- Plumb, Ian;
- Mohr, Nicholas;
- Hagen, Melissa;
- Wiegand, Ryan;
- Dumyati, Ghinwa;
- Harland, Karisa;
- Krishnadasan, Anusha;
- Gist, Jade;
- Abedi, Glen;
- Fleming-Dutra, Katherine;
- Chea, Nora;
- Lee, Jane;
- Barter, Devra;
- Brackney, Monica;
- Fridkin, Scott;
- Wilson, Lucy;
- Lovett, Sara;
- Ocampo, Valerie;
- Phipps, Erin;
- Marcus, Tiffanie;
- Smithline, Howard;
- Hou, Peter;
- Lee, Lilly;
- Moran, Gregory;
- Krebs, Elizabeth;
- Steele, Mark;
- Lim, Stephen;
- Schrading, Walter;
- Beiser, David;
- Faine, Brett;
- Haran, John;
- Nandi, Utsav;
- Chipman, Anne;
- LoVecchio, Frank;
- Talan, David;
- Pilishvili, Tamara;
- Chinnock, Brian
BACKGROUND: Protection against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]) can limit transmission and the risk of post-COVID conditions, and is particularly important among healthcare personnel. However, lower vaccine effectiveness (VE) has been reported since predominance of the Omicron SARS-CoV-2 variant. METHODS: We evaluated the VE of a monovalent messenger RNA (mRNA) booster dose against COVID-19 from October 2021 to June 2022 among US healthcare personnel. After matching case-participants with COVID-19 to control-participants by 2-week period and site, we used conditional logistic regression to estimate the VE of a booster dose compared with completing only 2 mRNA doses >150 days previously, adjusted for multiple covariates. RESULTS: Among 3279 case-participants and 3998 control-participants who had completed 2 mRNA doses, we estimated that the VE of a booster dose against COVID-19 declined from 86% (95% confidence interval, 81%-90%) during Delta predominance to 65% (58%-70%) during Omicron predominance. During Omicron predominance, VE declined from 73% (95% confidence interval, 67%-79%) 14-60 days after the booster dose, to 32% (4%-52%) ≥120 days after a booster dose. We found that VE was similar by age group, presence of underlying health conditions, and pregnancy status on the test date, as well as among immunocompromised participants. CONCLUSIONS: A booster dose conferred substantial protection against COVID-19 among healthcare personnel. However, VE was lower during Omicron predominance, and waning effectiveness was observed 4 months after booster dose receipt during this period. Our findings support recommendations to stay up to date on recommended doses of COVID-19 vaccines for all those eligible.