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Observational Study
. 2022 Feb;10(2):180-190.
doi: 10.1016/S2213-2600(21)00442-2. Epub 2021 Nov 26.

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  5 , Florian Reizine  5 , Sandrine Houzé  6 , Jean-François Timsit  6 , Xavier Iriart  7 , Béatrice Riu-Poulenc  7 , Boualem Sendid  8 , Saad Nseir  8 , Florence Persat  9 , Florent Wallet  9 , Patrice Le Pape  10 , Emmanuel Canet  10 , Ana Novara  2 , Melek Manai  2 , Estelle Cateau  11 , Arnaud W Thille  11 , Sophie Brun  12 , Yves Cohen  12 , Alexandre Alanio  13 , Bruno Mégarbane  13 , Muriel Cornet  14 , Nicolas Terzi  14 , Lionel Lamhaut  15 , Estelle Sabourin  15 , Guillaume Desoubeaux  16 , Stephan Ehrmann  16 , Christophe 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  5 , Yves Le Tulzo  5 , Philippe Seguin  5 , Hélène Guegan  5 , Brice Autier  5 , Matthieu Lesouhaitier  5 , Romain Pelletier  5 , Sorya Belaz  5 , Christine Bonnal  6 , Antoine Berry  7 , Jordan Leroy  8 , Nadine François  8 , Jean-Christophe Richard  9 , Sylvie Paulus  9 , Laurent Argaud  9 , Damien Dupont  9 , Jean Menotti  9 , Florent Morio  10 , Marie Soulié  12 , Carole Schwebel  14 , Cécile Garnaud  14 , Juliette Guitard  17 , Solène Le Gal  18 , Dorothée Quinio  18 , Jeff Morcet  5 , Bruno Laviolle  5 , Jean-Ralph Zahar  12 , Marie-Elisabeth Bougnoux  20
Affiliations
Observational Study

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

Jean-Pierre Gangneux et al. Lancet Respir Med. 2022 Feb.

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 (>14 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 (<1%) 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<0·0001).

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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Conflict of interest statement

Declaration of interests J-PG reports personal fees from Gilead and grants and personal fees from Pfizer, outside of the submitted work. ED reports grants and non-financial support from Merck Sharp & Dohme and Gilead and non-financial support from Pfizer and Astellas, outside of the submitted work. AF reports personal fees and non-financial support from Merck Sharp & Dohme, grants from Janssen, personal fees and non-financial support from Gilead, and non-financial support from Pfizer, outside of the submitted work. C-EL reports personal fees from Carmat, Merck, BioMérieux, Brahms (part of Thermo Fisher Scientific), Bayer Healthcare, and Faron, outside of the submitted work. FraB reports grants from Astellas, personal fees from Merck Sharp & Dohme, and non-financial support from Pfizer, Merck Sharp & Dohme, and Astellas, outside of the submitted work. J-FT reports personal fees from Pfizer, Merck, Astellas, and Gilead, outside of the submitted work. FP reports non-financial support from Gilead and Pfizer, outside of the submitted work. EmC reports personal fees from Gilead, Baxter, and Sanofi-Genzyme, outside of the submitted work. AA reports personal fees from Pfizer and Gilead, outside of the submitted work. MC reports grants from Pfizer, outside of the submitted work. JuM reports non-financial support from Gilead, outside of the submitted work. SE reports grants, personal fees, and non-financial support from Aerogen and Fisher & Paykel, outside of the submitted work. GV reports grants and personal fees from BioMérieux and grants from SOS Oxygène and Janssen, outside of the submitted work. JeM reports grants from Pfizer and Gilead, outside of the submitted work. J-RZ reports grants and personal fees from Merck Sharp & Dohme and personal fees from Novartis and Pfizer, outside of the submitted work. M-EB reports grants from Pfizer during the conduct of the study; grants and non-financial support from Gilead and Pfizer, and non-financial support from Merck Sharp & Dohme, outside of the submitted work. All other authors declare no competing interests.

Figures

Figure 1
Figure 1
Multivariate analysis of factors associated with pr/pb CAPA All significant variables in univariate analysis were included in the multivariate model, but only significant variables in the multivariate analysis are shown in the figure. CAPA=COVID-19-associated pulmonary aspergillosis.pr/pb=proven or probable.
Figure 2
Figure 2
Probability of survival according to pr/pb CAPA status Shading shows 95% CIs. No patients were censored. Data were missing for one patient in the non-pr/pb CAPA group. pr/pb=proven or probable. CAPA=COVID-19-associated pulmonary aspergillosis.
Figure 3
Figure 3
Multivariate analysis of factors associated with death All significant variables in univariate analysis were included in the multivariate model; only significant variables in the multivariate analysis and variables of interest (candidaemia) are shown in the figure.
See this image and copyright information in PMC

Comment in

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