Association Between Total Cell Free DNA and SARS-CoV-2 In Kidney Transplant Patients: A Preliminary Study

• Published in: Transplantation proceedings Vol. 54; no. 6; pp. 1446 - 1454
• Main Authors: Reusing, Jose Otto, Yoo, Jongwon, Desai, Amishi, Brossart, Katya, McCormick, Sarah, Malashevich, Allyson Koyen, Bloom, Michelle S., Fehringer, Gordon, White, Roseann, Billings, Paul R., Tabriziani, Hossein, Demko, Zachary P., Gauthier, Philippe, Akkina, Sanjeev K., David-Neto, Elias
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2022; The Authors. Published by Elsevier Inc
• Subjects: Biomarkers; Cell-Free Nucleic Acids; COVID-19; COVID-19 Testing; Graft Rejection; Humans; Kidney Transplantation - adverse effects; Retrospective Studies; SARS-CoV-2; Tissue Donors
• ISSN: 0041-1345; 1873-2623; 1873-2623
• DOI: 10.1016/j.transproceed.2022.02.027

Kidney transplant (KT) recipients are at high risk for developing severe COVID-19. Lowering immunosuppression levels in KT recipients with COVID-19 encourages native immune responses but can raise the risk of rejection. Donor-derived cell-free DNA (dd-cfDNA), reported as a fraction of total cfDNA, is a proven biomarker for KT rejection. Total cfDNA levels are elevated in patients with COVID-19, which may depress dd-cfDNA fractions, potentially leading to missed rejections. A retrospective analysis of 29 KT recipients hospitalized with COVID-19 between April and November 2020 examined total and dd-cfDNA levels. Blood samples were collected after onset of COVID-19, with follow-up samples collected from a subset of patients, when infection had likely subsided. After COVID-19 diagnosis, the median total cfDNA level was elevated (7.9 multiples of median [MoM]). A significant decrease in total cfDNA levels was observed between the first and second time points (6.2 MoM, 1.0 MoM; P <001). A significant positive association was identified between total cfDNA levels and COVID-19 severity (P = .02; R2 = .19). Two patients with biopsy-proven acute cellular rejection had dd-cfDNA fractions below the 1% cutoff for rejection (0.20% and 0.78%), with elevated total cfDNA levels of 7.9 MoM and 41.8 MoM, respectively. In this preliminary study, total cfDNA levels were elevated in KT patients with COVID-19, subsiding after resolution of infection. High total cfDNA levels may confound dd-cfDNA results, leading to failure to identify rejection. Considering total cfDNA levels is important in interpretation of dd-cfDNA tests for assessment of rejection in KT patients with COVID-19 or other infection.