Trajectory and Demographic Correlates of Antibodies to SARS-CoV-2 Nucleocapsid in Recently Infected Blood Donors, United States

Abstract

We evaluated antibodies to the nucleocapsid protein of SARS-CoV-2 in a large cohort of blood donors in the United States who were recently infected with the virus. Antibodies to the nucleocapsid protein of SARS-CoV-2 indicate previous infection but are subject to waning, potentially affecting epidemiologic studies. We longitudinally evaluated a cohort of 19,323 blood donors who had evidence of recent infection by using a widely available serologic test to determine the dynamics of such waning. We analyzed overall signal-to-cutoff values for 48,330 donations (average 2.5 donations/person) that had an average observation period of 102 days. The observed peak signal-to-cutoff value varied widely, but the waning rate was consistent across the range, with a half-life of 122 days. Within the cohort, only 0.75% of persons became seronegative. Factors predictive of higher peak values and longer time to seroreversion included increasing age, male sex, higher body mass index, and non-Caucasian race.

Keywords: COVID-19; N antibody; S antibody; SARS-CoV-2; United States; antibody; blood donors; coronavirus disease; coronaviruses; demographic correlates; half-life; nucleocapsid; respiratory infections; severe acute respiratory syndrome coronavirus 2; spike protein; trajectory; viruses; waning; zoonoses.

Figure 1

Potential nucleocapsid antibody test signal over time, showing likely sequence of S/CO values and seroconversion and seroreversion for nucleocapsid antibodies, in study of trajectory and demographic correlates of antibodies to SARS-CoV-2 nucleocapsid in recently infected blood donors, United States, June 2020‒June 2021. Each circle shows a potential value; solid circles indicate observed testing values and open circles theoretical unobserved points. The observed peak value is likely to be less that the true peak value and could occur before the true peak, in which case the slope could be affected. Blue line indicates the projected waning after the observed peak value. Ln, natural log; NC, nucleocapsid; S/CO, signal-to-cutoff value.

Figure 2

Longitudinal plot of all nucleocapsid-reactive donors with predicted slope (black dashed line) at mean observed peak S/CO in study of trajectory and demographic correlates of antibodies to SARS-CoV-2 nucleocapsid in recently infected blood donors, United States, June 2020‒June 2021. Shown are the overall dataset and a spaghetti plot of regression lines of S/CO values for each donor in the cohort. The natural log of observed peak values covered a range from ≈0 to ≈5.7, and the mean observation time was 101.7 days. Ln, natural log; NC, nucleocapsid; S/CO, signal-to-cutoff value.

Figure 3

Predicted values and actual S/CO values. A) Raw predicted peak S/CO values and actual donor serologic values by peak S/CO quartile (n = 30); B) intercept-adjusted predicted S/CO values and actual donor serologic values by peak S/CO quartile (n = 30). Dotted lines indicate predicted values and solid lines observed values. Quartiles were defined on the basis of their observed peak value. Samples were randomly chosen. Ln, natural log; NC, nucleocapsid; S/CO, sample-to-cutoff value.

Figure 4

Longitudinal plot of nucleocapsid reactive seroreverting donors in study of trajectory and demographic correlates of antibodies to SARS-CoV-2 nucleocapsid in recently infected blood donors, United States, June 2020‒June 2021. All seroreverting donors are plotted by their observed testing values. Black dashed lines are overlaid as indicators of the first and second deciles of peak S/COs across all donors to show low starting values of those who seroreverted. Decile lines are plotted by using the mean age (52 years) of donors, but seroreverting donors were slightly younger (49 years) and showed faster waning. Ln, natural log; NC, nucleocapsid; S/CO, signal-to-cutoff value.