Identification of Early Biomarkers of Mortality in COVID-19 Hospitalized Patients: A LASSO-Based Cox and Logistic Approach

This study aimed to identify possible early biomarkers of mortality among clinical and biochemical parameters, iron metabolism parameters, and cytokines detected within 24 h from admission in hospitalized COVID-19 patients. We enrolled 80 hospitalized patients (40 survivors and 40 non-survivors) wit...

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Main Authors: Anna Maria Fratta Pasini, Chiara Stranieri, Edoardo Giuseppe Di Leo, Lorenzo Bertolone, Antonino Aparo, Fabiana Busti, Annalisa Castagna, Alice Vianello, Fabio Chesini, Simonetta Friso, Domenico Girelli, Luciano Cominacini
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Language:English
Published: MDPI AG 2025-02-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/3/359
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author Anna Maria Fratta Pasini
Chiara Stranieri
Edoardo Giuseppe Di Leo
Lorenzo Bertolone
Antonino Aparo
Fabiana Busti
Annalisa Castagna
Alice Vianello
Fabio Chesini
Simonetta Friso
Domenico Girelli
Luciano Cominacini
author_facet Anna Maria Fratta Pasini
Chiara Stranieri
Edoardo Giuseppe Di Leo
Lorenzo Bertolone
Antonino Aparo
Fabiana Busti
Annalisa Castagna
Alice Vianello
Fabio Chesini
Simonetta Friso
Domenico Girelli
Luciano Cominacini
author_sort Anna Maria Fratta Pasini
collection DOAJ
description This study aimed to identify possible early biomarkers of mortality among clinical and biochemical parameters, iron metabolism parameters, and cytokines detected within 24 h from admission in hospitalized COVID-19 patients. We enrolled 80 hospitalized patients (40 survivors and 40 non-survivors) with COVID-19 pneumonia and acute respiratory failure. The median time from the onset of COVID-19 symptoms to hospital admission was lower in non-survivors than survivors (<i>p</i> < 0.05). Respiratory failure, expressed as the ratio of arterial oxygen partial pressure to the fraction of inspired oxygen (P/F), was more severe in non-survivors than survivors (<i>p</i> < 0.0001). Comorbidities were similar in both groups. Among biochemical parameters and cytokines, eGFR and interleukin (IL)-1β were found to be significantly lower (<i>p</i> < 0.05), while LDH, IL-10, and IL-8 were significantly higher in non-survivors than in survivors (<i>p</i> < 0.0005, <i>p</i> < 0.05 and <i>p</i> < 0.005, respectively). Among other parameters, LDH values distribution showed the most significant difference between study groups (<i>p</i> < 0.0001). LASSO feature selection combined with Cox proportional hazards and logistic regression models was applied to identify features distinguishing between survivors and non-survivors. Both approaches highlighted LDH as the strongest predictor, with IL-22 and creatinine emerging in the Cox model, while IL-10, eGFR, and creatinine were influential in the logistic model (AUC = 0.744 for Cox, 0.723 for logistic regression). In a similar manner, we applied linear regression for predicting LDH levels, identifying the P/F ratio as the top predictor, followed by IL-10 and eGFR (NRMSE = 0.128). Collectively, these findings underscore LDH’s critical role in mortality prediction, with P/F and IL-10 as key determinants of LDH increases in this Italian COVID-19 cohort.
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spelling doaj-art-d453e6fe101546fcbbdeda7955fdcfca2025-08-20T03:44:03ZengMDPI AGViruses1999-49152025-02-0117335910.3390/v17030359Identification of Early Biomarkers of Mortality in COVID-19 Hospitalized Patients: A LASSO-Based Cox and Logistic ApproachAnna Maria Fratta Pasini0Chiara Stranieri1Edoardo Giuseppe Di Leo2Lorenzo Bertolone3Antonino Aparo4Fabiana Busti5Annalisa Castagna6Alice Vianello7Fabio Chesini8Simonetta Friso9Domenico Girelli10Luciano Cominacini11Department of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, ItalyInterdepartmental Laboratory of Medical Research, Research Center LURM, University of Verona, 37134 Verona, ItalyDepartment of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Medicine, Section of Internal Medicine B, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Medicine, Section of Internal Medicine B, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, ItalyThis study aimed to identify possible early biomarkers of mortality among clinical and biochemical parameters, iron metabolism parameters, and cytokines detected within 24 h from admission in hospitalized COVID-19 patients. We enrolled 80 hospitalized patients (40 survivors and 40 non-survivors) with COVID-19 pneumonia and acute respiratory failure. The median time from the onset of COVID-19 symptoms to hospital admission was lower in non-survivors than survivors (<i>p</i> < 0.05). Respiratory failure, expressed as the ratio of arterial oxygen partial pressure to the fraction of inspired oxygen (P/F), was more severe in non-survivors than survivors (<i>p</i> < 0.0001). Comorbidities were similar in both groups. Among biochemical parameters and cytokines, eGFR and interleukin (IL)-1β were found to be significantly lower (<i>p</i> < 0.05), while LDH, IL-10, and IL-8 were significantly higher in non-survivors than in survivors (<i>p</i> < 0.0005, <i>p</i> < 0.05 and <i>p</i> < 0.005, respectively). Among other parameters, LDH values distribution showed the most significant difference between study groups (<i>p</i> < 0.0001). LASSO feature selection combined with Cox proportional hazards and logistic regression models was applied to identify features distinguishing between survivors and non-survivors. Both approaches highlighted LDH as the strongest predictor, with IL-22 and creatinine emerging in the Cox model, while IL-10, eGFR, and creatinine were influential in the logistic model (AUC = 0.744 for Cox, 0.723 for logistic regression). In a similar manner, we applied linear regression for predicting LDH levels, identifying the P/F ratio as the top predictor, followed by IL-10 and eGFR (NRMSE = 0.128). Collectively, these findings underscore LDH’s critical role in mortality prediction, with P/F and IL-10 as key determinants of LDH increases in this Italian COVID-19 cohort.https://www.mdpi.com/1999-4915/17/3/359COVID-19early biomarkersinterleukin-10lactate dehydrogenase
spellingShingle Anna Maria Fratta Pasini
Chiara Stranieri
Edoardo Giuseppe Di Leo
Lorenzo Bertolone
Antonino Aparo
Fabiana Busti
Annalisa Castagna
Alice Vianello
Fabio Chesini
Simonetta Friso
Domenico Girelli
Luciano Cominacini
Identification of Early Biomarkers of Mortality in COVID-19 Hospitalized Patients: A LASSO-Based Cox and Logistic Approach
Viruses
COVID-19
early biomarkers
interleukin-10
lactate dehydrogenase
title Identification of Early Biomarkers of Mortality in COVID-19 Hospitalized Patients: A LASSO-Based Cox and Logistic Approach
title_full Identification of Early Biomarkers of Mortality in COVID-19 Hospitalized Patients: A LASSO-Based Cox and Logistic Approach
title_fullStr Identification of Early Biomarkers of Mortality in COVID-19 Hospitalized Patients: A LASSO-Based Cox and Logistic Approach
title_full_unstemmed Identification of Early Biomarkers of Mortality in COVID-19 Hospitalized Patients: A LASSO-Based Cox and Logistic Approach
title_short Identification of Early Biomarkers of Mortality in COVID-19 Hospitalized Patients: A LASSO-Based Cox and Logistic Approach
title_sort identification of early biomarkers of mortality in covid 19 hospitalized patients a lasso based cox and logistic approach
topic COVID-19
early biomarkers
interleukin-10
lactate dehydrogenase
url https://www.mdpi.com/1999-4915/17/3/359
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