Comparative Effectiveness of the mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Adults With Underlying Medical Conditions: A Systematic Literature Review and Pairwise Meta-Analysis Using GRADE

Introduction: This systematic literature review and pairwise meta-analysis evaluated the comparative effectiveness of mRNA-1273 versus BNT162b in patients with at least one underlying medical condition at high risk for severe COVID-19. Methods: MEDLINE, Embase, and Cochrane databases were searched for relevant articles from January 1, 2019 to February 9, 2024. Studies reporting effectiveness data from at least two doses of mRNA-1273 and BNT162b2 vaccination in adults with medical conditions at high risk of developing severe COVID-19 according to the US Centers for Disease Control and Prevention were included. Outcomes of interest were SARS-CoV-2 infection (overall, symptomatic, and severe), hospitalization due to COVID-19, and death due to COVID-19. Risk ratios (RRs) were calculated with random effects models. Subgroup analyses by specific medical conditions, number of vaccinations, age, and SARS-CoV-2 variant were conducted. Heterogeneity between studies was estimated with chi-square testing. The certainty of evidence was assessed using the Grading of Recommendations, Assessments, Development, and Evaluations framework. Results: Sixty-five observational studies capturing the original/ancestral-containing primary series to Omicron-containing bivalent original-BA4-5 vaccinations were included in the meta-analysis. mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.79-0.92]; I2=92.5%), symptomatic SARS-CoV-2 infection (RR, 0.75 [95% CI, 0.65-0.86]; I2=62.3%), severe SARS-CoV-2 infection (RR, 0.83 [95% CI, 0.78-0.89]; I2=38.0%), hospitalization due to COVID-19 (RR, 0.88 [95% CI, 0.82-0.94]; I2=38.7%), and death due to COVID-19 (RR, 0.84 [95% CI, 0.76-0.93]; I2=1.3%) than BNT162b2. Findings were generally consistent across subgroups. Evidence certainty was low or very low because sufficiently powered randomized controlled trials are impractical in this heterogeneous population. Conclusion: Meta-analysis of 65 observational studies showed that vaccination with mRNA-1273 was associated with a significantly lower risk of SARS-CoV-2 infection and COVID-19-related hospitalization and death than BNT162b2 in patients with medical conditions at high risk of severe COVID-19.