Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: a European multicenter comparative cohort study

Anahita Rouzé (1, 2) , Elise Lemaitre (2) , Ignacio Martin-Loeches , Pedro Povoa , Emili Diaz , Rémy Nyga (3) , Antoni Torres , Matthieu Metzelard , Damien Du Cheyron , Fabien Lambiotte (4) , Fabienne Tamion (5) , Marie Labruyere (6) , Claire Boulle Geronimi (7) , Charles-Edouard Luyt (8) , Martine Nyunga (9) , Olivier Pouly (10) , Arnaud W Thille (11) , Bruno Megarbane (12, 13) , Anastasia Saade (14) , Eleni Magira , Jean-François Llitjos (15) , Iliana Ioannidou , Alexandre Pierre (16) , Jean Reignier (17) , Denis Garot (18) , Louis Kreitmann (19) , Jean-Luc Baudel (20) , Guillaume Voiriot (21) , Gaëtan Plantefeve (22) , Elise Morawiec (23, 24) , Pierre Asfar (25) , Alexandre Boyer (26) , Armand Mekontso-Dessap (27, 28) , Demosthenes Makris , Christophe Vinsonneau (29) , Pierre-Edouard Floch (30) , Clémence Marois (23, 31) , Adrian Ceccato , Antonio Artigas , Alexandre Gaudet (32) , David Nora , Marjorie Cornu (1, 2) , Alain Duhamel (2) , Julien Labreuche (2) , Saad Nseir (2, 1) , Julien Maizel (33, 34)

1 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
2 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
3 CHU Amiens-Picardie
4 Centre hospitalier [Valenciennes, Nord]
5 EnVI - Endothélium, valvulopathies et insuffisance cardiaque
6 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
7 Centre Hospitalier [Douai, Nord]
8 Institut de cardiologie [CHU Pitié-Salpêtrière]
9 Centre Hospitalier de Roubaix
10 UCL - Université catholique de Lille
11 CIC 1402 - CIC Poitiers – Centre d'investigation clinique de Poitiers
12 OPTeN (UMR_S 1144 / U1144) - Optimisation thérapeutique en Neuropsychopharmacologie
13 Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière]
14 AP-HP - Hopital Saint-Louis [AP-HP]
15 Hôpital Cochin [AP-HP]
16 Centre Hospitalier de Lens
17 CHU Nantes - Centre Hospitalier Universitaire de Nantes
18 Hôpital Bretonneau
19 HCL - Hospices Civils de Lyon
20 CHU Saint-Antoine [AP-HP]
21 CHU Tenon [AP-HP]
22 Centre Hospitalier Victor Dupouy
23 CHU Pitié-Salpêtrière [AP-HP]
24 UMRS 1158 - Neurophysiologie Respiratoire Expérimentale et Clinique
25 CHU Angers - Centre Hospitalier Universitaire d'Angers
26 CHU Bordeaux
27 CARMAS - Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis)
28 IMRB - Institut Mondor de Recherche Biomédicale
29 CH Béthune - Centre Hospitalier de Béthune
30 Hôpital Duchenne
31 CRSA - Centre de Recherche Saint-Antoine
32 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
33 MP3CV - Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517
34 coVAPid Study Group

Background Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. Methods This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. Results A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53–7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88–5.46, p < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization. Conclusions Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693 .

Mots clés: COVID-19; Intensive care unit; Invasive pulmonary aspergillosis; Mechanical ventilation; Severe influenza

Domaines: Sciences du Vivant [q-bio]

Anahita Rouzé, Elise Lemaitre, Ignacio Martin-Loeches, Pedro Povoa, Emili Diaz, et al.. Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: a European multicenter comparative cohort study. Critical Care, 2022, 26 (1), pp.11. ⟨10.1186/s13054-021-03874-1⟩. ⟨hal-03820642⟩