SARS-CoV-2 humoral immune responses in convalescent individuals over 12 months reveal severity-dependent antibody dynamics

Abstract Background Defining the kinetics of SARS-CoV-2 antibody responses is critical for informing the management of reinfections, vaccinations, and therapeutics of Coronavirus disease 2019 (COVID-19). Methods Using four antibody assays, we evaluated antibody titers against SARS-CoV-2 nucleocapsid...

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Main Authors: Nadia Siles Alvarado, Maisey Schuler, Cole Maguire, Dzifa A. Amengor, Annalee W. Nguyen, Rebecca E. Wilen, Jacob Rogers, Sam Bazzi, Blaine Caslin, Christopher DiPasquale, Melissa Abigania, Eric Olson, Janelle Creaturo, Kerin Hurley, Todd A. Triplett, Justin F. Rousseau, Stephen M. Strakowski, Dennis Wylie, Jennifer A. Maynard, Lauren I. R. Ehrlich, Esther Melamed
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Communications Medicine
Online Access:https://doi.org/10.1038/s43856-025-00828-4
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Summary:Abstract Background Defining the kinetics of SARS-CoV-2 antibody responses is critical for informing the management of reinfections, vaccinations, and therapeutics of Coronavirus disease 2019 (COVID-19). Methods Using four antibody assays, we evaluated antibody titers against SARS-CoV-2 nucleocapsid (N), spike (S), and receptor binding domain (RBD) in 98 convalescent participants with varying COVID-19 disease severities (asymptomatic, mild, moderate or severe) at 1, 3, 6, and 12-months post-SARS-CoV-2-positive PCR and in 17 non-vaccinated, non-infected controls. Results Increasing acute COVID-19 disease severity correlates with higher anti-N and anti-RBD titers throughout 12 months post-infection. Anti-N and anti-RBD titers decline over time in all participants, except for increased anti-RBD titers post-vaccination, with hospitalized participants exhibiting faster decay rates. Less than 50% of participants retain anti-N titers above controls at 12 months, with non-hospitalized participants falling below controls sooner. Nearly all participants maintain anti-RBD titers above controls for 12 months, suggesting long-term protection against severe reinfections. Nonetheless, by 6 months, few participants retain >50% of their initial 1-month anti-N or anti-RBD titers. Notably, vaccine-induced anti-RBD titers are higher in non-hospitalized participants. Lastly, early convalescent titers correlate with age but not with Post-Acute Sequelae of SARS-CoV-2 infection (PASC) status or steroid use. Conclusion Hospitalized participants initially develop higher anti-SARS-CoV-2 antibody titers that decline faster relative to non-hospitalized participants. While anti-N titers fall below control levels in some participants, anti-RBD titers remain above controls over 12 months, demonstrating long-lived antibody responses known to protect against severe disease. These findings advance our understanding of COVID-19 antibody dynamics.
ISSN:2730-664X