Eligible medical encounters were defined as those among adults aged ≥18 years who had received SARS-CoV-2 molecular testing (primarily reverse transcription–polymerase chain reaction assay within 14 days before or 72 hours after the admission or encounter) and a COVID-19–like illness discharge diagnosis. Vaccination status was documented in electronic health records and immunization registries. Full vaccination was defined as receipt of the second dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) mRNA vaccines, or a single dose of Ad26.COV2 (Janssen [Johnson & Johnson]) vaccine ≥14-days before the testing or encounter date. Patients who had received no COVID-19 vaccine doses were considered unvaccinated. Patients who had received 1 mRNA dose only or had received the second dose <14 days before testing or encounter date were excluded. VE was estimated using a test-negative design, calculating the odds of receiving a positive SARS-CoV-2 test result comparing fully vaccinated and unvaccinated patients (referent group). VE was adjusted for age, geographic region, calendar time (days from January 1 to medical event), and virus circulation, and weighted for inverse propensity to be vaccinated or unvaccinated (calculated separately for each VE model). VE estimates with 95% confidence intervals (CIs) that did not overlap were considered statistically different. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.^†

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