Effectiveness of a Third Dose of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 2022
Authors: Mark G. Thompson, Karthik Natarajan, Stephanie A. Irving, Elizabeth A. Rowley, Eric P. Griggs, Manjusha Gaglani, Nicola P. Klein, Shaun J. Grannis, Malini B. DeSilva, Edward Stenehjem, Sarah E. Reese, Monica Dickerson, Allison L. Naleway, Jungmi Han, Deepika Konatham, Charlene McEvoy, Suchitra Rao, Brian E. Dixon, Kristin Dascomb, Ned Lewis, Matthew E. Levy, Palak Patel, I-Chia Liao, Anupam B. Kharbanda, Michelle A. Barron, William F. Fadel, Nancy Grisel, Kristin Goddard, Duck-Hye Yang, Mehiret H. Wondimu, Kempapura Murthy, Nimish R. Valvi, Julie Arndorfer, Bruce Fireman, Margaret M. Dunne, Peter Embi, Eduardo Azziz-Baumgartner, Ousseny Zerbo, Catherine H. Bozio, Sue Reynolds, Jill Ferdinands, Jeremiah Williams, Ruth Link-Gelles, Stephanie J. Schrag, Jennifer R. Verani, Sarah Ball, Toan C. Ong
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Estimates of COVID-19 mRNA vaccine effectiveness (VE) have declined in recent months (1,2) because of waning vaccine induced immunity over time,* possible increased immune evasion by SARS-CoV-2 variants (3), or a combination of these and other factors. CDC recommends that all persons aged ≥12 years receive a third dose (booster) of an mRNA vaccine ≥5 months after receipt of the second mRNA vaccine dose and that immunocompromised individuals receive a third primary dose.† A third dose of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine increases neutralizing antibody levels (4), and three recent studies from Israel have shown improved effectiveness of a third dose in preventing COVID-19 associated with infections with the SARS-CoV-2 B.1.617.2 (Delta) variant (5-7). Yet, data are limited on the real-world effectiveness of third doses of COVID-19 mRNA vaccine in the United States, especially since the SARS-CoV-2 B.1.1.529 (Omicron) variant became predominant in mid-December 2021. The VISION Network§ examined VE by analyzing 222,772 encounters from 383 emergency departments (EDs) and urgent care (UC) clinics and 87,904 hospitalizations from 259 hospitals among adults aged ≥18 years across 10 states from August 26, 2021¶ to January 5, 2022. Analyses were stratified by the period before and after the Omicron variant became the predominant strain (>50% of sequenced viruses) at each study site. During the period of Delta predominance across study sites in the United States (August-mid-December 2021), VE against laboratory-confirmed COVID-19-associated ED and UC encounters was 86% 14-179 days after dose 2, 76% ≥180 days after dose 2, and 94% ≥14 days after dose 3. Estimates of VE for the same intervals after vaccination during Omicron variant predominance were 52%, 38%, and 82%, respectively. During the period of Delta variant predominance, VE against laboratory-confirmed COVID-19-associated hospitalizations was 90% 14-179 days after dose 2, 81% ≥180 days after dose 2, and 94% ≥14 days after dose 3. During Omicron variant predominance, VE estimates for the same intervals after vaccination were 81%, 57%, and 90%, respectively. The highest estimates of VE against COVID-19-associated ED and UC encounters or hospitalizations during both Delta- and Omicron-predominant periods were among adults who received a third dose of mRNA vaccine. All unvaccinated persons should get vaccinated as soon as possible. All adults who have received mRNA vaccines during their primary COVID-19 vaccination series should receive a third dose when eligible, and eligible persons should stay up to date with COVID-19 vaccinations.