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Prospective observational study of cell-free DNA as a prognostic biomarker in COVID-19 and bacterial sepsis:
Katharina Hoeter1, Elmo W I Neuberger2, Vanessa Jochum3
1Department of Anesthesiology, University Medical Centre of the Johannes Gutenberg-University, Langenbeckstr. 1, 55131, Mainz, Germany. katharina.hoeter@unimedizin-mainz.de.
Abstract:
Hyperinflammation and extensive cell damage characterize both COVID-19-sepsis and bacterial sepsis, contributing to poor clinical outcomes. Cell-free DNA (cfDNA), a damage-associated molecular pattern (DAMP), reflects ongoing tissue injury and may predict mortality. We aimed to evaluate cfDNA as a prognostic biomarker for 30-day mortality in ICU patients with COVID-19- vs. bacterial sepsis, and its association with inflammatory markers and disease progression. In a prospective observational study (ethics approval: 2020-15,535; DRKS-ID: DRKS00025222), cfDNA was quantified in 64 ICU patients (COVID-19-sepsis n = 27, bacterial sepsis n = 37) at four time points using quantitative PCR targeting 90 bp and 222 bp fragments of LINE-1 elements. An Integrity Index (222/90 bp) was calculated to infer the predominant mode of cell death. Nineteen healthy individuals served as controls. Associations with mortality and clinical parameters were analyzed using adjusted Cox regression, time-dependent models, and correlation analyses. Higher cfDNA levels (90 bp) within the first 24 h were strongly associated with 30-day (p = 0.003) and 180-day mortality (p = 0.003) in COVID-19-sepsis, but not in bacterial sepsis. COVID-19 patients showed significantly higher cfDNA levels (p < 0.01), which correlated with CRP, PCT, LDH, and lactate. The Integrity Index increased over time in bacterial sepsis and remained stable in COVID-19-sepsis, but was not predictive of survival. Elevated cfDNA levels were associated with ECMO therapy but not with renal replacement therapy. cfDNA is a valuable early prognostic biomarker in COVID-19-sepsis. Its rapid dynamics and strong correlation with clinical outcomes highlight its potential for real-time monitoring and risk stratification in viral sepsis.
Insights
Cell-free DNA (cfDNA) is a strong early predictor of mortality in intensive care unit (ICU) patients with COVID-19-sepsis. Elevated cfDNA levels in COVID-19-sepsis correlate with inflammatory markers and disease severity, aiding risk stratification.
Area of Science:
- Critical Care Medicine
- Molecular Biology
- Immunology
Background:
- Sepsis, including COVID-19-sepsis and bacterial sepsis, involves hyperinflammation and cell damage, leading to poor outcomes.
- Cell-free DNA (cfDNA), a damage-associated molecular pattern (DAMP), indicates tissue injury and may predict mortality.
- Prognostic biomarkers are crucial for managing sepsis patients in the intensive care unit (ICU).
Purpose of the Study:
- To evaluate cell-free DNA (cfDNA) as a prognostic biomarker for 30-day mortality in ICU patients with COVID-19-sepsis versus bacterial sepsis.
- To assess the association of cfDNA with inflammatory markers and disease progression in different sepsis types.
- To explore cfDNA's utility in differentiating sepsis etiologies and predicting clinical outcomes.
Main Methods:
- Prospective observational study involving 64 ICU patients (27 COVID-19-sepsis, 37 bacterial sepsis) and 19 healthy controls.
- Quantitative PCR was used to measure cfDNA levels (90 bp and 222 bp LINE-1 fragments) at four time points.
- An Integrity Index (222 bp/90 bp) was calculated to infer cell death modes; statistical analyses included Cox regression and correlation.
Main Results:
- Higher cfDNA levels (90 bp) within 24 hours strongly predicted 30-day and 180-day mortality in COVID-19-sepsis (p=0.003), but not bacterial sepsis.
- COVID-19-sepsis patients exhibited significantly higher cfDNA levels (p<0.01), correlating with CRP, PCT, LDH, and lactate.
- The cfDNA Integrity Index varied between sepsis types but did not predict survival; elevated cfDNA correlated with ECMO therapy.
Conclusions:
- Cell-free DNA (cfDNA) serves as a valuable early prognostic biomarker specifically in COVID-19-sepsis.
- The dynamic changes and strong clinical outcome correlations of cfDNA suggest potential for real-time monitoring and risk stratification in viral sepsis.
- cfDNA's distinct patterns in COVID-19-sepsis compared to bacterial sepsis highlight its differential prognostic value.
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