ArticleBMC infectious diseases2026
Cell-free nucleic acids as a non-invasive biomarker for predicting COVID-19 disease severity and outcome: a retrospective cohort study.
Article in BMC infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe COVID-19 pandemic highlighted the need for novel biomarkers to identify patients at risk of developing severe disease. Circulating cell-free nucleic acids (cfNAs) are released from injured host cells or can be derived from pathogens. As cfNA is suggested to be a useful biomarker in oncologic, autoimmune, and other diseases, the aim of our study was to investigate the role of serum cfNA in predicting the course and outcome of COVID-19 disease.
methodsWe conducted a retrospective cohort study at Vilnius University Hospital Santaros Klinikos, utilizing serum samples collected upon admission and accompanying health information obtained from the Vilnius Santaros Klinikos Biobank. A total of 108 adult COVID-19 patients hospitalized between November 24, 2020, and November 10, 2021, and 24 healthy controls were enrolled. cfDNA concentration was measured using capillary electrophoresis. cfRNA was detected using quantitative real-time PCR.
resultscfDNA concentration was higher in COVID-19 patients compared with controls (4.28 vs. 0.51 ng/µL, p < 0.001) and increased with disease severity: from 1.06 ng/µL in mild to 2.65 ng/µL in severe, and 6.68 ng/µL in critical disease. cfDNA levels were higher in intensive care unit (ICU) patients (6.68 vs. 2.30 ng/µL, p < 0.001), patients requiring advanced respiratory support (ARS) (7.11 vs. 2.74 ng/µL, p < 0.001), and non-survivors (16.68 vs. 3.44 ng/µL, p < 0.001). cfDNA showed high predictive values for ICU admission (AUC 0.79), ARS (AUC 0.77), and lethal outcome (AUC 0.81), outperforming other routine biomarkers. In logistic regression analysis, cfDNA remained an independent predictor for ICU admission (OR 1.21, 95%CI 1.08-1.36), ARS requirement (OR 1.15, 95%CI 1.03-1.28), and in-hospital mortality (OR 1.08, 95%CI 1.02-1.14), while serum SARS-CoV-2 RNAemia remained an independent predictor of ARS requirement (OR 4.18, 95%CI 1.15-15.20).
conclusionsHigher serum cfDNA concentrations were independently associated with greater COVID-19 disease severity, increased likelihood of requiring intensive care, ARS, and in-hospital mortality. cfDNA demonstrated superior prognostic performance, surpassing established biomarkers. Serum SARS-CoV-2 RNAemia was associated with the need for ARS. This indicates that cfNAs may serve as clinically valuable biomarkers for early risk stratification and outcome prediction in COVID-19 patients. Further validation in independent cohorts is required to confirm generalizability. CLINICAL TRIAL NUMBER: Not applicable.
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