ABSTRACT
Introduction: Donor derived cell-free DNA (dd-cfDNA) is an established noninvasive biomarker for immunologic rejection of donor tissue in organ transplant recipients. The ProsperaTM test, a SNP-based mmPCR methodology, evaluates ddcfDNA levels as a fraction of total cfDNA. Atypical elevations in total cfDNA, as seen in immunologic responses, could affect the assessment of active rejection (AR). dd-cfDNA has been analyzed in patients undergoing kidney transplants, however, early data suggests that dd-cfDNA behaves similarly following pancreas transplant. Here we present the clinical course of a pancreas transplant recipient with COVID-19 infection for whom, serial dd-cfDNA testing was performed. Case Description: A 51-year-old female received a deceased donor pancreas transplant in August, 2020. The patient was maintained on a triple immunosuppressive (IS) therapy regime, had stable amylase and lipase levels and no episodes of rejection. Six months later, the patient received the first dose of a COVID-19 vaccine, and the second dose three weeks later. The patient's spouse was diagnosed with COVID-19 and soon after, the patient had elevated pancreatic enzymes, 156 and 199 (prior labs 67 and 27) and presented with elevated temperature (100.4 F), cough, fatigue, loss of taste, diarrhea, myalgias and rhinorrhea. The patient was determined to have COVID-19 with a severity score of 2. IS was reduced and monoclonal ab therapy was initiated. dd-cfDNA fraction was 1.38%, indicated high-risk for AR, with corresponding total cfDNA elevated 10.2 multiples of the median (MoM). The patient was treated with Methylprednisolone 500 mg with a PO Prednisone tail. Three weeks later, the patient was negative for COVID-19 and IS was resumed. The dd-cfDNA fraction at this time was 1.59%, and total cfDNA decreased to 1.1 MoM. Subsequent weekly Prospera tests indicated dd-cfDNA fractions of 1.03%, 0.54%, and 0.81% with total cfDNA levels of 1.4 MoM, 1.3 MoM, and 0.94 MoM. Discussion: Measurement of dd-cfDNA can guide IS management in pancreas transplant recipients with COVID-19 undergoing AR. Viral infections and anti-rejection therapies can influence total cfDNA. Thus, continued monitoring of both total and ddcfDNA are needed to identify a true response to therapy.
ABSTRACT
Digitalization appears as a full mutation in the entire world, including health care. From applications (apps) to sensors, the digital is now fully integrated in daily life for patients. Monitoring treatments more easily and improving the design for drug packaging remain the most challenging points for medicines and the digitalization appears as a useful alternative. An overview of some relevant proposals that integrates personalization to users and drug forms is proposed with a specific focus on cardiology treatments and COVID-19 innovations.
ABSTRACT
Introduction: Donor-derived cell-free DNA (dd-cfDNA) assays are clinically validated to detect kidney transplant injury, reporting the donor fraction as a percentage of the total, or background, cfDNA. Various clinical factors can cause a significant increase in recipient cfDNA, contributing to higher background cfDNA and lower donor fraction, which may result in a false negative test result. Case Description: A 50+ year old woman with end-stage renal disease secondary to polycystic kidney disease presented with 4 days (d) of diffuse muscle pain at 11 months post-kidney transplant. In the emergency department she had a fever to 101°F, bilateral infiltrates on chest x-ray, and a positive COVID-19 (SARS-CoV-2) test. She remained febrile for 3d before developing acute respiratory distress requiring oxygen supplementation;her creatinine level was 3 mg/dL. Due to worsening of her respiratory status, she was intubated and started empirically on vancomycin, meropenem, and azithromycin;mycophenolate mofetil was discontinued. She rapidly progressed to septic shock requiring vasopressor therapy. Her renal function deteriorated, and she was started on continuous renal replacement therapy on hospital d7. She received leronlimab on hospital d7 and d14 and convalescent plasma on hospital d11. Tacrolimus was discontinued on hospital d10 and she continued prednisone at 5 mg/d. Dd-cfDNA testing to assess allograft injury and to rule out active rejection was performed. At hospital d20, her dd-cfDNA was 0.07% with an elevated background cfDNA of 28,569 arbitrary units (AU, ∼57X median value). At the second blood draw at hospital d25, her dd-cfDNA was 0.25% with a background cfDNA level reduced to 7,503 AU (∼15X median value). Discussion: In this case, infection with the SARS-CoV-2 virus was associated with a very elevated background cfDNA level, likely due to cellular apoptosis due to the immune process and/or tissue ischemia due to sepsis-associated hypoperfusion. Although this patient was not known to have active rejection of her allograft, the very high background levels complicate the interpretation of results, especially when donor fraction were reported.