Heterogeneous SARS-CoV-2 humoral response after COVID-19 vaccination and/or infection in the general population

Abstract

Assessment of the intensity, dynamics and determinants of the antibody response after SARS-CoV-2 infection or vaccination in the general population is critical to guide vaccination policies. This study characterized the anti-spike IgG titers in 13,971 participants included in a French multicohort population-based serological survey on COVID-19 between April and October 2020 and followed-up with serological testing between May and October 2021. Eight follow-up profiles were defined depending on SARS-CoV-2 infection (0, 1 or 2) and COVID-19 vaccination (0, 1, 2 or 3). The anti-spike titer was lower in adults with no vaccination even in case of infection or reinfection, while it was higher in adults with infection followed by vaccination. The anti-spike titer was negatively correlated with age in vaccinated but uninfected adults, whereas it was positively correlated with age in unvaccinated but infected adults. In adults with 2 vaccine injections and no infection, the vaccine protocol, age, gender, and time since the last vaccine injection were independently associated with the anti-spike titer. The decrease in anti-spike titer was much more rapid in vaccinated than in infected subjects. These results highlight the strong heterogeneity of the antibody response against SARS-CoV-2 in the general population depending on previous infection and vaccination.

Figure 1

Distribution (boxplot) of anti-spike IgG (ODR) according to follow-up profiles. (a) Anti-spike IgG (ODR). The dashed lines show the threshold values for a positive (≥ 1.1), indeterminate [0.8–1.1[ or negative (< 0.8) test result. (b) Proportion of participants with anti-spike IgG ≥ 264 BAU/mL according to follow-up profiles. Error bars represent 95% Confidence Intervals calculated using an exact method.

Figure 2

Distribution (boxplot) of anti-spike IgG (ODR) according to age groups by follow-up profiles (a–h). The dashed lines show the threshold values for a positive (≥ 1.1), indeterminate [0.8–1.1[ or negative (< 0.8) test result. Spearman correlation coefficients between age and log-IgG titer are presented.

Figure 3

Distribution (boxplot) of anti-spike IgG according to vaccine protocol. Abbreviations for first and second vaccine doses are AST = ChAdOx1 nCoV-19; MOD = mRNA-1273; PFI = BNT162b2. (a) Anti-spike IgG (ODR). The dashed lines show the threshold values for a positive (≥ 1.1), indeterminate [0.8–1.1[ or negative (< 0.8) test result. (b) Proportion of participants with anti-spike IgG ≥ 264 BAU/mL according to the vaccination protocol. Error bars represent 95% Confidence Intervals calculated using an exact method.

Figure 4

Scatter plot of anti-spike IgG (BAU/mL) according to time since the second vaccine dose by vaccine protocol, and locally weighted polynomial smoothing (LOESS) trend estimates. Abbreviations for first and second vaccine doses are AST = ChAdOx1 nCoV-19; MOD = mRNA-1273; PFI = BNT162b2. The dashed line at 264 BAU/mL was estimated to be associated with 80% vaccine efficacy against symptomatic infection with the Alpha (B.1.1.7) variant. Seventeen samples not shown.