Longitudinal analysis of serology and neutralizing antibody levels in COVID19 convalescents

Muecksch, Frauke; Wise, Helen; Batchelor, Becky; Squires, Maria; Semple, Elizabeth; Richardson, Claire; McGuire, Jacqueline; Clearly, Sarah; Furrie, Elizabeth; Greig, Neil; Hay, Gordon; Templeton, Kate; Lorenzi, Julio C C; Hatziioannou, Theodora; Jenks, Sara; Bieniasz, Paul D

BACKGROUND: Understanding the longitudinal trajectory of SARS-CoV-2 antibodies is crucial for diagnosis of prior infection and predicting future immunity. METHODS: We conducted a longitudinal analysis of COVID19 convalescents, using neutralizing antibody assays and SARS-CoV-2 serologic assay platforms employing SARS-CoV-2 spike (S) or nucleocapsid (N) antigens. RESULTS: Sensitivities of serologic assays to diagnose prior SARS-CoV-2 infection changed with time. One widely used commercial platform that had an initial sensitivity of >95% declined to 71% at 81-100 days post diagnosis. The trajectories of median binding antibody titers measured over ~3 to 4 months were not dependent on the use of SARS-CoV-2 N or S proteins as antigen. The median neutralization titer decreased by ~45% per month. Each serological assay gave quantitative antibody titers that correlated with SARS-CoV-2 neutralization titers, but S-based serological assay measurements better predicted neutralization potency. Correlation between S-binding and neutralization titers deteriorated with time and decreases in neutralization titers were not predicted by changes in S-binding antibody titers. CONCLUSIONS: Different SARS-CoV-2 serologic assays are more or less well suited for surveillance versus prediction of serum neutralization potency. Extended follow up should facilitate the establishment of appropriate serologic correlates of protection against SARS-CoV-2 reinfection.