Altered NGF and GDNF Levels Reveal Neuroimmune Dysregulation in COVID-19 Patients

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.