In the latest science review titled “Cell-free DNA: a Promising Biomarker in Infectious Diseases,” BGI-Research highlights the potential of cell-free DNA (cfDNA) as a non-invasive biomarker for the diagnosis, treatment, and prognosis of infectious diseases from both pathogen and host perspectives, along with the challenges and possible solutions in clinical settings. This review was published in Trends in Microbiology.
BGI-Research’s science review “Cell-free DNA: a Promising Biomarker in Infectious Diseases” is published in Trends in Microbiology.
Infectious diseases have long plagued human medicine and imposed a heavy burden on global public health. This threat has intensified with COVID-19, which has caused nearly 780 million infections and over 7.05 million deaths by July 2024, according to the World Health Organization (WHO).
Traditional diagnostic methods for infectious diseases face multiple challenges - low sensitivity, invasiveness, and long turnaround times - which often fail to meet patients' urgent needs for timely diagnosis and treatment. Additionally, traditional methods, primarily relying on culture and microscopy, often fail to detect infections promptly and may miss pathogen traces in the body. Over 50% of individuals with bloodstream infections are unaware of the responsible pathogen(s).
These disadvantages call for innovative, convenient, accurate, minimally invasive, and painless diagnostic technology for infectious disease diagnosis. The clinical testing of cfDNA as a biomarker for infectious diseases has emerged as a solution.
CfDNA is a free DNA fragment present in human body fluids, which contains both the circulating DNA fragments of the patient and DNA fragments from the pathogen. By detecting the composition and changes in cfDNA, it is possible to assess whether a patient is infected with a certain pathogen, the degree of infection, and predict the disease's development. This allows for early intervention or continuous monitoring in a targeted manner, providing an accurate basis for clinical decision-making.
The Origin and Characteristics of Cell-Free DNA.
The review discusses various strategies based on PCR and sequencing technologies for current cfDNA testing methods. It indicates that PCR technology can accurately identify the cfDNA of specific pathogens, helping physicians make rapid diagnoses of known or highly suspected sources of infections. Meanwhile, the fast-developing sequencing technology has broadened the application of cfDNA in pathogen identification and infection dynamics monitoring, enabling the identification of a wide range of pathogens, including rare and even unknown ones. This method has proven effective in both targeted and untargeted detection.
Origin, Release, Detection Methods, Analysis of cfDNA, and Its Utility in Infectious Diseases.
For viral infections, cfDNA can efficiently diagnose RNA viral infections such as SARS-CoV-2, assess the disease's severity, and predict the prognosis. For DNA viruses such as EBV, Hepatitis B virus, and HPV, cfDNA can help identify high-risk groups developing related cancers in the early asymptomatic stage, opening new pathways for disease prevention and early intervention.
For bacterial infection testing, cfDNA has shown excellent potential in diagnosing tuberculosis, sepsis, and other diseases. For example, CRISPR-based cfDNA testing method demonstrated high sensitivity and specificity of more than 90% in diagnosing both adult and pediatric tuberculosis. Additionally, the cfDNA testing method achieved 92.9% sensitivity in patients with suspected sepsis, especially those treated with antimicrobial therapy, significantly outperforming traditional blood culture methods.
In addition, by analyzing molecular features such as methylation patterns, cfDNA technology can reflect the tissue origin of the lesion, providing new perspectives for precise diagnosis and personalized treatment.
The key to early identification of infectious diseases in the future lies in developing and applying cutting-edge technologies (e.g., CRISPR- or third-generation sequencing-based cfDNA testing technology). In the future, these advanced technologies are expected to further enhance pathogen detection capability and enable early detection and dynamic tracking of infectious diseases.
This review also discusses the technical challenges of cfDNA testing in practical applications and potential solutions to these challenges.
The review can be accessed here: https://doi.org/10.1016/j.tim.2024.06.005
Source
WHO COVID-19 dashboard
Han, D. et al. (2020) Liquid biopsy for infectious diseases: a focus on microbial cell-free DNA sequencing. Theranostics 10, 5501–5513 https://www.thno.org/v10p5501.htm