Global absence and targeting of protective immune states in severe COVID-19.
Global absence and targeting of protective immune states in severe COVID-19.
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严重COVID-19中保护性免疫状态的全球缺失和靶向。
DOI：
10.1038/s41586-021-03234-7
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发表时间：
2021-03
期刊：
影响因子：
64.8
通讯作者：
Krummel MF
中科院分区：
文献类型：
--
作者：
Combes AJ;Courau T;Kuhn NF;Hu KH;Ray A;Chen WS;Chew NW;Cleary SJ;Kushnoor D;Reeder GC;Shen A;Tsui J;Hiam-Galvez KJ;Muñoz-Sandoval P;Zhu WS;Lee DS;Sun Y;You R;Magnen M;Rodriguez L;Im KW;Serwas NK;Leligdowicz A;Zamecnik CR;Loudermilk RP;Wilson MR;Ye CJ;Fragiadakis GK;Looney MR;Chan V;Ward A;Carrillo S;UCSF COMET Consortium;Matthay M;Erle DJ;Woodruff PG;Langelier C;Kangelaris K;Hendrickson CM;Calfee C;Rao AA;Krummel MF
虽然SARS-CoV-2感染在某些患者中具有多效性和全身性影响1 - 3，但许多其他患者的症状较轻。我们寻求全面了解COVID-19病理学的严重/轻度区别及其起源。我们执行了全血保存单细胞分析方案，以整合所有主要细胞类型（包括中性粒细胞、单核细胞、血小板、淋巴细胞和血清内容物）的贡献。轻度COVID-19疾病患者在每个细胞群中显示出干扰素刺激基因（ISG）表达的协调模式3，而这些细胞在重度疾病患者中全身缺失。与轻度疾病相比，严重的COVID-19患者也矛盾地产生非常高的抗SARS-CoV-2抗体滴度，并且具有较低的病毒载量。对重症患者血清的检查表明，他们独特地产生抗体，通过参与抑制细胞对干扰素反应的保守信号通路，在功能上阻断轻度疾病相关的ISG表达细胞的产生。在许多COVID-19患者以及可能在其他病毒感染中，过度热心的抗体反应使免疫系统对抗自身，这项研究定义了重症患者免疫治疗的目标，以重新参与病毒防御。在严重的COVID-19患者中，免疫系统无法产生定义轻度疾病的细胞;他们血清中的抗体积极阻止这些细胞的成功产生。
While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients1−3, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction in COVID-19 pathology, and its origins. We performed a whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferon-stimulated gene (ISG) expression3 across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease. Examination of the serum from severe patients demonstrates that they uniquely produce antibodies that functionally block the production of the mild disease-associated ISG-expressing cells, by engaging conserved signaling circuits that dampen cellular responses to interferons. Overzealous antibody responses pit the immune system against itself in many COVID-19 patients and perhaps in other viral infections and this study defines targets for immunotherapies in severe patients to re-engage viral defense. In severe COVID-19 patients, the immune system fails to generate cells that define mild disease; antibodies in their serum actively prevents the successful production of those cells.
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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：
64.5
作者：
Mason, Kylie D.;Carpinelli, Marina R.;Kile, Benjamin T.
通讯作者：
Kile, Benjamin T.
DOI：
10.1164/rccm.202005-1885oc
发表时间：
2020-12-01
影响因子：
24.7
作者：
Hue S;Beldi-Ferchiou A;Bendib I;Surenaud M;Fourati S;Frapard T;Rivoal S;Razazi K;Carteaux G;Delfau-Larue MH;Mekontso-Dessap A;Audureau E;de Prost N
通讯作者：
de Prost N
影响因子：
6.7
作者：
Bongiovanni, Dario;Santamaria, Gianluca;Bernlochner, Isabell
通讯作者：
Bernlochner, Isabell
影响因子：
15.9
作者：
Wang, Yanqun;Zhang, Lu;Zhao, Jincun
通讯作者：
Zhao, Jincun