• Mark W Tenforde, Wesley H Self, Katherine Adams, Manjusha Gaglani, Adit A Ginde, Tresa McNeal, Shekhar Ghamande, David J Douin, H Keipp Talbot, Jonathan D Casey, Nicholas M Mohr, Anne Zepeski, Nathan I Shapiro, Kevin W Gibbs, D Clark Files, David N Hager, Arber Shehu, Matthew E Prekker, Heidi L Erickson, Matthew C Exline, Michelle N Gong, Amira Mohamed, Daniel J Henning, Jay S Steingrub, Ithan D Peltan, Samuel M Brown, Emily T Martin, Arnold S Monto, Akram Khan, Catherine L Hough, Laurence W Busse, Caitlin C Ten Lohuis, Abhijit Duggal, Jennifer G Wilson, Alexandra June Gordon, Nida Qadir, Steven Y Chang, Christopher Mallow, Carolina Rivas, Hilary M Babcock, Jennie H Kwon, Natasha Halasa, James D Chappell, Adam S Lauring, Carlos G Grijalva, Todd W Rice, Ian D Jones, William B Stubblefield, Adrienne Baughman, Kelsey N Womack, Jillian P Rhoads, Christopher J Lindsell, Kimberly W Hart, Yuwei Zhu, Samantha M Olson, Miwako Kobayashi, Jennifer R Verani, Manish M Patel, and Influenza and Other Viruses in the Acutely Ill (IVY) Network.
• CDC COVID-19 Response Team, Atlanta, Georgia.
• JAMA. 2021 Nov 23; 326 (20): 204320542043-2054.

ImportanceA comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people.ObjectiveTo evaluate the association between vaccination with mRNA COVID-19 vaccines-mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)-and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease.Design, Setting, And ParticipantsA US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021.ExposuresCOVID-19 vaccination.Main Outcomes And MeasuresAssociations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression.ResultsAmong 4513 patients (median age, 59 years [IQR, 45-69]; 2202 [48.8%] women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P < .001) and weaker at more than 120 days since vaccination with BNT162b2 (5.8% vs 11.5%; aOR, 0.36; 95% CI, 0.27-0.49) than with mRNA-1273 (1.9% vs 8.3%; aOR, 0.15; 95% CI, 0.09-0.23) (P < .001). Among 1197 patients hospitalized with COVID-19, death or invasive mechanical ventilation by day 28 was associated with decreased likelihood of vaccination (12.0% vs 24.7%; aOR, 0.33; 95% CI, 0.19-0.58).Conclusions And RelevanceVaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation. These findings are consistent with risk reduction among vaccine breakthrough infections compared with absence of vaccination.

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