COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants
Authors: Bay Pierre , Audureau Etienne , Préau Sébastien , Favory Raphaël , Guigon Aurélie , Heming Nicholas , Gault Elyanne , Pham Tài , Chaghouri Amal , Turpin Matthieu , Morand-Joubert Laurence , Jochmans Sébastien , Pitsch Aurélia , Meireles Sylvie , Contou Damien , Henry Amandine , Joseph Adrien , Chaix Marie-Laure , Uhel Fabrice , Roux Damien , Descamps Diane , Emery Malo , Garcia-Sanchez Claudio , Levy David , Burrel Sonia , Mayaux Julien , Kimmoun Antoine , Hartard Cédric , Pène Frédéric , Rozenberg Flore , Gaudry Stéphane , Brichler Ségolène , Guillon Antoine , Handala Lynda , Tamion Fabienne , Moisan Alice , Daix Thomas , Hantz Sébastien , Delamaire Flora , Thibault Vincent , Souweine Bertrand , Henquell Cecile , Picard Lucile , Botterel Françoise , Rodriguez Christophe , Dessap Armand Mekontso , Pawlotsky Jean-Michel , Fourati Slim , de Prost Nicolas ,   the SEVARVIR investigators, Razazi Keyvan , Bellaïche Raphaël , Azoulay Elie , Timsit Jean-François , Voiriot Guillaume , de Montmollin Nina , Marot Stéphane , Gasperment Maxime , Urbina Tomas , Oufella Hafid Ait , Fofana Eric Maury Djeneba Bocar , Luyt Charles-Edouard , Annane Djillali , Meziani Ferhat , Jandeaux Louis-Marie , Fafi-Kremer Samira , Darreau Cédric , Thomin Jean , Dartevel Anaïs , Larrat Sylvie , Schvoerer Evelyne , La Combe Béatrice , Haouisee Séverine , Hraeich Sami , Fournier Pierre-Edouard , Colson Philippe , Canet Emmanuel , Imbert Berthe Marie , Thiery Guillaume , Pillet Sylvie , Coudroy Rémy , Leveque Nicolas , Saccheri Clément , Giordanengo Valérie , Klouche Kada , Tuaillon Edouard , Aubron Cécile , Tran Adissa , Tadié Jean-Marc , Plantier Jean-Christophe , Vallet Sophie 
Published: April 2024

Abstract
Background
During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11–28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants.

Methods
This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria.

Results
566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4–7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay.

Conclusion
This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.