Secondary Infections in Patients Hospitalized with COVID-19: Incidence and Predictive Factors

Ripa, Marco; Galli, Laura; Poli, Andrea; Oltolini, Chiara; Spagnuolo, Vincenzo; Mastrangelo, Andrea; Muccini, Camilla; Monti, Giacomo; De Luca, Giacomo; Landoni, Giovanni; Dagna, Lorenzo; Clementi, Massimo; Querini, Patrizia Rovere; Ciceri, Fabio; Tresoldi, Moreno; Lazzarin, Adriano; Zangrillo, Alberto; Scarpellini, Paolo; Castagna, Antonella

OBJECTIVES: Aim of our study was to describe the incidence and predictive factors of secondary infections in patients with COVID-19. METHODS: Cohort study on patients hospitalized with COVID-19 at IRCCS San Raffaele Hospital between February 25(th) and April 6th, 2020 (NCT04318366). We considered secondary bloodstream (BSIs) or possible lower respiratory tract infections (pLRTIs) occurred after 48 hours since hospital admission until death or discharge. We calculated multivariable Fine-Gray models, to assess factors associated with risk of secondary infections. RESULTS: Among 731 patients, a secondary infection was diagnosed in 68 patients (9.3%): 58/731 patients (7.9%) had at least one BSI and 22/731 patients (3.0%) at least one pLRTI. Overall 28-day cumulative incidence was 16.4% (95% CI 12.4% - 21.0%). The majority of BSIs was due to gram-positive pathogens (76/106 isolates, 71.7%), specifically coagulase-negative staphylococci (53/76, 69.7%), while among gram-negatives (23/106, 21.7%) Acinetobacter baumanii (7/23, 30.4%) and Escherichia coli (5/23, 21.7%) predominated. pLRTIs were mainly caused by gram-negative pathogens (14/26, 53.8%). Eleven patients were diagnosed with putative invasive aspergillosis. At multivariable analysis, factors associated with secondary infections were low baseline lymphocyte count (<0.7 vs >0.7 per 10(9)/L: subdistribution hazard ratios (sdHRs) 1.93 [95% CI 1.11-3.35]), baseline PaO(2)/FiO(2) (per 100-points lower: sdHRs 1.56 [95% CI 1.21-2.04]), and intensive-care unit (ICU) admission in the first 48 hours (sdHR 2.51 [95% CI 1.04-6.05]). CONCLUSIONS: Patients hospitalized with COVID-19 had a high incidence of secondary infections. At multivariable analysis, early need for ICU, respiratory failure, and severe lymphopenia, were identified as risk factors for secondary infections.