Absolute and Relative Vaccine Effectiveness of Primary and Booster Series of COVID-19 Vaccines (mRNA and Adenovirus Vector) Against COVID-19 Hospitalizations in the United States, December 2021–April 2022
Authors: Lewis Nathaniel M , Murray Nancy , Adams Katherine , Surie Diya , Gaglani Manjusha , Ginde Adit A , McNeal Tresa , Ghamande Shekhar , Douin David J , Talbot H Keipp , Casey Jonathan D , Mohr Nicholas M , Zepeski Anne , Shapiro Nathan I , Gibbs Kevin W , Files D Clark , 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 , Bender William , 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 , Rhoads Jillian P , McMorrow Meredith L , Tenforde Mark W , Self Wesley H , Patel Manish M ,   for the Influenza and Other Viruses in the Acutely Ill (IVY) Network, Gaglani Manjusha , McNeal Tresa , Ghamande Shekhar , Calhoun Nicole , Murthy Kempapura , Herrick Judy , McKillop Amanda , Hoffman Eric , Zayed Martha , Smith Michael , Steingrub Jay , Kozikowski Lori-Ann , Souza Lesley De , Ouellette Scott , Shapiro Nathan I , Bolstad Michael , Coviello Brianna , Ciottone Robert , Devilla Arnaldo , Grafals Ana , Higgins Conor , Ottanelli Carlo , Redman Kimberly , Scaffidi Douglas , Weingart Alexander , Patel Manish , Tenforde Mark , Lewis Nathaniel , Olson Samantha , Stephenson Meagan , Adams Katherine , Surie Diya , McMorrow Meredith , Tremarelli Maraia , Turbyfill Caitlin , Duggal Abhijit , Mehkri Omar , Mitchell Megan , Griffith Zachary , Brennan Connery , Ashok Kiran , Poynter Bryan , Busse Laurence , Bender William , Lohuis Caitlin ten , Stanley Nicholas , Zhang Sophia , Prekker Matthew , Erickson Heidi , Frosch Anne , Hendrickson Audrey , Caspers Sean , Tordsen Walker , Kaus Olivia , Scharber Tyler , Peltan Ithan , Brown Samuel , Lumpkin Jenna , Smith Cassie , Marshall Hunter , N David , Hager  , Shehu Arber , Ali Harith , Rothman Richard E , Gong Michelle , Mohamed Amira , Nair Rahul , Chen Jen-Ting (Tina) , Exline Matthew , Karow Sarah , Khan Maryiam , So Preston , So Madison , Schwartz Elizabeth , Botros Mena , Khan Akram , Hough Catherine L , Jung Haeun , Martinez Jesus , Luong Andrea , Huynh Bao , Ibrahim Habiba , Villanueva-Vargas Cynthia , Villanueva-Vargas Juliana , Quadri Suha , Wilson Jennifer G , Gordon Alexandra June , Perez Cynthia , Qadir Nida , Chang Steven , Frankel Trevor , Garner Omai , Chandrasekaran Sukantha , Ginde Adit , Douin David , Huynh David , Steinwand Aimee , Withers Cori , Driver Conner , Wright Shelby , Mohr Nicholas , Zepeski Anne , Nassar Paul , Landers Shannon , Nielsen Karin , Briggs Noble , Fairfield Cathy , Mallow Chris , Gershengorn Hayley , Rivas Carolina , Martin Emily , Monto Arnold , Lauring Adam , McSpadden EJ , Truscon Rachel , Kaniclides Anne , Thomas Lara , Bielak Ramsay , Valvano Weronika Damek , Fong Rebecca , Fitzsimmons William J , Blair Christopher , Gilbert Julie , Baker Leigh , Johnson Nicholas , Srinivasan Vasisht , Crider Christine D , Steinbock Kyle A , Paulsen Thomas C , Anderson Layla A , Self Wesley H , Talbot H Keipp , Lindsell Chris , Grijalva Carlos , Jones Ian , Halasa Natasha , Chappell James , Womack Kelsey , Rhoads Jillian , Baughman Adrienne , Kampe Christy , Johnson Jakea , Sturgill Jake , Hart Kim , McClellan Robert , Rice Todd , Casey Jonathan , Stubblefield William B , Zhu Yuwei , Short Laura L , Ezzell Lauren J , Whitsett Margaret E , McHenry Rendie E , Hargrave Samarian J , Blair Marcia , Luther Jennifer L , Pulido Claudia Guevara , Peterson Bryan P M , Files D Clark , Gibbs Kevin , LaRose Mary , Landreth Leigha , Hicks Madeline , Parks Lisa , Babcock Hilary , Kwon Jennie , Bongu Jahnavi , McDonald David , Cass Candice , Seiler Sondra , Park David , Hink Tiffany , Wallace Meghan , Burnham Carey-Ann , Arter Olivia G 
Published: December 2022

Abstract

Background
Coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) studies are increasingly reporting relative VE (rVE) comparing a primary series plus booster doses with a primary series only. Interpretation of rVE differs from traditional studies measuring absolute VE (aVE) of a vaccine regimen against an unvaccinated referent group. We estimated aVE and rVE against COVID-19 hospitalization in primary-series plus first-booster recipients of COVID-19 vaccines.

Methods
Booster-eligible immunocompetent adults hospitalized at 21 medical centers in the United States during December 25, 2021–April 4, 2022 were included. In a test-negative design, logistic regression with case status as the outcome and completion of primary vaccine series or primary series plus 1 booster dose as the predictors, adjusted for potential confounders, were used to estimate aVE and rVE.

Results
A total of 2060 patients were analyzed, including 1104 COVID-19 cases and 956 controls. Relative VE against COVID-19 hospitalization in boosted mRNA vaccine recipients versus primary series only was 66% (95% confidence interval [CI], 55%–74%); aVE was 81% (95% CI, 75%–86%) for boosted versus 46% (95% CI, 30%–58%) for primary. For boosted Janssen vaccine recipients versus primary series, rVE was 49% (95% CI, −9% to 76%); aVE was 62% (95% CI, 33%–79%) for boosted versus 36% (95% CI, −4% to 60%) for primary.

Conclusions
Vaccine booster doses increased protection against COVID-19 hospitalization compared with a primary series. Comparing rVE measures across studies can lead to flawed interpretations of the added value of a new vaccination regimen, whereas difference in aVE, when available, may be a more useful metric.