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

Background We 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 and previous infection status. Methods All consenting HCWs were invited to have their IgG levels measured before vaccination and at 6 subsequent timepoints using a quantitative S1/S2 IgG assay. All HCWs with suspected COVID-19 were PCR tested. We described trends in circulating IgG geometric mean concentration (GMC) by age, ethnicity, timing of boosting and previous infection status and compared strata using Kruskall-Wallis tests. Results Among 985 vaccinated HCWs, IgG titres between 1 month post 2 (nd) dose to pre-boosting gradually decreased in all age groups. Younger or previously infected individuals had higher initial post-vaccination IgG levels (p<0.001 in both cases); differences substantially decreased or disappeared at 7-9 months, before boosting. The proportion of individuals infected prior to initiating vaccination and re-infected after dose 1 was comparable to the proportion of breakthrough infection post-dose 2 in those not previously infected (4.2 vs 4.7%). Pre-infection IgG levels in the 40 participants with breakthrough infection after dose 2 were similar to levels measured at the same timepoint in vaccinated HCWs who remained uninfected (p>0.3). Post-dose3 IgG levels were more than 10-fold those 1month post-dose 2. Conclusions Immunity waned in all age groups and previously infected individuals, reversed by boosting. IgG titres decrease and reinfections in individuals with hybrid immunity (infection+vaccination) suggests they may also require further doses. Our study also highlights the difficulty in determining protective IgG levels.