The Effectiveness of the Third Dose of COVID-19 Vaccine: When Should It Be Performed?

Background: COVID-19 vaccination is the most significant step toward the long-term mitigation of SARS-CoV-2-related complication, avoiding disease and death and decreasing virus spread. This study aimed to evaluate, in a real-world setting, booster dose effectiveness to reduce COVID-19 risk considering the amount of time after the end of the two-dose vaccination cycle. A sub-analysis was conducted to adjust the booster dose effect for occupational and demographic factors.

Methods: About 16,000 COVID-19-vaccinated HCWs of three University Hospital Networks in Milan (HN1/HN2/HN3) were included in the study. Data were collected by Occupational Health Physicians of the HNs within specific computerized databases.

Results: In univariable analysis, booster dose administration displayed a slightly higher risk of infection with respect to not receiving it, OR = 1.18, with 95% confidence interval (C.I) [0.99, 1.41]. When the model was adjusted with the modulating effect of time from the completion of the vaccination cycle on booster dose administration, the latter resulted in strong protective effect against infection, OR = 0.43, 95% CI [0.26, 0.74]. However, considering the modifying influence of time from the vaccination cycle's completion, the administration of booster doses appeared to have a protective effect against infection. In HN1, students and resident physicians displayed lower odds of infection with respect to physicians. Lastly, a non-linear effect of age was reported.

Conclusions: Our findings suggest that the correct timing in vaccine scheduling and administration is critical to vaccine effectiveness. These findings, applicable to all vaccinations, should help in setting up more effective vaccination strategies.