Q&A: Reduced efficacy of COVID-19 vaccines in transplant recipients
A study of COVID-19 vaccine responses among kidney transplant recipients in Israel suggested that they may remain at high risk for COVID-19 even after vaccination, according to results published in The American Journal of Transplantation.
Researchers examined humoral responses in 136 kidney transplant recipients and 25 control patients who received both doses of the Pfizer-BioNTech vaccine. All members of the control group developed a positive response in the spike proteins compared with only 37.5% of transplant recipients who had a positive serology test, researchers reported.
“Based on these findings, we strongly suggest that all transplant recipients should be counseled to continue the practice of protective COVID-19 measures including wearing masks, hand hygiene, and social distancing,” Ayelet Grupper, MD, a nephrologist at Tel Aviv Medical Center, and colleagues wrote.
We spoke with Infectious Disease News Editorial Board Member Peter Chin-Hong, MD, professor of medicine and director of the transplant infectious disease program at the University of California, San Francisco, about the impact of COVID-19 on transplant programs and the efficacy of COVID-19 vaccines in transplant recipients.
Healio: What has been the overall impact of COVID-19 on transplant recipients and transplant programs?
Chin-Hong: Although we all feared excess transplant recipient mortality at the onset of the pandemic, the evidence is not clear. Because a large proportion of patients who underwent a transplant have comorbidities that put them at risk for severe COVID-19 disease and mortality such as heart disease and diabetes, the independent effect of transplantation is challenging to disentangle. One multicenter study comparing ICU COVID-19 solid-organ recipients with matched controls found no difference in rates of acute respiratory distress syndrome or death between groups. This has been the experience in my center as well. Although some smaller single-center studies have shown excess mortality in patients who underwent a transplant, many were conducted in regions with overwhelmed hospital systems at the time — for example, New York and Massachusetts — and this may be a modifying factor. The bottom line is that it is unclear but that it may not the doomsday diagnosis that we had all worried about initially.
Healio: What is your reaction to the findings in the study by Grupper and colleagues?
Chin-Hong: My reaction is that this is unfortunately not a surprising result. These findings corroborate many of the on-the-ground experiences and anecdotes that transplant professionals have been seeing and hearing about regarding their patients who underwent a transplant undergoing COVID-19 vaccination. We have known for a long time that patients who underwent a transplant do not have optimal immune responses following many vaccines. And although we held out hope that a relatively new vaccine technology — messenger RNA (mRNA) — would elicit better antibody responses in transplant recipients, this is not turning out to be true.
Healio: What are the reasons that a transplant recipient would have a reduced response to a COVID-19 vaccine, and what measures might increase that response?
Chin-Hong: There are multiple reasons. Time since transplantation (especially the first 3 months when immunosuppression is often the most pronounced), the amount and nature of immunosuppression and the occurrence of concomitant allograft rejection are important factors that can interfere with the production of neutralizing antibodies needed. The underlying disease that led to the organ transplantation, existing comordibities and advanced age are other factors that may attenuate an adequate immune response following vaccination.
Healio: Is there a COVID-19 vaccine that is recommended over the others for transplant recipients?
Chin-Hong: At this point, there have been not enough studies evaluating the differences in immune response in transplant recipients comparing the various COVID-19 vaccine types already developed. There are other future vaccine types that have not been used in transplant recipients widely. But I am not optimistic that any one will prove a clear winner using the current dosing strategy. Ultimately, passive COVID-19 immunization using convalescent sera and engineered antibody cocktails — barring circulating resistant variants — may be the bridge in protecting this vulnerable community as we figure out the best measures of immune response and the dosing strategy.
Healio: Are COVID-19 treatment and vaccination guidelines for transplant recipients sufficient?
Chin-Hong: I am more confident with extrapolating COVID-19 treatment guidelines in the general population to transplant recipients with COVID-19, except perhaps more studies need to be performed looking at the potential benefit of using antibody therapy in later stages of disease.
Healio: Are studies like the one conducted by Grupper and colleagues beginning to show that we will likely need to change how we approach vaccination in transplant recipients?
Chin-Hong: Based on these results, some centers have already discussed having a mycophenolate-free period before administering COVID-19 vaccines. Some have also wondered whether we should routinely test transplant recipients for an antibody response following COVID-19 vaccines lest we have false security that our patients would be safe in the community. Others believe that the antibody testing strategy may not be enough and we need a measure of T-cell response to give a more complete picture. More studies clearly need to be done in this population evaluating different dosing regimens — for example, administer a double dose, more doses, or boost with a different vaccine type — and certainly we will continue to prioritize vaccination before transplantation if given the choice. For the time being, perhaps we should advise all transplant recipients to mask/distance when they are around unvaccinated persons even if they are vaccinated.
Larger, multicenter studies also need to be performed to disentangle the group of nonresponders from the group who would benefit from traditional dosing. We need this information urgently. COVID-19 will be likely present in our lives for many years, if not indefinitely.