A Laboratory-Based Study on Multiple Biomarker Testing in the Diagnosis of COVID-19-Associated Pulmonary Aspergillosis (CAPA): Real-Life Data

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2023 Jan 8

PMID 36611406

Authors

Cornelia Lass-Florl

Miriam Knoll

Wilfried Posch

Michael Joannidis

Timo Mayerhofer

Robert Breitkopf

Romuald Bellmann

Affiliations

Soon will be listed here.

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 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 PCR. (3) Results: 241 respiratory samples from patients suffering from SARS-CoV-2 pneumonia were evaluated. Results showed both diagnostic tools, 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 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 PCR results. Positivity of a single biomarker is insufficient for a proper diagnosis. A broad spectrum of 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.

Citing Articles

Microbiological Non-Culture-Based Methods for Diagnosing Invasive Pulmonary Aspergillosis in ICU Patients.

Scharmann U, Verhasselt H, Kirchhoff L, Furnica D, Steinmann J, Rath P Diagnostics (Basel). 2023; 13(16).

PMID: 37627977 PMC: 10453445. DOI: 10.3390/diagnostics13162718.

References

Kariyawasam R, Dingle T, Kula B, Vandermeer B, Sligl W, Schwartz I . Defining COVID-19-associated pulmonary aspergillosis: systematic review and meta-analysis. Clin Microbiol Infect. 2022; 28(7):920-927. PMC: 8828380. DOI: 10.1016/j.cmi.2022.01.027. View

Prattes J, Wauters J, Giacobbe D, Salmanton-Garcia J, Maertens J, Bourgeois M . Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients-a multinational observational study by the European Confederation of Medical Mycology. Clin Microbiol Infect. 2021; 28(4):580-587. PMC: 8387556. DOI: 10.1016/j.cmi.2021.08.014. View

Tavakoli M, Shokohi T, Lass Florl C, Hedayati M, Hoenigl M . Immunological response to COVID-19 and its role as a predisposing factor in invasive aspergillosis. Curr Med Mycol. 2021; 6(4):75-79. PMC: 8226042. DOI: 10.18502/cmm.6.4.5442. View

Donnelly J, Chen S, Kauffman C, Steinbach W, Baddley J, Verweij P . Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis. 2019; 71(6):1367-1376. PMC: 7486838. DOI: 10.1093/cid/ciz1008. View

Lackner N, Thome C, Ofner D, Joannidis M, Mayerhofer T, Arora R . COVID-19 Associated Pulmonary Aspergillosis: Diagnostic Performance, Fungal Epidemiology and Antifungal Susceptibility. J Fungi (Basel). 2022; 8(2). PMC: 8875712. DOI: 10.3390/jof8020093. View

Lass-Florl C . How to make a fast diagnosis in invasive aspergillosis. Med Mycol. 2019; 57(Supplement_2):S155-S160. DOI: 10.1093/mmy/myy103. View

Lass-Florl C, Samardzic E, Knoll M . Serology anno 2021-fungal infections: from invasive to chronic. Clin Microbiol Infect. 2021; 27(9):1230-1241. DOI: 10.1016/j.cmi.2021.02.005. View

Borman A, Palmer M, Fraser M, Patterson Z, Mann C, Oliver D . COVID-19-Associated Invasive Aspergillosis: Data from the UK National Mycology Reference Laboratory. J Clin Microbiol. 2020; 59(1). PMC: 7771443. DOI: 10.1128/JCM.02136-20. View

Arastehfar A, Carvalho A, Houbraken J, Lombardi L, Garcia-Rubio R, Jenks J . and aspergillosis: From basics to clinics. Stud Mycol. 2021; 100:100115. PMC: 8131930. DOI: 10.1016/j.simyco.2021.100115. View

10.

Verweij P, Bruggemann R, Azoulay E, Bassetti M, Blot S, Buil J . Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis. Intensive Care Med. 2021; 47(8):819-834. PMC: 8220883. DOI: 10.1007/s00134-021-06449-4. View

11.

Blot S, Taccone F, Van den Abeele A, Bulpa P, Meersseman W, Brusselaers N . A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med. 2012; 186(1):56-64. DOI: 10.1164/rccm.201111-1978OC. View

12.

Rouze A, Lemaitre E, Martin-Loeches I, Povoa P, Diaz E, Nyga R . Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: a European multicenter comparative cohort study. Crit Care. 2022; 26(1):11. PMC: 8724752. DOI: 10.1186/s13054-021-03874-1. View

13.

Koehler P, Bassetti M, Chakrabarti A, Chen S, Colombo A, Hoenigl M . Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis. 2020; 21(6):e149-e162. PMC: 7833078. DOI: 10.1016/S1473-3099(20)30847-1. View

14.

Ullmann A, Aguado J, Arikan-Akdagli S, Denning D, Groll A, Lagrou K . Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018; 24 Suppl 1:e1-e38. DOI: 10.1016/j.cmi.2018.01.002. View

15.

Delliere S, Dudoignon E, Voicu S, Collet M, Fodil S, Plaud B . Combination of Mycological Criteria: a Better Surrogate to Identify COVID-19-Associated Pulmonary Aspergillosis Patients and Evaluate Prognosis?. J Clin Microbiol. 2022; 60(3):e0216921. PMC: 8925884. DOI: 10.1128/JCM.02169-21. View

16.

Lai C, Yu W . COVID-19 associated with pulmonary aspergillosis: A literature review. J Microbiol Immunol Infect. 2020; 54(1):46-53. PMC: 7513876. DOI: 10.1016/j.jmii.2020.09.004. View

17.

Bassetti M, Giacobbe D, Grecchi C, Rebuffi C, Zuccaro V, Scudeller L . Performance of existing definitions and tests for the diagnosis of invasive aspergillosis in critically ill, adult patients: A systematic review with qualitative evidence synthesis. J Infect. 2020; 81(1):131-146. DOI: 10.1016/j.jinf.2020.03.065. View

18.

Vandewoude K, Blot S, Depuydt P, Benoit D, Temmerman W, Colardyn F . Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients. Crit Care. 2006; 10(1):R31. PMC: 1550813. DOI: 10.1186/cc4823. View

19.

Paulussen C, Hallsworth J, Alvarez-Perez S, Nierman W, Hamill P, Blain D . Ecology of aspergillosis: insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species. Microb Biotechnol. 2016; 10(2):296-322. PMC: 5328810. DOI: 10.1111/1751-7915.12367. View

20.

Lass-Florl C, Mutschlechner W, Aigner M, Grif K, Marth C, Girschikofsky M . Utility of PCR in diagnosis of invasive fungal infections: real-life data from a multicenter study. J Clin Microbiol. 2012; 51(3):863-8. PMC: 3592065. DOI: 10.1128/JCM.02965-12. View