Kidney Transplant Therapy May Weaken COVID-19 Vaccine Response

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Fabry disease patients who have had a kidney transplant and are on immunosuppressive therapies may show a weaker response to a COVID-19 vaccine, including the booster, according to a study about two patients in France.

While one patient had significant increases in antibody levels against SARS-CoV-2, the virus that causes COVID-19, after the third dose of the vaccine, the other remained negative for such antibodies, even after the booster shot.

This example and previous data suggest that weaker or negative antibody-based responses may be associated with the type of immunosuppressive treatment used.

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More studies are needed to better understand the impact of immunosuppressive therapies on the effectiveness of COVID-19 vaccines, and the safety of a potential fourth dose for vulnerable patients, the researchers noted.

The study, “Humoral Immune Response to SARS-CoV-2 Vaccination after a Booster Vaccine Dose in Two Kidney Transplant Recipients with Fabry Disease and Variable Secondary Immunosuppressive Regimens,” was published in the journal Vaccines.

COVID-19 vaccines work by training the body’s immune system to recognize SARS-CoV-2, allowing a faster and more potent immune response in case of a future exposure.

While several real-world studies continue to show that vaccination is effective at preventing COVID-19 infections and severe disease, it’s still unclear whether it offers the same level of protection to patients receiving immunosuppressive treatments, such as organ transplant recipients.

Given that immunosuppressed patients may show weaker responses to COVID-19 vaccines and the protection provided by the initial dosage weakens slightly over time, particularly in older people, booster jabs are being recommended for them.

Now, researchers in France described the cases of two Fabry patients in their 60s who were on immunosuppressive treatment after a kidney transplant, and who responded differently to the Pfizer vaccine, sold as Comirnaty, including the booster shot.

Fabry disease, which generally affects males more severely than females, is an inherited condition characterized by the toxic accumulation of fatty molecules in body tissues, mainly those of the nervous system, heart, and kidneys. Over time, patients may develop kidney failure and need dialysis or a kidney transplant to survive.

The first patient, a 60-year-old man, underwent a kidney transplant at 31 due to end-stage kidney disease, about the same time he was diagnosed with Fabry disease. He had been on standard enzyme replacement therapy (ERT) since 2001, most commonly Fabrazyme (agalsidase beta).

The man showed stable kidney disease while on maintenance immunosuppressive therapy with ciclosporin A.

He completed the two-dose vaccine in March 2021 and showed a modest, but satisfactory, increase in antibody levels against SARS-CoV-2. Antibody levels increased more after the third dose in May.

Two months later, the man became infected with the delta variant of SARS-CoV-2, but showed only mild symptoms. A chest CT scan showed no signs of severe lung involvement, and his kidney function remained unchanged.

He did not need hospitalization and was managed at home, and COVID-19 resolved without clinical consequences.

His immune cell response to SARS-CoV-2 was studied subsequently in November, six months after the booster dose and three months after mild COVID-19 disease.

Results showed a modest, but significant, immune cell response to the virus, despite his immunosuppressive treatment. However, it was impossible then to know if the response was the result of the vaccination or the SARS-CoV-2 infection, the team noted.

The second patient, a 62-year-old man, was diagnosed with end-stage kidney disease at 39, prompting the diagnosis of Fabry. Two years later, in 2000, he received a new kidney, and he was receiving maintenance immunosuppressive therapy with tacrolimus and mycophenolate mofetil.

He had been on ERT since 2002, most often Fabrazyme.

The man completed the two-dose Comirnaty vaccine in February 2021 and was negative for anti-SARS-CoV-2 antibodies three months later, suggesting he did not have an appropriate response to the vaccine.

He received the booster shot in May, but one month later, no disease-specific antibodies were present. His immune cell response to the virus could not be explored, the team noted.

These findings are consistent with data from a previous observational study that showed a response to COVID-19 vaccines was limited among kidney transplant patients.

The study also found that the type of both immunosuppressive treatment, such as mycophenolic acid, and vaccine (Comirnaty over the Moderna vaccine, Spikevax) were major risk factors for patients’ weak vaccine responses.

Interestingly, the second patient was receiving mycophenolate mofetil, an inactive precursor of mycophenolic acid, known to have a significant influence on antibody-based immune responses.

“Both cases emphasize that patients with Fabry disease and [kidney transplant] are susceptible to develop a weak response to COVID-19 vaccination and highlight the importance of maintaining barrier protection measures,” the researchers wrote.

“Vaccination of family members should be encouraged to lower the risk of viral transmission to immunocompromised, transplanted patients, including vaccinated ones,” they added.

The researchers noted such protective measures should be taken until the impact of immunosuppressive therapies on the effectiveness of COVID-19 vaccination in both cell-based and antibody-based immune responses “is better understood.”

More studies are needed to assess the safety of a fourth dose for vulnerable populations, they added.