Demographic and clinical characteristics associated with variations in antibody response to BNT162b2 COVID-19 vaccination among healthcare workers at an academic medical centre: a longitudinal cohort analysis

Abstract

Objectives: We sought to understand the demographic and clinical factors associated with variations in longitudinal antibody response following completion of two-dose regiment of BNT162b2 vaccination.

Design: This study is a 10-month longitudinal cohort study of healthcare workers and serially measured anti-spike protein IgG (IgG-S) antibody levels using mixed linear models to examine their associations with participant characteristics.

Setting: A large, multisite academic medical centre in Southern California, USA.

Participants: A total of 843 healthcare workers met inclusion criteria including completion of an initial two-dose course of BNT162b2 vaccination, complete clinical history and at least two blood samples for analysis. Patients had an average age of 45±13 years, were 70% female and 7% with prior SARS-CoV-2 infection.

Results: Vaccine-induced IgG-S levels remained in the positive range for 99.6% of individuals up to 10 months after initial two-dose vaccination. Prior SARS-CoV-2 infection was the primary correlate of sustained higher postvaccination IgG-S levels (partial R²=0.133), with a 1.74±0.11 SD higher IgG-S response (p<0.001). Female sex (beta 0.27±0.06, p<0.001), younger age (0.01±0.00, p<0.001) and absence of hypertension (0.17±0.08, p=0.003) were also associated with persistently higher IgG-S responses. Notably, prior SARS-CoV-2 infection augmented the associations of sex (-0.42 for male sex, p=0.08) and modified the associations of hypertension (1.17, p=0.001), such that infection-naïve individuals with hypertension had persistently lower IgG-S levels whereas prior infected individuals with hypertension exhibited higher IgG-S levels that remained augmented over time.

Conclusions: While the IgG-S antibody response remains in the positive range for up to 10 months following initial mRNA vaccination in most adults, determinants of sustained higher antibody levels include prior SARS-CoV-2 infection, female sex, younger age and absence of hypertension. Certain determinants of the longitudinal antibody response appear significantly modified by prior infection status. These findings offer insights regarding factors that may influence the 'hybrid' immunity conferred by natural infection combined with vaccination.

Keywords: COVID-19; hypertension; infectious diseases.

Figure 1

Cohort development flow diagram.

Figure 2

Longitudinal trajectory of IgG-S antibody levels following completed BNT162b2 vaccination. Multivariable-adjusted longitudinal trajectories are shown for individuals with a history of prior COVID-19 infection (orange line) and for those without prior COVID-19 infection (green line). Longitudinal estimates with 95% confidence limits (shaded areas) are adjusted for age, sex and hypertension.

Figure 3

Longitudinal trajectory of IgG-S antibody levels following completed BNT162b2 vaccination by prior infection status and age. Multivariable-adjusted longitudinal trajectories are shown for individuals with a history of prior COVID-19 infection and for those without prior COVID-19 infection, including an interaction for age (above vs below median cohort age). Longitudinal estimates with 95% confidence limits (shaded areas) are adjusted for sex and hypertension.

Figure 4

Longitudinal trajectory of IgG-S antibody levels following completed BNT162b2 vaccination by prior infection status and sex. Multivariable-adjusted longitudinal trajectories are shown for individuals with a history of prior COVID-19 infection and for those without prior COVID-19 infection, including an interaction for sex. Longitudinal estimates with 95% confidence limits (shaded areas) are adjusted for age and hypertension.

Figure 5

Longitudinal trajectory of IgG-S antibody levels following completed BNT162b2 vaccination by prior infection and hypertension status. Multivariable-adjusted longitudinal trajectories are shown for individuals with a history of prior COVID-19 infection and for those without prior COVID-19 infection, including an interaction for sex. Longitudinal estimates with 95% confidence limits (shaded areas) are adjusted for age and sex.