Response to "SARS-CoV-2 vaccine effectiveness trumps immunogenicity in solid organ transplant recipients".

DISCLOSURE

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

We recently reported a SARS‐CoV‐2 infection breakthrough rate of 0.65% (3/459) among fully vaccinated adult solid organ transplant recipients (SOTr) at our institution as of May 18, 2021. The majority of fully vaccinated SOTr consisted of kidney recipients (319/459, 70%), with a minority of liver (85/459, 19%), heart (41/459, 9%), and multi‐visceral transplants (11/459, 2%). Sixty‐five percent was on a mycophenolate‐containing regimen (Table 1) and mycophenolate with tacrolimus and prednisone was the most common regimen (33%). In response to our letter, Mossad pointed out that our findings may not be generalizable to other centers whose SOTr population may be more highly immunosuppressed and/or more vulnerable to respiratory infections such as lung and multi‐visceral SOTr. Furthermore, Mossad noted that SOTr with prior undocumented SARS‐CoV‐2 infection and thus with some level of protection from reinfection might have been included.

TABLE 1

Immunosuppression of the 557 solid organ transplant recipients

Immunosuppression	n	%
Mycophenolate (mycophenolate mofetil/mycophenolic sodium)	364	65%
Prednisone	355	64%
Tacrolimus	433	78%
Belatacept	75	13%
Cyclosporine	49	9%
Azathioprine	41	7%
mTOR inhibitors	26	5%

Our results provide some insight into post‐vaccination SARS‐CoV‐2 breakthrough rates in a general SOTr population, although we agree with the study limitations highlighted by Mossad. While the possible inclusion of patients with prior undocumented SARS‐CoV‐2 infection is an important consideration, employing antibody testing to identify them is fraught with limitations since the sensitivity and specificity of serology can vary by assay and antibody titers that correlate with protective immunity are unknown. Moreover, some may not develop detectable IgG antibodies post‐infection and may have absent, limited, and/or short‐lived immunity depending on the corresponding level of immunosuppression.

In our study, fully vaccinated SOTr were at a median of 6.6 years (IQR 2.8–11.8) from transplant to vaccine receipt. Only 12/459 (2.6%) SOTr received the vaccine ≤1 year of transplant, and none developed breakthrough infection. The follow‐up time of the cohort was relatively short, and breakthrough infections could have occurred if follow‐up is extended. In order to gather more data, we revisited our cohort and extended follow‐up to June 30, 2021. Among 557 SOTr, 507 were fully vaccinated with a median follow‐up of 95 days (IQR 73–114). With the extended follow‐up, one additional kidney transplant recipient developed SARS‐CoV‐2 infection 67 days after the second BNT162b2 dose. He developed mild COVID‐19 and did not require hospitalization nor any intervention. In total, 4/507 (0.79%) fully vaccinated SOTr had mild breakthrough infection with none developing severe infection, suggesting that vaccination remains protective against severe COVID‐19.

Our study focused on the clinical effectiveness of the SARS‐CoV‐2 vaccine. Side effects were not reported as it was not the intention of the study. Also, chart review may not be able to describe side effects, particularly mild ones, accurately. In a prior study by Segev et al., severe reactions were rare among SOTr, and the incidence of reactogenicity was similar to that reported in the original clinical trials. In response to the comment, we reviewed episodes of rejection post‐vaccination in our cohort and found none.

We thank Mossad for his comments and thoughtful assessment of the data we presented. We agree that future studies are needed to verify our findings and assess long‐term vaccine effectiveness and impact on rejection.