Oxidative Stress and Cognitive Dysfunction After COVID-19

Overview

This observational cohort study will investigate the association between oxidative stress biomarkers and post-COVID-19 cognitive impairment. A total of 45 recovered COVID-19 patients aged 30-65 will be enrolled and followed at three intervals: 0-3, 3-6, and 6-12 months post-infection. Cognitive function will be assessed using standardized memory and attention tests, while venous blood samples will be analyzed for nitric oxide, AOPP, NETs, and extracellular nucleic acids. The study aims to identify early predictors of long COVID cognitive sequelae and evaluate biological mechanisms underlying persistent neurocognitive symptoms.

This prospective observational cohort study will aim to investigate whether markers of oxidative stress, including advanced oxidation protein products (AOPP), nitric oxide (NO), extracellular nucleic acids (DNA/RNA), and neutrophil extracellular traps (NETs), can predict cognitive dysfunction in patients recovering from COVID-19 pneumonia. Post-viral cognitive impairment, commonly referred to as "brain fog," has emerged as a major complication in long COVID patients. The estimated prevalence of neurocognitive deficits ranges from 21% to 65% depending on disease severity and follow-up duration . Even individuals with mild infection can present with persistent impairments in memory, attention, and executive function . Growing evidence suggests that oxidative stress plays a critical role in neurodegeneration and long-COVID symptoms . SARS-CoV-2 triggers an "oxidative storm," marked by excess production of reactive oxygen and nitrogen species, causing cellular injury . These species impair neurovascular coupling and lead to persistent endothelial dysfunction and neuroinflammation . Furthermore, cell-free DNA and RNA, key damage-associated molecular patterns (DAMPs), act as immune triggers via Toll-like receptor pathways . Another mechanism under scrutiny is NETosis, the extrusion of web-like neutrophil traps that damage endothelial cells, increase blood-brain barrier permeability, and drive systemic inflammation . Elevated NETs have been found in acute and chronic COVID-19 cases and may be a biomarker of persistent inflammation and thrombosis . Despite the biological plausibility of these mechanisms, there is limited longitudinal human data linking oxidative stress markers to cognitive outcomes in COVID-19 survivors. This study will follow participants for one year, evaluating neurocognitive performance and biochemical markers at three post-infection intervals: 0-3, 3-6, and 6-12 months.