Clinical consequences of the suboptimal effect of messenger RNA‐based SARS‐CoV‐2 vaccine in renal transplant recipients

Dear Editor,

Multiple studies reported increased COVID‐19‐associated mortality rates among kidney transplant recipients (KTR) compared with general population patients (20%–28% vs. 1%–5%) [1]. Therefore, KTR have been prioritized for vaccination. Messenger RNA (mRNA)‐based SARS‐CoV‐2 vaccines were found to have an efficacy of 95% in Phase 3 placebo‐controlled trials in the general population [2, 3]. However, KTR were not included. A growing body of evidence suggests low efficacy of mRNA‐based SARS‐CoV‐2 vaccines. These findings suggest a higher early risk for COVID‐19 despite the vaccination of immunocompromised patients.

As of May 9, 2021, 250 088 Croatian citizens received two doses of the SARS‐CoV‐2 vaccine [4]. This number included 164 patients from our cohort. Over the same period, 58 cases of symptomatic COVID‐19 were recorded after the completed vaccination, eight (13.7%) of them being KTR. Thus, COVID‐19 emerged in 0.02% of vaccinated individuals from the general population compared with 4.8% in KTR.

Eight patients (six males), aged 42 to 84 (mean 59.3) years developed COVID‐19 after the second dose of the BNT162b2 mRNA vaccine (Pfizer‐BioNTech) 30 μg administered via intramuscular injection in two doses, 21 days apart. Seven had unknown exposure settings, and one was in contact within the household. All have presented with fevers 14 to 18 days after the second vaccination, six requiring hospitalization for COVID‐19 pneumonia. The immunosuppressive protocol consisted of tacrolimus in five, cyclosporine in two, and everolimus in one patient, while all had mycophenolate mofetil and a steroid. One patient had anti‐thymocyte globulin for induction, and others received basiliximab. All have survived with stable renal allograft function. We have not determined serologic response while patients receive the vaccine at their local centers.

According to the recently published results, the humoral response of RTR to the mRNA‐vaccine BNT162b2 (Pfizer‐BioNTech), evaluated with an anti‐SARS‐CoV‐2 IgG CLIA 15.8 ± 3.0 days after the second dose, was significantly lower compared to healthy controls (22% vs. 100%; p = 0.0001) [5]. Our clinical results prove these laboratory findings. We were the first to report COVID‐19 after two doses of the SARS‐CoV‐2 vaccine [6], hoping these were isolated cases. However, with the third wave of SARS‐CoV‐2 infection spreading through Croatia, the number of clinically manifest COVID‐19 patients has been rapidly increasing despite the vaccination. Additionally, the clinical presentation was mild in only two patients, while others required hospitalization.

Inferior vaccination results are a well‐known problem in immunocompromised solid organ recipients. A meta‐analysis that included the data of 947 transplant recipients retrieved from 15 clinical trials showed significantly lower rates of seroconversion among transplant recipients receiving mycophenolate mofetil than other immunosuppressive agents. No significant correlation was found for other immunosuppressive drugs used for maintenance [7]. Boyarsky et al. have shown that transplant recipients receiving anti–metabolite maintenance immunosuppression therapy were less likely to develop an antibody response than those not receiving such immunosuppression therapy (37% vs. 63%, respectively) following vaccination with the mRNA‐based vaccine [8]. Higher estimated glomerular filtration rate, lower mycophenolic acid dose, younger age, and lower calcineurin inhibitors blood level were associated with antibody response 4 to 6 weeks after the BNT162b2 vaccine in RTR [9].

With the current knowledge, possible solutions may include additional doses of the vaccine, combination of mRNA‐based and vector‐based vaccines, which may have better efficacy. Additionally, temporary discontinuation or decrease in the dose of mycophenolate (possibly with increasing the dose of steroid) may help increase the vaccination response rate. However, such measures would require an individual approach. With the growing number of vaccinated KTR amidst the ongoing pandemic and continuous efforts of clinical researchers, we may soon reach the solution.

In conclusion, the mRNA‐based SARS‐CoV‐2 vaccine may have suboptimal efficacy KTR. Vaccination strategies for KTR may differ from the general population.

CONFLICT OF INTEREST

Author has no conflict of interests to declare.