Neurological complications of COVID-19

Ongoing COVID-19 pandemic posed unprecedented challenge for the healthcare system and changed a lot of aspects of our life. This disease caused by coronavirus SARS-CoV-2 that enters host cells due to interaction between S protein located in its surface with angiotensin converting enzyme 2 (ACE-2) located on the surface of the cells. Since a lot of cells expressing ACE2 located in the respiratory tract, initial clinical manifestations of COVID-19 associated with acute inflammation in the respiratory system: caught, sore throat, pneumonia, dyspnea, fever. In severe cases widespread inflammation in the lungs leads to insufficient supply of tissues and organs with oxygen.

Scientific studies aiming to reveal mechanisms of COVID-19 development showed that severe cases associated with dysregulated immune response characterized by overwhelming production of inflammatory cytokines released into systemic blood flow (cytokine release syndrome/cytokine storm) and exaggerated self-damaging activity of immune cells.

Despite primary focus of healthcare professionals on lung damage treatment, importance of extra-pulmonary complications of COVID-19 have been increasingly recognized due to follow-up studies of patients after recovery.

Neurological symptoms associated with COVID-19 include headache, dizziness, loss of smell and taste sensations, encephalopathy, encephalitis, etc. Despite some reports of SARS-CoV-2 presence in several brain regions and corresponding antibodies in cerebrospinal fluid (CSF), most of the studies failed to show severe viral infection of neural tissues or presence of SARS-CoV-2 in CSF. Thus, it was suggested that in majority of patients suffering from neurological complications of COVID-19 these pathologies caused not by massive viral load of neural tissues but by another mechanism associated with dysfunctions of neuronal circuits of the brain.

Even in the absence of severe viral infection of neural tissues, elevated levels of inflammatory cytokines in systemic blood circulation during COVID-19 may lead to mirror inflammatory response in the brain. It is known that brain has privileged position in relation to systemic blood circulation due to the blood-brain barrier. This system protecting brain from a wide range of substances circulating in systemic blood flow composed of blood vessels with specialized endothelial cells, basement membrane, astrocytes, microglia. However systemic immune challenge may trigger neuroinflammation due to the trafficking of inflammatory mediators into the nervous system via several routes. Endings of some fibers originating from neural centers located in brainstem express receptors for various inflammatory mediators known as damage-associated molecular patterns and pathogen-associated molecular patterns. Another pathway includes special transport mechanisms allowing inflammatory mediators from the blood to cross blood brain barrier. Also, systemic inflammation might result in local disruption of blood-brain barrier facilitating transfer of inflammatory mediators into the brain further.

Inflammatory reactions in central nervous system mostly driven by resident immune cells of the brain called microglia. Due to mechanisms mentioned above cytokine storm in COVID-19 may lead to over-activation of microglia cells. Initially, these cells migrate to cerebral vessels aiming to reinforce and protect blood brain barrier. However, prolonged activation of microglia due to circulation of inflammatory mediators in the blood might lead to dysfunction of these cells associated with impairment of blood brain barrier. This, in turn, may lead to an increased influx of inflammatory mediators and migration of activated immune cells from the blood into neural tissues. Being resident immune cells of the brain microglia intent to protect neural system from pathogens but over-activated microglia cells with increased expression of inflammatory genes have potential to disturb normal functioning of neuronal circuits and kill neurons. Thus, neuroinflammation triggered by COVID-19 might result in long-term neurological sequel even without viral infection of the brain after recovery from acute respiratory manifestations.

Taking into account this pathogenic mechanism, stem cell treatment represents promising approach aiming to decrease risk of neurological complications associated with COVID-19 and facilitate recovery of nervous system during post-COVID-19 period. Rationale for efficiency of such approach provided by studies that showed potent immunomodulatory properties of stem cells due to release of anti-inflammatory cytokines limiting inflammation. In addition to anti-inflammatory action, stem cells have important neuroprotective properties mediated by production of such neurotrophic factors as nerve growth factor, brain-derived neurotrophic factor, vascular endothelial growth factor.

In order to use anti-inflammatory and neuroprotective properties of stem cells to ameliorate neurological sequelae of COVID-19 Infinity Clinic offers personalized combinations of stem cells that include neural stem cells and additional types of stem cells that are chosen according to individual health status of each patient. 

Neurological complications of COVID-19
Neurological complications of COVID-19400600
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