# Non-invasive diagnosis of invasive fungal disease with cell-free DNA PCR

## TL;DR

This paper reviews how using cell-free DNA PCR can help diagnose invasive fungal diseases without invasive procedures, improving early detection and patient outcomes.

## Contribution

The paper introduces a novel non-invasive diagnostic approach using fungal cell-free DNA PCR for rapid and accurate detection of invasive fungal diseases.

## Key findings

- Fungal cell-free DNA PCR shows promise for diagnosing invasive aspergillosis, mucormycosis, and Pneumocystis pneumonia.
- A testing algorithm is proposed that combines non-invasive cfDNA PCR with invasive specimen collection when needed.
- Diagnostic stewardship is emphasized to optimize the use of fungal cfDNA PCR testing.

## Abstract

Invasive fungal disease (IFD) is a major cause of morbidity and mortality in the immunocompromised population. Early diagnosis is challenging due to the low sensitivity and non-specificity of non-invasive fungal biomarkers, the need for invasive specimen collection, and the limitations of culture and histopathology. Detection of circulating fungal cell-free DNA (cfDNA) in plasma and serum by polymerase chain reaction (PCR) represents a novel testing modality for rapid and accurate diagnosis of IFD. In this review, we summarize the performance characteristics of fungal cfDNA PCR for the diagnosis of invasive aspergillosis, mucormycosis, and Pneumocystis pneumonia. We discuss a testing algorithm that incorporates fungal cfDNA and the added diagnostic value of invasive specimen collection when non-invasive mold cfDNA PCR is performed first. Lastly, we discuss the role of diagnostic stewardship in fungal cfDNA PCR testing.