Abstract
This systematic review evaluates the efficacy and long-term effectiveness of the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) across diverse clinical and observational settings within the United States in Americans aged 16 and older. We conducted an extensive literature search utilizing various types of studies to assess the vaccine's performance in preventing symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes. Our initial search in PubMed on March 14, 2022, yielded 6,725 potentially relevant articles, with 26 undergoing full-text assessment and eight meeting the inclusion criteria. To incorporate the most up-to-date findings, a secondary search was conducted on July 6, 2024, using improved and refined Medical Subject Headings (MeSH) terms within the PubMed and Scopus databases. This expanded approach resulted in 78 potentially relevant articles from PubMed and 1,567 from Scopus, with 40 articles undergoing full-text assessment and an additional 14 articles meeting the inclusion criteria. Early clinical trials reported initial vaccine effectiveness (VE) up to 95% with sustained immunity in various populations. Observational studies and systematic reviews further confirmed VE above 90% against symptomatic infections and highlighted nearly complete protection against hospitalizations and deaths. Recent research underscores the critical role of booster doses in maintaining high VE, especially against emerging variants, showing restored effectiveness up to 95% and supporting their strategic importance in ongoing pandemic responses. Despite observed waning immunity and breakthrough infections, the BNT162b2 vaccine continues to exhibit robust protection across different demographic groups and under varying epidemiological conditions. Our findings advocate for continuous booster updates and adaptive vaccination strategies to manage emerging SARS-CoV-2 variants, reinforcing the pivotal role of mRNA vaccine technology in addressing global health emergencies.