Circulating cell-free DNA, peripheral lymphocyte subsets alterations and neutrophil lymphocyte ratio in assessment of COVID-19 severity

Innate Immun. 2021 Apr;27(3):240-250. doi: 10.1177/1753425921995577. Epub 2021 Mar 1.

Abstract

Cell destruction results in plasma accumulation of cell-free DNA (cfDNA). Dynamic changes in circulating lymphocytes are features of COVID-19. We aimed to investigate if cfDNA level can serve in stratification of COVID-19 patients, and if cfDNA level is associated with alterations in lymphocyte subsets and neutrophil-to-lymphocyte ratio (NLR). This cross-sectional comparative study enrolled 64 SARS-CoV-2-positive patients. Patients were subdivided to severe and non-severe groups. Plasma cfDNA concentration was determined by real-time quantitative PCR. Lymphocyte subsets were assessed by flow cytometry. There was significant increase in cfDNA among severe cases when compared with non-severe cases. cfDNA showed positive correlation with NLR and inverse correlation with T cell percentage. cfDNA positively correlated with ferritin and C-reactive protein. The output data of performed ROC curves to differentiate severe from non-severe cases revealed that cfDNA at cut-off ≥17.31 ng/µl and AUC of 0.96 yielded (93%) sensitivity and (73%) specificity. In summary, excessive release of cfDNA can serve as sensitive COVID-19 severity predictor. There is an association between cfDNA up-regulation and NLR up-regulation and T cell percentage down-regulation. cfDNA level can be used in stratification and personalized monitoring strategies in COVID-19 patients.

Keywords: COVID-19 monitoring; COVID-19 patients’ stratification; COVID-19 severity predictors; NLR; cfDNA; personalized biomarkers.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • C-Reactive Protein / analysis
  • COVID-19 / blood
  • COVID-19 / diagnosis*
  • COVID-19 / immunology*
  • Cross-Sectional Studies
  • DNA / blood*
  • Diagnosis, Differential
  • Female
  • Ferritins / blood
  • Humans
  • Lymphocyte Count
  • Lymphocyte Subsets / pathology*
  • Lymphocytes / pathology*
  • Male
  • Middle Aged
  • Neutrophils / pathology*
  • Predictive Value of Tests
  • Prognosis
  • ROC Curve
  • Sensitivity and Specificity
  • T-Lymphocytes / pathology
  • Young Adult

Substances

  • C-Reactive Protein
  • DNA
  • Ferritins