Guillain-Barré syndrome has been reported with varying severity in nineteen COVID-19 patients so far. The presented symptoms, which typically occurred approx. one week after the onset of respiratory symptoms, were facial weakness, difficulty breathing, inability to stand or walk, and difficulty weaning off respiratory ventilators. Scientists are unsure whether Guillain-Barré syndrome stems directly from COVID-19, possibly as a result of molecular mimicry, or whether it results from unrelated neurological problems.

Guillain-Barré Syndrome in COVID-19 Patients.

- Proximal weakness (generalized or bilateral leg weakness)
- Global flaccid weakness
- Urinary retention
- Reduced reflexes

Multisystem Inflammatory Syndrome in Children (MIS-C) in COVID-19 Patients: PNS Symptoms

Anosmia and ageusia have been widely reported in COVID-19 patients in Italy, especially in younger patients. Out of 417 patients with mild to moderate COVID-19 in Milan, Italy, 85.6% reported olfactory dysfunction, and from 202 patients with mild COVID-19 symptoms in another hospital in Italy, 64.4% had impaired sense of smell or taste.
In Wuhan, China, among 214 patients hospitalized for COVID-19 symptoms, only 5.1% and 5.6% had impaired smell or taste, with impairment more prevalent among patients with mild rather than severe COVID-19 (6-7% versus 3.0%).


Reported Cases of Anosmia and Ageusia in COVID-19 Patients 

Anosmia and dysgeusia are two common neurological manifestations seen in COVID-19 patients, and these symptoms might appear is over 10% of cases prior to other symptoms. Pneumonia, followed by ARDS, is the most common complication faced by COVID-19 patients. Patients with overactive expression of CXCL10, an inflammatory chemokine, is correlated with patients having a more serious reaction, and in mice, CXCL10 mutants showed less severe lung injury than those with enhanced expression. CXCL10 has been connected to COVID-19 related demyelination, which sustains the cytokine storm and may trigger ARDS, and therefore may be a common denominator between olfactory issues and disease severity.

Connections between Anosmia/Dysgeusia and Pulmonary Dysfunctions in COVID-19 Patients

- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Guillain-Barré Syndrome
- Loss of smell (hyposmia/anosmia) and taste (hypogeusia/ageusia)
- Serious damage to cranial nerves, peripheral nerves, and muscles


Syracuse University

Smith College

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

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

Mao et.al study finds that 36.4% of the COVID-19 patients surveyed presented neurologic symptoms, such as acute cerebrovascular events, impaired consciousness and skeletal muscle injury. Neurologists conducted a study (Jan. 16 - Feb. 19) (n=214, from 3 designated Wuhan hospitals) by retrospectively reviewing patient charts. Nervous system symptoms were found to be more prevalent in severe patients, affecting them disproportionately to their counterparts with regards to CNS function and muscle injury.

Increased neurologic symptoms in severely infected COVID-19 patients

- Encephalopathy (overall)
- Ischemic Stroke
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Induce brain and spine demyelinating lesions
- Mast cell activation
- Acute cerebrovascular disease 
- Intracranial hemorrhage
- Seizure (caused by meningitis)
- Neuroinflammatory syndromes 
- Post-infection cerebral changes

COVID-19 Reports on Patient Neurological Symptoms, Organized by Symptoms Affecting the CNS

COVID-19 Reports on Patient Neurological Symptoms, Organized by Symptoms Affecting the PNS

It was found early on that population with respiratory problems is at greater risk but risk factors include pre-existing diagnoses such as dementia, subarachnoid hemorrhage and epilepsy.  Increased risk is found when the acute care uses sedation, ventilation and delirium. 


Who is likely to suffer from neurocognitive symptoms

Up to 20% of COVID-19 patients who enter the intensive care unit (ICU) with neurological issues or deficits have a higher mortality risk. Even after recovering and leaving the ICU, patients may develop long-term neurological conditions such as depression, obsessive compulsive disorder, psychosis, Parkinson’s disease, and Alzheimer’s disease. ICU patients who take numerous medications or have pre-existing medical conditions can develop memory loss, slow processing speed, delirium, or even coma. Patients with multiple sclerosis, amyotrophic lateral sclerosis, and respiratory dysfunction may struggle to survive ICU hospitalization, and those on immunosuppressive medications may decline faster.


Effects of ICU Admission on COVID Patients with Neurological Issues

Effects on the nose, cranial nerves and brain
1) Anosmia and ageusia caused by inhibition of nasal and gustatory epithelial cells
2) Vessel occlusion in cerebral arteries caused by activation of cytokines and hypercoagulation pathways in the blood
3) Blood clots in the cerebral veins leading to cerebral venous thrombosis.
4) Seizures and/or encephalopathy from high levels of cytokines in the cerebral vessels damaging the blood-brain barrier, infiltrating the brain, and damaging neurons and glia 
5) Meningitis from artery damage
6) Cranial nerve damage from formation of auto-antibodies (molecular mimicry)

Figure 2. Pathophysiology of Neurological Abnormalities in COVID-19

Most researchers believe the neurological effect of the virus are an indirect result of either oxygen starvation to the brain (the “happy hypoxia” exhibited by many patients), or the byproduct of the body’s inflammatory response (the famed “cytokine storm”).  A pateints MRI brain scan showed signs of viral meningitis (inflammation of the brain), and a lumbar puncture detected Sars-CoV-2 in his cerebrospinal fluid.  Another patient had viral particals detected in the  endothelial cells lining the blood vessels of the brain itself. In fact, some scientists now suspect that the virus causes respiratory failure and death not through damage to the lungs but through damage to the brainstem.

How COVID-19 can damage the brain

- Stage I: anosmia, ageusia

- Stage II: blood clots, PNS damage

-Stage II: seizures, coma, encephalopathy


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