32 Decay of Anti-SARS-CoV-2 Nucleocapsid IgG in Seropositive Health Care Workers Over Time

Tiffany, B.; Cogo, J.; Bremner, R.; Zumbuhl, J.; Wood, L.; Sanders, S.

Study Objectives: Our understanding of the quality and duration of immunity to COVID-19 following natural infection remains important area of public health research. The long-term kinetics of IgG antibodies to the spike and nucleocapsid (N) proteins of the SARS-CoV-2 virus are of particular interest as easily measurable potential indirect markers of both previous infection and resistance to reinfection. Previous studies in hospitalized patients have found that anti-N IgG levels decline over time. We undertook this study to characterize the kinetics of anti-N IgG in a longitudinal cohort of health care workers in an acute hospital setting. Methods: All HCWs who were either employed or part of the medical staff at six acute-care hospitals in Phoenix, AZ in June 2019 were invited to participate in a long-term study of the impact of the COVID-19 pandemic on HCWs. A cohort of 1358 HCWs provided informed consent, filled out a questionnaire regarding their health care role and potential COVID-19 symptoms, and had blood drawn between June 15 th and August 15 th, 2020 (Draw 1). The questionnaire and blood draws were repeated in October 2020 (Draw 2), January 2021 (Draw 3), and April 2021. SARS-CoV-2 anti-N IgG was measured using the Abbott Architect platform, using a signal to cutoff ratio (S/Co) greater than 1.4 as a positive result. A participant’s first positive result was treated as Time 0. Anti-N IgG S/Co values at each time point were summarized as mean, median, and inter-quartile range, and differences over time were tested using the Friedman’s test. Results: 290 participants (21.4%) had at least one positive IgG, with a median S/Co of 4.96, IQR 2.37-6.67. The Month 3 median S/Co was 2.32, IQR 1.34-4.22, Month 6 median was 0.96, IQR 0.51-2.05, and Month 9 median was 0.60, IQR 0.26-1.29 (See Figure). Freidman’s test for differences was significant at p<0.0001 at all time points. No participant was hospitalized for their acute COVID-19 illness. 68/244 participants (27.4%) were seronegative at 3 months, 81/126 (64.3%) at six months, and 65/84 (77.4%) at nine months. Conclusion: In a cohort of health care workers with mild to moderate COVID-19, anti-N IgG levels steadily decreased over 9 months from the initial positive IgG. The high rates of conversion to seronegative over a relatively short time frame illustrate why antibody-based testing must be interpreted cautiously when used as a definitive marker of prior COVID infection. [Formula presented]