Demographic and Clinical Factors Associated With SARS-CoV-2 Anti-Nucleocapsid Antibody Response Among Previously Infected US Adults: The C4R Study
Abstract Despite the availability of effective vaccines and a recent decrease in annual deaths, coronavirus disease-2019 (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 (N) antibody responses following Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-nucleocapsid antibodies were measured from dried blood spots collected between February 2021-February 2023. Among 1419 Collaborative Cohort of Cohorts for COVID-19 Research (C4R) 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 post-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 co-morbidities 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.
Authors
- Jean M. Rock
- John S. Kim (ORCID: https://orcid.org/0000-0002-8887-150X)
- Rachel Bievenue
- Rebekah Boyle
- Elizabeth A. Regan (ORCID: https://orcid.org/0000-0003-0624-9184)
- Ryan T. Demmer (ORCID: https://orcid.org/0000-0003-3429-0379)
- Mitchell S.V. Elkind (ORCID: https://orcid.org/0000-0003-2562-1156)
- Mary Cushman (ORCID: https://orcid.org/0000-0002-7871-6143)
- Norrina B. Allen (ORCID: https://orcid.org/0000-0002-6993-4384)
- Carmen R. Isasi (ORCID: https://orcid.org/0000-0003-2700-9593)
- Alka M. Kanaya (ORCID: https://orcid.org/0000-0002-8903-1457)
- Joel Henderson (ORCID: https://orcid.org/0000-0002-9178-1708)
- Laura M. Raffield (ORCID: https://orcid.org/0000-0002-7892-193X)
- Victor E. Ortega (ORCID: https://orcid.org/0000-0002-3962-0528)
- Josef Coresh (ORCID: https://orcid.org/0000-0002-4598-0669)
- Russell P. Tracy (ORCID: https://orcid.org/0000-0002-0080-2420)
- Margaret F. Doyle (ORCID: https://orcid.org/0000-0001-6769-5386)
- Barry J. Make (ORCID: https://orcid.org/0000-0003-4349-8745)
- Elizabeth C. Oelsner (ORCID: https://orcid.org/0000-0002-7481-9671)
- Christina Wu (ORCID: https://orcid.org/0000-0001-6369-6189)
- Vanessa Xanthakis (ORCID: https://orcid.org/0000-0002-7352-621X)
- Sally E. Wenzel (ORCID: https://orcid.org/0000-0002-4242-0164)
- Pallavi Balte (ORCID: https://orcid.org/0000-0001-5610-3744)
- Linda M. Styer
- Prescott G. Woodruff (ORCID: https://orcid.org/0000-0003-3176-0603)
- Taison D. Bell
- Amber Pirzada (ORCID: https://orcid.org/0000-0003-0526-3611)
- Russell Bowler
- Shelley A. Cole (ORCID: https://orcid.org/0000-0002-2651-0127)
- Namratha R. Kandula (ORCID: https://orcid.org/0000-0003-2570-3426)
- Pamela J. Schreiner (ORCID: https://orcid.org/0000-0002-9920-6257)
- Yifei Sun (ORCID: https://orcid.org/0000-0002-6961-5500)
- Michaela Restivo Anderson (ORCID: https://orcid.org/0000-0001-9274-7643)
- Virginia J. Howard (ORCID: https://orcid.org/0000-0003-4912-9975)
- Nicholas John Mantis (ORCID: https://orcid.org/0000-0002-5083-8640)
- David A. Schwartz (ORCID: https://orcid.org/0000-0001-6743-8443)
- Joyce Lee (ORCID: https://orcid.org/0000-0002-5758-8365)
Institutions
- University of North Carolina at Chapel Hill (US)
Publication Details
- Journal
- UNC Libraries
- Published
- 2025-03-28
- DOI
- https://doi.org/10.17615/m3z5-nz83
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00