Optimizing the schedule of BNT162b2 COVID-19 against long COVID and associated quality of life losses

Background: The long-term impact of COVID-19 vaccination on post-acute COVID-19 symptoms and associated quality of life (QoL) changes remains incompletely described. This study aimed to explore the impact of the timing of COVID-19 priming and booster doses, on reporting long COVID symptoms and associated QoL changes. Methods: Individuals who had PCR testing for SARS-CoV-2 processed in government hospitals in Northern Israel between 15^th March 2021 and 15^th June 2022 were invited to answer serial online surveys collecting information on SARS-CoV-2 infection, vaccination status and post-acute symptoms every 3-4 months for two years. Participants were categorized into groups based on the number of doses received prior to infection. We compared these groups over time in terms of reporting post-COVID symptom clusters and QoL, using population-average and mixed-effects regression models, respectively. Results: A total of 4809 individuals are enrolled and respond to up to five follow-up surveys. Of these, 1377 (28.61%) report a positive SARS-CoV-2 test, while 3432 (71.39%) report a negative result. After adjustment for potential confounders, receiving at least three COVID-19 vaccine doses prior to infection is associated with a 34% reduction in the likelihood of reporting at least one long COVID symptom cluster compared to being unvaccinated (adjusted odds ratio [aOR] = 0.66, p = 0.022). Pre-infection vaccination is also associated with higher quality of life (QoL) scores (β = 0.07, p < 0.001). The estimated vaccine effectiveness of three pre-infection doses against long COVID over a two-year period is 26.5% (95% CI: 10.8–39.4). This protective effect remains stable over time. In contrast, vaccination received after infection shows no association with long COVID symptoms or QoL outcomes. Conclusions: Receiving at least three COVID-19 vaccine doses prior to SARS-CoV-2 infection provides a sustained protective effect against long COVID and its negative impact on quality of life for at least two years. The longer-term durability of this protection, the role of reinfection, and the influence of emerging viral variants remains to be investigated.