Oxidative Stress and Cognitive Dysfunction After COVID-19

NCT07029048 | Completed DMC

• 1 other identifier: OXYSTRESS-COVID-19
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID 19; Oxydative Stress; Cognitive Impairments

Keywords

COVID 19; cell-free DNA; Neutrophil Extracellular Trap; AOPP; memory; attention

Outcome Measures

Primary Outcomes (2)

• Change in Wechsler Memory Scale (WMS) Scores

  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).

  Measured at 0-3, 3-6, and 6-12 months after discharge.

• Change in Bourdon Attention Test Scores

  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).

  Measured at 0-3, 3-6, and 6-12 months after discharge.

Secondary Outcomes (3)

• Levels of Nitric Oxide (NO), AOPP, and Oxidised Proteins

  Measured at 0-3, 3-6, and 6-12 months after discharge.

• Extracellular DNA/RNA and CRF nucleic acids

  Measured at 0-3, 3-6, and 6-12 months after discharge.

• Neutrophil Extracellular Trap (NET) Levels

  Measured at 0-3, 3-6, and 6-12 months after discharge.

Study Arms (1)

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.

Other: Standard Post-COVID Rehabilitation Program

Interventions

Standard Post-COVID Rehabilitation Program 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.

Post-COVID-19 survivors followed over 12 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will involve adult patients who have recovered from PCR-confirmed COVID-19 pneumonia. Participants will be recruited at the time of discharge from inpatient treatment facilities in Karaganda, Kazakhstan. The target population includes individuals with or without subjective cognitive complaints during early recovery. All participants must have preserved consciousness at baseline, be able to provide informed consent, and meet the inclusion and exclusion criteria related to neuropsychiatric, respiratory, and systemic comorbidities. A balanced representation of genders will be encouraged. The study will longitudinally assess cognitive and biochemical parameters at three post-infection intervals: 0-3 months, 3-6 months, and 6-12 months.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Karaganda Medical University: lead

Study Sites (1)

Karaganda Medical University

Astana, 010000, Kazakhstan

Location

Related Publications (1)

• 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.

  BACKGROUND

MeSH Terms

Conditions

COVID-19; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator Zhumabekova Indira

Study Record Dates

• First Submitted: June 17, 2025
• First Posted: June 19, 2025
• Study Start: March 1, 2021
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: June 25, 2025

Record last verified: 2025-06

Locations

KA (1)