Extremely High Cell-free DNA Levels Observed in Renal Allograft Patient With SARS-CoV-2 Infection

Bunnapradist, Suphamai; Datta, Nakul; Schaenman, Joanna; Ioannou, Nick; Bloom, Michelle S.; Malhotra, Meenakshi; Tabriziani, Hossein; Gauthier, Philippe; Ahmed, Ebad; Billings, Paul R.; Lum, Erik L.

Beyond its widely recognized morbidity and mortality, coronavirus disease 2019 poses an additional health risk to renal allograft recipients. Detection and measurement of donor-derived cell-free DNA (dd-cfDNA), expressed as a fraction of the total cell-free DNA (cfDNA), has emerged as a noninvasive biomarker for allograft rejection. Here, we present a case report of a patient who was infected with severe acute respiratory syndrome coronavirus 2, 11 mo post–kidney transplant. The patient was serially monitored using an analytically and clinically validated massively multiplex PCR-based dd-cfDNA assay to assess allograft injury and risk for rejection. Over the course of infection, low dd-cfDNA fractions were observed (below the 1% cutoff) and were accompanied by unusually highly elevated levels of total cfDNA, which gradually declined as the infection resolved. The case study highlights the variability in total cfDNA levels during and after viral infection, and the need to consider both total and dd-cfDNA levels when clinically interpreting the results for allograft rejection. Furthermore, the study highlights the importance of serial testing, wherein an interplay between total cfDNA and dd-cfDNA can inform the optimization of a patient’s immunosuppressive treatment regimen in response to infection.