Assessing the Effectiveness of COVID-19 Vaccines: A Retrospective Test-negative Case-control Analysis during Pre-omicron and Omicron Periods

Matteo Gori^*
*Correspondence: Matteo Gori, Department of Translational Medicine, University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy, Email:

Introduction

The global rollout of COVID-19 vaccines in late 2020 and early 2021 marked a turning point in the fight against the pandemic. With vaccines demonstrating strong efficacy in preventing severe illness and death caused by the SARS-CoV-2 virus, widespread vaccination efforts began worldwide. However, as the virus evolved, new variants emerged that exhibited varying degrees of immune evasion. The Omicron variant, which was first identified in late 2021, became the dominant strain globally in early 2022, raising concerns about the continued effectiveness of vaccines. In response to these concerns, researchers have employed various study designs to assess the effectiveness of COVID-19 vaccines across different variants of the virus. One widely used approach is the test-negative case-control study, which compares the likelihood of vaccination between individuals who test positive for COVID-19 and those who test negative (controls). This retrospective study design allows for the evaluation of vaccine effectiveness in real-world settings and has been instrumental in assessing the impact of vaccines both before and after the emergence of Omicron [1,2].

Description

The SARS-CoV-2 virus is known for its ability to mutate over time. As it spreads, mutations in the virus's spike protein, which is the target of most COVID-19 vaccines, can lead to the emergence of new variants. Some variants, like Delta and Omicron, are particularly concerning because they carry mutations that may allow the virus to partially escape the immunity provided by previous infections or vaccinations. While vaccines remained effective against Delta, particularly in preventing severe disease, the increased transmissibility raised the importance of booster doses. Omicron contained an unusually large number of mutations in the spike protein, which made it less susceptible to neutralizing antibodies generated by vaccines and past infections. The variant's ability to escape immunity raised concerns about vaccine effectiveness, especially regarding the prevention of infection, although vaccines still appeared to provide protection against severe disease and hospitalization. A test-negative case-control study is an observational research design commonly used to assess vaccine effectiveness. In this design, individuals who have tested positive for a specific infection are compared to those who have tested negative for the infection. The key advantage of this study design is that it adjusts for healthcare-seeking behavior, which can bias estimates of vaccine effectiveness. In a test-negative design, both cases and controls are individuals who sought testing for the same reasons typically due to symptoms or exposure—thereby controlling for confounders like access to healthcare and testing availability [3-5].

Conclusion

The effectiveness of COVID-19 vaccines has remained high in preventing severe disease, hospitalization, and death, both in the pre-Omicron and Omicron periods. However, the emergence of the Omicron variant highlighted the virus's ability to partially escape vaccine-induced immunity, leading to a reduction in protection against symptomatic infection. Nonetheless, booster doses have proven essential in restoring vaccine efficacy, especially in preventing severe outcomes. Retrospective test-negative case-control studies provide critical insights into the real-world performance of vaccines, underscoring the continued importance of vaccination, including booster doses, in the ongoing fight against COVID-19. Despite the reduced effectiveness in preventing infection, vaccines continued to offer strong protection against severe disease, hospitalization, and death caused by Omicron. Test-negative studies showed that the effectiveness of vaccines in preventing severe outcomes remained relatively high, particularly for individuals who received booster doses.

Acknowledgement

None.

Conflict of Interest

None.

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