A Three-Dose COVID Vaccine Regimen For Immunocompromised Patients

While access to COVID-19 vaccines remains a major global health challenge, vaccines are now widely available for American adults and adolescents. The great efficacy of COVID-19 vaccines has allowed for excellent individual protection against severe disease. However, immunocompromised patients, representing a population of several million Americans, are a notable exception. Severe COVID-19 infections among fully vaccinated, immunocompromised patients have raised significant concerns about the effectiveness of vaccines for this group. An observational study by Boyarsky, et al., validated these concerns: Of 658 patients who had received solid organ transplants, 46% developed no antibody response after two doses of mRNA vaccine.1

In an attempt to improve vaccine efficacy, a third vaccine dose was evaluated in two observational studies of patients receiving immunosuppressive medications after solid organ transplantation (including heart and heart-lung). Werbel, et al., studied patients who had received two doses of mRNA vaccine and were given a third dose of either mRNA or adenovirus vaccine.2 Among 24 patients with negative SARS-CoV-2 spike antibody titers after the second vaccine dose, 16 (67%) had no antibodies 2 weeks after the third dose. In a subsequent study, Kamar, et al., evaluated solid organ transplant patients receiving the Pfizer-BioNTech mRNA vaccine for all three doses. Among 59 patients with negative SARS-CoV-2 antibody titers after two vaccine doses, 33 (56%) remained without antibodies 4 weeks after the third dose.3

Conclusion: A three-dose COVID-19 vaccine regimen may provide protection for immunocompromised patients who have not had adequate immunological response after two doses.


  1. 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.
  2. Werbel WA, Boyarsky BJ, Ou NT, et al. Safety and immunogenicity of a third dose of SARS-CoV-2 vaccine in solid organ transplant recipients: A case series. Ann Inter Med 2021;June 15: https://doi.org/10.7326/L21-0282.
  3. 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;June 23: DOI: 10.1056/NEJMc2108861.

Clinical Topics: Cardiovascular Care Team, Prevention

Keywords: COVID-19, SARS-CoV-2, Adenovirus Vaccines, Vaccines, Immunity, Herd, Global Health, RNA, Messenger, Vaccination, Immunocompromised Host, Antibody Formation, Disease Progression

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