COVID-19 vaccines effectiveness against symptomatic disease and severe outcomes, 2021-2022: a test-negative case-control study

Abstract

Objectives: This study aims to evaluate the effectiveness of COVID-19 vaccines in symptomatic and severe disease prevention. Study design: This is an observational, case-control test-negative study. Methods: Participants were adults with at least one symptom included in the WHO COVID-19 case definition who sought health care in a public emergency department between the 1st of November of 2021 and the 2nd of March of 2022, the period corresponding to the fifth pandemic wave in Portugal, dominated by the Omicron variant. We used multivariable regression models to estimate the odds ratio, comparing the odds of vaccination between test-positive cases and test-negative controls. This allowed us to calculate the absolute and relative vaccine effectiveness. Results: Our study sample included 1059 individuals (522 cases and 537 controls), with a median age of 56, 58% female. Compared to the primary scheme completed more than 180 days earlier, the relative effectiveness against symptomatic infection of a booster was 62.4% (95% CI: 45.3%, 74.2%, p <0.001). The effectiveness of the primary series against symptomatic infection peaked at 85.3% (CI 95%: 58.7%, 94.8%) between 14-90 days after the last inoculation, decreasing to 15.1% (CI 95%: -42.6%, 49.5%) after more than 180 days. Conclusions: Despite the known characteristics of immunologic evasion of the Omicron variant, our results show that vaccine effectiveness rises after a booster. The effectiveness lowered to less than 50% between 4 and 6 months after the last dose. Therefore, this is likely the appropriate time for a booster to restore immunity.