Risk factors associated with COVID-19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohort

Sarah Dellière; Emmanuel Dudoignon; Sofiane Fodil; Sebastian Voicu; Magalie Collet; Pierre-Antoine Oillic; Maud Salmona; François Dépret; Théo Ghelfenstein-Ferreira; Benoit Plaud; Benjamin Chousterman; Stéphane Bretagne; Elie Azoulay; Alexandre Mebazaa; Bruno Megarbane; Alexandre Alanio

doi:10.1016/j.cmi.2020.12.005

Risk factors associated with COVID-19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohort

Clin Microbiol Infect. 2020 Dec 13;27(5):790.e1-790.e5. doi: 10.1016/j.cmi.2020.12.005. Online ahead of print.

Authors

Sarah Dellière¹, Emmanuel Dudoignon², Sofiane Fodil³, Sebastian Voicu⁴, Magalie Collet², Pierre-Antoine Oillic⁵, Maud Salmona⁶, François Dépret⁷, Théo Ghelfenstein-Ferreira⁸, Benoit Plaud², Benjamin Chousterman², Stéphane Bretagne¹, Elie Azoulay³, Alexandre Mebazaa⁷, Bruno Megarbane⁴, Alexandre Alanio⁹

Affiliations

¹ Université de Paris, Laboratoire de Parasitologie-Mycologie, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Molecular Mycology Unit, CNRS UMR2000, National Reference Centre for Invasive Mycoses and Antifungals (NRCMA), Institut Pasteur, Paris, France.
² Université de Paris, FHU Promice, Département d'anesthésie-réanimation, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
³ Université de Paris, Médecine Intensive Réanimation, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
⁴ Université de Paris, Réanimation Médicale et Toxicologique, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris (AP-HP), INSERM UMRS-1144, Paris, France.
⁵ Université Paris-Saclay, Department of Anaesthesiology, Critical Care Medecine, Hôpital Universitaire Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin-Bicêtre, France.
⁶ Université de Paris, INSERM U976, team INSIGHT, Laboratoire de Virologie, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
⁷ Université de Paris, FHU Promice, Département d'anesthésie-réanimation, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; INI-CRCT Network, Nancy, France; INSERM U942, Paris, France.
⁸ Université de Paris, Laboratoire de Parasitologie-Mycologie, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
⁹ Université de Paris, Laboratoire de Parasitologie-Mycologie, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Molecular Mycology Unit, CNRS UMR2000, National Reference Centre for Invasive Mycoses and Antifungals (NRCMA), Institut Pasteur, Paris, France. Electronic address: alexandre.alanio@pasteur.fr.

Abstract

Objectives: The main objective of this study was to determine the incidence of invasive pulmonary aspergillosis (IPA) in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), and to describe the patient characteristics associated with IPA occurrence and to evaluate its impact on prognosis.

Methods: We conducted a retrospective cohort study including all successive COVID-19 patients, hospitalized in four ICUs, with secondary deterioration and one or more respiratory samples sent to the mycology department. We used a strengthened IPA testing strategy including seven mycological criteria. Patients were classified as probable IPA according to the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) classification if immunocompromised, and according to the recent COVID-19-associated IPA classification otherwise.

Results: Probable IPA was diagnosed in 21 out of the 366 COVID-19 patients (5.7%) admitted to the ICU and in the 108 patients (19.4%) who underwent respiratory sampling for deterioration. No significant differences were observed between patients with and without IPA regarding age, gender, medical history and severity on admission and during hospitalization. Treatment with azithromycin for ≥3 days was associated with the diagnosis of probable IPA (odds ratio 3.1, 95% confidence interval 1.1-8.5, p = 0.02). A trend was observed with high-dose dexamethasone and the occurrence of IPA. Overall mortality was higher in the IPA patients (15/21, 71.4% versus 32/87, 36.8%, p < 0.01).

Conclusion: IPA is a relatively frequent complication in severe COVID-19 patients and is responsible for increased mortality. Azithromycin, known to have immunomodulatory properties, may contribute to increase COVID-19 patient's susceptibility to IPA.

Keywords: Aspergillus; Azithromycin; COVID-19; Coronavirus; Corticosteroids; Critical care; Risk factors; SARS-CoV-2.