Among solid organ transplant recipients who had a suboptimal antibody response to standard SARS-CoV-2 vaccination and received a third dose, some had an increase in response whereas others did not, investigators reported in the Annals of Internal Medicine.

In a case series from Johns Hopkins Medical Institutions, 30 patients (median age 57 years; 17 women; 1 non-White) received a third dose of vaccine at a median 67 days after receiving the standard 2 doses of a COVID-19 mRNA vaccine (Pfizer-BioNTech or Moderna) and showing no (24 patients) or low (6 patients) antibody response. Only 6 patients received a third dose of the same vaccine. The rest received the alternate mRNA vaccine or the Johnson & Johnson/Janssen viral vector vaccine. None of the patients had previous SARS-CoV-2 infection.

Of the 6 patients with low-positive antibody titers before the third dose, all had high-positive antibody titers after the third dose, William A. Werbel, MD, and colleagues from Johns Hopkins Medical Institutions in Baltimore, Maryland, reported. Of the 24 patients with negative antibody titers before the third dose, 6 (25%) displayed high-positive antibody titers after the third dose, 2 (8%) had low-positive antibody titers, and 16 (67%) remained negative. That antibody titers increased after the third dose in one-third of patients with previously negative antibody titers and in all patients with previously low-positive antibody titers is “encouraging,” according to the investigators.

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In an interview with Renal & Urology News, Dr Werbel also suggested: “For persons who do not develop antibody responses to a third dose of a COVID-19 vaccine, consider alternative vaccine regimens such as adjuvanted vaccines, passive immunization with a long-acting monoclonal antibody, or modulating immunosuppressive medications if the risk for organ rejection is low, in concert with the transplant provider and/or in the context of a clinical trial.”

At this time, it’s not clear if one vaccine regimen is superior to another, Dr Werbel acknowledged. He also noted that transplant recipients may prefer not to pursue additional interventions and to remain vigilant in infection prevention.

The median time between transplantation and initial vaccination was 4.5 years. Of the 30 solid organ transplants, 23 were kidney, 2 heart, 3 liver, 1 lung, and 2 pancreas (including 1 kidney-pancreas transplant). In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine plus mycophenolate. In addition, corticosteroids were given to 24 patients, sirolimus to 1, and belatacept to 1.

“We were not able to determine relationships between immunosuppressive drugs and antibody response to third doses due to the small number of patients in this study,” according to Dr Werbel. “Our prior work indicates, however, that belatacept and mycophenolate are associated with poor response to a 2-dose mRNA series.”

With respect to COVID-19 vaccine reactions, the most frequent systemic reaction was mild or moderate fatigue in 14 participants, severe headache in 1, and severe myalgia in 1. No one experienced fever, anaphylactoid reactions, or neurologic complications.

One heart transplant recipient had biopsy-proven, antibody-mediated rejection 7 days after her third dose in the setting of acute volume overload, but her heart function remained normal. This patient did not experience an increase in COVID-19 antibody response. Her immunosuppression regimen was not intensified.

The team noted that no patient contracted COVID-19 during the short follow-up.

As far as the investigators are aware, their report is the first to document the use of a third dose of a COVID-19 vaccine in solid organ transplant recipients.

“We believe that these observations support the use of clinical trials to determine whether booster doses to prevent COVID-19 in transplant patients can be incorporated into clinical practice, as they have been for hepatitis B and influenza vaccination,” Dr Werbel stated.

“We are hoping to conduct a clinical trial of third vaccine dosing in kidney transplant recipients who had suboptimal antibody response to a standard mRNA series to deeply characterize the immune response before and after this intervention. Additionally, we are very interested in performing a clinical trial that compares different vaccine platforms as well as alternative methods to improve vaccine immune response such as changing underlying immunosuppressive drugs.”


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. Published online June 15, 2021. doi:10.7326/L21-0282