COVID 19NCT07029048
Oxidative Stress and Cognitive Dysfunction After COVID-19
An observational study of COVID 19 and Oxydative Stress, run by Karaganda Medical University at 1 site in Kazakhstan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID 19, Oxydative Stress, Cognitive Impairments
- What is being tested?
- Standard Post-COVID Rehabilitation Program
- How many people
- 45 participants
- Where
- 1 siteKazakhstan
- Study dates
- 1 Mar 2021to 1 Jun 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: Longitudinal Evaluation of Oxidative Stress Biomarkers and Cognitive Impairment in Post-COVID-19 Patients: A Prospective Observational Study
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.
Read the 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
- Being tested
- Standard Post-COVID Rehabilitation Program
- Keywords
- COVID 19, cell-free DNA, Neutrophil Extracellular Trap, AOPP, memory, attention
- Medical subject headings
- COVID-19, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard Post-COVID Rehabilitation ProgramOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Standard Post-COVID Rehabilitation Program |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 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: 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 via blood analysis at three time points.
Measured: Measured at 0-3, 3-6, and 6-12 months after discharge.
Extracellular DNA/RNA and CRF nucleic acids
Quantified in plasma and erythrocytes.
Measured: Measured at 0-3, 3-6, and 6-12 months after discharge.
Neutrophil Extracellular Trap (NET) Levels
Expressed as % of neutrophils, visualised microscopically.
Measured: Measured at 0-3, 3-6, and 6-12 months after discharge.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2025
- Study start1 Mar 2021
- Primary completion1 Jun 2023
- Study completion1 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID 19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karaganda Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yessenbay Gulfairuz, Karaganda Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07029048
- Sponsor's protocol ID
- OXYSTRESS-COVID-19
- Status last verified
- Jun 2025
- First submitted
- 17 Jun 2025
- Last updated
- 25 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Longitudinal Evaluation of Oxidative Stress Biomarkers and Cognitive Impairment in Post-COVID-19 Patients: A Prospective Observational Study
- ClinicalTrials.gov ID
- NCT07029048
- Acronym / sponsor ID
- OXYSTRESS-COVID-19
- Conditions
- COVID 19, Oxydative Stress, Cognitive Impairments
- Keywords
- COVID 19, cell-free DNA, Neutrophil Extracellular Trap, AOPP, memory, attention
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Karaganda Medical UniversityUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 1 Jun 2023 (actual)
- Study completion
- 1 Jun 2023 (actual)
- First posted
- 19 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Post-COVID-19 survivors followed over 12 months | – | Other: Standard Post-COVID Rehabilitation ProgramPrimary 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- History of CNS disease (e.g., dementia, stroke, TBI)
- Psychiatric illness
- Decompensated comorbidities (diabetes, cardiovascular, renal, or hepatic failure)
- Alcohol/drug abuse
- Uncontrolled hypertension
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard Post-COVID Rehabilitation ProgramThis 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. | Other | Post-COVID-19 survivors followed over 12 months |
Primary outcome
Change in Wechsler Memory Scale (WMS) Scores
Time frame: 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
Time frame: 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).
3 secondary outcomes
Levels of Nitric Oxide (NO), AOPP, and Oxidised Proteins
Time frame: Measured at 0-3, 3-6, and 6-12 months after discharge.
Extracellular DNA/RNA and CRF nucleic acids
Time frame: Measured at 0-3, 3-6, and 6-12 months after discharge.
Neutrophil Extracellular Trap (NET) Levels
Time frame: Measured at 0-3, 3-6, and 6-12 months after discharge.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2025.
- Results publication1. 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID 19 and Oxydative Stress, run by Karaganda Medical University at 1 site in Kazakhstan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kazakhstan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Wechsler Memory Scale (WMS) Scores (time frame: Measured at 0-3, 3-6, and 6-12 months after discharge.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07029048, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2025.