Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19.
Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19.
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疾病范围内的炎症特征表明，GM-CSF在严重的Covid-19中起着独特的作用。
DOI：
10.1126/sciimmunol.abg9873
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发表时间：
2021-03-10
影响因子：
24.8
通讯作者：
ISARIC4C investigators
中科院分区：
文献类型：
--
作者：
Thwaites RS;Sanchez Sevilla Uruchurtu A;Siggins MK;Liew F;Russell CD;Moore SC;Fairfield C;Carter E;Abrams S;Short CE;Thaventhiran T;Bergstrom E;Gardener Z;Ascough S;Chiu C;Docherty AB;Hunt D;Crow YJ;Solomon T;Taylor GP;Turtle L;Harrison EM;Dunning J;Semple MG;Baillie JK;Openshaw PJ;ISARIC4C investigators
GM-CSF在早期升高，随着严重程度而增加，并且是COVID-19炎症反应的核心，但不是严重的流感。虽然现在广泛接受宿主炎症反应导致肺损伤，但驱动严重程度并将2019冠状病毒病（COVID-19）与其他病毒性肺病区分开来的途径仍然缺乏特征。我们分析了通过前瞻性多中心ISARIC 4C研究招募的471名住院患者和39名轻度疾病门诊患者的血浆样本，从而能够对COVID-19严重程度的全谱反应进行广泛表征。许多炎性细胞因子和趋化因子（包括IL-6、CXCL 10和GM-CSF）水平的进行性升高与严重程度相关，并伴有内皮损伤和血栓形成标志物的升高。主成分和网络分析表明，IL-6和GM-CSF在COVID-19发病机制中发挥着核心作用。将这些特征与来自致命性流感患者的存档样本进行比较，IL-6在两种情况下均同样升高，而GM-CSF仅在COVID-19中突出。这些发现进一步确定了表征和区分严重和致命COVID-19的关键炎症、血栓形成和血管因素。
GM-CSF is elevated early, scaled with severity, and is central to the inflammatory response in COVID-19, but not severe influenza. While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways that drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral lung diseases remain poorly characterized. We analyzed plasma samples from 471 hospitalized patients recruited through the prospective multicenter ISARIC4C study and 39 outpatients with mild disease, enabling extensive characterization of responses across a full spectrum of COVID-19 severity. Progressive elevation of levels of numerous inflammatory cytokines and chemokines (including IL-6, CXCL10, and GM-CSF) were associated with severity and accompanied by elevated markers of endothelial injury and thrombosis. Principal component and network analyses demonstrated central roles for IL-6 and GM-CSF in COVID-19 pathogenesis. Comparing these profiles to archived samples from patients with fatal influenza, IL-6 was equally elevated in both conditions whereas GM-CSF was prominent only in COVID-19. These findings further identify the key inflammatory, thrombotic, and vascular factors that characterize and distinguish severe and fatal COVID-19.
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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：
64.8
作者：
通讯作者：
--
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
32.4
作者：
Burzynski, Laura C.;Humphry, Melanie;Clarke, Murray C. H.
通讯作者：
Clarke, Murray C. H.
影响因子：
64.8
作者：
Carvelli, Julien;Demaria, Olivier;Vivier, Eric
通讯作者：
Vivier, Eric