Influenza- and COVID-19-Associated Pulmonary Aspergillosis: Are the Pictures Different?

Florian Reizine ,Kieran Pinceaux ,Yoann Launey ,Sorya Belaz ,Mathieu Léderlin ,Brendan Le Daré ,Christelle Boglione-Kerrien ,Yves Le Tulzo ,Benoît Painvin ,Hélène Guegan ,Mathieu Lesouhaitier ,Adel Maamar ,David Luque-Paz ,Astrid Bacle ,Christophe Camus ,Brice Autier ,Arnaud Gacouin ,Florence Robert‐Gangneux ,Jean‐Marc Tadié ,Alexandre Mansour ,Jean‐Pierre Gangneux

doi:10.3390/jof7050388

Abstract

Invasive pulmonary aspergillosis (IPA) in intensive care unit patients is a major concern. Influenza-associated acute respiratory distress syndrome (ARDS) and severe COVID-19 patients are both at risk of developing invasive fungal diseases. We used the new international definitions of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) to compare the demographic, clinical, biological, and radiological aspects of IAPA and CAPA in a monocentric retrospective study. A total of 120 patients were included, 71 with influenza and 49 with COVID-19-associated ARDS. Among them, 27 fulfilled the newly published criteria of IPA: 17/71 IAPA (23.9%) and 10/49 CAPA (20.4%). Kaplan–Meier curves showed significantly higher 90-day mortality for IPA patients overall (p = 0.032), whereas mortality did not differ between CAPA and IAPA patients. Radiological findings showed differences between IAPA and CAPA, with a higher proportion of features suggestive of IPA during IAPA. Lastly, a wide proportion of IPA patients had low plasma voriconazole concentrations with a higher delay to reach concentrations > 2 mg/L in CAPA vs. IAPA patients (p = 0.045). Severe COVID-19 and influenza patients appeared very similar in terms of prevalence of IPA and outcome. The dramatic consequences on the patients’ prognosis emphasize the need for a better awareness in these particular populations.

Highlights

Invasive pulmonary aspergillosis (IPA) has been mainly described in patients with severe neutrophil dysfunction, especially those with prolonged neutropenia [1]
Therapeutic drug monitoring of voriconazole more challenging for COVID-19-associated pulmonary aspergillosis (CAPA) patients Lower proportion of patients presenting radiological features suggestive of IPA among CAPA patients. In this single-center study, 22.5% of patients admitted to the intensive care unit (ICU) for a severe viral infection, such as COVID-19 (20.4%) or Influenza pneumonia (23.9%), developed IPA
A similar prevalence of IPA in ICU patients was observed in the two major representative series of severe influenza (19.2% in a Dutch-Belgian multicenter study on 432 patients, [8]) and COVID-19 patients (19.6% probable and possible CAPA in a French multicenter prospective study with 509 patients included [16])

Summary

Introduction

Invasive pulmonary aspergillosis (IPA) has been mainly described in patients with severe neutrophil dysfunction, especially those with prolonged neutropenia [1]. The diversity of the patient backgrounds is reflected by their clinical and biological presentation and the criteria that should be used for case definition. Generic consensus definitions, such as those of the European Organization for Research and Treatment of Cancer/Mycosis Study Group Education and Research Consortium (EORTC/MSGERC) or the AspICU [1,3,5], are sometimes not adapted to specific groups of patients [6]. Higher mortality than for patients without IPA among both CAPA and IAPA patients. Therapeutic drug monitoring of voriconazole more challenging for CAPA patients Lower proportion of patients presenting radiological features suggestive of IPA among CAPA patients

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