The Intersect Between COVID-19 and Multiple Sclerosis

In part 1 of this video, Joseph Berger, MD, FACP, FAAN, FANA, Professor of Neurology, University of Pennsylvania; Associate Director, Multiple Sclerosis Division at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, discusses his recent presentation “Examining the Intersect of COVID and MS,” given virtually at Neurology Week. Dr. Berger addresses concerns regarding a correlation between SARS-CoV-2 and Multiple Sclerosis.

Read the Transcript:

Dr. Joseph Berger: I'm Joseph Berger. I'm a Professor of Neurology at the University of Pennsylvania. I am also the Associate Director of the MS Center at the Perelman School of Medicine at the University of Pennsylvania.

We'll talk initially about COVID and MS, the intersect between the two of them. Where the intersections are include the fact that there has been concern expressed that the manifestations of MS may be magnified by an infection like SARS-CoV-2, that MS itself may increase the risk of both morbidity and mortality with SARS-CoV-2 whether it's MS or the disease modifying therapies that one has.

Then, there's been a lot of concern about vaccination for COVID and the response of individuals to the vaccines. Can you safely vaccinate the MS patient, and will they mount the same response? They're the predominant questions.

The other thing that is important is, those manifestations of COVID-19, neurologic manifestations, neurologic consequences that can masquerade as MS or an MS-like illness. All of those things will be covered in this particular talk, as well as a background on COVID-19.

As people know, we now have well over 600,000 deaths in the United States and roughly half of the American adult population remains unvaccinated, certain states being more affected with unvaccinated people than others.

We now have an increase in a strain of COVID referred to as the Delta strain, which developed in India and not only increases the likelihood of acquiring the infection over the strains that initially appeared, but may be associated with different disease manifestation and perhaps even worsening of the disease manifestations.

Now, COVID is the consequence of SARS-CoV-2, and it is a coronavirus. Then, there are a number of coronaviruses that had been previously described, two of which had been associated with epidemics previously. One was SARS, which is Severe Acute Respiratory Syndrome, and the others the Middle Eastern Respiratory Syndrome.

The virus that causes SARS, which is SARS-CoV-1 is very similar genetically, and also uses the same binding receptor, as the SARS-CoV-2, its classes COVID-19.

The binding receptor that it uses is the angiotensin-converting enzyme type II receptor, which is expressed in many, many different tissues, including neurologic tissue. You find it in the brain. You can find it in, for instance, oligodendrocytes.

It is found in the olfactory epithelium, not necessarily the olfactory nerves, and binds there, and it's one of the common manifestations is loss of sense of smell, because of the binding of the virus to the H2 receptor in the olfactory epithelium, in what's called the sustentacular cells, and damage that it causes there.

Deaths that we see, and the severe illness that we see with COVID-19 are, for the most part, the consequence of an over abundant immune reaction to the virus, and the genesis of something called the systemic inflammatory response.

Therefore, it is this over aggressive immune response that leads in most instances, to the morbidity and mortality that we see, which is largely but not exclusively pulmonary, in some instances, there are neurologic complications that occur as a consequence.

We know that individuals with underlying disease, certain ones anyhow, have increased susceptibility to the morbidity and mortality associated with COVID-19, but for the most part, these are non-neurologic, so they're things like chronic metabolic syndrome, obesity, hypertension, diabetes, chronic lung disease, asthma.

If one looks at other conditions that people have, in which they end up being hospitalized, it's only a minority of individuals that have neurologic disease as an underlying risk factor for severe COVID-19.

Now, as I mentioned earlier, there are a lot of neurologic complications that occur in association with COVID-19. Some are the direct complication of viral infection, the viral invasion. Some are the indirect consequence.

Those that are the direct consequence are things like the loss of sense of smell and taste, meningitis, encephalitis, and cerebrovasculitis. In some instances, a myelitis and inflammation of the spinal cord triggered by the virus, involvement of peripheral nerves and involvement of the muscles whereas the muscles have been invaded by the virus.

No portion of the neuroaxis is immune to this virus. Then, we have the indirect effects, which affect the nervous system and are likely far more common. These include the hypoxia that occurs with involvement of the lungs, so people become encephalopathic from that. They may not even realize that they're hypoxic.

In other words, they may not be experiencing significant shortness of breath, and yet have altered cognition as a consequence of the hypoxia they're experiencing. There is a cytokine storm, which is this robust immune response that occurs and can lead to an encephalopathy.

There is a particular encephalopathy called acute necrotizing encephalopathy we see with it. It can cause a hypercoagulable state. Therefore, stroke is observed, and there are metabolic abnormalities that occur with COVID-19 that can manifest as neurologic disease.

The ones that we're most interested in where we're looking for the intersection between COVID-19 and MS are the autoimmune disorders triggered by the infection. Among these are acute disseminated encephalomyelitis. What's also been seen as optic neuritis as an autoimmune phenomenon. These can be mistaken for MS.

There are others as well, not as commonly mistaken for MS. Things like Guillain-Barre syndrome and Miller Fisher syndrome that also have been described in association with COVID-19. There's this panel of autoimmune neuroinflammatory conditions.

In summary, these include acute disseminated encephalomyelitis, acute necrotizing encephalitis, which is due to this cytokine storm, optic neuritis, acute transverse myelitis, inflammation of the spinal cord.

Both neuromyelitis optica positive and myelin oligodendrocyte glycoprotein positive neuromyelitis optica have been...Or I should say neuromyelitis optica syndrome...Have been seen in the face of COVID infection. See Miller Fisher syndrome, Guillain-Barre syndrome, and autoimmune myopathy, all of them reported.

Interestingly, they didn't occur weeks after the infection. In many instances, while the person is still symptomatic with COVID-19, these autoimmune neurologic disorders have made their appearance. So, we will sometimes see them even from the inception of the realization that they're infected with COVID-19.