Correlation between cell free-DNA levels, COVID-19 severity seen among transplant patients
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A strong positive correlation between cell free-DNA levels and COVID-19 severity exists among kidney transplant patients, according to data published in Transplant Proceedings.
Further, researchers found cell free-DNA (cfDNA) levels are elevated at time of the infection and lower once the infection fades.
“Kidney transplant recipients are at high risk for developing severe COVID-19. Lowering immunosuppression levels in kidney transplant 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 kidney transplant rejection. Total cfDNA levels are elevated in COVID-19 patients, which may depress dd-cfDNA fractions, potentially leading to missed rejections,” Sanjeev K. Akkina, MD, an associate professor of medicine in transplant nephrology at Loyola University Medical Center, and colleagues wrote. They added, “Here, we present results of dd-cfDNA testing in a series of hospitalized kidney transplant patients with COVID-19, examining the effect of COVID-19 infection on the total cfDNA levels, and the effect on dd-cfDNA fractions.”
In a retrospective analysis, researchers evaluated data for 29 kidney transplant patients (median age was 58 years) hospitalized with COVID-19 between April and November 2020 at Loyola University Medical Center in the U.S. and Hospital das Clinicas of University of São Paulo in Brazil. Following COVID-19 infections, patients received a dd-cfDNA test and provided blood samples. Using massively multiplexed-PCR and next-generation sequencing, researchers analyzed all blood samples. A subset of patients participated in follow-ups after COVID-19 clearance.
Analyses revealed the median total cfDNA level increased after COVID-19 diagnoses (7.9 multiples of median [MoM]). However, researchers found the levels decreased between the time of the first and second follow-ups (6.2 MoM, 1 MoM).
Among the 29 kidney transplant patients, two patients with biopsy-proven acute cellular rejection showed dd-cfDNA fractions below the 1% cutoff for kidney rejection, with high cfDNA levels of 7.9 MoM and 41.8 MoM.
“The data presented herein indicate an association between elevated total cfDNA and COVID-19 infection and its severity in hospitalized kidney transplant patients. Additionally, when using dd-cfDNA testing for monitoring allograft rejection in individuals with COVID-19, consideration of total cfDNA levels along with the dd-cfDNA fraction is important to ensure that cases of rejection are not missed,” Akkina and colleagues wrote. They added, “As this is a preliminary study, future studies will be needed to validate the relationship between total cfDNA and dd-cfDNA levels and COVID-19 infection in kidney transplant patients.”
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