Renal Transplant Service, Hospital das Clinicas, University of São Paulo School of Medicine, São Paulo, Brazil.
Loyola University Medical Center, Maywood, Illinois.
Transplant Proc. 2022 Jul-Aug;54(6):1446-1454. doi: 10.1016/j.transproceed.2022.02.027. Epub 2022 Mar 15.
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; R = .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.
肾移植（KT）受者发生严重 COVID-19 的风险较高。降低 COVID-19 肾移植受者的免疫抑制水平可促进固有免疫反应，但会增加排斥反应的风险。供体来源的无细胞 DNA（dd-cfDNA）作为总 cfDNA 的一部分报告，是肾移植排斥反应的一种已证实的生物标志物。COVID-19 患者的总 cfDNA 水平升高，这可能会降低 dd-cfDNA 分数，从而导致排斥反应漏诊。
对 2020 年 4 月至 11 月期间因 COVID-19 住院的 29 名 KT 受者进行回顾性分析，检测总 cfDNA 和 dd-cfDNA 水平。在 COVID-19 发病后采集血样，对部分患者在感染可能消退后采集随访样本。
COVID-19 诊断后，总 cfDNA 水平中位数升高（7.9 倍中位数[MoM]）。首次和第二次检测之间，总 cfDNA 水平显著下降（6.2 MoM，1.0 MoM；P <001）。总 cfDNA 水平与 COVID-19 严重程度之间存在显著正相关（P =.02；R =.19）。两名经活检证实为急性细胞性排斥反应的患者 dd-cfDNA 分数低于排斥反应的 1%截止值（0.20%和 0.78%），总 cfDNA 水平分别为 7.9 MoM 和 41.8 MoM。
在这项初步研究中，COVID-19 肾移植受者的总 cfDNA 水平升高，感染消退后下降。高总 cfDNA 水平可能会干扰 dd-cfDNA 结果，导致排斥反应漏诊。在解释 dd-cfDNA 检测以评估 COVID-19 或其他感染的肾移植受者的排斥反应时，考虑总 cfDNA 水平非常重要。
