Evaluation of the Real-World Effectiveness of Vaccines against COVID-19 at a Local Level: Protocol for a Test-Negative Case-Control Study.

Vaccines against COVID-19 approved for use in the EU/EEA have been shown to be highly effective against wild-type SARS-CoV-2. However, their effectiveness against new variants may be reduced. This study aims to evaluate the effectiveness of vaccines against COVID-19 in the prevention of symptomatic and severe disease, during pre- and post-omicron phases. Individuals who sought treatment at the emergency department of a Portuguese hospital with COVID-19-like disease and were tested for SARS-CoV-2 are the subjects of the study. Patients who received a positive result are considered cases, while those with negative results are the controls. The test-negative case-control method is one of the study designs recommended by WHO to estimate the effectiveness of vaccines against COVID-19. The main advantage of this design is that it controls for the healthcare seeking bias, commonly present in traditional cohort and case-control designs. This study may have broad implications for understanding the real-world performance of the COVID-19 vaccines at the local level, which may play a key role in promoting adherence to vaccination. Moreover, this study may contribute to inform decisions regarding booster doses and variant-specific vaccine formulations leading to the control of this and future pandemics.