Supervisor Elham AbolFateh
Editor in Chief Mohamed Wadie

Neurological Manifestations of COVID-19, Op-ed


Fri 10 Jul 2020 | 08:59 AM
Basant ahmed

 

So far, COVID-19 has been primarily known as a respiratory disease, but growing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases.

Studies from China and France have investigated the prevalence of neurological disorders in COVID-19 patients. These studies have shown that 36% of patients have neurological symptoms. Many of these symptoms were mild and include things like headache or dizziness that could be caused by a robust immune response.

Neurologic manifestations fall into 3 categories: central nervous system manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), and skeletal muscular injury manifestations.

Loss of Smell and Taste

Two possible mechanisms for COVID-19 induced anosmia have been proposed. First, ACE2 receptors, which coronaviruses are known to bind to, are ubiquitous in both the lungs and the olfactory epithelium, and that COVID-19 can damage existing olfactory receptor cells as well as stem cells and other supporting mechanisms.

Second, many viruses, including coronaviruses, can propagate via the olfactory nerve and thereby infect and damage the olfactory bulb. Coronavirus RNA has been found in olfactory areas of the brain, and some COVID-19 patients display neurological symptoms.

Further research will be needed to confirm the validity of these proposed mechanisms, and there are potentially longer-term psychological effects of this virus still to be understood.

Loss of smell and taste may indicate that the virus travels from the nose along the nerve pathways to the olfactory bulb in the brain. But it can also travel through the peripheral nerves or through the walls of cerebral vessels to the medulla, the respiratory center, or the hypothalamus.

Neurotropism of COVID-19

Indeed, all previous types of coronaviruses are known to be neuroinvasive. So, chances are that COVID-19 can invade neurons as well.

Several reports have provided evidences to the neurotropism of COVID-19. Elderly patients with chronic underlying medical conditions are at increased risk of encephalopathy in the setting of acute infections.

In addition, COVID-19 patients, especially severe cases, frequently present severe systemic manifestations such as hypoxia, viremia, cytokine storm and coagulopathy which can induce encephalopathy in addition to the direct effects of COVID-19.

There are essentially two principal routes for viruses to gain entry into the CNS: hematogenous or neuronal retrograde dissemination.

To infect a cell, the virus must first attach to a receptor on that cell surface. COVID-19 enters the host cell via a ACE2 — exactly like SARS-CoV. Obviously, ACE2 is expressed on the cell surface of the human respiratory tract. But the brain has been reported to express ACE2 receptors that have been detected over glial cells and neurons, which makes them a potential target of COVID-19.

If the mechanisms of the effects of the virus on the brain and the nervous system can be elucidated, it is possible that some antiviral agents could also improve the survival chances of patients by reducing the viral infection of the nervous system.

Headache

A headache isn't a common symptom of the virus, but about 14% of people infected with COVID-19 have experienced it, according to the Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). It’s clear that some of those headaches are pretty intense.

The reports on the neurological findings are increasing rapidly and headache seems to be the leader on the symptom list. Headache was reported in 11%-34% of the hospitalized COVID-19 patients.

A headache can be caused by many factors related to the coronavirus, such as the physical discomfort of constant coughing and a stuffy sinus. Anxiety, a lack of sleep, not eating properly, and failing to stay hydrated can also lead to headache.

The most striking features of the headache are sudden to gradual onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID-19. Symptomatic COVID-19 patients, around 6%-10%, also reported headache as a presenting symptom.

The possible pathophysiological mechanisms of headache include activation of peripheral trigeminal nerve endings by the COVID-19 directly or through the vasculopathy and/or increased circulating pro-inflammatory cytokines and hypoxia.

Many viruses, from those that cause the common cold to the flu to COVID-19, cause the body to respond in ways that try to destroy the infection. One response is that immune cells release proteins called cytokines that cause inflammation, fever, fatigue and headache.

Headache, a common non-respiratory symptom of COVID-19, it should not be overlooked, and its characteristics should be recorded with scrutiny.

The Risk of Blood Clots is High

COVID-19 is one of the most clot-causing diseases. A third of hospital patients develop dangerous blood clots. As well as causing severe respiratory problems, there is mounting evidence COVID-19 causes abnormalities in blood clotting.

Coronavirus causes damaging blood clots from brain to toes. Patients with severe COVID-19 infection appear to be at greater risk of developing blood clots in the veins and arteries. These blood clots can lead to life-threatening conditions in people with COVID-19, including stroke.

Advanced age and underlying health conditions may also be at play. Both increase one's risk for stroke. This population is also more likely to experience severe illness from a coronavirus infection.

Serious symptoms of a blood clot are pain, redness and swelling. Symptoms of stroke are confusion, dizziness and numbness. These symptoms necessitate admission to the emergency department. The same goes for chest pain and difficulty breathing, which could indicate a clot in the lungs — yet another complication experts are seeing in COVID-19 patients.

There are also COVID-19 patients having ischaemic strokes, where a blood clot blocks the flow of blood and oxygen to the brain. Some of these patients have stroke risk factors (for example high blood pressure, diabetes or obesity), though their strokes have been particularly severe.

It seems that this is because the blood rapidly becomes thickened in COVID-19 and, in these patients, there have been multiple blood clots in the arteries feeding blood to the brain, even in patients already receiving blood thinners. In others, there is brain bleeding due to weakened blood vessels, perhaps inflamed by the effects of the virus.

By Dr. Magdy Badran