Oxidative Stress and Cognitive Dysfunction After COVID-19

Completed

• Conditions: COVID 19; Oxydative Stress; Cognitive Impairments

• Registration Number: NCT07029048
• Lead Sponsor: Karaganda Medical University

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2021-03-01
• Primary Completion: 2023-06-01
• Study Completion: 2023-06-01
• Status Verified: 2025-06
• Study First Submitted: 2025-06-17
• Study First Submitted QC: 2025-06-17
• Study First Posted: 2025-06-19
• Last Update Submitted: 2025-06-19
• Last Update Posted: 2025-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in Wechsler Memory Scale (WMS) Scores	Measured at 0-3, 3-6, and 6-12 months after discharge.	Assessment of memory function using the Wechsler Memory Scale, which measures different memory domains including working memory, visual memory, and auditory memory.; Scoring Range: 50 to 150 (higher scores indicate better memory performance).
Change in Bourdon Attention Test Scores	Measured at 0-3, 3-6, and 6-12 months after discharge.	Assessment of sustained attention and processing speed using the Bourdon Attention Test, which records the number of correctly marked target symbols within a given time.; Scoring Range: 0 to 15 (higher scores indicate better attention and processing accuracy).

Secondary Outcome Measures

Name	Time	Method
Extracellular DNA/RNA and CRF nucleic acids	Measured at 0-3, 3-6, and 6-12 months after discharge.	Quantified in plasma and erythrocytes.
Neutrophil Extracellular Trap (NET) Levels	Measured at 0-3, 3-6, and 6-12 months after discharge.	Expressed as % of neutrophils, visualised microscopically.
Levels of Nitric Oxide (NO), AOPP, and Oxidised Proteins	Measured at 0-3, 3-6, and 6-12 months after discharge.	Measured via blood analysis at three time points.

Trial Locations

Locations (1)

Karaganda Medical University; 🇰🇿 Astana, Kazakhstan