Long-Term Persistence of Spike Protein Antibody and Predictive Modeling of Antibody Dynamics After Infection With Severe Acute Respiratory Syndrome Coronavirus 2.
Grandjean, Louis;
Saso, Anja;
Torres Ortiz, Arturo;
Lam, Tanya;
Hatcher, James;
Thistlethwayte, Rosie;
Harris, Mark;
Best, Timothy;
Johnson, Marina;
Wagstaffe, Helen;
+8 more...Ralph, Elizabeth;
Mai, Annabelle;
Colijn, Caroline;
Breuer, Judith;
Buckland, Matthew;
Gilmour, Kimberly;
Goldblatt, David;
COVID-19 Staff Testing of Antibody Responses Study (Co-Stars) te;
Co-Stars Study Team;
(2021)
Long-Term Persistence of Spike Protein Antibody and Predictive Modeling of Antibody Dynamics After Infection With Severe Acute Respiratory Syndrome Coronavirus 2.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 74 (7).
pp. 1220-1229.
ISSN 1058-4838
DOI: https://doi.org/10.1093/cid/ciab607
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BACKGROUND: Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to neutralize the virus in vitro and prevent disease in animal challenge models on reexposure. However, the current understanding of SARS-CoV-2 humoral dynamics and longevity is conflicting. METHODS: The COVID-19 Staff Testing of Antibody Responses Study (Co-Stars) prospectively enrolled 3679 healthcare workers to comprehensively characterize the kinetics of SARS-CoV-2 spike protein (S), receptor-binding domain, and nucleoprotein (N) antibodies in parallel. Participants screening seropositive had serial monthly serological testing for a maximum of 7 months with the Meso Scale Discovery Assay. Survival analysis determined the proportion of seroreversion, while 2 hierarchical gamma models predicted the upper and lower bounds of long-term antibody trajectory. RESULTS: A total of 1163 monthly samples were provided from 349 seropositive participants. At 200 days after symptoms, >95% of participants had detectable S antibodies, compared with 75% with detectable N antibodies. S antibody was predicted to remain detectable in 95% of participants until 465 days (95% confidence interval, 370-575 days) using a "continuous-decay" model and indefinitely using a "decay-to-plateau" model to account for antibody secretion by long-lived plasma cells. S-antibody titers were correlated strongly with surrogate neutralization in vitro (R2 = 0.72). N antibodies, however, decayed rapidly with a half-life of 60 days (95% confidence interval, 52-68 days). CONCLUSIONS: The Co-Stars data presented here provide evidence for long-term persistence of neutralizing S antibodies. This has important implications for the duration of functional immunity after SARS-CoV-2 infection. In contrast, the rapid decay of N antibodies must be considered in future seroprevalence studies and public health decision-making. This is the first study to establish a mathematical framework capable of predicting long-term humoral dynamics after SARS-CoV-2 infection. CLINICAL TRIALS REGISTRATION: NCT04380896.
