Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Adults with Underlying Medical Conditions: Systematic Literature Review and Pairwise Meta-Analysis Using GRADE
Xuan Wang, Ankit Pahwa, Mary T. Bausch-Jurken, Anushri Chitkara, Pawana Sharma, Mia Malmenäs, Sonam Vats, Michael G. Whitfield, Kira Zhi Hua Lai, Priyadarsini Dasari, Ritu Gupta, Maria Nassim, Nicolas Van de Velde, Nathan Green, Ekkehard Beck
Abstract
This systematic literature review and pairwise meta-analysis evaluated the comparative effectiveness of mRNA-1273 versus BNT162b2 in patients with at least one underlying medical condition at high risk for severe COVID-19. 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. 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]; I 2 = 92.5%), symptomatic SARS-CoV-2 infection (RR, 0.75 [95% CI, 0.65–0.86]; I 2 = 62.3%), severe SARS-CoV-2 infection (RR, 0.83 [95% CI, 0.78–0.89]; I 2 = 38.0%), hospitalization due to COVID-19 (RR, 0.88 [95% CI, 0.82–0.94]; I 2 = 38.7%), and death due to COVID-19 (RR, 0.84 [95% CI, 0.76–0.93]; I 2 = 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. 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.