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Long-Term Persistence of Spike Antibody and Predictive Modeling of Antibody Dynamics Following Infection with SARS-CoV-2

Grandjean, L; Saso, A; Ortiz, AT; Lam, T; Hatcher, J; Thistlethwayte, R; Harris, M; ... Co-Stars Study Team, .; + view all (2021) Long-Term Persistence of Spike Antibody and Predictive Modeling of Antibody Dynamics Following Infection with SARS-CoV-2. Clinical Infectious Disease 10.1093/cid/ciab607. (In press). Green open access

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Abstract

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 upon re-exposure. However, current understanding of SARS-CoV-2 humoral dynamics and longevity is conflicting. METHODS: The Co-Stars study prospectively enrolled 3679 healthcare workers to comprehensively characterize the kinetics of SARS-CoV-2 spike (S), receptor-binding-domain (RBD) and nucleoprotein (N) antibodies in parallel. Participants screening seropositive had serial monthly serological testing for a maximum of 7 months with the Mesoscale Discovery Assay. Survival analysis determined the proportion of sero-reversion while two 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 post-symptoms, >95% of participants had detectable S-antibodies compared to 75% with detectable N-antibodies. S-antibody was predicted to remain detectable in 95% of participants until 465 days [95%CI 370-575] 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 correlated strongly with surrogate neutralization in-vitro (R 2=0.72). N-antibodies, however, decayed rapidly with a half-life of 60 days [95%CI 52-68]. CONCLUSIONS: The Co-STAR's study data presented here provides evidence for long-term persistence of neutralizing S-antibodies. This has important implications for the duration of functional immunity following 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 following SARS-CoV-2 infection.

Type: Article
Title: Long-Term Persistence of Spike Antibody and Predictive Modeling of Antibody Dynamics Following Infection with SARS-CoV-2
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/cid/ciab607
Publisher version: https://doi.org/10.1093/cid/ciab607
Language: English
Additional information: © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: COVID-19, ELISA, Immunity, SARS-CoV-2, antibody, kinetics, neutralization, nucleoprotein, serology, virus,  spike protein
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10131119
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