Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy
Authors: Giacomo Grasselli, Massimiliano Greco, Alberto Zanella, Giovanni Albano, Massimo Antonelli, Giacomo Bellani, Ezio Bonanomi, Luca Cabrini, Eleonora Carlesso, Gianpaolo Castelli, Sergio Cattaneo, Danilo Cereda, Sergio Colombo, Antonio Coluccello, Giuseppe Crescini, Andrea Forastieri Molinari, Giuseppe Foti, Roberto Fumagalli, Giorgio Antonio Iotti, Thomas Langer, Nicola Latronico, Ferdinando Luca Lorini, Francesco Mojoli, Giuseppe Natalini, Carla Maria Pessina, Vito Marco Ranieri, Roberto Rech, Luigia Scudeller, Antonio Rosano, Enrico Storti, B. Taylor Thompson, Marcello Tirani, Pier Giorgio Villani, Antonio Pesenti, Maurizio Cecconi, Emiliano Agosteo, Giovanni Albano, Andrea Albertin, Armando Alborghetti, Giorgio Aldegheri, Benvenuto Antonini, Enrico Barbara, Giulia Bardelloni, Sabrina Basilico, Nicolangela Belgiorno, Giacomo Bellani, Enrico Beretta, Angela Berselli, Leonardo Bianciardi, Ezio Bonanomi, Stefano Bonazzi, Massimo Borelli, Nicola Bottino, Nicola Bronzini, Serena Brusatori, Luca Cabrini, Carlo Capra, Livio Carnevale, Gianpaolo Castelli, Emanuele Catena, Sergio Cattaneo, Maurizio Cecconi, Simona Celotti, Stefania Cerutti, Davide Chiumello, Silvia Cirri, Giuseppe Citerio, Sergio Colombo, Antonio Coluccello, Davide Coppini, Alberto Corona, Paolo Cortellazzi, Elena Costantini, Remo Daniel Covello, Giuseppe Crescini, Gianluca De Filippi, Marco Dei Poli, Paolo Dughi, Fulvia Fieni, Gaetano Florio, Andrea Forastieri Molinari, Giuseppe Foti, Roberto Fumagalli, Marco Galletti, Giorgio Antonio Gallioli, Hedwige Gay, Marco Gemma, Paolo Gnesin, Giacomo Grasselli, Stefano Greco, Massimiliano Greco, Paolo Grosso, Luca Guatteri, Davide Guzzon, Giorgio Antonio Iotti, Roberto Keim, Thomas Langer, Nicola Latronico, Andrea Lombardo, Ferdinando Luca Lorini, Filippo Mamprin, Giovanni Marino, Francesco Marino, Guido Merli, Antonio Micucci, Carmine Rocco Militano, Francesco Mojoli, Giacomo Monti, Stefano Muttini, Samantha Nadalin, Giuseppe Natalini, Paolo Perazzo, Giovanni Battista Perego, Luciano Perotti, Antonio Pesenti, Carla Maria Pessina, Nicola Petrucci, Angelo Pezzi, Simone Piva, Gina Portella, Alessandro Protti, Milena Racagni, Danilo Radrizzani, Maurizio Raimondi, Marco Ranucci, Roberto Rech, Mario Riccio, Antonio Rosano, Patrizia Ruggeri, Giuseppe Sala, Luca Salvi, Pietro Sebastiano, Paolo Severgnini, Donato Sigurtà, Nino Stocchetti, Enrico Storti, Matteo Subert, Mario Tavola, Serena Todaro, Francesca Torriglia, Daniela Tubiolo, Roberto Valsecchi, Pier Giorgio Villani, Uberto Viola, Giovanni Vitale, Massimo Zambon, Alberto Zanella, Elena Zoia
Journal: JAMA Internal Medicine (2020)

<h3>Importance</h3> Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU). <h3>Objective</h3> To evaluate the independent risk factors associated with mortality of patients with COVID-19 requiring treatment in ICUs in the Lombardy region of Italy. <h3>Design, Setting, and Participants</h3> This retrospective, observational cohort study included 3988 consecutive critically ill patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinating center (Fondazione IRCCS [Istituto di Ricovero e Cura a Carattere Scientifico] Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network from February 20 to April 22, 2020. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by real-time reverse transcriptase–polymerase chain reaction assay of nasopharyngeal swabs. Follow-up was completed on May 30, 2020. <h3>Exposures</h3> Baseline characteristics, comorbidities, long-term medications, and ventilatory support at ICU admission. <h3>Main Outcomes and Measures</h3> Time to death in days from ICU admission to hospital discharge. The independent risk factors associated with mortality were evaluated with a multivariable Cox proportional hazards regression. <h3>Results</h3> Of the 3988 patients included in this cohort study, the median age was 63 (interquartile range [IQR] 56-69) years; 3188 (79.9%; 95% CI, 78.7%-81.1%) were men, and 1998 of 3300 (60.5%; 95% CI, 58.9%-62.2%) had at least 1 comorbidity. At ICU admission, 2929 patients (87.3%; 95% CI, 86.1%-88.4%) required invasive mechanical ventilation (IMV). The median follow-up was 44 (95% CI, 40-47; IQR, 11-69; range, 0-100) days; median time from symptoms onset to ICU admission was 10 (95% CI, 9-10; IQR, 6-14) days; median length of ICU stay was 12 (95% CI, 12-13; IQR, 6-21) days; and median length of IMV was 10 (95% CI, 10-11; IQR, 6-17) days. Cumulative observation time was 164 305 patient-days. Hospital and ICU mortality rates were 12 (95% CI, 11-12) and 27 (95% CI, 26-29) per 1000 patients-days, respectively. In the subgroup of the first 1715 patients, as of May 30, 2020, 865 (50.4%) had been discharged from the ICU, 836 (48.7%) had died in the ICU, and 14 (0.8%) were still in the ICU; overall, 915 patients (53.4%) died in the hospital. Independent risk factors associated with mortality included older age (hazard ratio [HR], 1.75; 95% CI, 1.60-1.92), male sex (HR, 1.57; 95% CI, 1.31-1.88), high fraction of inspired oxygen (Fio<sub>2</sub>) (HR, 1.14; 95% CI, 1.10-1.19), high positive end-expiratory pressure (HR, 1.04; 95% CI, 1.01-1.06) or low Pao<sub>2</sub>:Fio<sub>2</sub>ratio (HR, 0.80; 95% CI, 0.74-0.87) on ICU admission, and history of chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.28-2.19), hypercholesterolemia (HR, 1.25; 95% CI, 1.02-1.52), and type 2 diabetes (HR, 1.18; 95% CI, 1.01-1.39). No medication was independently associated with mortality (angiotensin-converting enzyme inhibitors HR, 1.17; 95% CI, 0.97-1.42; angiotensin receptor blockers HR, 1.05; 95% CI, 0.85-1.29). <h3>Conclusions and Relevance</h3> In this retrospective cohort study of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed COVID-19, most patients required IMV. The mortality rate and absolute mortality were high.