Stable neutralizing antibody levels 6 months after mild and severe COVID-19 episodes.
Stable neutralizing antibody levels 6 months after mild and severe COVID-19 episodes.
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在轻度和重度新冠肺炎发作6个月后，中和抗体水平稳定。
DOI：
10.1016/j.medj.2021.01.005
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发表时间：
2021-03-12
期刊：
影响因子：
--
通讯作者：
Blanco J
中科院分区：
文献类型：
--
作者：
Pradenas E;Trinité B;Urrea V;Marfil S;Ávila-Nieto C;Rodríguez de la Concepción ML;Tarrés-Freixas F;Pérez-Yanes S;Rovirosa C;Ainsua-Enrich E;Rodon J;Vergara-Alert J;Segalés J;Guallar V;Valencia A;Izquierdo-Useros N;Paredes R;Mateu L;Chamorro A;Massanella M;Carrillo J;Clotet B;Blanco J
了解SARS-CoV-2免疫的中期动力学是公共卫生控制大流行和疫苗开发的基石。然而，目前的证据是基于有限的测量，忽视了这些变化的时间模式。我们对随访时间超过6个月的COVID-19患者的前瞻性队列进行了纵向分析。使用表达SARS-CoV-2S蛋白的HIV报告假病毒评价中和活性。通过ELISA针对S2亚基、受体结合结构域（RBD）和核蛋白（NP）评价IgG抗体滴度。使用混合效应模型进行统计分析。我们发现，轻度或无症状感染的个体在症状发作或诊断后持续6个月，中和活性出现了微不足道的衰减。住院患者的中和滴度较高，呈2相模式下降，最初快速下降，第80天后显著减缓。尽管有这种初始衰减，但与轻度症状相比，住院患者在6个月时的中和活性仍然较高。中期中和活性的缓慢下降与抗RBD、S2或NP抗体滴度的陡峭斜率形成对比，所有这些抗体滴度在随访期间均显示出持续下降。我们的研究结果加强了这样一个假设，即针对SARS-CoV-2的中和免疫应答的质量在康复后阶段不断发展。这项研究是由资助，（赠款编号。SLD 016至J.B.以及SLD 015至J.C.），（补助金编号：J.C.的PI 17/01518和PI 18/01332），2017年SGR 252，以及众筹计划，和。资助者在研究设计、数据收集和分析、出版决定或手稿准备方面没有任何作用。E. P.得到了来自（ANID; 72180406）的博士生资助。CA- N.获得了（FI）的博士资助。S.P.- Y.支持和。评估针对SARS-CoV-2的中和反应的持久性对于预测恢复期后COVID-19患者的保护水平至关重要。我们对210名SARS-CoV-2感染者进行了为期6个月的监测，这些人具有各种症状（从无症状感染到严重疾病）。我们的研究结果表明，中和抗体在感染后至少6个月内是稳定的。然而，轻度或无症状感染者的中和抗体滴度较低，再次感染的风险可能较高。尽管维持了中和抗体，但总抗体滴度随时间缓慢但逐渐下降，无明显稳定。这一观察结果需要进一步分析，以评价病毒持续存在或病毒再暴露在维持中和滴度中的潜在作用。Pradenas等人描述了抗SARS-CoV-2中和抗体的动力学，并证明了它们与临床严重程度的相关性，以及它们至少6个月的稳定性，尽管IgG滴度不断衰减。这些发现有助于我们了解中期免疫反应及其对群体免疫的影响。
Understanding mid-term kinetics of immunity to SARS-CoV-2 is the cornerstone for public health control of the pandemic and vaccine development. However, current evidence is rather based on limited measurements, losing sight of the temporal pattern of these changes. We conducted a longitudinal analysis on a prospective cohort of COVID-19 patients followed up for >6 months. Neutralizing activity was evaluated using HIV reporter pseudoviruses expressing SARS-CoV-2 S protein. IgG antibody titer was evaluated by ELISA against the S2 subunit, the receptor binding domain (RBD), and the nucleoprotein (NP). Statistical analyses were carried out using mixed-effects models. We found that individuals with mild or asymptomatic infection experienced an insignificant decay in neutralizing activity, which persisted 6 months after symptom onset or diagnosis. Hospitalized individuals showed higher neutralizing titers, which decreased following a 2-phase pattern, with an initial rapid decline that significantly slowed after day 80. Despite this initial decay, neutralizing activity at 6 months remained higher among hospitalized individuals compared to mild symptomatic. The slow decline in neutralizing activity at mid-term contrasted with the steep slope of anti-RBD, S2, or NP antibody titers, all of them showing a constant decline over the follow-up period. Our results reinforce the hypothesis that the quality of the neutralizing immune response against SARS-CoV-2 evolves over the post-convalescent stage. This study was funded by , the (grant nos. SLD016 to J.B. and SLD015 to J.C.), the (grant nos. PI17/01518 and PI18/01332 to J.C.), 2017 SGR 252, and the crowdfunding initiatives , , and . The funders had no role in the study design, the data collection and analysis, the decision to publish, or the preparation of the manuscript. E.P. was supported by a doctoral grant from the (ANID; 72180406). C.A.-N. was supported by a doctoral grant from (FI). S.P.-Y. was supported by and . Assessing the durability of neutralizing responses against SARS-CoV-2 is crucial to predict the level of protection in post-convalescent COVID-19 patients. We monitored for >6 months a cohort of 210 SARS-CoV-2-infected individuals with a wide range of symptoms (from asymptomatic infection to severe disease). Our results indicate that neutralizing antibodies are stable for at least 6 months after infection. However, individuals with mild or asymptomatic infection developed lower titers of neutralizing antibodies and could be at higher risk of reinfection. Despite the maintenance of neutralizing antibodies, total antibody titers slowly but gradually declined over time without apparent stabilization. This observation requires further analysis to evaluate the potential role of viral persistence or viral re-exposure in maintaining neutralization titers. Pradenas et al. describe the kinetics of neutralizing antibodies against SARS-CoV-2 and demonstrate their association with clinical severity and their stability for at least 6 months, despite constant decay of IgG titers. These findings help us to understand the mid-term immune response and the impact on herd immunity.
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DOI：
10.1136/bmj.m4509
发表时间：
2020-11-27
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Pastor-Barriuso R;Pérez-Gómez B;Hernán MA;Pérez-Olmeda M;Yotti R;Oteo-Iglesias J;Sanmartín JL;León-Gómez I;Fernández-García A;Fernández-Navarro P;Cruz I;Martín M;Delgado-Sanz C;Fernández de Larrea N;León Paniagua J;Muñoz-Montalvo JF;Blanco F;Larrauri A;Pollán M;ENE-COVID Study Group
通讯作者：
ENE-COVID Study Group
影响因子：
11.8
作者：
Wu LP;Wang NC;Chang YH;Tian XY;Na DY;Zhang LY;Zheng L;Lan T;Wang LF;Liang GD
通讯作者：
Liang GD
影响因子：
64.8
作者：
Gaebler C;Wang Z;Lorenzi JCC;Muecksch F;Finkin S;Tokuyama M;Cho A;Jankovic M;Schaefer-Babajew D;Oliveira TY;Cipolla M;Viant C;Barnes CO;Bram Y;Breton G;Hägglöf T;Mendoza P;Hurley A;Turroja M;Gordon K;Millard KG;Ramos V;Schmidt F;Weisblum Y;Jha D;Tankelevich M;Martinez-Delgado G;Yee J;Patel R;Dizon J;Unson-O'Brien C;Shimeliovich I;Robbiani DF;Zhao Z;Gazumyan A;Schwartz RE;Hatziioannou T;Bjorkman PJ;Mehandru S;Bieniasz PD;Caskey M;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
9.4
作者：
Addetia A;Crawford KHD;Dingens A;Zhu H;Roychoudhury P;Huang ML;Jerome KR;Bloom JD;Greninger AL
通讯作者：
Greninger AL
影响因子：
11.8
作者：
Wang, Xiaoli;Guo, Xianghua;Wang, Quanyi
通讯作者：
Wang, Quanyi