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