Assessing the Association between Biomarkers and COVID-19 Mortality Using the Joint Modelling Approach

Author:

Di Maso Matteo1ORCID,Delbue Serena2ORCID,Sampietro Maurizio3,Ferraroni Monica14ORCID,Modenese Annalisa3,Dolci Maria2ORCID,Ambrogi Federico15ORCID,Ferrante Pasquale23

Affiliation:

1. Department of Clinical Sciences and Community Health, Branch of Medical Statistics, Biometry and Epidemiology “G.A. Maccacaro”, Università degli Studi di Milano, 20133 Milan, Italy

2. Department of Biochemical, Surgical & Dental Sciences, Università degli Studi di Milano, 20122 Milan, Italy

3. Istituto Clinico Città Studi, 20131 Milan, Italy

4. Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy

5. Laboratory of Biostatistics and Data Management, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy

Abstract

We evaluated the association between biomarkers and COVID-19 mortality. Baseline characteristics of 403 COVID-19 patients included sex and age; biomarkers, measured throughout the follow-up, included lymphocytes, neutrophils, ferritin, C-reactive protein, glucose, and LDH. Hazard ratios (HRs) and corresponding 95% credible intervals (CIs) were estimated through joint models (JMs) using a Bayesian approach. We fitted univariable (a single biomarker) and multivariable (all biomarkers) JMs. In univariable analyses, all biomarkers were significantly associated with COVID-19 mortality. In multivariable analysis, HRs were 1.78 (95% CI: 1.13–2.87) with a doubling of neutrophils levels, 1.49 (95% CI: 1.19–1.95) with a doubling of C-reactive protein levels, 2.66 (95% CI: 1.45–4.95) for an increase of 100 mg/dL of glucose, and 1.31 (95% CI: 1.12–1.55) for an increase of 100 U/L of LDH. No evidence of association was observed for lymphocytes and ferritin in multivariable analysis. Men had a higher COVID-19 mortality risk than women (HR = 1.75; 95% CI: 1.07–2.80) and age showed the strongest effect with a rapid increase from 60 years. These findings using JM confirm the usefulness of biomarkers in assessing COVID-19 severity and mortality. Monitoring trend patterns of such biomarkers can provide additional help in tailoring the appropriate care pathway.

Funder

Italian Ministry of Education, Universities and Research

University of Milan

Publisher

MDPI AG

Reference72 articles.

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3. Risk and Protective Factors for COVID-19 Morbidity, Severity, and Mortality;Zhang;Clin. Rev. Allergy Immunol.,2022

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