key: cord-317918-pl625ela authors: 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 title: Secondary Infections in Patients Hospitalized with COVID-19: Incidence and Predictive Factors date: 2020-10-24 journal: Clin Microbiol Infect DOI: 10.1016/j.cmi.2020.10.021 sha: doc_id: 317918 cord_uid: pl625ela 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. The pandemic caused by SARS-CoV-2 has affected more than thirty-two million patients worldwide as of Patients with no microbiology specimens requested were considered without secondary infections. We compared characteristics and outcomes of patients who had at least one secondary infection during 144 hospitalization and those who did not using chi-square test or Fisher exact test for categorical variables and 145 Mann-Whitney U test for continuous variables. In the analysis, we used three scores (the cytolysis score, the coagulation score, and the inflammation score), 147 defined as the number of laboratory parameters with markedly elevated values (values at or above the 75th 148 percentile). Absolute lymphocyte counts were stratified on the 25th percentile (at or below We subsequently performed inverse probability-weighted (IPW) competing risks multivariable analyses to 159 simultaneously account for indication bias associated with the treatment with biologic immunosuppressive 160 drugs and competing death for the estimation of the cumulative incidence of patients with secondary 161 infections, to provide a more accurate estimate of secondary infections burden [15, 16] . A logistic regression analysis was applied to estimate the propensity of biologic immunosuppressive drugs use, 163 conditioned on a pre-specified list of baseline covariates; the predicted probabilities of biologic 164 immunosuppressive drugs treatment (propensity-score) were used to calculate the stabilized IPW in order to 165 account for non-randomization to biological drugs in this observational study. The inverses of these propensities were used as weights in multivariable Fine-Gray models assessing the 167 association between demographic and other clinical or laboratory factors and the risk of secondary infections. All statistical tests were two-sided at 5% level and were performed using SAS 9.4 (Statistical Analyses System 169 Inc, Cary, NC, USA). Further details on the cytolysis score, the coagulation score, and the inflammation score definitions and on the 171 statistical analyses are provided in the supplementary material. In our cohort, the incidence rate of BSIs appears significantly higher compared to previous reports concerning 230 nosocomial and ICU-related BSIs in European countries [21, 22] (ranging from 0.5 to 1.3 and 0.7 to 6.6 per 231 1000-PDFU, respectively). Similarly, the incidence rate of pLRTIs among patients with COVID-19 admitted to 232 the ICU appears to be higher compared with historical European cohorts [22] Clinical Characteristics of Coronavirus Disease 323 2019 in China Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New 326 Clinical course and outcomes of critically ill patients 328 with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The 329 COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic 331 staging proposal COVID-19: consider cytokine 333 storm syndromes and immunosuppression Should we stimulate or suppress Bacterial and fungal coinfection among European Centre for Disease Prevention and Control. Incidence and attributable mortality of 370 healthcare-associated infections in intensive care units in Europe Associated Pulmonary Aspergillosis Prevalence of putative invasive pulmonary 377 aspergillosis in critically ill patients with COVID-19. The Lancet Respiratory Medicine Diagnosing 380 COVID-19-associated pulmonary aspergillosis COVID-19: don't neglect antimicrobial 382 stewardship principles! Pathological findings of COVID-19 associated with 384 acute respiratory distress syndrome An interpretable mortality prediction Days since hospitalization Gray's test: p=0.052 BL absolute lymphocyte count ≤0.7 per 10 9 /L BL absolute lymphocyte count >0.7 per 10 9 /L Follow-up (days) Patients with BL PaO 2 /FiO 2 ≤200 (95% confidence interval) Patients with BL PaO 2 /FiO 2 >200