Absolute and Relative Vaccine Effectiveness of Primary and Booster Series of COVID-19 Vaccines (mRNA and Adenovirus Vector) Against COVID-19 Hospitalizations in the United States, December 2021-April 2022

Abstract

Background: Coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) studies are increasingly reporting relative VE (rVE) comparing a primary series plus booster doses with a primary series only. Interpretation of rVE differs from traditional studies measuring absolute VE (aVE) of a vaccine regimen against an unvaccinated referent group. We estimated aVE and rVE against COVID-19 hospitalization in primary-series plus first-booster recipients of COVID-19 vaccines.

Methods: Booster-eligible immunocompetent adults hospitalized at 21 medical centers in the United States during December 25, 2021-April 4, 2022 were included. In a test-negative design, logistic regression with case status as the outcome and completion of primary vaccine series or primary series plus 1 booster dose as the predictors, adjusted for potential confounders, were used to estimate aVE and rVE.

Results: A total of 2060 patients were analyzed, including 1104 COVID-19 cases and 956 controls. Relative VE against COVID-19 hospitalization in boosted mRNA vaccine recipients versus primary series only was 66% (95% confidence interval [CI], 55%-74%); aVE was 81% (95% CI, 75%-86%) for boosted versus 46% (95% CI, 30%-58%) for primary. For boosted Janssen vaccine recipients versus primary series, rVE was 49% (95% CI, -9% to 76%); aVE was 62% (95% CI, 33%-79%) for boosted versus 36% (95% CI, -4% to 60%) for primary.

Conclusions: Vaccine booster doses increased protection against COVID-19 hospitalization compared with a primary series. Comparing rVE measures across studies can lead to flawed interpretations of the added value of a new vaccination regimen, whereas difference in aVE, when available, may be a more useful metric.

Keywords: COVID-19; absolute vaccine effectiveness; booster vaccine series; primary vaccine series; relative vaccine effectiveness.

Figure 1.

Absolute and relative vaccine effectiveness (rVE) against hospitalization (point estimates [95% confidence intervals]) for primary series plus first mRNA booster dose and mRNA vaccine primary series alone (overall, 18–64 years and ≥65 years), December 2021–April 2022. The rVE point estimates at the left of each age category are denoted by red dots, absolute vaccine effectiveness (aVE) point estimates in the middle and at the right of each age category are denoted by yellow dots, and 95% confidence intervals are delineated by black vertical lines going through the corresponding dots for each point estimate.

Figure 2.

Absolute and relative vaccine effectiveness (rVE) against hospitalization (point estimates [95% confidence intervals]) for mRNA and Janssen vaccine primary series plus first booster dose and primary series alone, December 2021–April 2022. The rVE point estimates are denoted by red dots at the left of each vaccine type category, absolute vaccine effectiveness (aVE) point estimates are denoted by yellow dots in the middle and at the right of each vaccine type, and 95% confidence intervals are delineated by black vertical lines going through the corresponding dots for each point estimate.

Figure 3.

Scenario exercise comparing events averted by primary series alone and primary series plus first booster vaccine dose (n = 2000). Clustered bars show the additional number of events averted by adding a vaccine booster (purple/middle section of each bar) to a primary series alone (blue/bottom section of each bar). Unvaccinated persons are represented by the yellow/top section of each bar. Abbreviations: aVE, absolute vaccine effectiveness; rVE, relative vaccine effectiveness; VE, vaccine effectiveness.