Abstract P1063: Association of Demographic and Clinical Factors with SARS-CoV-2 Anti-Nucleocapsid Antibody Response Among Previously Infected US Adults: The C4R Study
Authors: Ryan Demmer, Chaoqi Wu, John Kim, Yifei Sun, Pallavi Balte, Mary Cushman, Rebekah Boyle, Russell Tracy, Linda Styer, Taison Bell, Michaela Anderson, Norrina Allen, Pamela Schreiner, Russell Bowler, David Schwartz, Joyce Lee, Vanessa Xanthakis, Jean Rock, Rachel Bievenue, Amber Pirzada, Margaret Doyle, Elizabeth Regan, Barry Make, Alka Kanaya, Namratha Kandula, S Morganroth, Joe Coresh, Carmen Isasi, Laura Raffield, Mitchell Elkind, Virginia Howard, Victor Ortega, Prescott Woodruff, Shelley Cole, Joel Henderson, Nicholas Mantis, Elizabeth Oelsner
Journal: Circulation (2025)

Background: 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 of anti-nucleocapsid (N) antibody response to infection provide insights into host immunobiology of adaptive immune response, which holds promise for identifying high-risk individuals for adverse acute and chronic COVID-19 outcomes. Hypothesis: Among participants previously infected with SARS-CoV-2, traditional vascular disease risk factors are associated with higher anti-N antibodies while vaccination is associated with lower anti-N antibodies. Methods: Among previously infected participants, anti-N antibodies were measured from dried blood spots collected between February 2021-February 2023 among 1,419 Collaborative Cohort of Cohorts for COVID-19 Research (C4R) participants with prior SARS-CoV-2 infection. We measured anti-N IgG antibodies reported as median fluorescence intensity (MFI) units; reactivity (i.e., seropositivity) was defined based on MFI above a validated threshold. Vascular disease risk factors were assessed via pre-pandemic in-person examination, questionnaires, and medical record review. Multivariable generalized linear models regressed anti-N reactivity (modified Poisson) or LN transformed MFI (linear). Results: Among 1,419 participants with prior infection, mean age (standard deviation) was 65.8(12.1) years, 61% were women, and 42.8% were self-reported from a race/ethnicity minority group. Participant reactivity to nucleocapsid peaked at 69% by 4 months post-infection and waned to only 44% ≥12 months after infection. After multivariable adjustment, higher anti-N antibody response was associated with older age, Hispanic (vs. White) or American Indian (vs. White) race/ethnicity, lower income and education, former smoking, and higher anti-spike antibody levels. Asian race (vs. White) and vaccination ( even after infection ) were associated with lower nucleocapsid reactivity; common cardiometabolic co-morbidities were not associated with anti-N reactivity or levels (Figures 1 and 2). Conclusions: Among participants previously infected with SARS-CoV-2, select sociodemographic and behavioral risk factors were associated with higher anti-N antibody levels while vaccination was associated with lower anti-N antibody levels. The observation that vaccination, even after infection, is related to lower anti-N antibody levels merits further investigation.