It has been over a year since the World Health Organization declared SARS-CoV-2/COVID-19 as a global pandemic on March 11, 2020. While a large number of SARS-CoV-2 infections result in mild symptoms, the overall death toll is staggering with over 3.6 million deaths worldwide and nearly 600,000 deaths in the United States alone as of June 6, 2021.¹ Underlying comorbidities such as diabetes, hypertension, and cardiac or pulmonary disease, significantly increase the risk of death due to COVID-19.  In fact, an early systematic review and meta-analysis found a case fatality rate (CFR) of 12-14% for patients with two to five comorbidities, nearly double the baseline CFR of 7%.²

Patients with heart failure and those who have undergone heart transplantation may be at increased risk of mortality from COVID-19 due to comorbidities and immunosuppression.³ As vaccines for COVID-19 have become available, many providers are receiving questions regarding vaccine recommendations for this population. The International Society for Heart and Lung Transplantation (ISHLT) and the American Society for Transplantation (AST) have both released guidance regarding COVID-19 vaccination in patients with chronic heart or lung failure and those who have undergone thoracic transplantation.^3,4

• There are three COVID-19 vaccines available in the U.S. under Emergency Use Authorization (EUA); the Moderna and Pfizer-BioNTech mRNA vaccines and the Janssen (Johnson & Johnson) adenoviral vector vaccine, with other vaccines in various stages of development and review. 
  • While recipients of organ transplants were excluded, the mRNA vaccine trials otherwise showed 94-95% overall efficacy with efficacy of ≥86% (Moderna) and ≥92% (Pfizer-BioNTech) observed across age, sex, race and ethnicity categories and among persons with underlying medical conditions.  No specific safety concerns were identified in subgroup analyses by age, race, ethnicity, underlying medical conditions or previous SARS-CoV-2 infection.^5,6
  • The Janssen (Johnson & Johnson) adenoviral vector vaccine trial, while also excluding recipients of organ transplants, showed 66% overall efficacy with efficacy of ≥63% across age, sex, race, ethnic categories and among persons with underlying medical conditions. No specific safety concerns were identified in subgroup analyses by age, race, ethnicity, underlying medical conditions or previous SARS-CoV-2 infection.⁷ However, by April 21, 2021, nearly 8 million doses of the vaccine had been administered and while safety monitoring data found that 97% of reported reactions after vaccination were non-serious, 17 thrombotic events with thrombocytopenia had been reported, primarily central venous sinus thrombosis with thrombocytopenia in 14.⁸  The U.S. Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) initially recommended a pause on the use of the Janssen (Johnson & Johnson) COVID-19 vaccine on April 12, 2021, but this was lifted on April 23, 2021, following a thorough safety review after which it was felt the known and potential benefits outweighed its known and potential risks.⁹
• As transplant recipients were not included in the large vaccine trials, there is currently little data on efficacy, safety or durability in this population. 
  • Data from an observational study of 741 transplant recipients having received both doses of the Pfizer-BioNTech or Moderna mRNA vaccine showed rates of adverse events expected with vaccine reactogenicity such as injection-site pain (85% after dose 1, 77% after dose 2), fatigue (36% after dose 1, 56% after dose 2), and headache (28% after dose 1, 42% after dose 2). Importantly, there were no reported cases neurological diagnoses (Guillain-Barré syndrome or Bell's Palsy) or anaphylaxis requiring epinephrine.  There was one case of acute rejection diagnosed after the second vaccine dose.¹⁰
  • Data from an observational study of 658 transplant recipients having received both doses of the Pfizer-BioNTech or Moderna mRNA vaccine showed the development of anti-spike antibody production to be reduced as compared to the general population.¹¹ Of all transplant recipients, only 54% showed antibody response after dose 2 (56% of heart transplant recipients).  Of note, this study did not report on other immune responses to the vaccines, such as T-cell response, or clinical endpoints such as COVID-19 infection after vaccination. More information is needed to fully understand the clinical impact of this reduced antibody response to better counsel patients as to their risk of COVID-19 infection despite vaccination.
  • There are even more limited data regarding the Janssen (Johnson & Johnson) adenoviral vector COVID-19 vaccine. Of 12 transplant recipients, one study has shown only two patients developed positive anti-spike antibody testing.¹²
• The risk of COVID-19 morbidity and mortality is high in transplant recipients and the risks of COVID-19 vaccination appear to be low despite likely reduced vaccine efficacy, thus the AST and ISHLT have recommended vaccination of both patients with heart failure as well as heart transplant recipients.^3,4
• The ISHLT and AST recommend that patients receive the COVID-19 vaccine prior to transplantation when possible. While it is preferred that patients would complete the vaccine series two weeks or more prior to transplantation, transplantation should not be routinely delayed.^3,4 If patients with heart failure undergo heart transplantation and have only received one vaccine of the series, there are no data regarding optimal timing to receive the second vaccine after transplantation. Similar with post-transplant vaccine timing, it is currently recommended patients receive the second vaccine at least one month after transplantation.^3,4
• Current recommendations suggest transplant recipients should wait at least one month after transplant surgery to receive the COVID-19 vaccine, keeping in line with recommendations for other vaccines. This allows for routine reduction of immunosuppression after transplantation to hopefully allow for improved efficacy of the vaccine. However, COVID-19 vaccination should be postponed for three to six months following T-cell or B-cell depleting therapies (such as anti-thymocyte globulin, rituximab, etc.), whether given for induction immunosuppression or as treatment for rejection.^3,4
• Similar with the general population, patients with heart failure or heart transplant recipients who have had COVID-19 should still proceed with receiving the vaccine once they have recovered from the acute infection.

Both the ISHLT and AST recommend against routine testing of SARS-CoV-2 serology following vaccination as correlates of immunity are unclear and recommendations for protective measures, such as mask wearing and physical distancing in public, are unchanged regardless of vaccination or antibody status.^3,4

References

1. COVID-19 Projections. Institute for Health Metrics and Evaluation. Available here. Accessed June 11, 2021.
2. Mahumud RA, Kamara JK, Renzaho AMN. The epidemiological burden and overall distribution of chronic comorbidities in coronavirus disease-2019 among 202,005 infected patients: evidence from a systematic review and meta-analysis. Infection 2020;48:813-33.
3. SARS-CoV-2 Vaccination in Heart and Lung Transplantation, MCS and PH. International Society for Heart and Lung Transplantation, updated May 21, 2021. Available here.
4. 2019-nCoV (Coronavirus): FAQs for Organ Transplantation. Updated April 12, 2021. American Society for Transplantation. Available here.
5. Oliver SE, Gargano JW, Marin M, et al.  The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Moderna COVID-19 Vaccine – United States, December 2020. MMWR 2021;69:1653-56.
6. Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine – United States, December 2020. MMWR 2020;69:1922-24.
7. 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 2021;70(9):329-32.
8. Shay DK, Gee J, Su JR, et al.  Safety Monitoring of the Janssen (Johnson & Johnson) COVID-19 Vaccine – United States, March-April 2021.  MMWR 2021;70:680-4.
9. FDA and CDC Lift Recommended Pause on Johnson & Johnson (Janssen) COVID-19 Vaccine Use Following Thorough Safety Review. Press Release April 23, 20221.  Available here.
10. Ou MT, Boyarsky BJ, Motter JD, et al.  Safety and reactogenicity of 2 doses of sars-cov-2 vaccination in solid organ transplant recipients. Transplantation 2021;Apr 9:[Epub ahead of print].
11. Boyarsky BJ, Werbel WA, Avery RK, et al.  Antibody response to 2-dose SARS-Cov-2 mRNA vaccine series in solid organ transplant recipients. JAMA 2021;325:2204-6.
12. Boyarsky BJ, Chiang TP-Y, Ou MT, et al. Antibody response to the Janssen COVID-19 vaccine in solid organ transplant recipients. Transplantation 2021;105;e82-3.

Clinical Topics: Cardiac Surgery, COVID-19 Hub, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant, Hypertension

Keywords: Heart Failure, COVID-19, Antilymphocyte Serum, Transplantation, Ethnic Groups, Pandemics, Antibody Formation, RNA, Messenger, Follow-Up Studies, Heart Transplantation, Organ Transplantation, Lung Transplantation, Immunosuppression, Vaccination, Morbidity, Diabetes Mellitus, Hypertension, Headache, Hypersensitivity, Fatigue, World Health Organization, Epinephrine, B-Lymphocytes, T-Lymphocytes

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