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Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study

Jean-Pierre Gangneux 1 Eric Dannaoui 2 Arnaud Fekkar 3 Charles-Edouard Luyt 3 Françoise Botterel 4 Nicolas de Prost 4 Jean-Marc Tadié 1 Florian Reizine 1 Sandrine Houzé 5 Jean-François Timsit 5 Xavier Iriart 6 Béatrice Riu-Poulenc 6 Boualem Sendid 7 Saad Nseir 7 Florence Persat 8 Florent Wallet 8 Patrice Le Pape 9 Emmanuel Canet 9 Ana Novara 2 Melek Manai 2 Estelle Cateau 10 Arnaud W Thille 10 Sophie Brun 11 yves Cohen 11 Alexandre Alanio 12 Bruno Megarbane 12 Muriel Cornet 13 Nicolas Terzi 13 Lionel Lamhaut 14 Estelle Sabourin 14 Guillaume Desoubeaux 15, 16 Stephan Ehrmann 15 C. Hennequin 17 Guillaume Voiriot 17 Gilles Nevez 18 Cécile Aubron 18 Valérie Letscher-Bru 19 Ferhat Meziani 19 Marion Blaize 3 Julien Mayaux 3 Antoine Monsel 3 Frédérique Boquel 4 Florence Robert-Gangneux 1 yves Le Tulzo 1 Philippe Seguin 1 Hélène Guegan 1 Brice Autier 1 Matthieu Lesouhaitier 1 Romain Pelletier 1 Sorya Belaz 1 Christine Bonnal 5 Antoine Berry 6 Jordan Leroy 7 Nadine François 7 Jean-Christophe Richard 8 Sylvie Paulus 8 Laurent Argaud 8 Damien Dupont 8 Jean Menotti 8 Florian Morio 9 Marie Soulié 11 Carole Schwebel 13 Cécile Garnaud 13 Juliette Guitard 17 Solène Le Gal 19 Dorothée Quinio 19 Jeff Morcet 1 Bruno Laviolle 1 Jean-Ralph Zahar 11 Marie-Elizabeth Bougnoux 14 
Abstract : BACKGROUND: Patients with severe COVID-19 have emerged as a population at high risk of invasive fungal infections (IFIs). However, to our knowledge, the prevalence of IFIs has not yet been assessed in large populations of mechanically ventilated patients. We aimed to identify the prevalence, risk factors, and mortality associated with IFIs in mechanically ventilated patients with COVID-19 under intensive care. METHODS: We performed a national, multicentre, observational cohort study in 18 French intensive care units (ICUs). We retrospectively and prospectively enrolled adult patients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and requiring mechanical ventilation for acute respiratory distress syndrome, with all demographic and clinical and biological follow-up data anonymised and collected from electronic case report forms. Patients were systematically screened for respiratory fungal microorganisms once or twice a week during the period of mechanical ventilation up to ICU discharge. The primary outcome was the prevalence of IFIs in all eligible participants with a minimum of three microbiological samples screened during ICU admission, with proven or probable (pr/pb) COVID-19-associated pulmonary aspergillosis (CAPA) classified according to the recent ECMM/ISHAM definitions. Secondary outcomes were risk factors of pr/pb CAPA, ICU mortality between the pr/pb CAPA and non-pr/pb CAPA groups, and associations of pr/pb CAPA and related variables with ICU mortality, identified by regression models. The MYCOVID study is registered with ClinicalTrials.gov, NCT04368221. FINDINGS: Between Feb 29 and July 9, 2020, we enrolled 565 mechanically ventilated patients with COVID-19. 509 patients with at least three screening samples were analysed (mean age 59·4 years [SD 12·5], 400 [79%] men). 128 (25%) patients had 138 episodes of pr/pb or possible IFIs. 76 (15%) patients fulfilled the criteria for pr/pb CAPA. According to multivariate analysis, age older than 62 years (odds ratio [OR] 2·34 [95% CI 1·39-3·92], p=0·0013), treatment with dexamethasone and anti-IL-6 (OR 2·71 [1·12-6·56], p=0·027), and long duration of mechanical ventilation (\textgreater14 days; OR 2·16 [1·14-4·09], p=0·019) were independently associated with pr/pb CAPA. 38 (7%) patients had one or more other pr/pb IFIs: 32 (6%) had candidaemia, six (1%) had invasive mucormycosis, and one (\textless1%) had invasive fusariosis. Multivariate analysis of associations with death, adjusted for candidaemia, for the 509 patients identified three significant factors: age older than 62 years (hazard ratio [HR] 1·71 [95% CI 1·26-2·32], p=0·0005), solid organ transplantation (HR 2·46 [1·53-3·95], p=0·0002), and pr/pb CAPA (HR 1·45 [95% CI 1·03-2·03], p=0·033). At time of ICU discharge, survival curves showed that overall ICU mortality was significantly higher in patients with pr/pb CAPA than in those without, at 61·8% (95% CI 50·0-72·8) versus 32·1% (27·7-36·7; p\textless0·0001). INTERPRETATION: This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19. FUNDING: Pfizer.
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Submitted on : Friday, June 3, 2022 - 11:41:55 AM
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Jean-Pierre Gangneux, Eric Dannaoui, Arnaud Fekkar, Charles-Edouard Luyt, Françoise Botterel, et al.. Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study. Lancet Respiratory medicine, Elsevier, 2022, 10 (2), pp.180-190. ⟨10.1016/s2213-2600(21)00442-2⟩. ⟨inserm-03587204⟩

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