Sequential Analysis of Binding and Neutralizing Antibody in COVID-19 Convalescent Patients at 14 Months After SARS-CoV-2 Infection

Background: Durability of SARS-CoV-2 Spike antibody responses after infection provides information relevant to understanding protection against COVID-19 in humans. We report the results of a follow-up evaluation of anti-SARS-CoV-2 antibodies in 23 convalescent patients with a median follow-up of 14 months (range 12.4-15.4) post first symptom onset.Findings: We found persistence of antibodies for all four specificities tested [Spike, Spike Receptor Binding Domain (Spike-RBD), Nucleocapsid, Nucleocapsid RNA Binding Domain (N-RBD)]. Anti-Spike antibodies persist at higher levels than anti-Nucleocapsid antibodies. The durability analysis supports a bi-phasic antibody decay with longer half-lives of antibodies after 6 months and antibody persistence for up to 14 months. Patients infected with the Wuhan (WA1) strain maintained strong cross-reactive recognition of Alpha and Delta Spike-RBD but significantly reduced binding to Beta and Mu Spike-RBD. Sixty percent of convalescent patients with detectable WA1-specific NAb also showed strong neutralization of the Delta variant. These data show that convalescent patients maintain functional antibody responses for more than one year after infection. One patient from this cohort showed strong increase of both Spike and Nucleocapsid antibodies at 14 months postinfection with robust cross-reactive antibodies and neutralization of a panel of Spike variants including Beta and Gamma, suggesting SARS-CoV-2 re-exposure. This patient provides an example of anti-Spike immunity able to control infection to asymptomatic level.Interpretations: The antibodies from SARS-CoV-2 convalescent patients persist over 14 months and continue to maintain cross-reactivity and strong functional properties.Trial Registration: This study included plasma donors who participated in a phase 2 study (NCT04408209 and NCT04743388)Funding: This work was supported by funds from the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research to G.N.P. and B.K.F. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.Declaration of Interest: The authors have declared that no conflict of interest exists.Ethical Approval: The study was approved by the local ethics committees of all participating hospitals.