Epidemiology of Invasive Pulmonary Aspergillosis Among Intubated Patients With COVID-19: A Prospective Study
Authors: Bartoletti Michele , Pascale Renato , Cricca Monica , Rinaldi Matteo , Maccaro Angelo , Bussini Linda , Fornaro Giacomo , Tonetti Tommaso , Pizzilli Giacinto , Francalanci Eugenia , Giuntoli Lorenzo , Rubin Arianna , Moroni Alessandra , Ambretti Simone , Trapani Filippo , Vatamanu Oana , Ranieri Vito Marco , Castelli Andrea , Baiocchi Massimo , Lewis Russell , Giannella Maddalena , Viale Pierluigi ,   PREDICO Study Group, Raumer Luigi , Guerra Luca , Tumietto Fabio , Cascavilla Alessandra , Zamparini Eleonora , Verucchi Gabriella , Coladonato Simona , Ianniruberto Stefano , Attard Luciano , Volpato Marina Tadolini Francesca , Virgili Giulio , Rossi Nicolò , Del Turco Elena Rosselli , Guardigni Viola , Fasulo Giovanni , Dentale Nicola , Fulgaro Ciro , Legnani Giorgio , Campaci Emanuele , Basso Cristina , Zuppiroli Alberto , Passino Amalia Sanna , Tesini Giulia , Angelelli Lucia , Badeanu Adriana , Rossi Agostino , Santangelo Giulia , Dauti Flovia , Koprivika Vidak , Roncagli Nicholas , Tzimas Ioannis , Liuzzi Guido Maria , Baxhaku Irid , Pasinelli Letizia , Neri Mattia , Zanaboni Tommaso , Dell’Omo Francesco , Gori Alice , Zavatta Idina , Antonini Stefano , Pironi Chiara , Piccini Elena , Esposito Luca , Zuccotti Alessandro , Urbinati Giacomo , Pratelli Agnese , Sarti Alberto , Semprini Michela , Evangelisti Enrico , D’Onofrio Mara , Sasdelli Giuseppe 
Published: July 2020

Abstract

Background
We evaluated the incidence of invasive pulmonary aspergillosis among intubated patients with critical COVID-19 and evaluated different case definitions of invasive aspergillosis.

Methods
Prospective, multicenter study in adult patients with microbiologically confirmed COVID-19 receiving mechanical ventilation. All included participants underwent a screening protocol for invasive pulmonary aspergillosis with bronchoalveolar lavage galactomannan and cultures performed on admission at 7 days and in case of clinical deterioration. Cases were classified as coronavirus-associated pulmonary aspergillosis (CAPA) according to previous consensus definitions. The new definition was compared with putative invasive pulmonary aspergillosis (PIPA).

Results
108 patients were enrolled. Probable CAPA was diagnosed in 30 (27.7%) patients after a median of 4 (2–8) days from intensive care unit (ICU) admission. Kaplan-Meier curves showed a significantly higher 30-day mortality rate from ICU admission among patients with either CAPA (44% vs 19%, P = .002) or PIPA (74% vs 26%, P &lt; .001) when compared with patients not fulfilling criteria for aspergillosis. The association between CAPA (OR, 3.53; 95% CI, 1.29–9.67; P = .014) or PIPA (OR, 11.60; 95% CI, 3.24–41.29; P &lt; .001) with 30-day mortality from ICU admission was confirmed, even after adjustment for confounders with a logistic regression model. Among patients with CAPA receiving voriconazole treatment (13 patients; 43%) a trend toward lower mortality (46% vs 59%; P = .30) and reduction in galactomannan index in consecutive samples were observed.

Conclusions
We found a high incidence of CAPA among critically ill COVID-19 patients and its occurrence seems to change the natural course of disease.