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

Abstract

Objectives: This study aimed to describe the longitudinal evolution of neutralizing antibody titres (NtAb) in three different cohorts of healthcare workers (HCWs), including vaccinated HCWs with and without a previous SARS-CoV-2 infection and previously infected unvaccinated HCWs. 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 HCWs and after about 2 months (N_60), 10 months (N_300) and 13 months (N_390) from natural infection in unvaccinated HCWs. NtAb were measured by authentic virus neutralization with a SARS-CoV-2 B.1 isolate circulating in Italy at HCW enrolment.

Results: Sixty-two HCWs were enrolled. NtAb were comparable in infected HCWs with no or mild disease at all the study points. NtAb of uninfected HCWs were significantly lower with respect to those of previously infected HCWs at V1_20, V2_20 and V2_90. The median NtAb fold decrease from V2_20 to V2_90 was higher in the uninfected HCWs with respect to those with mild infection (6.26 vs 2.58, p=0.03) and to asymptomatic HCWs (6.26 vs 3.67, p=0.022). The median Nabt at N_390 was significantly lower than at N_60 (p=0.007).

Conclusions: In uninfected HCWs 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 with previously infected, vaccinated HCWs. Although low, Nabt were still at a detectable level after 13 months in two-thirds of previously infected and unvaccinated HCWs.

Keywords: Asymptomatic; BNT162b2 mRNA COVID-19 vaccine; COVID-19; Healthcare workers; Mild disease; Neutralizing antibodies.

Figure 1

Neutralizing antibody titres in previously infected (n=23) and uninfected healthcare workers (n=13) tested at V0, V1_20, V2_20 and V2_90. Data are reported as longitudinal course and as individual ID₅₀ values at each study time The same symbols indicate the same HCWs at different time points ID₅₀: reciprocal value of the sample dilution that showed a 50% protection of virus cytopathic effect V0: before receiving the first dose V1_20: 20±2 days after the first dose V2_20: 20±3 days after the second dose V2_90: 90±2 days after the second dose

Figure 2

Neutralizing antibody titres in previously infected (n=23) and uninfected healthcare workers (n=13) tested at V0, V1_20, V2_20 and V2_90, and in unvaccinated HCWs (n=9) tested at N_60, N_300 and N_390. Data are reported as individual ID₅₀ values and as median value at each study time The same symbols indicate the same HCWs at different time points ID₅₀: reciprocal value of the sample dilution that showed a 50% protection of virus cytopathic effect V0: before receiving the first dose V1_20: 20±2 days after the first dose V2_20: 20±3 days after the second dose V2_90: 90±2 days after the second dose N_60: baseline, after about 2 months from diagnosis N_300: after a median of 291 days from diagnosis N_390: after a median of 394 days from diagnosis

Figure 3

Neutralizing antibody titres at N_300 (after a median of 291 days from diagnosis in unvaccinated HCWs), corresponding to V0 in vaccinated HCWs and at N_390 (after a median of 394 days from diagnosis), corresponding to the last time point of vaccinated HCWs (V2_90: 90±2 days after the second dose). Data are reported as individual ID₅₀ values and as median value at each study time. The same symbols indicate the same HCWs at different time points. ID₅₀: reciprocal value of the sample dilution that showed a 50% protection of virus cytopathic effect V0: before receiving the first dose V2_90: 90±2 days after the second dose N_300: after a median of 291 days from diagnosis N_390: after a median of 394 days from diagnosis