Delayed production of neutralizing antibodies correlates with fatal COVID-19.
Delayed production of neutralizing antibodies correlates with fatal COVID-19.
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DOI：
10.1038/s41591-021-01355-0
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发表时间：
2021-07
期刊：
影响因子：
82.9
通讯作者：
Iwasaki A
中科院分区：
文献类型：
--
作者：
Lucas C;Klein J;Sundaram ME;Liu F;Wong P;Silva J;Mao T;Oh JE;Mohanty S;Huang J;Tokuyama M;Lu P;Venkataraman A;Park A;Israelow B;Vogels CBF;Muenker MC;Chang CH;Casanovas-Massana A;Moore AJ;Zell J;Fournier JB;Yale IMPACT Research Team;Wyllie AL;Campbell M;Lee AI;Chun HJ;Grubaugh ND;Schulz WL;Farhadian S;Dela Cruz C;Ring AM;Shaw AC;Wisnewski AV;Yildirim I;Ko AI;Omer SB;Iwasaki A
最近的研究为2019冠状病毒病（COVID-19）的先天和适应性免疫动力学提供了见解。然而，控制COVID-19疾病结果的抗体反应的确切特征仍不清楚。在这项研究中，我们分析了229名无症状、轻度、中度和重度COVID-19患者随时间推移的体液免疫应答，以探讨抗体应答在疾病严重程度和死亡率方面的性质。我们观察到抗刺突（S）免疫球蛋白G（IgG）水平、住院时间和与更严重临床进展相关的临床参数之间的相关性。虽然高抗S IgG水平与疾病严重程度相关，但这种相关性具有时间依赖性。死亡患者的总体体液反应并不高于出院患者。然而，他们安装了一个强大的，但延迟，反应，测量抗S，抗受体结合域IgG和中和抗体（NAb）水平相比，幸存者。延迟血清转换动力学与死亡患者中病毒控制受损相关。最后，虽然85%的患者的血清在他们的疾病过程中表现出一定的中和能力，NAb的产生前14天的疾病发作出现作为一个关键因素的恢复。这些数据表明，COVID-19死亡率与抗病毒抗体水平本身无关，而是与NAb产生的延迟动力学相关。
Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). However, the exact features of antibody responses that govern COVID-19 disease outcomes remain unclear. In this study, we analyzed humoral immune responses in 229 patients with asymptomatic, mild, moderate and severe COVID-19 over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-spike (S) immunoglobulin G (IgG) levels, length of hospitalization and clinical parameters associated with worse clinical progression. Although high anti-S IgG levels correlated with worse disease severity, such correlation was time dependent. Deceased patients did not have higher overall humoral response than discharged patients. However, they mounted a robust, yet delayed, response, measured by anti-S, anti-receptor-binding domain IgG and neutralizing antibody (NAb) levels compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, although sera from 85% of patients displayed some neutralization capacity during their disease course, NAb generation before 14 d of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se but, rather, with the delayed kinetics of NAb production.
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DOI：
10.1056/nejmoa2029849
发表时间：
2021-01-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
影响因子：
6.4
作者：
Guthmiller JJ;Stovicek O;Wang J;Changrob S;Li L;Halfmann P;Zheng NY;Utset H;Stamper CT;Dugan HL;Miller WD;Huang M;Dai YN;Nelson CA;Hall PD;Jansen M;Shanmugarajah K;Donington JS;Krammer F;Fremont DH;Joachimiak A;Kawaoka Y;Tesic V;Madariaga ML;Wilson PC
通讯作者：
Wilson PC
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
64.5
作者：
Garcia-Beltran, Wilfredo F;Lam, Evan C;Balazs, Alejandro B
通讯作者：
Balazs, Alejandro B
影响因子：
82.9
作者：
Amanat F;Stadlbauer D;Strohmeier S;Nguyen THO;Chromikova V;McMahon M;Jiang K;Arunkumar GA;Jurczyszak D;Polanco J;Bermudez-Gonzalez M;Kleiner G;Aydillo T;Miorin L;Fierer DS;Lugo LA;Kojic EM;Stoever J;Liu STH;Cunningham-Rundles C;Felgner PL;Moran T;García-Sastre A;Caplivski D;Cheng AC;Kedzierska K;Vapalahti O;Hepojoki JM;Simon V;Krammer F
通讯作者：
Krammer F