The test-negative design (TND) is widely used to estimate COVID-19 vaccine effectiveness (VE). Biased estimates of VE may result from effects of at-home SARS-CoV-2 rapid diagnostic test (RDT) results on decisions to seek healthcare. To investigate magnitude of potential bias, we constructed decision trees with input probabilities obtained from longitudinal surveys of U.S. adults between March 2022-October 2023. Prevalence of at-home RDT use and healthcare seeking following a positive or negative RDT result was estimated by participant vaccination status and socio-demographic characteristics. At true VE values ranging from 5% to 95%, we defined bias as the difference between the observed and true VE. Among 1,918 symptomatic adults, prevalence of at-home RDT use was higher among vaccinated (37%) versus unvaccinated (22%) participants. At-home RDT use was associated with seeking care, and participants reporting positive RDT were more likely than those reporting negative RDT to have sought care when ill. In primary analyses, we observed downward bias in VE estimates that increased in magnitude when true VE was low. Variations in proportions of vaccination, at-home RDT use and healthcare seeking by socio-demographic characteristics may impact VE estimates. Further evaluation of potential impact of at-home RDT use on VE estimates is warranted.

Denis Nash reports a relationship with Gilead Sciences Inc that includes consulting or advisory. Denis Nash reports a relationship with AbbVie Inc that includes consulting or advisory. The City University of New York (CUNY) School of Public Health received research support from Pfizer during the conduct of this study that was paid directly to CUNY, with Dr. Nash serving as the Principal Investigator.

Funding for this project is provided by The National Institute of Allergy and Infectious Diseases (NIAID), award number UH3AI133675 (MPIs: D Nash and C Grov), Pfizer Inc., the CUNY Institute for Implementation Science in Population Health (cunyisph.org) and the COVID-19 Grant Program of the CUNY Graduate School of Public Health and Health Policy. The funders played no role in the production of this manuscript nor necessarily endorse the findings.

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