Antibody-mediated Immunogenicity against SARS-CoV-2 following priming, boosting and hybrid immunity: insights from 11 months of follow-up of a healthcare worker cohort in Israel, December 2020-October 2021

ABSTRACT

BackgroundWe determined circulating anti-S SARS-CoV-2 IgG antibody titres in a vaccinated healthcare workers (HCWs) cohort from Northern Israel in the 11 months following primary vaccination according to age, ethnicity, boosting timing and previous infection status. MethodsAll consenting HCWs were invited to have their circulating IgG levels measured before vaccination and at 6 subsequent timepoints. All HCWs with suspected COVID-19 were PCR tested. We described trends in circulating IgG geometric mean concentration by age, ethnicity, timing of boosting and previous infection status and compared strata using Kruskall-Wallis tests. ResultsAmong 985 vaccinated HCWs. IgG titres gradually decreased in all groups over the study duration. Younger or previously infected individuals had higher initial IgG levels (p<0.001 in both cases); differences substantially decreased or disappeared at 7-9 months, before boosting. Pre-infection IgG levels in infected participants were similar to levels measured at the same timepoint in HCWs who remained uninfected (p>0.3). IgG GMC in those boosted 6-7 months after dose 2 was lower compared with those boosted 8-9 months after (1999-vs 2736, p=0.02). ConclusionsImmunity waned 6 months post-priming in all age groups and in previously infected individuals, reversed by boosting. IgG titres decrease among previously infected individuals and the proportion of reinfected individuals in this group, comparable to the proportion of breakthrough infection in previously uninfected individuals suggests individuals with hybrid immunity (infection+vaccination) may also require further doses. Our study also highlights the difficulty in determining protective IgG levels and the need to clarify the optimal timing in 3 dose regimens