Introduction: Neutrophil extracellular traps (NETs) release (i.e., NETosis) has been recently implicated in the pathomechanism underlying severe end-organ damage in
Coronavirus Disease 2019 (COVID-19) and could present a novel therapeutic target. We aimed to determine whether circulating levels of
cell-free DNA (
cfDNA), a surrogate for NETosis, may be associated with the development of
acute kidney injury (AKI), a major contributor to poor outcomes and mortality in
COVID-19. Methods: Blood samples were collected prospectively from adult patients infected with SARS-CoV-2 presenting to the emergency department (ED). Circulating levels of
cfDNA were quantified from patients' serum. Further assessment of correlations between
cfDNA levels and markers of AKI (i.e., serum
creatinine (SCr),
cystatin C,
neutrophil gelatinase-associated lipocalin (NGAL)),
biomarkers of
thrombotic microangiopathy and of
inflammation in patients' serum was performed. Results: Fifty-one
COVID-19 patients were enrolled.
cfDNA levels were found to be significantly higher in those who developed severe AKI (p < 0.001) and those needing
renal replacement therapy (p = 0.020).
cfDNA positively correlated with ED SCr, NGAL,
cystatin C, neutrophil count, neutrophil-to-lymphocyte ratio, C3a, C5a, Scb5-9,
IL-6,
IL-8,
IL-10, TNF-α, LDH, CRP,
ferritin, and
fibrinogen and negatively correlated with ADAMTS13/
von-Willebrand factor ratio and lymphocyte count. In a multivariate logistic regression, a one-unit increase in
cfDNA value was associated with 4.6% increased odds of severe AKI (OR = 1.046; p = 0.040). Finally,
cfDNA significantly correlated with established NETs components,
myeloperoxidase, and
neutrophil elastase. Conclusion: Intravascular NETosis could be an important contributing factor in the development of microthrombosis and COVID-19-associated AKI. Further research is urgently needed to understand the role of NETosis in
COVID-19 and evaluate therapeutic avenues for targeting this process.