Oxidative Stress and Cognitive Dysfunction After COVID-19

NCT ID: NCT07029048

Last Updated: 2025-06-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 45 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2023-06-01

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.

Conditions

COVID 19; Oxydative Stress; Cognitive Impairments

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Post-COVID-19 survivors followed over 12 months

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.

Standard Post-COVID Rehabilitation Program

Intervention Type: OTHER

This standardized rehabilitation intervention includes a 14-day inpatient course comprising physiotherapy, therapeutic exercises, massage, and respiratory gymnastics. The program is delivered equally to all participants regardless of cognitive status and is intended to promote post-viral recovery in patients recently discharged following COVID-19 pneumonia. No specific cognitive therapy or pharmacological treatment is administered during the rehabilitation period. The intervention is used as background care, not as an experimental variable.

Interventions

Standard Post-COVID Rehabilitation Program

This standardized rehabilitation intervention includes a 14-day inpatient course comprising physiotherapy, therapeutic exercises, massage, and respiratory gymnastics. The program is delivered equally to all participants regardless of cognitive status and is intended to promote post-viral recovery in patients recently discharged following COVID-19 pneumonia. No specific cognitive therapy or pharmacological treatment is administered during the rehabilitation period. The intervention is used as background care, not as an experimental variable.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karaganda Medical University

OTHER

Sponsor Role: lead

Responsible Party

Yessenbay Gulfairuz

Principal Investigator Zhumabekova Indira

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Karaganda Medical University

Astana, , Kazakhstan

Countries

Kazakhstan

References

1. Premraj L, Kannapadi NV, Briggs J, Seal SM, Battaglini D, Fanning J, et al. Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis. J Neurol Sci. 2022;434:120162. 2. Becker JH, Lin JJ, Doernberg M, Stone K, Navis A, Festa JR, et al. Assessment of Cognitive Function in Patients After COVID-19 Infection. JAMA Netw Open. 2021;4(10):e2130645. 3. Graham EL, Clark JR, Orban ZS, Lim PH, Szymanski AL, Taylor C, et al. Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 "long haulers". Ann Clin Transl Neurol. 2021;8(5):1073-1085. 4. Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 6-month neurological and psychiatric outcomes in 236,379 survivors of COVID-19. Lancet Psychiatry. 2021;8(5):416-427. 5. Hosp JA, Dressing A, Blazhenets G, Bormann T, Rau A, Schwabenland M, et al. Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19. Brain. 2021;144(4):1263-1276. 6. Cichoż-Lach H, Michalak A. Oxidative stress as a crucial factor in liver diseases. World J Gastroenterol. 2014;20(25):8082-8091. 7. Delgado-Roche L, Mesta F. Oxidative Stress as Key Player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection. Arch Med Res. 2020;51(5):384-387. 8. Cecchini R, Cecchini AL. SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression. Med Hypotheses. 2020;143:110102. 9. Islam MT, Sarkar C, El-Kersh DM, Jain S, Mitra S, Debnath M, et al. COVID-19 and neurodegeneration: The contribution of oxidative stress and inflammation. Oxid Med Cell Longev. 2022;2022:9503143. 10. Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer's disease. Redox Biol. 2018;14:450-464. 11. Maes M, Vojdani A, Galecki P. Redox dysregulation, immuno-inflammatory pathways, and neuropsychiatric disorders in Long COVID. Mol Neurobiol. 2022;59(3):1859-1882.

Reference Type: BACKGROUND

Other Identifiers

OXYSTRESS-COVID-19

Identifier Type: -

Identifier Source: org_study_id