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

Abstract

To estimate the incidence, timing, and severity of SARS-CoV-2 breakthrough infections in fully vaccinated healthcare personnel (HCP). We prospectively studied 6496 fully vaccinated HCP from November 15, 2021 through April 17, 2022. Full COVID-19 vaccination was defined as a complete primary vaccination series followed by a booster dose at least six months later. A total of 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, 4 were hospitalized for 3-6 days (hospitalization rate among HCP with COVID-19: 0.3%). No intubation or death occurred. SARS-CoV-2 breakthrough infections occurred at a mean of 16.2 weeks after the last vaccine dose. Multivariable 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 an increased likelihood in developing COVID-19 rather than asymptomatic SARS-CoV-2 infection (OR: 1.58; 95% CI: 1.01-2.46; p-value=0.045) compared to administering a vaccine dose later. The likelihood of developing COVID-19 versus asymptomatic infection increased by 7% weekly after the last COVID-19 vaccine dose (OR: 1.07; 95% CI: 1.03-1.11; p-value=0.001). SARS-CoV-2 breakthrough infections are common among fully (boosted) vaccinated HCP. However, full COVID-19 vaccination offered considerable protection against hospitalization. Our 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 urgently needed.