Durability of Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Booster Vaccine Protection Against Omicron Among Healthcare Workers With a Vaccine Mandate

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread rapidly throughout the world since being identified in South Africa in November 2021. Few studies have assessed primary series and booster vaccine effectiveness against Omicron among US healthcare workers Methods We conducted a test-negative case-control design to estimate BNT162b2 and mRNA1273 primary vaccination and booster effectiveness against SARS-CoV-2 infection and symptomatic coronavirus disease 2019 during an Omicron surge among employees of the University of Pennsylvania Health System. The study period was between 1 July 2021 and 5 April 2022. We defined the Delta period as 1 July to 12 December 2021 and the Omicron period as beginning 12 December 21. Results Our sample included 14 520 tests (2776 [19%] positive)-7422 (506 [7%] positive) during Delta and 7098 (2270 [32%] positive) during Omicron. Benchmarked against Delta, the vaccine effectiveness of 2 vaccine doses was lower during Omicron, with no significant protection against infection. Booster doses added significant protection, although they also showed reduced effectiveness during Omicron. Compared with findings in employees who had received 2 vaccine doses, 3 doses of BNT162b2 had a relative effectiveness of 50% (95% confidence interval, 42%-56%) during Omicron, relative to 78% (63%-87%) during Delta; 3 doses of mRNA1273 had a relative effectiveness of 56% (45%-65%) during Omicron, relative to 96% (82%-99%) during Delta. Restricting the sample to symptomatic tests yielded similar results to our primary analysis. After initial waning in BNT162b2 booster protection against infection, it remained largely stable for >= 16 weeks after vaccination. Conclusions Our findings provide a strong rationale for boosters among healthcare workers in the Omicron era. A test-negative case control study of healthcare workers with a vaccine mandate found lower vaccine effectiveness for 2 severe acute respiratory syndrome coronavirus 2 messenger RNA vaccine doses during Omicron than during a Delta period; booster doses added significant protection.