Testing behaviour may bias observational studies of vaccine effectiveness

Recent observational studies suggest that vaccines may have little effect in preventing infection with the Omicron variant of severe acute respiratory syndrome coronavirus 2. However, the observed effects may be confounded by patient factors, preventive behaviours, or differences in testing behaviour. To assess potential confounding, we examined differences in testing behaviour between unvaccinated and vaccinated populations.

We recruited 1,526 Australian adults for an online randomized study about coronavirus disease 2019 (COVID-19) testing in late 2021, collecting self-reported vaccination status and three measures of COVID-19 testing behaviour: testing in past month or ever and test intention if they woke with a sore throat. We examined the association between testing intentions and vaccination status in the trial's baseline data.

Of the 1,526 participants (mean age 31 y), 22% had a COVID-19 test in the past month and 61% ever; 17% were unvaccinated, 11% were partially vaccinated (one dose), and 71% were fully vaccinated (two or more doses). Fully vaccinated participants were twice as likely as those who were unvaccinated (relative risk [RR] 2.2, 95% CI 1.8 to 2.8, p < 0.001) to report positive COVID testing intentions. Partially vaccinated participants had less positive intentions than fully vaccinated participants (RR 0.68, 95% CI 0.52 to 0.89, p < 0.001) but higher intentions than unvaccinated participants (RR 1.5, 95% CI 1.4 to 1.6, p = 0.002).

Vaccination predicted greater COVID-19 testing intentions and would substantially bias observed vaccine effectiveness. To account for differential testing behaviours, test-negative designs are currently the preferred option, but their assumptions need more thorough examination.