Neurological Manifestations of COVID-19 Infection

Podcast Transcript

Alex Rae-Grant, MD:  Neuro Pathways, the Cleveland Clinic podcast for medical professionals, exploring the latest research discoveries and clinical advances in the fields of neurology, psychiatry, neuro surgery and neuro rehab.

As reports of COVID-19 case series from China and elsewhere start to accumulate, we're getting a clearer picture of how infection with the virus known as SARS-CoV-2 can cause emerging neurological features.

In today's episode of Neuro Pathways, we're discussing the neurological manifestations of COVID-19 infection.  I'm your host, Alex Rae-Grant, neurologist in Cleveland Clinic's Neurological Institute. I'm very pleased to have Dr. Jeffrey Cohen join us for today's conversation. Dr. Cohen is the Director of the Experimental Therapeutics Program in Cleveland Clinic's Mellen Center for Multiple Sclerosis Treatment and Research. He is also professor of neurology in Cleveland Clinic's Lerner College of Medicine. Jeff, Welcome the Neuro Pathways.

Jeffrey Cohen, MD:  Thank you for inviting me, Alex.

Alex Rae-Grant, MD:  So Jeff, we're beginning to see in more and more data published on neurological manifestations of COVID-19 infection. Can you tell us a bit about neurological manifestations and what's being seen in patients diagnosed with this disease?

Jeffrey Cohen, MD:  Well, the COVID-19 pandemic has disrupted all aspects of life, including effects on healthcare and health. And it's turning out to be quite a complicated infection. So the neurologic complications are increasingly being recognized.

One aspect of neurologic involvement is a consequence of the severe hypoxemic respiratory failure, sometimes accompanied by cardio toxicity, liver failure, renal failure. So it's a metabolic encephalopathy associated with critical illness. One of the things we've learned is, is that among the risk factors for severe COVID-19 infection are comorbidities, including cardiovascular risk factors. So we've also seen a stroke in association with COVID-19 infection.

But beyond that, there are several very interesting secondary complications of the infection. So one is a cytokine release inflammatory syndrome that frequently develops several weeks into the illness with very high circulating levels of a variety of inflammatory cytokines, including interleukin 6, tumor necrosis factor alpha, interferon gamma, plus a number of other ones. And so there may be some neurologic consequences of that.

There also may be virus infection of the endothelial cells, the cells that line the blood vessels leading to a thrombotic condition, which can cause a stroke. And we've seen stroke in young people with COVID-19 infection, including as the presenting manifestation. And then finally there may be what looks like a vasculitis, a Kawasaki disease-like illness, particularly in young children.

Alex Rae-Grant, MD:  So it sounds like, Jeff, there's a number of different mechanisms of neurological injuries that occur. I had heard there were a number of reported cases of Guillain-Barre syndrome and then a recent encephalitis picture. So it seems like it's diversifying a bit, isn't it?

Jeffrey Cohen, MD:  Right. So as we're becoming better at diagnosing COVID-19, we're also recognizing some other neurologic manifestations, which previously were thought to be rare, but now appear to be somewhat more common than we realized.

Some of those are immune mediated, as you mentioned. So illnesses that look like Guillain-Barre syndrome or other acute CNS inflammatory demyelinating conditions. But there also may be in some patients, a direct viral infection of the central nervous system. And there have been emerging cases of a meningoencephalitis-like illness in some people. And also perhaps infection of neurons in certain key areas of the brain. For example, those involved with cardiopulmonary regulation, which may also contribute to the respiratory failure.

Other symptoms, which are of interest include ageusia, loss of taste, and anosmia, loss of smell. These symptoms are of interest because first of all, they're unusual. And secondly, because they can occur acutely with only mild other symptoms, or in some cases proceeding other symptoms. In some patients they may be due to inflammation of the nasal pharynx. But in other cases, it's been hypothesized that they result from direct viral infection of olfactory bulb neurons, or other neurons within the central nervous system involved in taste and smell. So it's an infection that causes a myriad of manifestations through a variety of mechanisms.

Alex Rae-Grant, MD:  Yeah, it does seem that it's spreading to different neurological systems as we speak. Maybe Jeff, can we go back to stroke. It seems to be a major complication, as you mentioned, vascular risk factors and possibly related to other mechanisms. This seems to be affecting younger people as well as older people. Is there anything else we need to say about stroke in this condition?

Jeffrey Cohen, MD:  So stroke is turning out to be an important neurologic manifestation of COVID-19. And there's probably two scenarios. One is the older patient with cardiovascular comorbidities. Who may develop a stroke in association with a critical COVID-19 infection.

The other setting that we're recognizing increasingly is stroke in young people. And that may be due to either the hypercoagulable state that the virus infection may induce, or it may be due to a vasculitis-like illness. So if one encounters a stroke in a young person, COVID-19 is an important consideration.

Alex Rae-Grant, MD:  So let's shift the discussion a bit. So, many of us manage patients with various neurological disorders, some people on immunological medication. So, the protocols seem to be changing daily and a number of societies put out some guidance, but what steps is the Cleveland Clinic and the Mellen Center, what steps are we taking to provide safe patient care in this time?

Jeffrey Cohen, MD:  Well, so there's been a lot of concern in the MS field, my area of expertise, about whether multiple sclerosis might increase the susceptibility to infection or the severity of the infection. Including as a consequence of the disease modifying therapies that we use to treat MS, all of which are immunomodulatory in some way. Thankfully the current indications are that people with multiple sclerosis are not more susceptible to the infection or at risk for a more severe infection. And that the disease modifying therapies also don't increase the susceptibility of or severity of the infection.

There are a number of other considerations however. Some of the disease modifying therapies are relatively long-acting. So in some patients, particularly if they're not already on disease modifying therapy, it may be prudent to weigh the benefits and the risk anticipating that we might learn more about the infection. The second consideration is that some of our more potent therapies are administered by intravenous infusion, which does increase the risk of exposure to infection as patients go to an infusion center. And then finally, something that we're becoming increasingly concerned with, is whether the disease modifying might interfere with the ability of someone to mount a response to a vaccination when those become available.

So it's still a complicated situation, but at present, we've not made major changes in how we're treating multiple sclerosis as a result of COVID-19. The other issues that are important to advise one's patients about are that, even as we're starting to open up and people are going out in public more, it's important for people with chronic illnesses such as multiple sclerosis, to practice good infection prevention measures. Including limiting contacts with people that may be infected, practice hand-washing have people wear masks to protect each other.

And the other final aspect is, is that people with MS, like other chronic illnesses, need not to neglect the care for their multiple sclerosis. So one of our concerns is that people may be foregoing testing or forgoing treatment for fear of infection. And it's important to advise patients not to do that.

Alex Rae-Grant, MD:  Yeah, thanks, Jeff. I actually want to reconfirm that. I just Zoom meeting a patient a couple of days ago, who had stopped her MS medication and just had a relapse of optic neuritis off medicine. And certainly a concern of people are stopping their medicine they need for their disease.

It's a pretty crazy time in healthcare and in society in general. And we've had to change how we communicate with our patients. Can you give the audience a sense of how the Mellen team is communicating with patients during the pandemic and how that's working out?

Jeffrey Cohen, MD:  Well, so we had, even before the pandemic, we had already been developing a distance health capability. We see a lot of patients, some of whom travel a long distance, and we wanted to be able to maintain contact with them. And it may be difficult for them to travel. So we had already been developing the capability to interact with patients at a distance.

And then with the pandemic and with our center, like many other centers, closing down our in-person visits, we very rapidly shifted to virtual visits. And that's actually gone quite well. Patients like it. It allows us to interact with them, at least on the computer screen, face-to-face. It's better than a phone call. So I expect that even as we start to open up our clinical program, that we'll still maintain a sizable proportion of visits that are done virtually.

Alex Rae-Grant, MD:  That was the next thing I was going to ask is, how do you see things once, and we all hope it will, once the pandemic settles down. Do you see that changing other things about what we do in medicine, distance medicine approaches?

Jeffrey Cohen, MD:  Well, I think in some ways it may increase our ability to interact with patients. When we relied solely on face-to-face visits, we almost saw the smallest frequency possible. Whereas now, I expect that we'll intersperse face-to-face visits with virtual visits.

It's not only applicable to visits with physicians and advanced practice clinicians, but it also may be very helpful for things such as a social work, health psychology. And actually physical speech, occupational therapy, all of those can be done virtually. So I think in some ways, now that we've started thinking outside the box, it may allow us to administer some of those programs for patients at a distance.

Alex Rae-Grant, MD:  Well, certainly has allowed us to think it through in a pretty rapid way and change process pretty quickly. Jeff, let me ask you, there's quite a bit going on in terms of research on COVID-19 infection at the Cleveland Clinic. As a leader in that research, can you tell us some of the things that are going on in that area?

Jeffrey Cohen, MD:  Well, so we've been pursuing several lines of research. One is just to gather more data on the manifestations of the infection, and what are the factors that determine the risk of the infection and the severity of the infection. We have the advantage that we see and test quite a large number of people, so it's allowed us to identify some of those factors. And as I alluded to earlier, many of those are older age, overall health including the presence of comorbidities, some medications.

But it turns out that it's made us very aware of the social determinants of health, so that people that have less access to healthcare don't have the luxury of staying home, who must work. And who work in jobs that require them to be exposed to other people, are at higher risk for the infection. So that's been one line of research. Another line of research has been to test potential therapies for the infection itself and for some of the complications of the infection. And then finally, more basic research to try to understand the mechanisms of the infection and the mechanisms by which it causes complications.

Alex Rae-Grant, MD:  Well, that's great. Is there any other major closing remarks or takeaways from our conversation you want the audience to hear?

Jeffrey Cohen, MD:  Well, so I would say that like everybody, this has been a difficult time. And as I think I started by saying, the COVID-19 pandemic has disrupted many aspects of life, including healthcare. It's also shown a light on some aspects of healthcare that we already knew were problematic, but it's really emphasized some of those. So hopefully we'll get through this pandemic and also learn from it.

Alex Rae-Grant, MD:  Yeah, it would be nice if we could take the best learnings from it and move forward in medicine. Well, Jeff, I want to thank you for taking the time to discuss this area of medicine, it certainly ... We're all thinking about right now and glad to hear that we're doing our part. So thank you very much for helping.

Jeffrey Cohen, MD:  Well, thank you, Alex.

Alex Rae-Grant, MD:  This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you get your podcasts. And don't forget you can access real-time updates from experts in Cleveland Clinic's Neurological Institute, on our Consult QD website, that's consultqd.clevelandclinic.org/neuro, or follow us on Twitter @cleclinicmd, all one word that's at C-L-E clinic M-D on Twitter. Thank you for listening. Please join us again soon.