[Skip to Content]
[Skip to Content Landing]

Association of BNT162b2 mRNA and mRNA-1273 Vaccines With COVID-19 Infection and Hospitalization Among Patients With Cirrhosis

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Are COVID-19 mRNA vaccines associated with decrease in COVID-19 infections and death in a real-world setting among patients with cirrhosis of the liver?

Findings  In this retrospective cohort study of US veterans with cirrhosis that compared 20 037 patients who received either a Pfizer BNT162b2 mRNA or a Moderna mRNA-1273 COVID-19 vaccine with 20 037 propensity score matched controls, receipt of 1 dose of either vaccine was associated with a 64.8% reduction in COVID-19 infections and 100% reduction in hospitalization or death due to COVID-19 infection after 28 days.

Meaning  This cohort study found that mRNA vaccines against COVID-19 were associated with reduced COVID-19 infections in individuals with cirrhosis, despite hyporesponsiveness to other vaccines.


Importance  Two mRNA-based vaccines against coronavirus disease 2019 (COVID-19) were found to be highly efficacious in phase 3 clinical trials in the US. However, patients with chronic illnesses, including cirrhosis, were excluded from clinical trials. Patients with cirrhosis have immune dysregulation that is associated with vaccine hyporesponsiveness.

Objective  To study the association of receipt of the Pfizer BNT162b2 mRNA or the Moderna mRNA-1273 vaccines in patients with cirrhosis compared with a propensity-matched control group of patients at similar risk of infection and severe disease from COVID-19.

Design, Setting, and Participants  We performed a retrospective cohort study of patients with cirrhosis who received at least 1 dose of a COVID-19 mRNA vaccine at the Veterans Health Administration. Patients who received at least 1 dose of the vaccine (n = 20 037) were propensity matched with 20 037 controls to assess the associations of vaccination with new COVID-19 infection and COVID-19 hospitalization and death.

Exposures  Receipt of at least 1 dose of the BNT162b2 mRNA or the mRNA-1273 vaccines between December 18, 2020, and March 17, 2021.

Main Outcomes and Measures  COVID-19 infection as documented by a positive result for COVID-19 by polymerase chain reaction, hospitalization, and death due to COVID-19 infection.

Results  The median (interquartile range) age of the vaccinated individuals in the study cohort was 69.1 (8.4) years and 19 465 (97.2%) of the participants in each of the vaccinated and unvaccinated groups were male, consistent with a US veteran population. The mRNA-1273 vaccine was administered in 10 236 (51%) and the BNT162b2 mRNA in 9801 (49%) patients. Approximately 99.7% of patients who received the first dose of either vaccine with a follow-up of 42 days or more received a second dose. The number of COVID-19 infections in the vaccine recipients was similar to the control group in days 0 to 7, 7 to 14, 14 to 21, and 21 to 28 after the first dose. After 28 days, receipt of 1 dose of an mRNA vaccine was associated with a 64.8% reduction in COVID-19 infections and 100% protection against hospitalization or death due to COVID-19 infection. The association of reduced COVID-19 infections after the first dose was lower among patients with decompensated (50.3%) compared with compensated cirrhosis (66.8%).Receipt of a second dose was associated with a 78.6% reduction in COVID-19 infections and 100% reduction in COVID-19–related hospitalization or death after 7 days.

Conclusions and Relevance  This cohort study of US veterans found that mRNA vaccine administration was associated with a delayed but modest reduction in COVID-19 infection but an excellent reduction in COVID-19–related hospitalization or death in patients with cirrhosis.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: June 21, 2021.

Published Online: July 13, 2021. doi:10.1001/jamainternmed.2021.4325

Corresponding Author: Binu V. John, MD, MPH, Affiliate Associate Professor, University of Miami Miller School of Medicine, Chief of Hepatology, Bruce W Carter VA Medical Center, 1201 NW 16th St, Miami, FL 33125 (binu.john@va.gov).

Author Contributions: Drs John and Dahman had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: John, Deng, Mahmud, Dahman.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: John, Deng, Dahman.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: John, Deng, Mahmud, Kaplan, Dahman.

Obtained funding: John, Dahman.

Administrative, technical, or material support: John, Scheinberg, Taddei, Kaplan, Labrada, Dahman.

Supervision: John, Dahman.

Conflict of Interest Disclosures: None reported.

Funding/Support: Services supporting the analysis and interpretation of the data of this research project were generated by the VCU Massey Cancer Center Biostatistics Shared Resource, supported, in part, with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.

Role of the Funder/Sponsor: The VCU Massey Cancer Center Biostatistics Shared Resource had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The authors prepared this work in their personal capacity. The opinions expressed in this article are the author's own and do not reflect the view of the Department of Veterans Affairs or the US government.

Additional Contributions: We acknowledge data and support from the VA COVID-19 shared data resource.

Polack  FP , Thomas  SJ , Kitchin  N ,  et al; C4591001 Clinical Trial Group.  Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.   N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577PubMedGoogle ScholarCrossref
Baden  LR , El Sahly  HM , Essink  B ,  et al; COVE Study Group.  Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.   N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389PubMedGoogle ScholarCrossref
Marjot  T , Webb  GJ , Barritt  AS ,  et al.  SARS-CoV-2 vaccination in patients with liver disease: responding to the next big question.   Lancet Gastroenterol Hepatol. 2021;6(3):156-158. doi:10.1016/S2468-1253(21)00008-XPubMedGoogle ScholarCrossref
Bonnel  AR , Bunchorntavakul  C , Reddy  KR .  Immune dysfunction and infections in patients with cirrhosis.   Clin Gastroenterol Hepatol. 2011;9(9):727-738. doi:10.1016/j.cgh.2011.02.031PubMedGoogle ScholarCrossref
McCashland  TM , Preheim  LC , Gentry  MJ .  Pneumococcal vaccine response in cirrhosis and liver transplantation.   J Infect Dis. 2000;181(2):757-760. doi:10.1086/315245PubMedGoogle ScholarCrossref
Fix  OK , Blumberg  EA , Chang  KM ,  et al; AASLD COVID-19 Vaccine Working Group.  AASLD Expert Panel Consensus Statement: vaccines to prevent COVID-19 infection in patients with liver disease.   Hepatology. 2021; Epub ahead of print. doi:10.1002/hep.31751PubMedGoogle Scholar
John  BV , Aitcheson  G , Schwartz  KB ,  et al.  Male gender is associated with higher rates of liver-related mortality in primary biliary cholangitis and cirrhosis.   Hepatology. 2021. Published online February 26, 2021. doi:10.1002/hep.31776PubMedGoogle Scholar
Davies  NG , Klepac  P , Liu  Y , Prem  K , Jit  M , Eggo  RM ; CMMID COVID-19 working group.  Age-dependent effects in the transmission and control of COVID-19 epidemics.   Nat Med. 2020;26(8):1205-1211. doi:10.1038/s41591-020-0962-9PubMedGoogle ScholarCrossref
Bwire  GM .  Coronavirus: why men are more vulnerable to Covid-19 than women?   SN Compr Clin Med. 2020;1-3.PubMedGoogle Scholar
Rentsch  CT , Kidwai-Khan  F , Tate  JP ,  et al.  Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study.   PLoS Med. 2020;17(9):e1003379. doi:10.1371/journal.pmed.1003379PubMedGoogle Scholar
Ejaz  H , Alsrhani  A , Zafar  A ,  et al.  COVID-19 and comorbidities: Deleterious impact on infected patients.   J Infect Public Health. 2020;13(12):1833-1839. doi:10.1016/j.jiph.2020.07.014PubMedGoogle ScholarCrossref
Marjot  T , Moon  AM , Cook  JA ,  et al.  Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: An international registry study.   J Hepatol. 2021;74(3):567-577. doi:10.1016/j.jhep.2020.09.024PubMedGoogle ScholarCrossref
Jepsen  P , Vilstrup  H , Lash  TL .  Development and validation of a comorbidity scoring system for patients with cirrhosis.   Gastroenterology. 2014;146(1):147-156. doi:10.1053/j.gastro.2013.09.019PubMedGoogle ScholarCrossref
Kaplan  DE , Dai  F , Aytaman  A ,  et al; VOCAL Study Group.  Development and performance of an algorithm to estimate the Child-Turcotte-Pugh score from a national electronic healthcare database.   Clin Gastroenterol Hepatol. 2015;13(13):2333-41.e1, 6. doi:10.1016/j.cgh.2015.07.010PubMedGoogle ScholarCrossref
Beste  LA , Leipertz  SL , Green  PK , Dominitz  JA , Ross  D , Ioannou  GN .  Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US veterans, 2001-2013.   Gastroenterology. 2015;149(6):1471-1482.e5.PubMedGoogle ScholarCrossref
Kompaniyets  L , Goodman  AB , Belay  B ,  et al.  Body mass index and risk for COVID-19-related hospitalization, intensive care unit admission, invasive mechanical ventilation, and death—United States, March-December 2020.   MMWR Morb Mortal Wkly Rep. 2021;70(10):355-361. doi:10.15585/mmwr.mm7010e4PubMedGoogle ScholarCrossref
Vardavas  CI , Nikitara  K .  COVID-19 and smoking: A systematic review of the evidence.   Tob Induc Dis. 2020;18:20. doi:10.18332/tid/119324PubMedGoogle ScholarCrossref
Center for Disease Control. Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html Accessed April 1, 2021.
Aggeletopoulou  I , Davoulou  P , Konstantakis  C , Thomopoulos  K , Triantos  C .  Response to hepatitis B vaccination in patients with liver cirrhosis.   Rev Med Virol. 2017;27(6). doi:10.1002/rmv.1942PubMedGoogle Scholar
Leise  MD , Talwalkar  JA .  Immunizations in chronic liver disease: what should be done and what is the evidence.   Curr Gastroenterol Rep. 2013;15(1):300. doi:10.1007/s11894-012-0300-6PubMedGoogle ScholarCrossref
Dagan  N , Barda  N , Kepten  E ,  et al.  BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting.   N Engl J Med. 2021;384(15):1412-1423.PubMedGoogle ScholarCrossref
Kirby  T .  New variant of SARS-CoV-2 in UK causes surge of COVID-19.   Lancet Respir Med. 2021;9(2):e20-e21. doi:10.1016/S2213-2600(21)00005-9PubMedGoogle ScholarCrossref
Branswell  H.   New coronavirus variant could become dominant strain in March, CDC warns.   Stat. Accessed January15, 2021. https://www.statnews.com/2021/01/15/covid19-b117-variant-cdc/Google Scholar
Galloway  SE , Paul  P , MacCannell  DR ,  et al.  Emergence of SARS-CoV-2 B.1.1.7 lineage—United States, December 29, 2020-January 12, 2021.   MMWR Morb Mortal Wkly Rep. 2021;70(3):95-99. doi:10.15585/mmwr.mm7003e2PubMedGoogle ScholarCrossref
Oliver  SE , Gargano  JW , Scobie  H ,  et al.  The Advisory Committee on Immunization Practices’ Interim recommendation for use of Janssen COVID-19 vaccine—United States, February 2021.   MMWR Morb Mortal Wkly Rep. 2021;70(9):329-332. doi:10.15585/mmwr.mm7009e4PubMedGoogle ScholarCrossref
Food and Drug Administration. Janssen COVID-19 vaccine emergency use authorization. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2021. Accessed March 26, 2021 https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/Janssen-covid-19-vaccine
John  BV , Schwartz  K , Scheinberg  AR ,  et al.  Evaluation within thirty days of referral for liver transplantation is associated with reduced mortality: a multi-center analysis of patients referred within the VA Health System.   Transplantation. 2020. doi:10.1097/TP.0000000000003615PubMedGoogle Scholar
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience

Lookup An Activity


My Saved Searches

You currently have no searches saved.


My Saved Courses

You currently have no courses saved.