# Prognostic Value of Biomarkers in COVID-19: Associations with Disease Severity, Viral Variants, and Comorbidities—A Retrospective Observational Single-Center Cohort Study

**Authors:** Zoran Barušić, Kristian Bodulić, Sanja Zember, Renata Laškaj, Rok Čivljak, Ivan Puljiz, Ivan-Christian Kurolt, Željka Mačak Šafranko, Lidija Cvetko Krajinović, Petra Svoboda Karić, Alemka Markotić

PMC · DOI: 10.3390/life15040634 · 2025-04-10

## TL;DR

This study identifies biomarkers linked to severe and fatal outcomes in hospitalized COVID-19 patients, including cardiac and inflammatory markers.

## Contribution

The study identifies key biomarkers associated with disease severity, viral variants, and comorbidities in hospitalized COVID-19 patients.

## Key findings

- Deceased and severe patients had elevated biomarkers like hs-troponin T, CRP, and IL-6 at admission.
- Delta variant infections showed higher proinflammatory and cardiac biomarker levels.
- Random forest models predicted fatal outcomes with 84.1% accuracy using lymphocyte percentage, D-dimers, and hs-troponin T.

## Abstract

Coronavirus disease (COVID-19) exhibits a wide spectrum of clinical severity and has been associated with specific biomarkers linked to disease progression and outcomes. This retrospective study analyzed sera from 1222 adult COVID-19 patients hospitalized at the University Hospital for Infectious Diseases in Croatia. We examined the association between several laboratory biomarker levels measured at patient admission and disease severity, fatal outcomes, viral variants and clinical parameters. Deceased patients and surviving patients with severe COVID-19 exhibited significantly elevated levels of several biomarkers on admission, including hs-troponin T, N-terminal pro-brain natriuretic peptide, creatine kinase, C-reactive protein, procalcitonin, interleukin-6, lactate dehydrogenase, lactate, urea and creatinine. Random forest models identified lymphocyte percentage, D-dimers, and hs-troponin T as the most important biomarkers for fatal outcome prediction, achieving 84.1% accuracy. Patients infected with the Delta SARS-CoV-2 variant exhibited significantly higher levels of proinflammatory, cardiac and renal biomarkers. Vaccination correlated with reduced proinflammatory parameters and higher lymphocyte proportions. Hypertension, chronic renal disease and diabetes were associated with increased cardiac, renal and metabolic biomarker levels, respectively. These findings highlight the association of several laboratory biomarkers with COVID-19 severity, viral variants, vaccination status and comorbidities, potentially offering prognostic insights into COVID-19 outcomes.

## Linked entities

- **Proteins:** IL6 (interleukin 6)
- **Diseases:** COVID-19 (MONDO:0100096), chronic renal disease (MONDO:0005300), diabetes (MONDO:0005015)

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}
- **Diseases:** diabetes (MESH:D003920), Hypertension (MESH:D006973), COVID-19 (MESH:D000086382), Coronavirus disease (MESH:D018352), Infectious Diseases (MESH:D003141), chronic renal disease (MESH:D051436)
- **Chemicals:** urea (MESH:D014508), lactate (MESH:D019344), D (MESH:D003903), creatinine (MESH:D003404)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12028838/full.md

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Source: https://tomesphere.com/paper/PMC12028838