Timing of last COVID-19 vaccine dose and SARS-CoV-2 breakthrough infections in fully (boosted) vaccinated healthcare personnel

Aim: To estimate the incidence, timing and severity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) breakthrough infections in fully vaccinated healthcare personnel (HCP).

Methods: In total, 6496 fully vaccinated HCP were analysed prospectively from 15^th November 2021 to 17^th April 2022. Full coronavirus disease 2019 (COVID-19) vaccination was defined as a complete primary vaccination series followed by a booster dose at least 6 months later.

Results: Overall, 1845 SARS-CoV-2 breakthrough infections occurred (28.4 episodes per 100 HCP), of which 1493 (80.9%) were COVID-19 cases and 352 (19.1%) were asymptomatic infections. Of the 1493 HCP with COVID-19, four were hospitalized for 3-6 days (hospitalization rate among HCP with COVID-19: 0.3%). No intubations or deaths occurred. SARS-CoV-2 breakthrough infections occurred at a mean of 16.2 weeks after the last vaccine dose. Multi-variable regression analyses showed that among the 1845 HCP with a breakthrough infection, the administration of a COVID-19 vaccine dose ≥16.2 weeks before the infection was associated with increased likelihood of developing COVID-19 rather than asymptomatic SARS-CoV-2 infection [odds ratio (OR) 1.58, 95% confidence interval (CI) 1.01-2.46; P=0.045] compared with administering a vaccine dose later. The likelihood of developing COVID-19 compared with asymptomatic infection increased by 7% weekly after the last COVID-19 vaccine dose (OR 1.07, 95% CI 1.03-1.11; P=0.001).

Conclusion: SARS-CoV-2 breakthrough infections are common among fully (boosted) vaccinated HCP. However, full COVID-19 vaccination offered considerable protection against hospitalization. These findings may contribute to defining the optimal timing for booster vaccinations. More efficient COVID-19 vaccines that will also confer protection against SARS-CoV-2 infection are needed urgently.