Journal Article

Demographic and Clinical Factors Associated With SARS-CoV-2 Anti-Nucleocapsid Antibody Response Among Previously Infected US Adults: The C4R Study

Lee, Joyce S, Raffield, Laura M, Howard, Virginia J, Coresh, Josef, Wenzel, Sally E, Wu, Chaoqi, Kim, John S, Cole, Shelley A, Schreiner, Pamela J, Tracy, Russell P, Regan, Elizabeth A, Styer, Linda M, Kandula, Namratha R, Ortega, Victor E, Bell, Taison D, Bowler, Russell, Sun, Yifei, Pirzada, Amber, Allen, Norrina B, Schwartz, David A, Woodruff, Prescott, Henderson, Joel M, Oelsner, Elizabeth C, Make, Barry J, Cushman, Mary, Mantis, Nicholas J, Balte, Pallavi, Xanthakis, Vanessa, Isasi, Carmen R, Doyle, Margaret, Anderson, Michaela R, Bievenue, Rachel, Kanaya, Alka M, Demmer, Ryan T, Boyle, Rebekah, Rock, Jean M, Elkind, Mitchell S V

2025

Overview

Despite the availability of effective vaccines and a recent decrease in annual deaths, COVID-19 remains a leading cause of death. Serological studies provide insights into host immunobiology of adaptive immune response to infection, which holds promise for identifying high-risk individuals for adverse COVID-19 outcomes. We investigated correlates of anti-nucleocapsid antibody responses following SARS-CoV-2 infection in a US population-based meta-cohort of adults participating in longstanding National Institutes of Health–funded cohort studies. Anti-nucleocapsid antibodies were measured from dried blood spots collected between February 2021 and February 2023. Among 1419 Collaborative Cohort of Cohorts for COVID-19 Research participants with prior SARS-CoV-2 infection, the mean age (standard deviation) was 65.8 (12.1), 61% were women, and 42.8% self-reported membership in a race/ethnicity minority group. The proportion of participants reactive to nucleocapsid peaked at 69% by 4 months after infection and waned to only 44% ≥12 months after infection. Higher anti-nucleocapsid antibody response was associated with older age, Hispanic or American Indian Alaskan Native (vs White) race/ethnicity, lower income, lower education, former smoking, and higher anti-spike antibody levels. Asian race (vs White) and vaccination (even after infection) were associated with lower nucleocapsid reactivity. Neither vaccine manufacturer nor common cardiometabolic comorbidities were not associated with anti-nucleocapsid response. These findings inform the underlying immunobiology of adaptive immune response to infection, as well as the potential utility of anti-nucleocapsid antibody response for clinical practice and COVID-19 serosurveillance.