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Longitudinal variation in SARS-CoV-2 antibody levels and emergence of viral variants: implications for the ability of serological assays to predict immunity.

By Frauke Muecksch, Helen Wise, Kate Templeton, Becky Batchelor, Maria Squires, Kirsty McCance, Lisa Jarvis, Kristen Malloy, Elizabeth Furrie, Claire Richardson, Jacqueline MacGuire, Ian Godber, Alana Burns, Sally Mavin, Fengwen Zhang, Fabian Schmidt, Paul Bieniasz, Sara Jenks, Theodora Hatziioannou

Posted 07 Jul 2021
medRxiv DOI: 10.1101/2021.07.02.21259939

Background Serological assays are being deployed to monitor antibody responses in SARS-CoV-2 convalescents and vaccine recipients. There is a need to determine whether such assays can predict immunity, as antibody levels wane and viral variants emerge. Methods We measured antibodies in a cohort of SARS-CoV-2 infected patients using several high-throughput serological tests and functional neutralization assays. The effects of time and spike protein sequence variation on the performance and predictive value of the various assays was assessed. Findings Neutralizing antibody titers decreased over the first few months post-infection but stabilized 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 neutralizing antibody titers than assays based on nucleocapsid, but performance was variable and manufacturer positivity thresholds were not able to predict the presence or absence of detectable neutralizing activity. Even though there was some deterioration in correlation between serological measurements and functional neutralization activity, some assays maintained an ability to predict neutralizing titers, even against variants of concern. Interpretation The ability of high throughput serological assays to predict neutralizing antibody titers is likely crucial for evaluation of immunity at the population scale. These data will facilitate the selection of the most suitable assays as surrogates of functional neutralizing activity and suggest that such measurements may have utility in clinical practice.

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