, Paris, France

[32] Univ Hlth Sci, Bakirkoy Dr Sadi Konuk Training & Res Hosp, Pediat Infect Dis Unit, Istanbul, Turkiye

[33] St Louis Hosp, AP HP, Dept Immunol, Paris, France

[34] INSERM, UMR 1137 IAME, Paris, France

[35] INSERM, UMR 1272 Hypoxie & Poumon, Bobigny, France

[36] CH St Denis, Pneumol & Infectiol Dept, St Denis, France

[37] Fdn IRCCS Policlin San Matteo, Neonatal Intens Care Unit, Pavia, Italy

[38] Fdn IRCCS Policlin San Matteo, Rianimaz 1, Anesthesia & Intens Care, Pavia, Italy

[39] Fdn IRCCS Policlin San Matteo, Microbiol & Virol Dept, Mol Virol Unit, Pavia, Italy

[40] Hosp Civils Lyon, Lab Immunol, Hop Edouard Herriot, Lyon, France

[41] Univ Claude Bernard Lyon 1, Hosp Civils Lyon, Hop Edouard Herriot BioMerieux, Pathophysiol Injury Induced Immunosuppress,EA 742, Lyon, France

[42] Univ Claude Bernard Lyon 1, Ecole Normale Super Lyon, UMR5308, CNRS,CIRI,INSERM U1111, Lyon, France

[43] Univ Sharjah, Coll Med, Sharjah Inst Med Res, Sharjah, U Arab Emirates

[44] King Saud Univ, Coll Med, Immunol Res Lab, Riyadh, Saudi Arabia

[45] Sorbonne Univ, Hop Pitie Salpetriere, AP HP, INSERM U1136,Serv Virol,Inst Pierre Louis Epidemi, Paris, France

[46] Louis Mourier Hosp, AP HP, Internal Med Dept, Paris, France

[47] Shupyk Natl Healthcare Univ Ukraine, Kiev, Ukraine

[48] I Horbachevsky Ternopil Natl Med Univ, Dept Childrens Dis & Pediat Surg, Ternopol, Ukraine

[49] Josip Juraj Strossmayer Univ Osijek, Univ Zagreb, Childrens Hosp Zagreb, Med Fac Osijek,Sch Med,Dept Pediat, Zagreb, Croatia

[50] Foch Hosp, Intens Care Unit, Suresne, France

来源：

SCIENCE IMMUNOLOGY | 2023年 / 8卷 / 90期

关键词：

AUTOANTIBODIES;

D O I：

10.1126/sciimmunol.abp8966

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. 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.

引用

页数：1

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