Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study.
Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study.
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DOI：
10.1016/s2666-5247(21)00025-2
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发表时间：
2021-06
期刊：
影响因子：
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通讯作者：
Wang LF
中科院分区：
文献类型：
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作者：
Chia WN;Zhu F;Ong SWX;Young BE;Fong SW;Le Bert N;Tan CW;Tiu C;Zhang J;Tan SY;Pada S;Chan YH;Tham CYL;Kunasegaran K;Chen MI;Low JGH;Leo YS;Renia L;Bertoletti A;Ng LFP;Lye DC;Wang LF
研究发现，中和抗体与抗SARS-CoV-2的结合抗体的衰减率不同。个体患者水平的中和抗体消退率对免疫力寿命的影响仍未知。我们的目的是研究随着时间的推移，中和抗体减弱和IgG亲合力成熟的峰值水平和动态，并将其与临床参数，细胞因子和T细胞应答相关联。我们对从COVID-19中恢复至症状发作后第180天的患者进行了一项纵向研究，通过使用先前验证的替代病毒中和试验监测中和抗体水平的变化。抗体亲和力和其他免疫指标的变化，在不同的恢复阶段进行了测定，并与临床特征。使用机器学习算法，将中和抗体水平的时间变化分为五组，并用于预测中和抗体介导的免疫的寿命。我们接触了517名参与研究的患者，其中288名同意接受门诊随访和系列血液样本采集。对164名患者进行了随访，并采集了足够的血液样本进行分析，共采集了546份血清样本，其中包括症状发作后180天内采集的128份血液样本。我们确定了五种不同的中和抗体动力学模式，如下所示：阴性，在我们的采样间隔内，在30%抑制水平下未产生中和抗体的个体（19例[12%]/164例患者）;迅速减弱，症状发作后20天左右具有不同水平中和抗体的个体，但在不到180天的时间里（164例患者中的44例[27%]）;缓慢消退，症状发作后180天仍保持中和抗体阳性的个体（46例[28%]/164例患者）;持续存在，尽管中和抗体峰值水平不同，但这些个体的中和抗体衰减最小（164例患者中的52例[32%]）;和延迟应答，一个小组在晚期恢复期（症状发作后90或180天; 164例患者中的3例[2%]）显示中和抗体意外增加。中和抗体的持久性与疾病的严重程度和促炎细胞因子、趋化因子和生长因子的持续水平相关。相比之下，不同中和抗体动力学组之间的T细胞应答相似。基于不同的衰变动力学，我们建立了一种预测算法，揭示了广泛的中和抗体寿命，从大约40天到几十年不等。从COVID-19中康复的患者的中和抗体反应动力学差异很大，只能在个体水平上准确确定免疫寿命的预测。我们的研究结果强调了公共卫生和社会措施在持续的大流行疫情应对中的重要性，并可能对疫苗接种后的免疫力寿命产生影响。国家医学研究理事会、生物医学研究理事会和A * 星星，新加坡。
Studies have found different waning rates of neutralising antibodies compared with binding antibodies against SARS-CoV-2. The impact of neutralising antibody waning rate at the individual patient level on the longevity of immunity remains unknown. We aimed to investigate the peak levels and dynamics of neutralising antibody waning and IgG avidity maturation over time, and correlate this with clinical parameters, cytokines, and T-cell responses. We did a longitudinal study of patients who had recovered from COVID-19 up to day 180 post-symptom onset by monitoring changes in neutralising antibody levels using a previously validated surrogate virus neutralisation test. Changes in antibody avidities and other immune markers at different convalescent stages were determined and correlated with clinical features. Using a machine learning algorithm, temporal change in neutralising antibody levels was classified into five groups and used to predict the longevity of neutralising antibody-mediated immunity. We approached 517 patients for participation in the study, of whom 288 consented for outpatient follow-up and collection of serial blood samples. 164 patients were followed up and had adequate blood samples collected for analysis, with a total of 546 serum samples collected, including 128 blood samples taken up to 180 days post-symptom onset. We identified five distinctive patterns of neutralising antibody dynamics as follows: negative, individuals who did not, at our intervals of sampling, develop neutralising antibodies at the 30% inhibition level (19 [12%] of 164 patients); rapid waning, individuals who had varying levels of neutralising antibodies from around 20 days after symptom onset, but seroreverted in less than 180 days (44 [27%] of 164 patients); slow waning, individuals who remained neutralising antibody-positive at 180 days post-symptom onset (46 [28%] of 164 patients); persistent, although with varying peak neutralising antibody levels, these individuals had minimal neutralising antibody decay (52 [32%] of 164 patients); and delayed response, a small group that showed an unexpected increase of neutralising antibodies during late convalescence (at 90 or 180 days after symptom onset; three [2%] of 164 patients). Persistence of neutralising antibodies was associated with disease severity and sustained level of pro-inflammatory cytokines, chemokines, and growth factors. By contrast, T-cell responses were similar among the different neutralising antibody dynamics groups. On the basis of the different decay dynamics, we established a prediction algorithm that revealed a wide range of neutralising antibody longevity, varying from around 40 days to many decades. Neutralising antibody response dynamics in patients who have recovered from COVID-19 vary greatly, and prediction of immune longevity can only be accurately determined at the individual level. Our findings emphasise the importance of public health and social measures in the ongoing pandemic outbreak response, and might have implications for longevity of immunity after vaccination. National Medical Research Council, Biomedical Research Council, and A*STAR, Singapore.