Factors Influencing Level and Persistence of Anti SARS-CoV-2 IgG after BNT162b2 Vaccine: Evidence from a Large Cohort of Healthcare Workers

Abstract

We aimed at evaluating quantitative IgG response to BNT162b2 COVID-19 vaccine among health care workers (HCW), and exploring the role of demographic, clinical, and occupational factors as predictors of IgG levels. On May 2021, among 6687 HCW at the largest tertiary care University-Hospital of Northwestern Italy, at a median of 15 weeks (Interquartile range-IQR 13.6–16.0) after second-dose, serological response was present in 99.8%. Seropositivity was >97% in all the subgroups, except those self-reporting immunodeficiency (94.9%). Overall, the median serological IgG value was 990 BAU/mL (IQR 551–1870), with most of subjects with previous SARS-CoV-2 infection or with shorter time lapse (2–8 weeks) between vaccination and serology with values in the highest quintile (>2080). At multivariable analysis, significant predictors of lower values were increasing age, male, current smoking, immunodeficiency, recent occupational contacts, and increasing time lapse from vaccination; conversely, previous infection and recent household contacts were significantly associated with higher IgG levels. Subjects with previous infection kept a very high level (around 2000 BAU/mL) up to 120 days. These results, besides supporting a high serological response up to 4–5 months, suggest predictive factors of faster decay of IgG levels that could be useful in tailoring vaccination strategies.

Cellular Immune Response to BNT162b2 mRNA COVID-19 Vaccine in a Large Cohort of Healthcare Workers in a Tertiary Care University Hospital

“…We previously documented a clear inverse association between age and humoral response in our cohort of vaccinated HCW, consistent with literature data [15]; on the other hand, in this study, cellular immunity in terms of responsiveness and level of response was directly correlated with increasing age; other studies performed on HCW found non-significant reduction in T-cell response with increasing age [12,25,38] or even a vaccine-induced CD8+ T cell response enhanced in older males [23]. Although our observation deserves further evaluation, it is likely that pre-existing cross-reactive immune responses could play a role, as previously discussed.…”

“…Considering clinical features, the self-reported occurrence of immunodeficiency tended to be associated, although not significantly, with low responsiveness and level of IFN-γ production, as already seen for serology. Similarly, the self-reported occurrence of autoimmune diseases also tended to be associated to lower levels of cellular immunity, whereas no significant association was found for serology in our previous study [15]. Although we have to consider the limit of self-reporting, it is likely that impairment in immune responses in immune-mediated diseases, as well as specific therapies, may play a relevant role in vaccine immunogenicity, as already described for example in multiple sclerosis and immune-mediated inflammatory rheumatic diseases [49][50][51][52][53] or immunodeficiency [54,55].…”

“…Table S2 graphically summarizes the directions of the associations between some individual characteristics and post-vaccination T-cell response observed in the present study, in comparison with those previously observed between the same factors and postvaccination serological values [15].…”

“…Subsequently, in a random subset of workers among those attending the serological survey, we evaluated the cellular immune response. To this purpose, we randomly extracted a sample of 550 vaccinated subjects, stratified by levels (quintiles) of serological IgG values (1 • quintile: ≤475 BAU/mL; 2 • quintile: 476-789 BAU/mL; 3 • quintile: 790-1250 BAU/mL; 4 • quintile: 1251-2079 BAU/mL and 5 • quintile: ≥2080 BAU/mL) [15]. In the lowest quintile we also included nine subjects with a previous negative post vaccination serological test who agreed to attend the study.…”

“…We previously reported, in a large population of health care workers (HCW), the serological response at 4–5 months post-BNT162b2 administration, which was present in up to 99% of subjects [ 15 ]. Herein, we report the SARS-CoV-2 specific T-cell responses in a random sample of these subjects at a median of 7.2 months following vaccination, using a commercially available test, and explorative analyses on factors potentially influencing the magnitude and duration of the cellular immune response (including prior SARS-CoV-2 exposure).…”