# Altered NGF and GDNF levels reveal neuroimmune dysregulation in COVID-19 patients

**Authors:** Lale Saka Baraz, Evrim Ataca, Nur Duzen Oflas, Seyma Canavar Kosali, Busra Usta, Alihan Oral, Mustafa Cihangiroglu, Metin Ozgen, Demet Yalcin Kehribar

PMC · DOI: 10.1038/s41598-026-40236-9 · 2026-02-19

## TL;DR

This study finds that NGF and GDNF levels are altered in hospitalized COVID-19 patients, suggesting a role in neuroimmune dysregulation.

## Contribution

The study identifies NGF and GDNF as potential biomarkers for neuroimmune responses in COVID-19.

## Key findings

- NGF levels were significantly lower in hospitalized COVID-19 patients compared to healthy individuals.
- GDNF remained persistently suppressed during hospitalization, indicating a role in chronic neuroimmune regulation.

## Abstract

Neurotrophins such as nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) are crucial for neuronal maintenance and immune regulation. However, their dynamics during coronavirus disease 2019 (COVID-19) remain unclear. In this prospective study, 30 hospitalized patients with PCR-confirmed COVID-19 were evaluated longitudinally. Serum NGF, GDNF, and conventional inflammatory markers (CRP, ESR, fibrinogen, ferritin, D-dimer, LDH, hematological counts) were measured on Day 1, Day 4, and at discharge. A control group of 37 healthy individuals was included for cross-sectional comparison. Both NGF and GDNF levels were significantly lower in COVID-19 patients at admission compared with healthy individuals. NGF showed a modest early decline from Day 1 to Day 4, followed by partial recovery at discharge, whereas GDNF remained stable throughout hospitalization. Inflammatory markers demonstrated expected clinical trajectories: CRP, ESR, LDH, and fibrinogen decreased during recovery, while WBC, neutrophils, and platelets increased. Ferritin and D-dimer showed no meaningful temporal changes. NGF appears to reflect acute neuroimmune activation in COVID-19 and may serve as a dynamic biomarker of early inflammatory resolution. Conversely, GDNF remained persistently suppressed, suggesting a distinct role in chronic neuroimmune regulation. These findings highlight NGF and GDNF as potential targets for monitoring and modulating neuroimmune responses in COVID-19 and other inflammation-driven conditions.

## Linked entities

- **Proteins:** NGF (nerve growth factor), GDNF (glial cell derived neurotrophic factor)
- **Diseases:** coronavirus disease 2019 (MONDO:0100096), COVID-19 (MONDO:0100096)

## Full-text entities

- **Genes:** GDNF (glial cell derived neurotrophic factor) [NCBI Gene 2668] {aka ATF, ATF1, ATF2, HFB1-GDNF, HSCR3}, NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}
- **Diseases:** neuroimmune dysregulation (MESH:D021081), Inflammatory (MESH:D007249), COVID-19 (MESH:D000086382)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13018267/full.md

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Source: https://tomesphere.com/paper/PMC13018267