Vaccine Effectiveness of Primary Series and Booster Doses against Omicron Variant COVID-19-Associated Hospitalization in the United States
Authors: Adams Katherine , Rhoads Jillian P. , Surie Diya , Gaglani Manjusha , Ginde Adit A. , McNeal Tresa , Ghamande Shekhar , Huynh David , Talbot H. Keipp , Casey Jonathan D. , Mohr Nicholas M. , Zepeski Anne , Shapiro Nathan I. , Gibbs Kevin W. , Files D. Clark , Hicks Madeline , Hager David N. , Ali Harith , Prekker Matthew E. , Frosch Anne E. , Exline Matthew C. , Gong Michelle N. , Mohamed Amira , Johnson Nicholas J. , Srinivasan Vasisht , Steingrub Jay S. , Peltan Ithan D. , Brown Samuel M. , Martin Emily T. , Monto Arnold S. , Lauring Adam S. , Khan Akram , Hough Catherine L. , Busse Laurence W. , ten Lohuis Caitlin C. , Duggal Abhijit , Wilson Jennifer G. , Gordon Alexandra June , Qadir Nida , Chang Steven Y. , Mallow Christopher , Rivas Carolina , Babcock Hilary M. , Kwon Jennie H. , Chappell James D. , Halasa Natasha , Grijalva Carlos G. , Rice Todd W. , Stubblefield William B. , Baughman Adrienne , Lindsell Christopher J. , Hart Kimberly W. , Lester Sandra N. , Thornburg Natalie J. , Park SoHee , McMorrow Meredith L. , Patel Manish M. , Tenforde Mark W. , Self Wesley H. 
Published: June 2022

Objectives: To compare the effectiveness of a primary COVID-19 vaccine series plus a booster dose with a primary series alone for the prevention of Omicron variant COVID-19 hospitalization.

Design: Multicenter observational case-control study using the test-negative design to evaluate vaccine effectiveness (VE).

Setting: Twenty-one hospitals in the United States (US).

Participants: 3,181 adults hospitalized with an acute respiratory illness between December 26, 2021 and April 30, 2022, a period of SARS-CoV-2 Omicron variant (BA.1, BA.2) predominance. Participants included 1,572 (49%) case-patients with laboratory confirmed COVID-19 and 1,609 (51%) control patients who tested negative for SARS-CoV-2. Median age was 64 years, 48% were female, and 21% were immunocompromised; 798 (25%) were vaccinated with a primary series plus booster, 1,326 (42%) were vaccinated with a primary series alone, and 1,057 (33%) were unvaccinated.

Main Outcome Measures: VE against COVID-19 hospitalization was calculated for a primary series plus a booster and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. VE analyses were stratified by immune status (immunocompetent; immunocompromised) because the recommended vaccine schedules are different for these groups. The primary analysis evaluated all COVID-19 vaccine types combined and secondary analyses evaluated specific vaccine products.

Results: Among immunocompetent patients, VE against Omicron COVID-19 hospitalization for a primary series plus one booster of any vaccine product dose was 77% (95% CI: 71–82%), and for a primary series alone was 44% (95% CI: 31–54%) (p<0.001). VE was higher for a boosted regimen than a primary series alone for both mRNA vaccines used in the US (BNT162b2: primary series plus booster VE 80% (95% CI: 73-85%), primary series alone VE 46% (95% CI: 30-58%) [p<0.001]; mRNA-1273: primary series plus booster VE 77% (95% CI: 67-83%), primary series alone VE 47% (95% CI: 30-60%) [p<0.001]). Among immunocompromised patients, VE for a primary series of any vaccine product against Omicron COVID-19 hospitalization was 60% (95% CI: 41-73%). Insufficient sample size has accumulated to calculate effectiveness of boosted regimens for immunocompromised patients.

Conclusions: Among immunocompetent people, a booster dose of COVID-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing COVID-19 hospitalization due to the Omicron variant.