# Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19

**Authors:** Biljana Popovska Jovičić, Ivana Raković, Nemanja Đorđević, Jagoda Gavrilović, Predrag Čanović, Ružica Radojević Marjanović, Sara Petrović, Katarina B. Milosavljević, Ana Divjak, Nenad Stanković, Milan Paunović, Miloš Z. Milosavljević

PMC · DOI: 10.1515/med-2025-1246 · Open Medicine · 2025-07-24

## TL;DR

This study shows that lower levels of CD4 and CD8 lymphocytes in COVID-19 patients are linked to more severe illness and worse outcomes.

## Contribution

The study identifies CD4+ and CD8+ lymphocyte levels as significant prognostic biomarkers for severe COVID-19 outcomes.

## Key findings

- Low CD4+ and CD8+ T cell values correlate with severe clinical presentation in hospitalized COVID-19 patients.
- Decreased CD4+ and CD8+ levels are associated with increased need for oxygen therapy and poor disease outcomes.
- ROC analysis established cutoff values for CD4+ and CD8+ levels to predict disease severity and outcomes.

## Abstract

The main objective of this study was to investigate the association between CD4+ and CD8+ lymphocyte values and disease severity, need for oxygen therapy and disease outcomes.

The research was designed as a cross-sectional observational study.

This study was conducted at the Clinic for Infectious Diseases, University Clinical Center Kragujevac, as a COVID-19 treatment center.

The study group consisted of a total of 101 adult hospitalized patients with confirmed COVID-19 infection, excluding patients under 18 years of age, patients with malignant diseases, tuberculosis, hepatitis, immune disorders, pregnant women, or HIV-positive patients. SARS-CoV2 infection was diagnosed by rapid antigen tests or real-time reverse transcription polymerase chain reaction from a nasal swab.

The patients were classified into two groups based on oxygen therapy needs, disease severity, and disease outcomes.

Low CD4+ and CD8+ T cell values were associated with severe clinical presentation, more need for oxygen therapy as well as poor disease outcome. Receiver operating characteristic analysis provided cutoff values to support predicting the aforementioned variables, establishing CD4+ and CD8+ values as significant prognostic biomarkers. Future studies should be aimed at identifying factors that lead to gender differences in the immune response.

## Linked entities

- **Diseases:** COVID-19 (MONDO:0100096), tuberculosis (MONDO:0018076), hepatitis (MONDO:0002251)

## Full-text entities

- **Genes:** CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}
- **Diseases:** malignant diseases (MESH:D009369), hepatitis (MESH:D056486), immune disorders (MESH:D007154), COVID-19 (MESH:D000086382), Infectious Diseases (MESH:D003141), tuberculosis (MESH:D014376)
- **Chemicals:** oxygen (MESH:D010100)
- **Species:** Human immunodeficiency virus 1 (no rank) [taxon 11676], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12290374/full.md

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Source: https://tomesphere.com/paper/PMC12290374