Faster decay of neutralizing antibodies in never infected than previously infected healthcare workers three months after the second BNT162b2 mRNA COVID-19 vaccine dose

Objectives: Our aim was to describe the longitudinal evolution of neutralizing antibody titres (NtAb) in three different cohorts of healthcare workers including vaccinated individuals with and without a previous SARS-CoV-2 infection and previously infected unvaccinated subjects. COVID-19 was mild or asymptomatic in those experiencing infection. Methods: NtAb was tested before BNT162b2 mRNA COVID-19 vaccine (V0), 20±2 days after the first dose (V1_20), 20±3 days (V2_20) and 90±2 days (V2_90) after the second dose in vaccinated HCW and after about 2 months (N_60), 10 months (N_300) and 13 months (N_390) from natural infection in unvaccinated HCW. NtAb was measured by authentic virus neutralization with a SARS-CoV-2 B.1 isolate circulating in Italy at HCW enrolment. Results: Sixty-two HCW were enrolled. NtAb were comparable in infected HCW with no or mild disease at all the study points. NtAb of uninfected HCW were significantly lower with respect to those of previously infected subjects at V1_20, V2_20 and V2_90. The median NtAb fold decrease from V2_20 to V2_90 was higher in the uninfected subjects with respect to subjects with mild infection (6.26 vs 2.58, p=0.03) and to asymptomatic HCW (6.26 vs 3.67, p=0.022). The median Nabt at N_390 was significantly lower with respect to N_60, p=0.007). Conclusions: In uninfected subjects completing the two-dose vaccine schedule, a third mRNA vaccine dose is a reasonable option to counteract the substantial NtAb decline occurring at a significantly higher rate compared to previously infected, vaccinated subjects. Although at low level Nabt are still at detectable level after 13 months in two third of previously infected and not vaccinated subjects.