Association between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity

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

doi:10.1001/jama.2021.19499

Association between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity

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. ExlineMichelle 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

Research output: Contribution to journal › Article › peer-review

265 Scopus citations

Abstract

Importance: A 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. Objective: To 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 Participants: A 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. Exposures: COVID-19 vaccination. Main Outcomes and Measures: Associations 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. Results: Among 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 Relevance: Vaccination 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.

Original language	English (US)
Pages (from-to)	2043-2054
Number of pages	12
Journal	JAMA - Journal of the American Medical Association
Volume	326
Issue number	20
DOIs	https://doi.org/10.1001/jama.2021.19499
State	Published - Nov 30 2021

ASJC Scopus subject areas

Medicine(all)

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10.1001/jama.2021.19499

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Tenforde, M. W., Self, W. H., Adams, K., Gaglani, M., Ginde, A. A., McNeal, T., Ghamande, S., Douin, D. J., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., ... Patel, M. M. (2021). Association between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity. JAMA - Journal of the American Medical Association, 326(20), 2043-2054. https://doi.org/10.1001/jama.2021.19499

Tenforde, MW, Self, WH, Adams, K, Gaglani, M, Ginde, AA, McNeal, T, Ghamande, S, Douin, DJ, Talbot, HK, Casey, JD, Mohr, NM, Zepeski, A, Shapiro, NI, Gibbs, KW, Files, DC, Hager, DN, Shehu, A, Prekker, ME, Erickson, HL, Exline, MC, Gong, MN, Mohamed, A, Henning, DJ, Steingrub, JS, Peltan, ID, Brown, SM, Martin, ET, Monto, AS, Khan, A , Hough, CL, Busse, LW, Ten Lohuis, CC, Duggal, A, Wilson, JG, Gordon, AJ, Qadir, N, Chang, SY, Mallow, C, Rivas, C, Babcock, HM, Kwon, JH, Halasa, N, Chappell, JD, Lauring, AS, Grijalva, CG, Rice, TW, Jones, ID, Stubblefield, WB, Baughman, A, Womack, KN, Rhoads, JP, Lindsell, CJ, Hart, KW, Zhu, Y, Olson, SM, Kobayashi, M, Verani, JR & Patel, MM 2021, 'Association between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity', JAMA - Journal of the American Medical Association, vol. 326, no. 20, pp. 2043-2054. https://doi.org/10.1001/jama.2021.19499

@article{76520ce38c6c400ab86b52fca7886471,

title = "Association between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity",

abstract = "Importance: A 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. Objective: To 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 Participants: A 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. Exposures: COVID-19 vaccination. Main Outcomes and Measures: Associations 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. Results: Among 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 Relevance: Vaccination 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.",

author = "Tenforde, {Mark W.} and Self, {Wesley H.} and Katherine Adams and Manjusha Gaglani and Ginde, {Adit A.} and Tresa McNeal and Shekhar Ghamande and Douin, {David J.} and Talbot, {H. Keipp} and Casey, {Jonathan D.} and Mohr, {Nicholas M.} and Anne Zepeski and Shapiro, {Nathan I.} and Gibbs, {Kevin W.} and Files, {D. Clark} and Hager, {David N.} and Arber Shehu and Prekker, {Matthew E.} and Erickson, {Heidi L.} and Exline, {Matthew C.} and Gong, {Michelle N.} and Amira Mohamed and Henning, {Daniel J.} and Steingrub, {Jay S.} and Peltan, {Ithan D.} and Brown, {Samuel M.} and Martin, {Emily T.} and Monto, {Arnold S.} and Akram Khan and Hough, {Catherine L.} and Busse, {Laurence W.} and {Ten Lohuis}, {Caitlin C.} and Abhijit Duggal and Wilson, {Jennifer G.} and Gordon, {Alexandra June} and Nida Qadir and Chang, {Steven Y.} and Christopher Mallow and Carolina Rivas and Babcock, {Hilary M.} and Kwon, {Jennie H.} and Natasha Halasa and Chappell, {James D.} and Lauring, {Adam S.} and Grijalva, {Carlos G.} and Rice, {Todd W.} and Jones, {Ian D.} and Stubblefield, {William B.} and Adrienne Baughman and Womack, {Kelsey N.} and Rhoads, {Jillian P.} and Lindsell, {Christopher J.} and Hart, {Kimberly W.} and Yuwei Zhu and Olson, {Samantha M.} and Miwako Kobayashi and Verani, {Jennifer R.} and Patel, {Manish M.}",

note = "Funding Information: receiving grants from the Centers for Disease Control and Prevention (CDC) (principal investigator of the primary funding contract from CDC for this work) during the conduct of the study. Dr Gaglani reported receiving grants from CDC, Vanderbilt University Medical Center, Baylor Scott & White Health (BSWH), and the IVY study during the conduct of the study; grants from CDC–BSWH HAIVEN influenza/COVID-19 vaccine effectiveness study, CDC–BSWH ambulatory US influenza/ COVID-19 vaccine effectiveness study, CDC–Abt Associates BSWH RECOVER COVID-19/influenza study, and CDC–Westat BSWH VISION COVID-19/ influenza study outside the submitted work; and Pfizer BSWH Independent Grants for Learning & Change for meningococcal vaccination of adolescents and an institutional contract with Janssen (BSWH Observational RSV Study in infants). Dr Ginde reported receiving grants from CDC during the conduct of the study; and grants from the National Institutes of Health (NIH), Department of Defense, and AbbVie outside the submitted work. Dr McNeal reported receiving grants from the CDC HAIVEN study group that become the IVY-3 study group during the conduct of the study. Dr Talbot reported receiving grants from CDC during the conduct of the study. Dr Casey reported receiving grants from NIH K23HL153584 outside the submitted work. Dr Mohr reported receiving grants from CDC during the conduct of the study. Dr Shapiro reported receiving grants from CDC during the conduct of the study. Dr Files reported receiving grants from CDC during the conduct of the study and personal fees from Cytovale and Medpace outside the submitted work. Dr Prekker reported receiving grants from CDC during the conduct of the study. Dr Exline reported receiving a speaking honorarium from Abbott Laboratories outside the submitted work. Dr Gong reported receiving grants from CDC during the conduct of the study; grants from NIH to conduct clinical trials on COVID-19 and non–COVID-19 outside the submitted work; and data and safety monitoring board fees for participating in Regeneron trials outside the submitted work. Dr Henning reported receiving grants from CDC during the conduct of the study. Dr Peltan reported receiving grants from CDC during the conduct of the study; grants from NIH, Intermountain Research and Medical Foundation, and Janssen Pharmaceuticals outside the submitted work; and payment to Intermountain Medical Center for subject enrollment from Regeneron and Asahi Kasei Pharma outside the submitted work. Dr Brown reported receiving grants from CDC during the conduct of the study. Dr Martin reported receiving grants from CDC during the conduct of the study and personal fees from Pfizer outside the submitted work. Dr Khan reported receiving grants from United Therapeutics, Actelion Pharmaceuticals, Eli Lilly, Johnson & Johnson, Regeneron Pharmaceuticals, and Gilead Sciences outside the submitted work. Dr Hough reported receiving grants from CDC during the conduct of the study and grants from NIH outside the submitted work. Dr Wilson reported receiving grants from CDC/Vanderbilt during the conduct of the study. Dr Chang reported receiving personal fees from La Jolla Pharmaceuticals and PureTech Health outside the submitted work. Dr Babcock reported receiving grants from CDC during the conduct of the study. Dr Kwon reported receiving grants from NIH National Institute of Allergy and Infectious Diseases (award 1K23 AI137321-01A1) outside the submitted work. Dr Halasa reported receiving grants from CDC during the conduct of the study; grants from Sanofi outside the submitted work; and hemagglutination inhibition and microneutralization testing, vaccine donation, and grants from Quidel outside the submitted work. Dr Chappell reported receiving grants from CDC during the conduct of the study. Dr Lauring reported receiving consulting fees from Sanofi for an influenza antiviral and fees from Roche as a member of an influenza antiviral trial steering committee outside the submitted work. Dr Grijalva reported receiving a contract from CDC during the conduct of the study; consulting fees from Pfizer, Merck, and Sanofi; a contract from CDC, Campbell Alliance, and the Food and Drug Administration outside the submitted work; and grants from NIH and the Agency for Healthcare Research and Quality outside the submitted work. Dr Rice reported receiving grants from CDC during the conduct of the study and personal fees from Cumberland Pharmaceuticals, Sanofi, and Cytovale outside the submitted work. Dr Lindsell reported receiving grants from CDC to Vanderbilt University during the conduct of the study; grants from NIH to institution, grants from Department of Defense to institution, contracts to Vanderbilt University for research services from bioM{\'e}rieux, Endpoint Health, and Entegrion. In addition, he had a patent for risk stratification in sepsis and septic shock, issued to Cincinnati Children's Hospital Medical Center. Dr Zhu reported receiving grants from CDC during the conduct of the study. No other disclosures were reported. Publisher Copyright: {\textcopyright} 2021 American Medical Association. All rights reserved.",

year = "2021",

month = nov,

day = "30",

doi = "10.1001/jama.2021.19499",

language = "English (US)",

volume = "326",

pages = "2043--2054",

journal = "JAMA - Journal of the American Medical Association",

issn = "0002-9955",

publisher = "American Medical Association",

number = "20",

}

TY - JOUR

T1 - Association between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity

AU - Tenforde, Mark W.

AU - Self, Wesley H.

AU - Adams, Katherine

AU - Gaglani, Manjusha

AU - Ginde, Adit A.

AU - McNeal, Tresa

AU - Ghamande, Shekhar

AU - Douin, David J.

AU - Talbot, H. Keipp

AU - Casey, Jonathan D.

AU - Mohr, Nicholas M.

AU - Zepeski, Anne

AU - Shapiro, Nathan I.

AU - Gibbs, Kevin W.

AU - Files, D. Clark

AU - Hager, David N.

AU - Shehu, Arber

AU - Prekker, Matthew E.

AU - Erickson, Heidi L.

AU - Exline, Matthew C.

AU - Gong, Michelle N.

AU - Mohamed, Amira

AU - Henning, Daniel J.

AU - Steingrub, Jay S.

AU - Peltan, Ithan D.

AU - Brown, Samuel M.

AU - Martin, Emily T.

AU - Monto, Arnold S.

AU - Khan, Akram

AU - Hough, Catherine L.

AU - Busse, Laurence W.

AU - Ten Lohuis, Caitlin C.

AU - Duggal, Abhijit

AU - Wilson, Jennifer G.

AU - Gordon, Alexandra June

AU - Qadir, Nida

AU - Chang, Steven Y.

AU - Mallow, Christopher

AU - Rivas, Carolina

AU - Babcock, Hilary M.

AU - Kwon, Jennie H.

AU - Halasa, Natasha

AU - Chappell, James D.

AU - Lauring, Adam S.

AU - Grijalva, Carlos G.

AU - Rice, Todd W.

AU - Jones, Ian D.

AU - Stubblefield, William B.

AU - Baughman, Adrienne

AU - Womack, Kelsey N.

AU - Rhoads, Jillian P.

AU - Lindsell, Christopher J.

AU - Hart, Kimberly W.

AU - Zhu, Yuwei

AU - Olson, Samantha M.

AU - Kobayashi, Miwako

AU - Verani, Jennifer R.

AU - Patel, Manish M.

N1 - Funding Information: receiving grants from the Centers for Disease Control and Prevention (CDC) (principal investigator of the primary funding contract from CDC for this work) during the conduct of the study. Dr Gaglani reported receiving grants from CDC, Vanderbilt University Medical Center, Baylor Scott & White Health (BSWH), and the IVY study during the conduct of the study; grants from CDC–BSWH HAIVEN influenza/COVID-19 vaccine effectiveness study, CDC–BSWH ambulatory US influenza/ COVID-19 vaccine effectiveness study, CDC–Abt Associates BSWH RECOVER COVID-19/influenza study, and CDC–Westat BSWH VISION COVID-19/ influenza study outside the submitted work; and Pfizer BSWH Independent Grants for Learning & Change for meningococcal vaccination of adolescents and an institutional contract with Janssen (BSWH Observational RSV Study in infants). Dr Ginde reported receiving grants from CDC during the conduct of the study; and grants from the National Institutes of Health (NIH), Department of Defense, and AbbVie outside the submitted work. Dr McNeal reported receiving grants from the CDC HAIVEN study group that become the IVY-3 study group during the conduct of the study. Dr Talbot reported receiving grants from CDC during the conduct of the study. Dr Casey reported receiving grants from NIH K23HL153584 outside the submitted work. Dr Mohr reported receiving grants from CDC during the conduct of the study. Dr Shapiro reported receiving grants from CDC during the conduct of the study. Dr Files reported receiving grants from CDC during the conduct of the study and personal fees from Cytovale and Medpace outside the submitted work. Dr Prekker reported receiving grants from CDC during the conduct of the study. Dr Exline reported receiving a speaking honorarium from Abbott Laboratories outside the submitted work. Dr Gong reported receiving grants from CDC during the conduct of the study; grants from NIH to conduct clinical trials on COVID-19 and non–COVID-19 outside the submitted work; and data and safety monitoring board fees for participating in Regeneron trials outside the submitted work. Dr Henning reported receiving grants from CDC during the conduct of the study. Dr Peltan reported receiving grants from CDC during the conduct of the study; grants from NIH, Intermountain Research and Medical Foundation, and Janssen Pharmaceuticals outside the submitted work; and payment to Intermountain Medical Center for subject enrollment from Regeneron and Asahi Kasei Pharma outside the submitted work. Dr Brown reported receiving grants from CDC during the conduct of the study. Dr Martin reported receiving grants from CDC during the conduct of the study and personal fees from Pfizer outside the submitted work. Dr Khan reported receiving grants from United Therapeutics, Actelion Pharmaceuticals, Eli Lilly, Johnson & Johnson, Regeneron Pharmaceuticals, and Gilead Sciences outside the submitted work. Dr Hough reported receiving grants from CDC during the conduct of the study and grants from NIH outside the submitted work. Dr Wilson reported receiving grants from CDC/Vanderbilt during the conduct of the study. Dr Chang reported receiving personal fees from La Jolla Pharmaceuticals and PureTech Health outside the submitted work. Dr Babcock reported receiving grants from CDC during the conduct of the study. Dr Kwon reported receiving grants from NIH National Institute of Allergy and Infectious Diseases (award 1K23 AI137321-01A1) outside the submitted work. Dr Halasa reported receiving grants from CDC during the conduct of the study; grants from Sanofi outside the submitted work; and hemagglutination inhibition and microneutralization testing, vaccine donation, and grants from Quidel outside the submitted work. Dr Chappell reported receiving grants from CDC during the conduct of the study. Dr Lauring reported receiving consulting fees from Sanofi for an influenza antiviral and fees from Roche as a member of an influenza antiviral trial steering committee outside the submitted work. Dr Grijalva reported receiving a contract from CDC during the conduct of the study; consulting fees from Pfizer, Merck, and Sanofi; a contract from CDC, Campbell Alliance, and the Food and Drug Administration outside the submitted work; and grants from NIH and the Agency for Healthcare Research and Quality outside the submitted work. Dr Rice reported receiving grants from CDC during the conduct of the study and personal fees from Cumberland Pharmaceuticals, Sanofi, and Cytovale outside the submitted work. Dr Lindsell reported receiving grants from CDC to Vanderbilt University during the conduct of the study; grants from NIH to institution, grants from Department of Defense to institution, contracts to Vanderbilt University for research services from bioMérieux, Endpoint Health, and Entegrion. In addition, he had a patent for risk stratification in sepsis and septic shock, issued to Cincinnati Children's Hospital Medical Center. Dr Zhu reported receiving grants from CDC during the conduct of the study. No other disclosures were reported. Publisher Copyright: © 2021 American Medical Association. All rights reserved.

PY - 2021/11/30

Y1 - 2021/11/30

N2 - Importance: A 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. Objective: To 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 Participants: A 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. Exposures: COVID-19 vaccination. Main Outcomes and Measures: Associations 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. Results: Among 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 Relevance: Vaccination 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.

AB - Importance: A 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. Objective: To 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 Participants: A 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. Exposures: COVID-19 vaccination. Main Outcomes and Measures: Associations 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. Results: Among 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 Relevance: Vaccination 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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UR - http://www.scopus.com/inward/citedby.url?scp=85118788106&partnerID=8YFLogxK

U2 - 10.1001/jama.2021.19499

DO - 10.1001/jama.2021.19499

M3 - Article

C2 - 34734975

AN - SCOPUS:85118788106

SN - 0002-9955

VL - 326

SP - 2043

EP - 2054

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

IS - 20

ER -

Association between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity

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