*Purpose: Advanced age is associated with impaired humoral immune response to SARS-CoV-2 mRNA vaccines in kidney transplant recipients (KTR), however mechanisms are poorly understood. Frailty syndrome assessment in geriatric KTR may reveal the most vulnerable population.

*Methods: This is the subcohort analysis of prospective study (NCT04832841) dealing with seroconversion after SARS-CoV-2 mRNA vaccination. In 101 KTR aged 70+ who were SARS-CoV-2 naïve, the Fried frailty components were evaluated. Antibodies against S1 and S2 subunit of SARS-CoV-2 were evaluated >14 days after second dose of mRNA vaccines using immunochemiluminescent assay (cut off 9.5 AU/ml, sensitivity of 91.2% and specificity of 90.2%). The clinical variables affecting the humoral response were analyzed by multivariable binary regression model based on results of univariable analysis.

*Results: The seroconversion after SARS-CoV-2 vaccination was observed in 33 out of 101 (33%) KTR. In the univariable regression model, eGFR (OR=1.03, p=0.001), MMF-free immunosuppression (OR=4.32, p=0.002), physical inactivity (OR=0.36, p=0.039), grip strength (OR=1.05, p=0.045), male gender (OR=2.09, p=0.09), and Fried frailty score (OR=0.74, p=0.09) were associated with seroconversion. Multivariable binary logistic regression model adjusted for KTR age and gender retained as independent significant predictors for seroconversion the Fried frailty cumulative score (OR=0.6, p=0.048), eGFR (OR=1.05, p<0.001), MMF-free immunosuppression (OR=8.25, p=0.001) and longer follow-up from transplantation (OR=1.01, p=0.021).

*Conclusions: The frailty but not age itself is associated with impaired humoral response to SARS-CoV-2 mRNA vaccines in KTR. Intervention to reduce physical inactivity prior to vaccination may improve seroconversion rate in elderly KTR.

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