COVID-19 patients in ICUs: study reveals an increased risk of invasive fungal secondary infections

Teams at Rennes University Hospital – University of Rennes 1, Necker-Enfants Malades Hospital (part of the Paris Public Hospital Network or AP-HP), Georges-Pompidou European Hospital (AP-HP) – Université de Paris, Avicenne Hospital (AP-HP) – University Sorbonne Paris Nord and the Institut Pasteur conducted a prospective multicenter study to determine the impact of fungal infections in patients in ICUs with severe forms of COVID-19. The MYCOVID study coordinated by Professor Jean-Pierre Gangneux, Dr. Eric Dannaoui, Professor Jean-Ralph Zahar and Dr. Marie-Elisabeth Bougnoux revealed a particularly high risk of invasive fungal secondary infections affecting 22% of intubated and mechanically ventilated COVID-19 patients in ICUs. The results of this study initiated in April 2020 were published in The Lancet Respiratory Medicine scientific journal on November 26, 2021.

Determining the impact of fungal infections in patients with severe forms of COVID-19: an unprecedented field of investigation

It has been demonstrated that patients with severe influenza virus respiratory infections are at high risk of acute respiratory distress syndrome (ARDS) and susceptible to developing invasive aspergillosis, a secondary infection caused by microscopic fungi. SARS-CoV-2 infection can also cause severe ARDS requiring mechanical ventilation. COVID-19 patients are therefore at risk of developing invasive fungal infections (IFIs) such as invasive aspergillosis. The vast majority of published single-center cohort studies report variable prevalence of IFIs. Previously, no active surveillance studies have been conducted to assess the prevalence, risk factors and outcome of IFIs for a homogenous population of patients with COVID-19 in ICUs. This is precisely what the MYCOVID study set out to achieve.

"We're talking about microscopic fungi that are widely encountered in our everyday lives. Aspergillus, for instance, is a fungus that grows on jam and moldy fruit. However, in some cases of severe inflammation such as those caused by COVID-19, these fungal infections can exacerbate the situation." Professor Jean-Pierre Gangneux, head of the parasitology and mycology laboratory at Rennes University Hospital and study coordinator. He is a professor at the University of Rennes 1 conducting research at the Research Institute for Environmental and Occupational Health (Irset).

This study conducted on an exceptional scale revealed a high number of invasive fungal infections

With 18 centers and 576 patients enrolled in France, MYCOVID is the multicenter prospective study with the largest cohort of patients mechanically ventilated in ICUs and systematically screened for IFI's using various markers. Firstly, MYCOVID documents a surprisingly high number of proven or probable IFI episodes (N=114/509 analyzable patients, 22.4%) in these patients. Proven or probable invasive pulmonary aspergillosis and candidemia emerged as the two most common infections with overall prevalence of 14.9% and 6.2% respectively. In these COVID-19 patients, aspergillosis is linked to a higher risk of death with overall mortality of 61.8% versus 32.1% in patients with severe COVID-19 but no secondary fungal infection. Finally, dexamethasone combined with anti-IL-6R, two key drugs for treating severe forms of COVID-19, significantly increase the risk of patients developing invasive pulmonary aspergillosis.

"The high prevalence and mortality associated with invasive aspergillosis and candidemia revealed by the MYCOVID study highlight the urgent need to establish an index of suspicion and implement active surveillance of IFI's in patients with severe forms of COVID-19 in ICUs." Dr. Marie-Elisabeth Bougnoux, Necker-Enfants Malades Hospital (AP-HP) / Université de Paris / Fungal Biology and Pathogenicity Unit at the Institut Pasteur.

Further studies are required to determine whether early antifungal treatment or prophylaxis are necessary.

Source

Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study, The Lancet Respiratory Medicine, November 26, 2021

Gangneux JP*, Dannaoui E*, Fekkar A, Luyt CE, Botterel F, De Prost N, Tadié JM, Reizine F, Houzé S, Timsit JF, Iriart X, Riu-Poulenc B, Sendid B, Nseir S, Persat F, Wallet F, Le Pape P, Canet E, Novara A, Manai M, Cateau E, Thille AW, Brun S, Cohen Y, Alanio A, Mégarbane B, Cornet M, Terzi N, Lamhaut L, Sabourin E, Desoubeaux G, Ehrmann S, Hennequin C, Voiriot G, Nevez G, Aubron C, Letscher-Bru V, Meziani F, Blaize M, Mayaux J, Monsel A, Boquel F, Robert-Gangneux F, Le Tulzo Y, Seguin P, Guegan H, Autier B, Lesouhaitier M, Pelletier R, Belaz S, Bonnal C, Berry A, Leroy J, François N, Richard JC, Paulus S, Argaud L, Dupont D, Menotti J, Morio F, Soulié M, Schwebel C, Garnaud C, Guitard J, Le Gal S, Quinio D, Morcet J, Laviolle B, Zahar JR*, Bougnoux ME*.

*contributed equally

The Lancet Respiratory Medicine, 2021 Nov 26:S2213-2600(21)00442-2. doi: 10.1016/S2213-2600(21)00442-2. Epub ahead of print. PMID: 34843666 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00442-2/fulltext