Longitudinal variation in SARS-CoV-2 antibody levels and emergence of viral variants: a serological analysis.
Longitudinal variation in SARS-CoV-2 antibody levels and emergence of viral variants: a serological analysis.
复制标题
SARS-CoV-2抗体水平的纵向变化和病毒变体的出现：血清学分析
DOI：
10.1016/s2666-5247(22)00090-8
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发表时间：
2022-07
期刊：
影响因子：
38.2
通讯作者：
Hatziioannou, Theodora
中科院分区：
文献类型：
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作者：
Muecksch, Frauke;Wise, Helen;Templeton, Kate;Batchelor, Becky;Squires, Maria;McCance, Kirsty;Jarvis, Lisa;Malloy, Kristen;Furrie, Elizabeth;Richardson, Claire;MacGuire, Jacqueline;Godber, Ian;Burns, Alana;Mavin, Sally;Zhang, Fengwen;Schmidt, Fabian;Bieniasz, Paul D.;Jenks, Sara;Hatziioannou, Theodora
血清学检测正在用于监测SARS-CoV-2感染者和接种COVID-19疫苗者的抗体反应。我们的目的是确定这种检测是否可以预测中和抗体滴度的抗体水平下降和病毒变异体的出现。我们使用10种高通量血清学检测和功能性中和试验测量了112名SARS-CoV-2感染者血清样本中的抗体水平。在基线和最多4次后续访视时采集血清样本。我们评估了时间和刺突蛋白序列变异对各种测定的性能和预测值的影响。我们使用非参数斯皮尔曼相关性对各个时间点进行相关性分析，并使用双尾Wilcoxon配对符号秩检验确定时间点之间的差异。中和抗体滴度在感染后的头几个月内下降，但此后稳定在感染后不久观察到的水平的约30%。通常用于测量SARS-CoV-2抗体的血清学检测显示出一系列灵敏度，这些灵敏度随着时间的推移而不同程度地下降。基于刺突蛋白的血清学测定生成的定量测量结果在预测中和抗体滴度方面优于基于核衣壳的测定结果，但性能可变，并且生产商阳性阈值无法预测是否存在可检测的中和活性。尽管我们观察到血清学测量值与功能性中和活性之间的相关性有所恶化，但一些检测试剂盒仍能够预测中和滴度，即使是针对关注的变体。高通量血清学检测预测中和抗体滴度的能力可能对评价人群免疫力至关重要。这些数据可以促进选择最合适的测定作为功能中和活性的替代物，并表明这种测量在临床实践中可能是有用的。美国国立卫生研究院和国家卫生服务研究苏格兰生物资源。
Serological assays are being used to monitor antibody responses in individuals who had SARS-CoV-2 infection and those who received a COVID-19 vaccine. We aimed to determine whether such assays can predict neutralising antibody titres as antibody levels wane and viral variants emerge. We measured antibody levels in serum samples from a cohort of 112 participants with SARS-CoV-2 infection using ten high-throughput serological tests and functional neutralisation assays. Serum samples were taken at baseline and at up to four subsequent visits. We assessed the effects of time and spike protein sequence variation on the performance and predictive value of the various assays. We did correlation analyses for individual timepoints using non-parametric Spearman correlation, and differences between timepoints were determined by use of a two-tailed Wilcoxon matched-pairs signed rank test. Neutralising antibody titres decreased over the first few months post-infection but stabilised thereafter, at about 30% of the level observed shortly after infection. Serological assays commonly used to measure antibodies against SARS-CoV-2 displayed a range of sensitivities that declined to varying extents over time. Quantitative measurements generated by serological assays based on the spike protein were better at predicting neutralising antibody titres than those based on nucleocapsid, but performance was variable, and manufacturer positivity thresholds were not able to predict the presence or absence of detectable neutralising activity. Although we observed some deterioration in correlation between serological measurements and functional neutralisation activity, some assays maintained an ability to predict neutralising titres, even against variants of concern. The ability of high-throughput serological assays to predict neutralising antibody titres is likely to be crucial for evaluation of immunity at the population scale. These data can facilitate the selection of the most suitable assays as surrogates of functional neutralising activity and suggest that such measurements might be useful in clinical practice. US National Institutes of Health and National Health Service Research Scotland BioResource.