Prediction of humoral and cellular immune response to COVID-19 mRNA vaccination by TTV load in kidney transplant recipients and hemodialysis patients.

Abstract

Immunosuppressed individuals such as kidney transplant recipients (KTR) and hemodialysis patients (DP) show impaired immune responses to COVID-19 vaccination. Plasma Torque Teno Virus (TTV) DNA load is used as surrogate for the individual degree of immunosuppression. We now assessed the association of TTV load at time of COVID-19 vaccination with humoral and cellular immune response rates to vaccination in KTR, DP, and healthy medical personnel (MP). A total of 100 KTR, 115 DP and 54 MP were included. All were SARS-CoV-2 seronegative at the time of vaccination with either BNT162b2 or mRNA-1273. Plasma TTV loads were assessed at the time of first vaccination. After two-dose vaccination, seroconversion (de novo detection of SARS-CoV-2 S1-IgA and/or IgG) was determined. In addition, cellular responses as assessed by interferon γ release and neutralizing antibodies were assessed in a subset of participants. ROC analyses were performed to define TTV load cut-offs predicting specific immune responses to vaccination. Plasma TTV loads at the time of first vaccination were negatively associated with seroconversion after two-dose vaccination in KTR (OR 0.87, 95% CI 0.76-0.99). TTV loads were significantly lower in KTR who developed humoral and cellular immune responses to vaccination compared to non-responders (p=0.0411 and 0.0030, respectively). Of patients with TTV loads above 106 copies/ml, none developed cellular immune responses against SARS-CoV-2, and only 2 of 17 (12%) seroconverted in response to vaccination. Plasma TTV loads at the time of first vaccination in immunosuppressed individuals may be useful to predict individual vaccine-specific immune responses.