Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings

SPS commentary:

This study provided real-world estimates of effectiveness of all three Covid-19 vaccines authorised in the US: BNT162b2 (Pfizer–BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Johnson & Johnson–Janssen). The effectiveness of the Ad26.COV2.S vaccine was found to be 68% against laboratory-confirmed SARS-CoV-2 infection leading to hospitalisation and 73% against infection leading to an emergency department or urgent care clinic visit

The study employed a test-negative design in which the case patients were those who tested positive for SARS-CoV-2, and the control patients were those who tested negative. Vaccine effectiveness was estimated by comparing the odds of vaccination between cases and controls. According to an editorial, the test-negative design of this study has been routinely used to estimate vaccine effectiveness against seasonal influenza, but its application in studies of Covid-19, although increasingly common, is new. It questions how to interpret critically the effectiveness estimates resulting from such a design. It identified four important points to consider:

• First, are there unmeasured differences between vaccinated and unvaccinated persons that may influence the occurrence of Covid-19?
• Second, are cases and controls sampled without bias?
• Third, is the patient’s SARS-CoV-2 infection status or vaccination status misclassified?
• Finally, are the results generalizable to populations that have different access to medical care or different health care–seeking behaviours?

It suggests that owing to their applicability to large electronic health records and their logistic simplicity relative to large prospective cohorts, test-negative designs can be expected to play an important role in monitoring the effectiveness of Covid-19 vaccines in the US and elsewhere.