Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs.
Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs.
复制标题
DOI：
10.1126/sciimmunol.abp8966
复制
发表时间：
2023-12-22
影响因子：
24.8
通讯作者：
中科院分区：
文献类型：
--
作者：
危及生命的重症新冠肺炎病例被归因于已经处于危险之中的人对SARS-CoV-2疫苗的抗体反应不佳或减弱。在未接种疫苗的人群中，至少15%的新冠肺炎肺炎危重病例是由预先存在的自身抗体(自动抗体)中和I型IFN构成的；然而，它们对接种疫苗人群中低氧血症突破性病例的作用尚不清楚。在这里，我们研究了48名个体(年龄20-86岁)，他们接种了2剂信使核糖核酸疫苗，并在2周至4个月后发生突破性感染，出现低氧性新冠肺炎肺炎。在血浆中检测疫苗的抗体水平、病毒的中和力和I型IFN的自身抗体。42名患者没有已知的B细胞免疫缺陷，对疫苗的抗体反应正常。其中10例(24%)有自身抗体中和I型IFN(年龄43~86岁)。在这10例患者中，8例自身抗体中和了干扰素-α-2和干扰素-ω，2例仅中和了干扰素-ω。无患者中和干扰素-β。7例中和10 ng/mLI型干扰素，3例仅中和100 pg/mLI型干扰素。7名患者有效地中和了SARS-CoV-2 D614G和Delta变种(B.1.617.2)，而1名患者中和Delta的效率略低。三名患者中有两名仅中和100pg/mLI型IFN，中和D61G和Delta的效率较低。尽管接种了两次信使核糖核酸疫苗，并存在能够中和SARS-CoV-2的循环抗体，但自动抗体中和I型IFN可能是相当大比例新冠肺炎肺炎低氧性病例的基础，突显了这一特别脆弱人群的重要性。尽管存在SARS-CoV-2中和抗体，但在接受新冠肺炎基因免疫的低氧血症患者中，仍有20%的人发现了I型干扰素自身抗体。
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. Type I IFN auto-Abs are found in 20% of hypoxemic, mRNA vaccinated COVID-19 patients despite SARS-CoV-2 neutralizing antibodies.
登录
查看更多内容
影响因子：
9.1
作者：
Khanmohammadi S;Rezaei N;Khazaei M;Shirkani A
通讯作者：
Shirkani A
危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
DOI：
10.1038/s41577-021-00522-1
发表时间：
2021-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Carvalho T;Krammer F;Iwasaki A
通讯作者：
Iwasaki A
DOI：
10.1056/nejmoa2116846
发表时间：
2022-01-27
期刊：
The New England journal of medicine
影响因子：
--
作者：
Gottlieb RL;Vaca CE;Paredes R;Mera J;Webb BJ;Perez G;Oguchi G;Ryan P;Nielsen BU;Brown M;Hidalgo A;Sachdeva Y;Mittal S;Osiyemi O;Skarbinski J;Juneja K;Hyland RH;Osinusi A;Chen S;Camus G;Abdelghany M;Davies S;Behenna-Renton N;Duff F;Marty FM;Katz MJ;Ginde AA;Brown SM;Schiffer JT;Hill JA;GS-US-540-9012 (PINETREE) Investigators
通讯作者：
GS-US-540-9012 (PINETREE) Investigators
DOI：
10.1056/nejmoa2109072
发表时间：
2021-10-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bergwerk M;Gonen T;Lustig Y;Amit S;Lipsitch M;Cohen C;Mandelboim M;Levin EG;Rubin C;Indenbaum V;Tal I;Zavitan M;Zuckerman N;Bar-Chaim A;Kreiss Y;Regev-Yochay G
通讯作者：
Regev-Yochay G