Oxidative Stress and Cognitive Dysfunction After COVID-19

Karaganda Medical University

Status: Completed

Conditions: Oxydative Stress; COVID 19; Cognitive Impairments

Treatments: Other: Standard Post-COVID Rehabilitation Program

Study type: Observational

Funder types: Other

Identifiers

NCT07029048

OXYSTRESS-COVID-19

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 45 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age > 18 years
• Confirmed history of COVID-19 pneumonia (PCR and CT-verified)
• Recovered and discharged from COVID-19 hospital unit
• Able to provide informed consent
• Either presence or absence of self-reported cognitive complaints

Exclusion criteria

• History of CNS disease (e.g., dementia, stroke, TBI)
• Psychiatric illness
• Decompensated comorbidities (diabetes, cardiovascular, renal, or hepatic failure)
• Alcohol/drug abuse
• Uncontrolled hypertension
• Acute respiratory insufficiency or fever at time of assessment

Trial design

45 participants in 1 patient group

Post-COVID-19 survivors followed over 12 months

Description:

Primary Objective: To investigate the association between oxidative stress biomarkers (e.g., cell-free DNA, AOPP, NETs, OMB, NO) and cognitive impairment (memory and attention deficits) in post-COVID-19 patients. Secondary Objectives: To assess the longitudinal dynamics of oxidative stress markers at 0-3, 3-6, and 6-12 months post-COVID. To identify biochemical predictors of persistent cognitive dysfunction.

Treatment:

Other: Standard Post-COVID Rehabilitation Program