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Published on: March 22, 2012
A Laboratory-Based Study on Multiple Biomarker Testing in the Diagnosis of COVID-19-Associated Pulmonary
Cornelia Lass-Flörl1, Miriam Knoll1, Wilfried Posch1
1Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, A-6020 Innsbruck, Austria.
Insights
Diagnosing COVID-19-associated pulmonary aspergillosis (CAPA) is challenging. Direct microscopy is recommended alongside biomarkers like galactomannan enzyme immunoassay (GM-EIA) and Aspergillus PCR to avoid overestimating fungal infections.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Pulmonology
Background:
- COVID-19-associated pulmonary aspergillosis (CAPA) is linked to increased mortality.
- Accurate diagnosis of CAPA is difficult, leading to variable incidence rates.
- Reliable diagnostic methods are crucial for effective CAPA management.
Purpose of the Study:
- To evaluate the diagnostic performance of galactomannan enzyme immunoassay (GM-EIA) and Aspergillus PCR.
- To compare these biomarkers against direct fungal microscopy for CAPA diagnosis.
- To assess the utility of combined biomarker testing in respiratory samples from COVID-19 patients.
Main Methods:
- Analysis of 241 respiratory tract specimens from SARS-CoV-2 pneumonia patients.
- Comparison of direct fungal microscopy (gold standard) with GM-EIA and Aspergillus PCR.
- Evaluation of Aspergillus culture-positive and culture-negative samples.
Main Results:
- Aspergillus PCR and GM-EIA showed a sensitivity of 0.90 and specificity of 0.77.
- Negative predictive value (NPV) was 0.95, and positive predictive value (PPV) was 0.58.
- Intermittent positive/negative results were frequent with non-bronchoalveolar lavage (BAL) samples, indicating biomarker limitations.
Conclusions:
- Combined biomarker testing presents challenges in diagnosing CAPA.
- Direct microscopy is essential in respiratory specimens to prevent overestimation of fungal infections.
- A wide range of Aspergillus species were identified in the evaluated samples.
Abstract:
(1) Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) raises concerns to contribute to an increased mortality. The incidence of CAPA varies widely within hospitals and countries, partly because of difficulties in obtaining a reliable diagnosis. (2) Methods: Here, we assessed Aspergillus culture-positive and culture-negative respiratory tract specimens via direct fungal microscopy (gold standard) and compared the results with galactomannan enzyme immunoassay (GM-EIA) and Aspergillus PCR. (3) Results: 241 respiratory samples from patients suffering from SARS-CoV-2 pneumonia were evaluated. Results showed both diagnostic tools, Aspergillus PCR and GM-EIA, to be positive or negative displaying a sensitivity of 0.90, a specificity of 0.77, a negative predictive value (NPV) of 0.95, and a positive predictive value (PPV) of 0.58 in Aspergillus sp. culture and microscopic-positive specimens. Non-bronchoalveolar lavage (BAL) samples, obtained within a few days from the same patient, showed a high frequency of intermittent positive or negative GM-EIA or Aspergillus PCR results. Positivity of a single biomarker is insufficient for a proper diagnosis. A broad spectrum of Aspergillus species was detected. (4) Conclusions: Our study highlights the challenges of combined biomarker testing as part of diagnosing CAPA. From the results presented, we highly recommend the additional performance of direct microscopy in respiratory specimens to avoid overestimation of fungal infections by applying biomarkers.

