Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies.
Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies.
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DOI：
10.1007/s10875-022-01252-2
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发表时间：
2022-08
影响因子：
9.1
通讯作者：
Goffinet, Christine
中科院分区：
文献类型：
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作者：
Akbil, Bengisu;Meyer, Tim;Stubbemann, Paula;Thibeault, Charlotte;Staudacher, Olga;Niemeyer, Daniela;Jansen, Jenny;Muehlemann, Barbara;Doehn, Jan;Tabeling, Christoph;Nusshag, Christian;Hirzel, Cedric;Sanchez, David Soekler;Nieters, Alexandra;Lother, Achim;Duerschmied, Daniel;Schallner, Nils;Lieberum, Jan Nikolaus;August, Dietrich;Rieg, Siegbert;Falcone, Valeria;Hengel, Hartmut;Koelsch, Uwe;Unterwalder, Nadine;Huebner, Ralf-Harto;Jones, Terry C.;Suttorp, Norbert;Drosten, Christian;Warnatz, Klaus;Spinetti, Thibaud;Schefold, Joerg C.;Doerner, Thomas;Sander, Leif Erik;Corman, Victor M.;Merle, Uta;Kurth, Florian;von Bernuth, Horst;Meisel, Christian;Goffinet, Christine
6% 至 19% 的重症 COVID-19 患者表现出针对 I 型干扰素 (IFN-AAB) 的循环自身抗体。在这里，我们建立了一种临床适用的策略，用于早期识别 IFN-AAB 阳性患者，以进行潜在的后续临床干预。我们通过 ELISA 分析了来自四家医院的 430 名 COVID-19 患者的血清中是否存在 IFN-AAB。通过竞争测定和基于病毒感染的中和测定评估结合特异性和中和活性。我们定义了与 IFN-AAB 阳性相关的临床参数。在危重患者亚组中，我们分析了治疗性血浆置换 (TPE) 对 IFN-AAB、SARS-CoV-2 抗体水平和临床结果的影响。在所有队列中的 COVID-19 患者中，中和 IFN-α 和 IFN-ω 的 AAB 的患病率为 4.2% (18/430)，而在未感染的对照队列中无法检测到。中和性 IFN-AAB 仅在严重受影响（最高 WHO 评分 6-8）、主要为男性 (83%) 的患者中可检测到（在 237 名重症 COVID-19 患者中，IFN-α-AAB 为 7.6%，18/237，IFN-ω-AAB 为 4.6%，11/237）。 IFN-AAB 存在于症状出现后早期和疾病高峰期。入院时发烧和需氧量与中和 IFN-AAB 阳性同时出现。 IFN-AAB 与较低的生存概率相关（无 IFN-AAB 的患者生存概率为 7.7%，而无 IFN-AAB 的患者生存概率为 80.9%）。与未接受 TPE 的患者相比，TPE 降低了五分之三患者的 IFN-AAB 水平，并且可能会增加 IFN-AAB 阳性患者的生存率。 IFN-AAB 可能作为严重 COVID-19 发展的早期生物标志物。我们建议对住院的 COVID-19 患者进行常规筛查，以快速识别最有可能从特定治疗中受益的 IFN-AAB 患者。在线版本包含可在 10.1007/s10875-022-01252-2 获取的补充材料。
Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable strategy for early identification of IFN-AAB-positive patients for potential subsequent clinical interventions. We analyzed sera of 430 COVID-19 patients from four hospitals for presence of IFN-AABs by ELISA. Binding specificity and neutralizing activity were evaluated via competition assay and virus-infection-based neutralization assay. We defined clinical parameters associated with IFN-AAB positivity. In a subgroup of critically ill patients, we analyzed effects of therapeutic plasma exchange (TPE) on the levels of IFN-AABs, SARS-CoV-2 antibodies and clinical outcome. The prevalence of neutralizing AABs to IFN-α and IFN-ω in COVID-19 patients from all cohorts was 4.2% (18/430), while being undetectable in an uninfected control cohort. Neutralizing IFN-AABs were detectable exclusively in critically affected (max. WHO score 6–8), predominantly male (83%) patients (7.6%, 18/237 for IFN-α-AABs and 4.6%, 11/237 for IFN-ω-AABs in 237 patients with critical COVID-19). IFN-AABs were present early post-symptom onset and at the peak of disease. Fever and oxygen requirement at hospital admission co-presented with neutralizing IFN-AAB positivity. IFN-AABs were associated with lower probability of survival (7.7% versus 80.9% in patients without IFN-AABs). TPE reduced levels of IFN-AABs in three of five patients and may increase survival of IFN-AAB-positive patients compared to those not undergoing TPE. IFN-AABs may serve as early biomarker for the development of severe COVID-19. We propose to implement routine screening of hospitalized COVID-19 patients for rapid identification of patients with IFN-AABs who most likely benefit from specific therapies. The online version contains supplementary material available at 10.1007/s10875-022-01252-2.
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影响因子：
--
作者：
Nusshag C;Morath C;Speer C;Kaelble F;Zeier M;Boxberger M;Schulze-Schleithoff E;Fiedler MO;Weigand MA;Merle U
通讯作者：
Merle U
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：
7.3
作者：
Ferré EMN;Schmitt MM;Ochoa S;Rosen LB;Shaw ER;Burbelo PD;Stoddard JL;Rampertaap S;DiMaggio T;Bergerson JRE;Rosenzweig SD;Notarangelo LD;Holland SM;Lionakis MS
通讯作者：
Lionakis MS
影响因子：
2.2
作者：
Guven, Esin;Duus, Karen;Houen, Gunnar
通讯作者：
Houen, Gunnar
影响因子：
7.5
作者：
Kurth, Florian;Roennefarth, Maria;Sander, Leif Erik
通讯作者：
Sander, Leif Erik