PURPOSE: Advanced age is associated with an impaired humoral immune response to SARS-CoV-2 mRNA vaccination in kidney transplant recipients (KTR). The mechanisms are, however, poorly understood. Frailty syndrome assessment may determine the most vulnerable population. METHODS: This study is a secondary analysis of a prospective study (NCT04832841) regarding seroconversion after BNT162b2 vaccination, including 101 SARS-CoV-2 naïve KTR 70 years and older. The Fried frailty components were evaluated, and antibodies against S1 and S2 subunits of SARS-CoV-2 were examined > 14 days after the second dose of BNT162b2 vaccine. RESULTS: Seroconversion was observed in 33 KTR. Male gender, eGFR, MMF-free immunosuppression, and a lower frailty score were associated with higher seroconversion rates in univariable regression. Concerning frailty components, physical inactivity had the most negative effect on seroconversion (OR = 0.36, 95% CI 0.14-0.95, p = 0.039). In a multivariable regression adjusted for eGFR, MMF-free immunosuppression, time from transplant and gender, pre-frail (OR = 0.27, 95% CI 0.07-1.00, p = 0.050), and frail status (OR = 0.14, 95% CI 0.03-0.73, p = 0.019) were associated with an increased risk of unresponsiveness to SARS-CoV-2 vaccines. CONCLUSION: Frailty was associated with an impaired humoral response to SARS-CoV-2 mRNA vaccination in older SARS-CoV-2 naïve KTR. TRAIL REGISTRATION: This study is registered under the identifier NCT04832841 on ClinicalTrials.gov.

Department of Immunology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Nephrology Institute for Clinical and Experimental Medicine Prague Czech Republic

Information Technology Department Institute for Clinical and Experimental Medicine Prague Czech Republic

The 3rd Faculty of Medicine Charles University Prague Czech Republic

Transplantation Laboratory Institute for Clinical and Experimental Medicine Prague Czech Republic

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Hilbrands LB, Duivenvoorden R, Vart P, et al. COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration. Nephrol Dial Transplant. 2020;35(11):1973–1983. doi: 10.1093/ndt/gfaa261. PubMed DOI PMC

Marion O, Del Bello A, Abravanel F, et al. Predictive factors for humoral response after 2-dose SARS-CoV-2 vaccine in solid organ transplant patients. Transplant Direct. 2021;8(1):e1248. doi: 10.1097/txd.0000000000001248. PubMed DOI PMC

Grupper A, Rabinowich L, Schwartz D, et al. Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus. Am J Transplant. 2021;21(8):2719–2726. doi: 10.1111/ajt.16615. PubMed DOI PMC

Benotmane I, Gautier-Vargas G, Cognard N, et al. Low immunization rates among kidney transplant recipients who received 2 doses of the mRNA-1273 SARS-CoV-2 vaccine. Kidney Int. 2021;99(6):1498–1500. doi: 10.1016/j.kint.2021.04.005. PubMed DOI PMC

Magicova M, Zahradka I, Fialova M, et al. Determinants of immune response to anti-SARS-CoV-2 mRNA vaccines in kidney transplant recipients: a prospective cohort study. Transplantation. 2022 doi: 10.1097/TP.0000000000004044. PubMed DOI PMC

Hariharan S, Israni AK, Danovitch G. Long-term survival after kidney transplantation. N Engl J Med. 2021;385(8):729–743. doi: 10.1056/nejmra2014530. PubMed DOI

Demaret J, Corroyer-Simovic B, Alidjinou EK, et al. Impaired functional T-cell response to SARS-CoV-2 after two doses of BNT162b2 mRNA vaccine in older people. Front Immunol. 2021 doi: 10.3389/fimmu.2021.778679. PubMed DOI PMC

Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: Evidence for a phenotype. Journals Gerontol Ser A Biol Sci Med Sci. 2001 doi: 10.1093/gerona/56.3.m146. PubMed DOI

Yao X, Hamilton RG, Weng N, et al. Frailty is associated with impairment of vaccine-induced antibody response and increase in post-vaccination influenza infection in community-dwelling older adults. Vaccine. 2011;29(31):5015–5021. doi: 10.1016/j.vaccine.2011.04.077. PubMed DOI PMC

Moehling KK, Nowalk MP, Lin CJ, et al. The effect of frailty on HAI response to influenza vaccine among community-dwelling adults ≥ 50 years of age. Hum Vaccines Immunother. 2018;14(2):361–367. doi: 10.1080/21645515.2017.1405883. PubMed DOI PMC

Loeb N, Andrew MK, Loeb M, et al. Frailty is associated with increased hemagglutination- inhibition titers in a 4-year randomized trial comparing standard- And high-dose influenza vaccination. Open Forum Infect Dis. 2020 doi: 10.1093/OFID/OFAA148. PubMed DOI PMC

Salmerón Ríos S, Mas Romero M, Cortés Zamora EB, et al. Immunogenicity of the BNT162b2 vaccine in frail or disabled nursing home residents: COVID-A study. J Am Geriatr Soc. 2021;69(6):1441–1447. doi: 10.1111/jgs.17153. PubMed DOI PMC

Magicova M, Fialova M, Zahradka I, et al. Humoral response to SARS-CoV-2 is well preserved and symptom dependent in kidney transplant recipients. Am J Transplant. 2021;21(12):3926–3935. doi: 10.1111/ajt.16746. PubMed DOI PMC

McAdams-DeMarco MA, Law A, Salter ML, et al. Frailty and early hospital readmission after kidney transplantation. Am J Transplant. 2013;13(8):2091–2095. doi: 10.1111/ajt.12300. PubMed DOI PMC

McAdams-DeMarco MA, Ying H, Olorundare I, et al. Individual frailty components and mortality in kidney transplant recipients. Transplantation. 2017;101(9):2126–2132. doi: 10.1097/TP.0000000000001546. PubMed DOI PMC

Chu NM, Ruck J, Chen X, et al. Long-term trajectories of frailty and its components after kidney transplantation. J Gerontol Ser A. 2022 doi: 10.1093/gerona/glac051. PubMed DOI PMC

Dor-Haim H, Katzburg S, Revach P, Levine H, Barak S. The impact of COVID-19 lockdown on physical activity and weight gain among active adult population in Israel: a cross-sectional study. BMC Public Health. 2021 doi: 10.1186/s12889-021-11523-z. PubMed DOI PMC

Schuler PB, Leblanc PA, Marzilli TS (2003) Effect of physical activity on the production of specific antibody in response to the 1998–99 influenza virus vaccine in older adults. J Sports Med Phys Fitness 43(3):404. http://www.ncbi.nlm.nih.gov/pubmed/14625524. PubMed

Edwards KM, Burns VE, Allen LM, et al. Eccentric exercise as an adjuvant to influenza vaccination in humans. Brain Behav Immun. 2007;21(2):209–217. doi: 10.1016/J.BBI.2006.04.158. PubMed DOI

Collier DA, Ferreira IATM, Kotagiri P, et al. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2. Nature. 2021;596(7872):417–422. doi: 10.1038/s41586-021-03739-1. PubMed DOI PMC

McAdams-Demarco MA, Law A, Tan J, et al. Frailty, mycophenolate reduction, and graft loss in kidney transplant recipients. Transplantation. 2015;99(4):805–810. doi: 10.1097/TP.0000000000000444. PubMed DOI PMC

Moehling KK, Zhai B, Schwarzmann WE, et al. The impact of physical frailty on the response to inactivated influenza vaccine in older adults. Aging (Albany NY) 2020;12(24):24633–24650. doi: 10.18632/aging.202207. PubMed DOI PMC

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