Cardiac Transplant Patients Should Receive a Booster For COVID-19 Vaccination

A federal advisory committee at the Centers for Disease Control and Prevention has shared data suggesting that a third dose of vaccine would be beneficial in immunocompromised patients such as transplant recipients and the U.S. Food and Drug Administration on Aug. 12 authorized COVID-19 vaccine booster shots for people with weakened immune systems. Health officials in France and Israel are already giving third doses of mRNA vaccines to people with severely compromised immune systems.

Solid-organ transplant recipients exhibit a weak immune response to vaccination against SARS-CoV-2).1 Patients with clinically or therapeutically suppressed immunity (e.g., transplant recipients, patients on cancer treatment or on immunosuppressive therapy), patients with rheumatologic conditions, immunodeficiency syndrome, hematopoietic cell cancers, asplenia, advanced kidney disease (e.g., dialysis or nephrotic syndrome) are more likely to get severely ill from COVID-19, have prolonged SARS-CoV-2 infection and have a higher susceptibility to infection with SARS-COV-2 variants.2-4 In the normal population, mRNA COVID-19 vaccination is highly effective with initial efficacy at around 95-97% and with efficacy maintained at approximately 75-77% after 250 days.5

Unfortunately, in immunocompromised individuals, the standard mRNA vaccination strategy for COVID-19 has suboptimal protection. Immune response to vaccination is significantly lower in these patients than the normal population. Data show that mRNA vaccine efficacy against new variants such as Delta B.1.617.2 is around 79-88% in the normal population after the second dose, but even lower in the immunocompromised patients.6,7

Percent antibody response after mRNA vaccination, even with two doses, are among the lowest in solid-organ transplant recipients compared with normal population or with other immunocompromised states such as hemodialysis or cancer patients, underlying the necessity for a booster vaccination in transplant recipient patients.1,8-10 Approximately half of cardiac transplant recipients do not generate IgG antibodies following two doses of SARS-CoV-2 mRNA vaccine.8

Evolving evidence supports that a booster with a third dose of the mRNA vaccination in solid-organ transplant recipients is safe and effective, with evidence of improvement in immunogenicity and protection from clinical COVID-19 infection.9,11,12 Initial reports of case series are now followed by strong evidence from a randomized clinical trial demonstrating that a third dose of mRNA vaccine given to 120 solid organ transplant recipients (18 of which were heart transplant recipients) three months after the first two doses resulted in a substantially higher immunogenicity compared with placebo and was quite safe.9,11,12 No hospitalizations or any cases of organ rejection were reported among the patients who received the booster dose of the mRNA vaccine.

These data support that a third dose of the mRNA vaccination is highly beneficial with low risk in solid-organ transplant patients and should be considered in cardiac transplant recipients. It should be kept in mind that in the recently published randomized clinical trial, even after the third dose, only 55% of the transplant recipients had an antibody level above the protective threshold of 100 U per milliliter. Thus, barrier measures should continue to be maintained, and vaccination of the relatives and contacts of these patients should be strongly enforced in addition to the third booster consideration in cardiac transplant patients.11


  1. Boyarsky BJ, Werbel WA, Avery RK, et al. Immunogenicity of a single dose of a SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients. JAMA 2021;325:1784-6.
  2. Lewis NM, Chu VT, Ye D, et al. Household transmission of SARS-CoV-2 in the United States. Clin Infect Dis 2020;Aug 16:ciaa1166.
  3. Choi B, Choudhary MC, Regan J, et al. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N Engl J Med 2020;383:2291-3.
  4. Clark SA, Clark LE, Pan J, et al. SARS-CoV-2 evolution in an immunocompromised host reveals shared neutralization escape mechanisms. Cell 2021;184:2605-17.
  5. Khoury DS, Cromer D, Reynaldi A, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med 2021;27:1205-11.
  6. Sheikh A, McMenamin J, Taylor B, et al. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021;397:2461-2.
  7. Bernal JL, Andrews N, Gower C, et al. Effectiveness of Covid-19 vaccines against B.1.617.2 (Delta) variant. N Engl J Med 2021;385:585-94.
  8. Ben Zadok OI, Shaul AA, Ben-Avraham B, et al. Immunogenicity of the BNT162b2 mRNA vaccine in heart transplant recipients – a prospective cohort study. Eur J Heart Fail 2021;May 8:[Epub ahead of print].
  9. Werbel WA, Boyarsky BJ, Ou MT, et al. Safety and immunogenicity of a third dose of SARS-CoV-2 vaccine in solid organ transplant recipients: A case series. Ann Intern Med 2021;June 15:L21-0282.
  10. CDC ACIP Meeting slides.
  11. Kamar N, Abravanel F. Marion O, et al. Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients. N Engl J Med 2021;385:661-2.
  12. Hall VG, Ferreira VH, Ku T, et al. Randomized trial of a third dose of mRNA-1273 vaccine in transplant recipients. N Engl J Med 2021;Aug 11:[Epub ahead of print].

Keywords: COVID-19, SARS-CoV-2, Vaccines, Vaccination, Transplantation, Antibody Formation, Nephrotic Syndrome, Advisory Committees, Immunoglobulin G, RNA, Messenger, United States Food and Drug Administration, Renal Dialysis, Organ Transplantation, Immunization, Secondary, Immunocompromised Host, Heart Transplantation, Immune System, Centers for Disease Control and Prevention, U.S., Hematopoietic Stem Cell Transplantation, Arthritis, Rheumatoid, Reference Standards

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