Effectiveness of Covid-19 vaccines against SARS-CoV-2 Omicron variant (B.1.1.529): A systematic review with meta-analysis and meta-regression

Summary Background There is a need for evaluation regarding vaccine effectiveness (VE) and the urgency of booster vaccination against Covid-19 B.1.1.529 (Omicron) variant. Methods Systematic search was conducted on April 6th, 2022, on databases (PubMed, ScienceDirect, CENTRAL, Web of Science, Scopus). VE difference (VED) estimates were assessed using random-effects model and DerSimonian-Laird tau estimators. Two models result, i.e., within 3 months and within 3 months or more, are compared. VE versus time meta-regression analysis was evaluated using mixed-effects model with Restricted-Maximum Likelihood tau estimators and Hartung-Knapp adjustments. Findings Ad26.COV2.S, BNT162b2, ChAdOx1 nCov-19, and mRNA-1273 vaccines were included in the analyses. Compared to full dose, booster dose of overall vaccines provided better protection against any (VED=22% (95%CI 15%-29%), p<0.001), severe (VED=20% (95%CI 8%-32%), p=0.001) and symptomatic (VED=22% (95%CI 11%-34%), p<0.001) Omicron infections within 3 months, as well as within 3 months or more (VED=30% (95%CI 24%-37%), p<0.001 for any, VED=18% (95%CI 13%-23%), p<0.001 for severe and VED=37% (95%CI 29%-46%), p<0.001 for symptomatic infections). The meta-regression analysis of overall vaccines revealed that the full dose VE against any and symptomatic Omicron infections were significantly reduced each month by 3.0% (95%CI 0.9%-4.8%, p=0.004) and 5.2% (95%CI 3.3%-7.1%, p=0.006), respectively; whereas booster dose effectiveness against severe and symptomatic Omicron infections were decreased by 3.7% (95%CI 5.1%-12.6%, p=0.030) and 3.9% (95%CI 1.2%-6.5%, p=0.006), respectively. Interpretation Compared to full dose only, a booster dose addition provides better protection against B.1.1.529 infection. Although the VE estimates of Ad26.COV2.S, BNT162b2, ChAdOx1 nCov-19, and mRNA-1273 vaccines against B.1.1.529 infection after both full and booster doses are generally moderate, and the booster dose provides excellent protection against severe infection, it is important to note that the VE estimates decline over time, suggesting the need for a regular Covid-19 booster injection after certain period of time to maintain VE.