Vaccine-induced protection against severe COVID-19, hospitalization, and death is of the utmost importance, especially in the elderly. However, limited data are available on humoral immune responses following COVID-19 vaccination in the general population across a broad age range. We performed an integrated analysis of the effect of age, sex, and prior SARS-CoV-2 infection on Spike S1-specific (S1) IgG concentrations up to three months post-BNT162b2 (Pfizer/BioNTech; Comirnaty) vaccination. In total, 1735 persons, eligible for COVID-19 vaccination through the national program, were recruited from the general population (12 to 92 years old). Sixty percent were female, and the median vaccination interval was 35 days (interquartile range, IQR: 35–35). All participants had seroconverted to S1 one month after two vaccine doses. S1 IgG was higher in participants with a history of SARS-CoV-2 infection (median: 4535 BAU/mL, IQR: 2341–7205) compared to infection-naive persons (1842 BAU/mL, 1019–3116), p < 0.001. In infection-naive persons, linear mixed effects regression showed a strong negative association between age and S1 IgG (p < 0.001) across the entire age range. Females had higher S1 IgG than males (p < 0.001). In persons with an infection history, age nor sex was associated with S1 IgG concentrations. The lower magnitude of S1 antibodies in older persons following COVID-19 vaccination will affect long-term protection.
Background PIENTER 3 (P3) is the third nationwide serological survey in the Netherlands, conducted in 2016/17. The overall response rate was 13.9%, following a decreasing trend in response compared to the previous two PIENTER studies (1995/1996 and 2006/2007). During P3 a non-response survey was used to investigate non-response bias. We assess P3 representativeness and potential sources of non-response bias, and trends in decreasing participation rates across all PIENTER studies. Methods P3 invitees were classified into survey response types (RTs): Full Participants (FP), Questionnaire Only (QO), Non-Response Questionnaire (NRQ) and Absolute Non-Responders (ANR). FP demographic and health indicator data were compared with Dutch national statistics, and then the RTs were compared to each other. Random Forest algorithms were used to predict an invitee’s RT. Finally, FPs from all three PIENTERs were compared to investigate the profile of national survey participants through time. Results P3 FPs were in general healthier, younger and higher educated than the Dutch population. Random forest was not able to differentiate between FPs and ANRs, but when predicting FPs from NRQs we found evidence of healthy-responder bias. Participants of the three PIENTERs were found to be similar, but we found that, in line with national trends, P3 participants were less inclined to vaccinate than previous cohorts. Discussion As vaccination coverage is high in the Netherlands, P3 remains a powerful tool to monitor population-level protection against vaccine preventable diseases (VPDs). Participants of all three PIENTERS do not differ and there can be compared through time. However, future PIENTER studies should continue to focus on improving recruitment from under-represented groups but consider alternative survey modes to improve overall response.
Vaccine-induced protection of the population against severe COVID-19, hospitalization and death is of utmost importance, especially in the elderly. However, limited data are available on humoral immune responses following COVID-19 vaccination in the general population across a broad age range. We performed an integrated analysis of the effect of age, sex and prior SARS-CoV-2 infection on Spike S1-specific (S1) IgG concentrations up to three months post BNT162b2 vaccination. 1·735 persons, eligible for COVID-19 vaccination through the national program, were recruited from the general population (12 to 92 years old). Sixty percent were female and the median vaccination interval was 35 days (interquartile range, IQR: 35-35). All participants had seroconverted to S1 one month after two doses of vaccine. S1 IgG was higher in participants with a history of SARS-CoV-2 infection (median: 4·535 BAU/ml, IQR: 2·341-7·205) compared to infection-naïve persons (1·842 BAU/ml, 1·019-3·116) after two doses, p<0.001. In infection-naïve persons, linear mixed effects regression showed a strong negative association between age and S1 IgG one month after the first vaccination (p<0.001) across the entire age range. The association was still present after the second vaccination, but less pronounced. Females had higher S1 IgG than males after both the first and second vaccination (p<0.001); although this difference was lower after the second dose. In persons with an infection history, age nor sex was associated with peak S1 IgG. As IgG decreased with age and time since vaccination, older persons may become at risk of infection, especially with escape variants such as Omicron.
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