This observational cohort study will investigate the association between oxidative stressbiomarkers and post-COVID-19 cognitive impairment. A total of 45 recovered COVID-19patients aged 30-65 will be enrolled and followed at three intervals: 0-3, 3-6, and 6-12months post-infection. Cognitive function will be assessed using standardized memory andattention tests, while venous blood samples will be analyzed for nitric oxide, AOPP,NETs, and extracellular nucleic acids. The study aims to identify early predictors oflong COVID cognitive sequelae and evaluate biological mechanisms underlying persistentneurocognitive symptoms.
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.
Other: 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.
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
Karaganda Medical University
Astana, Kazakhstan
Not Provided