The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
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DOI：
10.1073/pnas.2200413119
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发表时间：
2022-05-24
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
越来越多的证据表明，预先存在的自身抗体中和I型干扰素（IFN）是威胁生命的COVID-19肺炎的强有力决定因素。重要的是要按年龄和性别估计它们对SARS-CoV-2感染后COVID-19死亡率的定量影响，因为这些自身抗体的患病率和COVID-19死亡风险都随年龄增加而增加，男性更高。使用未接种疫苗的1，261名死亡患者和34，159名普通人群的样本，我们发现针对I型IFN的自身抗体强烈增加了所有年龄段的SARS-CoV-2感染死亡率，男性和女性都是如此。抗I型干扰素的自身抗体是威胁生命的COVID-19的强烈和常见的预测因子。测试这些自身抗体应考虑在一般人群。严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）感染致死率（IFR）从儿童期开始每5岁增加一倍。在各年龄组中，在约20%的死亡患者中发现了中和IFN-α、IFN-ω和/或IFN-β的循环自身抗体，在一般人群中，在年龄>70岁的4%的个体中，在约1%的个体中发现了中和IFN-α、IFN-ω和/或IFN-β的循环自身抗体<70 y and in >。在大流行之前，我们对1,261名未接种疫苗的死亡患者和34,159名普通人群进行了抽样，估计了携带中和I型IFN的自身抗体的个体相对于非携带者的IFR和各年龄组的相对死亡风险（RRD）。与任何自身抗体组合相关的RRD在70岁以下的受试者中较高。对中和IFN-α2或IFN-ω的自身抗体，RRD分别为17.0（95%置信区间：11.7至24.7）和5.8对于<70岁和≥70岁的个体，RRD分别为4.5至7.4，而对于中和两种分子的自身抗体，RRD为188.3（44.8至774.4）和7.2（5.0至10.3）。相反，IFR随着年龄的增长而增加，从0.17%（0.12至0.31）对于<40岁的个体，为26.7%（20.3 - 35.2）对于≥80岁的患者，中和IFN-α2或IFN-ω的自身抗体，中和两者的自身抗体阳性率为0.84%（0.31 ~ 8.28）~ 40.5%（27.82 ~ 61.20）。针对I型IFN的自身抗体会增加IFR，并与高RRD相关，尤其是在中和IFN-α2和IFN-ω时。值得注意的是，IFR随着年龄的增长而增加，而RRD随着年龄的增长而减少。对I型干扰素的自身免疫是COVID-19死亡的一个强而常见的预测因子。
There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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DOI：
10.1126/science.abj7965
发表时间：
2021-11-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Casanova JL;Abel L
通讯作者：
Abel L
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
影响因子：
82.9
作者：
Brodin, Petter
通讯作者：
Brodin, Petter
影响因子：
11.8
作者：
Döffinger, R;Helbert, MR;Kumararatne, DS
通讯作者：
Kumararatne, DS
影响因子：
24.8
作者：
Bastard P;Gervais A;Le Voyer T;Rosain J;Philippot Q;Manry J;Michailidis E;Hoffmann HH;Eto S;Garcia-Prat M;Bizien L;Parra-Martínez A;Yang R;Haljasmägi L;Migaud M;Särekannu K;Maslovskaja J;de Prost N;Tandjaoui-Lambiotte Y;Luyt CE;Amador-Borrero B;Gaudet A;Poissy J;Morel P;Richard P;Cognasse F;Troya J;Trouillet-Assant S;Belot A;Saker K;Garçon P;Rivière JG;Lagier JC;Gentile S;Rosen LB;Shaw E;Morio T;Tanaka J;Dalmau D;Tharaux PL;Sene D;Stepanian A;Megarbane B;Triantafyllia V;Fekkar A;Heath JR;Franco JL;Anaya JM;Solé-Violán J;Imberti L;Biondi A;Bonfanti P;Castagnoli R;Delmonte OM;Zhang Y;Snow AL;Holland SM;Biggs C;Moncada-Vélez M;Arias AA;Lorenzo L;Boucherit S;Coulibaly B;Anglicheau D;Planas AM;Haerynck F;Duvlis S;Nussbaum RL;Ozcelik T;Keles S;Bousfiha AA;El Bakkouri J;Ramirez-Santana C;Paul S;Pan-Hammarström Q;Hammarström L;Dupont A;Kurolap A;Metz CN;Aiuti A;Casari G;Lampasona V;Ciceri F;Barreiros LA;Dominguez-Garrido E;Vidigal M;Zatz M;van de Beek D;Sahanic S;Tancevski I;Stepanovskyy Y;Boyarchuk O;Nukui Y;Tsumura M;Vidaur L;Tangye SG;Burrel S;Duffy D;Quintana-Murci L;Klocperk A;Kann NY;Shcherbina A;Lau YL;Leung D;Coulongeat M;Marlet J;Koning R;Reyes LF;Chauvineau-Grenier A;Venet F;Monneret G;Nussenzweig MC;Arrestier R;Boudhabhay I;Baris-Feldman H;Hagin D;Wauters J;Meyts I;Dyer AH;Kennelly SP;Bourke NM;Halwani R;Sharif-Askari NS;Dorgham K;Sallette J;Sedkaoui SM;AlKhater S;Rigo-Bonnin R;Morandeira F;Roussel L;Vinh DC;Ostrowski SR;Condino-Neto A;Prando C;Bonradenko A;Spaan AN;Gilardin L;Fellay J;Lyonnet S;Bilguvar K;Lifton RP;Mane S;HGID Lab;COVID Clinicians;COVID-STORM Clinicians;NIAID Immune Response to COVID Group;NH-COVAIR Study Group;Danish CHGE;Danish Blood Donor Study;St. James's Hospital;SARS CoV2 Interest group;French COVID Cohort Study Group;Imagine COVID-Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19;Biobank Investigators;COVID Human Genetic Effort;CONSTANCES cohort;3C-Dijon Study;Cerba Health-Care;Etablissement du Sang study group;Anderson MS;Boisson B;Béziat V;Zhang SY;Vandreakos E;Hermine O;Pujol A;Peterson P;Mogensen TH;Rowen L;Mond J;Debette S;de Lamballerie X;Duval X;Mentré F;Zins M;Soler-Palacin P;Colobran R;Gorochov G;Solanich X;Susen S;Martinez-Picado J;Raoult D;Vasse M;Gregersen PK;Piemonti L;Rodríguez-Gallego C;Notarangelo LD;Su HC;Kisand K;Okada S;Puel A;Jouanguy E;Rice CM;Tiberghien P;Zhang Q;Cobat A;Abel L;Casanova JL
通讯作者：
Casanova JL