Since patients who have recovered from SARS-Cov2 show abnormal protein folding and aggregation, the infection may lead to brain degeneration decades after recovery. By following up with patients affected by COVID-19 and recording their neurological deficits, we may detect plausible connections between COVID-19 and risk of developing aging-associated and neurodegenerative disorders such as Parkinson’s disease.


Cause of Long-Term Brain Degeneration in Patients Recovered from Acute SARS-Cov2 Infection

Cytokine storm can cause small strokes, and if recovered hospital patients continue to experience poor memory, attention, or slow processing speed 6-8 months after discharge, they should see a neurologist. Those with low scores in certain cognitive domains should consider receiving brain rehabilitation in order to restore their cognitive capacity which would reduce their risk for developing a worse case of age-related cognitive decline later in life.

Cause and Treatment for Long-Term Cognitive Decline in Patients Recovered from Acute SARS-Cov2 Infection

In the coming decades, healthcare systems will likely face an influx of patients with:

- Depression

- Anxiety

- Post Traumatic Stress Disorder (PTSD)

- Insomnia

- Psychosis

Mental Disorders Expected to Arise from COVID-19 Pandemic

- Brain degeneration

- Cognitive decline

- Mental disorders


Syracuse University

COVID-19 patients have shown symptoms of direct and indirect neurological effects, from changes in taste and smell, to immunologic factors in cerebral spinal fluid (CSF).  It is unknown whether these phenomena are the result of neurological damage, of SARS-CoV-2 infection, and/or of indirect effects of the immune response. Furthermore, studies in mice have shown that neurons are susceptible to infection, suggesting that cells of the CNS may contribute to the deteriorating breathing and respiratory function of COVID-19 patients. The image below is an early hypothesized mechanism of viral entry through nasal and oral mucosa cells, though there is not yet any evidence to support this hypothesis.

Effects of COVID-19 on the Central Nervous System

Fotuhi, M., Mian, A., Meysami, S., & Raji, C. A. (2020). Neurobiology of COVID-19. Journal of Alzheimers Disease, 76(1), 3-19. doi:10.3233/jad-200581
https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200581

Neurobiology of COVID-19

Many of the known coronaviruses are neurotropic, meaning they are able to infect neuron cells.  If these observed trends carry over to SARS-CoV-2, they could help to elucidate how the CNS is affected by COVID-19.  Some of the key observations include:

- human coronavirus OC43 was shown to transmit itself to different neurons via axons in mice
- neuronal ACE2 expression in mice was found to be in different pre-autonomic regions of the brain which could explain why infected COVID-19 patients with dangerously low blood oxygen levels don't gasp for air
- SARS-CoV was found to infect regions of the brain that deal with cardiopulmonary regulation in human ACE2 knock-in mice
- SARS-CoV patient autopsies showed that the virus affected neurons more than any other kind of cell

Trends in Other Coronaviruses Affecting the CNS
 Relevant to COVID-19

- Neuronal ACE2 Expression as a Risk Factor for COVID-19
- Neuronal ACE2 Internalization in COVID-19
- ACE2 Expression in BBB
- ACE2 Expression in neuroglial cells
- ACE2 Expression in the ENS and Choroid Plexas

ACE2 and its Implications in SARS-CoV2 infection of the CNS

- Autoimmune Response Contribution to Neurological Symptoms.
- Neuro-Immune Cellular Interactions from SARS-CoV-2 Infection.

Indirect/Downstream effects of SARS-CoV-2 on the CNS.

Even in the absence of typical respiratory symptoms such as fever, cough, and shortness of breath, various patients diagnosed with COVID-19 have presented neurological symptoms, such as:

- acute cerebrovascular diseases

- impaired consciousness

-  skeletal muscle injury

- encephalopathy (symptoms: ischemic stroke)

- loss of smell (anosmia) and taste (ageusia)

- stroke

- cranial nerve deficits

- delirium

- meningitis

- paralysis

- seizures

- neuroinflammatory syndromes

- high pressure CSF

- muscle stiffness

The list below includes less-common neurological symptoms of COVID-19:
- Guillain–Barré syndrome (GBS)
- Multisystem Inflammatory Syndrome in Children (MIS-C)

Neurological symptoms Presented in COVID-19 Patients

Expected Long-Term Outcomes of Acute SARS-Cov2 Infection on CNS

- Hypothesized Mechanisms for SARS-CoV-2 Direct Invasion of the CNS
- Controversy: Is SARS-CoV-2 "Neuroinvasive"?

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