*Purpose: The COVID-19 pandemic portends significant morbidity and mortality in immunocompromised individuals. Vaccination against COVID-19 among immunocompromised population is an essential step to minimize deadly complications. Numerous studies have shown an association between immune status, disease severity, and suboptimal responsiveness to vaccination. Additionally, data suggests that elevated IgG levels correlated with host viral neutralization. We herein present data indicating that induction and maintenance immunosuppression therapy affects responsiveness to vaccination among kidney transplant recipients.

*Methods: The study data was retrospectively analyzed for 48 kidney transplant patients who received mRNA type COVID-19 vaccine at our institution. Majority of patients received vaccination between January and March 2021; two doses in total. The 30 days post-vaccination SARS-CoV-2 spike antigen-specific IgG levels were measured to assess immunological response to vaccine.

*Results: The included patients underwent kidney transplantation between 1983 and 2020. Among these patients, 35% showed detectable peak COVID IgG serum levels 30 days after the 2nd vaccine dose. A total of 31 patients (65%) did not show any response; majority of these non-responders (62%) were heavily immunocompromised, either on high dose Mycophenolate (at least 720 mg twice daily) in addition to standard Calcineurin inhibitor/Sirolimus+/-Prednisone), or had received high dose Thymoglobulin (6 mg/kg or more) within a year of vaccination. Among immunocompetent patients, over 95% immunological responsiveness or viral neutralization after the second vaccination dose has been reported.

*Conclusions: Anti-thymocyte globulin as induction immunosuppression and anti-metabolites like Mycophenolate as maintenance immunosuppression serve as the cornerstone of transplantation management. However, their utilization impacts B cell proliferation, thereby reducing antibody production and the effectiveness of the SARS-CoV-2 vaccine in transplant patients. The ability of these immunosuppressive medications to suppress responsiveness to the SARS CoV-2 vaccine supports the need for 1) regular immunological surveillance post-vaccination among transplant patients, and 2) the need for a third or possibly fourth booster dose to achieve a sustained and effective response.

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