Impact of Pre-Infection COVID-19 Vaccination on the Incidence and Severity of Post-COVID Syndrome: A Systematic Review and Meta-Analysis

This systematic review critically evaluated the impact of a pre-infection COVID-19 vaccination on the incidence and severity of post-COVID-19 syndrome and aimed to assess the potential protective effect across different vaccines and patient demographics. This study hypothesized that vaccination before infection substantially reduces the risk and severity of post-COVID-19 syndrome. In October 2023, a comprehensive literature search was conducted across three databases, PubMed, Embase, and Scopus, focusing on studies published up to that date. Utilizing a wide array of keywords, the search strategy adhered to the PRISMA guidelines and was registered in the Open Science Framework. The inclusion criteria comprised studies focusing on patients with a breakthrough SARS-CoV-2 infection who developed post-COVID-19 syndrome. We included a total of 13 articles that met the inclusion criteria, analyzing more than 10 million patients with a mean age of 50.6 years, showing that the incidence of intensive care unit (ICU) admissions post-vaccination was as low as 2.4%, with a significant reduction in mortality risk (OR 0.66, 95% CI 0.58-0.74). The prevalence of post-COVID-19 syndrome symptoms was lower in vaccinated individuals (9.5%) compared to unvaccinated (14.6%), with a notable decrease in activity-limiting symptoms (adjusted OR 0.59, 95% CI 0.48-0.73). Vaccinated patients also showed a quicker recovery and return to work (HR 1.37, 95% CI 1.04-1.79). The pooled odds ratio of 0.77 indicates that vaccination is associated with a 23% reduction in the risk of developing post-COVID-19 syndrome (95% CI 0.75-0.79). Despite the protective effects observed, a substantial heterogeneity among the studies was noted. In conclusion, a pre-infection COVID-19 vaccination is associated with a significant reduction in the risk and severity of post-COVID-19 syndrome. However, the observed heterogeneity across studies suggests a need for further research with standardized methods to fully comprehend vaccine efficacy against long COVID.