Pooled analysis of efficacy of the fourth mRNA-based COVID-19 vaccine dose in eliciting anti-SARS-CoV-2 serum antibody response in the general immunocompetent population

Since the opportunity of widespread administration of the fourth mRNA-based coronavirus disease 2019 (COVID-19) vaccine dose remains controversial, this article provides a pooled analysis of the efficacy of the second COVID-19 mRNA-based homologous vaccine booster in eliciting anti-SARS-CoV-2 serum antibody response in general immunocompetent populations. Methods: We conducted a digital search in Medline using the keywords "fourth dose" or "second booster" and "antibodies" and "COVID-19" or "SARS-CoV-2" and "BNT162b2" or "mRNA-1273", to identify all clinical studies which evaluated the anti-SARS-CoV-2 serum antibody response after the fourth mRNA-based COVID-19 homologous vaccine dose administration in general immunocompetent populations compared to the response seen before its administration and after the first booster. Results: Four studies totaling 571 recipients of the second mRNA-based COVID-19 vaccine booster were finally included in our analysis. The weighted mean difference (WMD) ratio of anti-SARS-CoV-2 serum antibodies levels measured after and before administration of the fourth vaccine dose was 9.7 (95% CI, 6.5-12.9) in those receiving BNT162b2 and 12.0 (95% CI, 5.8-18.2) in those receiving mRNA-1273, respectively. The WMD ratio of anti-SARS-CoV-2 serum antibodies levels measured at the peak of the fourth and third vaccine doses was 1.4 (95% CI, 1.2-1.7) in those receiving BNT162b2 and 1.9 (95% CI, 1.5-2.4) in those receiving mRNA-1273, respectively. Conclusion: Our data confirm the efficacy of the fourth mRNA-based COVID-19 vaccine dose in restoring a satisfactory level of anti-SARS-CoV-2 serum antibodies, though such effectiveness seems only marginally superior to that of the first booster.