Abstract

Background and aimsThere is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and resultsRetrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5–3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. ConclusionsImpaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.

Highlights

  • As of July 10, 2020, there have been over 12 million of confirmed cases of COVID-19, with 549,247 deaths worldwide [1]

  • Among COVID-19 patients, there was a higher prevalence of men (61.7%) and elderly (54.8% of patients aged !65 years; median age 67 years, interquartile range (IQR): 55e79 years) (Table 1)

  • We found no association between obesity and inhospital mortality, data confirmed by complete-case analysis restricted to 1517 patients without missing data on body mass index (BMI) and by distinguishing obesity as stage 1 (BMI Z 30e34.9 kg/m2) and stage 2 (BMI !35 kg/m2) (Supplementary Table 6)

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Summary

Introduction

As of July 10, 2020, there have been over 12 million of confirmed cases of COVID-19, with 549,247 deaths worldwide [1]. Some laboratory parameters such as elevated levels of C-reactive protein (CRP), cardiac troponins and interleukin-6 resulted associated with a higher risk of death. Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6e14.7 for age !85 vs 18 e44 y); HR Z 4.7; 2.9e7.7 for estimated glomerular filtration rate levels

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