Combination of mycological criteria: a better surrogate to identify COVID-19 associated pulmonary aspergillosis patients and evaluate prognosis?

Combination of mycological criteria: a better surrogate to identify COVID-19 associated pulmonary aspergillosis patients and evaluate prognosis?

Author:

Sarah DellièreEmmanuel DudoignonSébastian VoicuMagalie ColletSofiane FodilBenoit PlaudBenjamin ChoustermanStéphane BretagneElie AzoulayAlexandre MebazaaFrançois DépretBruno MégarbaneAlexandre Alanio

Date: 5 January 2022

Abstract:

Introduction: Diagnosis of COVID-19 associated pulmonary aspergillosis remains unclear especially in non-immunocompromised patients. The aim of this study was to evaluate seven mycological criteria and their combination in a large homogenous cohort of patients. Methods: All successive patients (n=176) hospitalized for COVID-19 requiring mechanical ventilation and who clinically worsened despite appropriate standard of care were included over a one-year period. Direct examination, culture, Aspergillus qPCR (Af-qPCR) and galactomannan was performed on all respiratory samples (n=350). Serum galactomannan, ß-D-glucan and plasma Af-qPCR were also assessed. Criteria were analyzed alone or in combination in relation to mortality rate. Results: Mortality was significantly different in patients with 0, ≤2 and ≥3 positive criteria (logrank test, p=0.04) with death rate of 43.1, 58.1 and 76.4% respectively. Direct examination, plasma qPCR and serum galactomannan were associated with a 100% mortality rate. Bronchoalveolar lavage (BAL) galactomannan and positive respiratory sample culture were often found as isolated markers (28.1 and 34.1%) and poorly repeatable when a second sample was obtained. Aspergillus DNA was detected in 13.1% of samples (46/350) with significantly lower Cq when associated with at least one other criteria (30.2 vs 35.8) (p<0.001). Conclusion: Combination of markers and/or blood biomarkers and/or direct respiratory sample examination seems more likely to identify patients with CAPA. Af-qPCR may help identifying false positive results of BAL galactomannan testing and culture on respiratory samples while quantifying fungal burden accurately.

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