Diagnostic performance and longitudinal analysis of fungal biomarkers in COVID-19 associated pulmonary aspergillosis

Berrin Er; Ahmet Gorkem Er; Dolunay Gulmez; Taha Koray Sahin; Gökhan Metan; Zeynep Saribas; Sevtap Arikan-Akdagli; Omrum Uzun

doi:10.1016/j.heliyon.2023.e21721

Diagnostic performance and longitudinal analysis of fungal biomarkers in COVID-19 associated pulmonary aspergillosis

Heliyon. 2023 Oct 26;9(11):e21721. doi: 10.1016/j.heliyon.2023.e21721. eCollection 2023 Nov.

Authors

Berrin Er¹, Ahmet Gorkem Er^{2

3}, Dolunay Gulmez⁴, Taha Koray Sahin⁵, Gökhan Metan², Zeynep Saribas⁴, Sevtap Arikan-Akdagli⁴, Omrum Uzun²

Affiliations

¹ Division of Intensive Care, Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey.
² Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
³ Department of Health Informatics, Middle East Technical University, Ankara, Turkey.
⁴ Department of Medical Microbiology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
⁵ Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Abstract

Objectives: Galactomannan lateral flow assay (GM-LFA) is a reliable test for COVID-19 associated pulmonary aspergillosis (CAPA) diagnosis. We aimed to assess the diagnostic performance of GM-LFA with different case definitions, the association between the longitudinal measurements of serum GM-ELISA, GM-LFA, and the risk of death.

Methods: Serum and nondirected bronchial lavage (NBL) samples were periodically collected. The sensitivity and specificity analysis for GM-LFA was done in different time periods. Longitudinal analysis was done with the joint model framework.

Results: A total of 207 patients were evaluated. On the day of CAPA diagnosis, serum GM-LFA had a sensitivity of 42 % (95 % CI: 23-63) and specificity of 82 % (95 % CI: 78-84), while NBL GM-LFA had a sensitivity of 73 % (95 % CI: 45-92), specificity of 85 % (95 % CI: 76-91) for CAPA. Sensitivity decreased through the following days in both samples. Univariate joint model analysis showed that increasing GM-LFA and GM-ELISA levels were associated with increased mortality, and that effect remained same with serum GM-ELISA in multivariate joint model analysis.

Conclusion: GM-LFA, particularly in NBL samples, seems to be a reliable method for CAPA diagnosis. For detecting patients with higher risk of mortality, longitudinal measurement of serum GM-ELISA can be useful.

Keywords: CAPA; Joint model; Lateral flow assay; Screening.