Effectiveness of the Booster Doses of mRNA Vaccine Against SARS-CoV-2 Omicron Infection and its Severe Outcomes: A Systematic Review and Meta-Analysis

Background: The rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant has raised concerns regarding waning vaccine-induced immunity and durability. We conducted a systematic review and meta-analysis to assess the magnitude and duration of the effectiveness of the booster doses (third and fourth doses) of mRNA vaccines (BNT162b2 and mRNA-1273) against SARS-CoV-2 infection and severe COVID-19 outcomes due to the Omicron variant and its sub-lineages BA.1 and BA.2.Methods: In this systematic review and meta-analysis, we conducted a comprehensive search in electronic databases and other resources from January 2020 to December 2022 to identify relevant studies that assessed the effectiveness of BNT162b2 and mRNA-1273 vaccine booster doses against SARS-CoV-2 infection and severe COVID-19 outcomes caused by the Omicron variant. Using random-effects meta-analysis, we estimated the pooled effectiveness of mRNA vaccine booster doses against SARS-CoV-2 infection, symptomatic infection, hospitalisation, intensive care unit admission, mechanical ventilation, oxygen support, and death due to the Omicron variant. Furthermore, we compared vaccine effectiveness (VE) of the third dose versus the primary dose, no vaccination, and the fourth dose at different time points after booster vaccination. Independent reviewers performed the study selection, data extraction, risk of bias assessment, and certainty of evidence using the GRADE approach. This review was registered with the PROSPERO database (CRD42023376698).Findings: This review included 50 studies. Compared to the primary dose, the pooled VE of third-dose mRNA vaccines against SARS-CoV-2 infection was 48·86% (95% CI 44·90–52·82, I2=95·79%) at ≥14 days, and gradually decreased to 38·01% (95% CI 13·90–62·13, I2=68·14%) at ≥90 days after the third dose vaccination. Compared with the third dose, the fourth dose VE against SARS-CoV-2 infection among older people aged ³60 years peaked at 14–30 days (VE 56·70% [95% CI 50·36–63·04], I2=98·02%), then quickly declined at 61–90 days after the last booster dose vaccination (VE 22% [95% CI 6·40–37·60]). Similar trends were observed in symptomatic infections. Compared with no vaccination, the VE of third-dose mRNA vaccines was 75·84% (95% CI 40·56–111·12, I2=98·62%) against BA.1 infection, and 70·41% (95% CI 49·94–90.88, I2=88·87%) against BA.2 infection at ≥7 days after the third-dose vaccination. The third-dose VE against hospitalisation remained stable over time and retained with 79·30% (95% CI 58·65–99·94, I2=88·10%) at 91–120 days, compared with the no vaccination. For older people aged ³60 years, compared with the third dose VE, the fourth-dose VE up to 60 days was 67·54% (95% CI 59·76–75·33, I2=59·33%) for hospitalisation and 77·88% (95% CI 72·55–83·21, I2=0%) for death due to Omicron.Interpretation: The VE of mRNA booster doses against SARS-CoV-2 infection and symptomatic infection caused by the Omicron variant waned within months. An mRNA booster can provide substantial protection against severe COVID-19 outcomes for 6 months. These findings support the need for a booster dose within 6 months of the primary or third-dose vaccination.Funding: None.Declaration of Interest: None.