Possible Long-Term Neurologic Complications Between COVID and MS

In part 2 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 discusses whether patients with MS are at a higher risk of COVID-19, and if there are known risks between disease modifying therapies and COVID-19 symptoms.

Read the Transcript:

Then, lastly in terms of COVID-19 and neurologic complications, there is a long-term sequelae that are associated with neurologic symptoms. It's estimated that as many as 10 to 15 percent have long-term sequelae. Among the long-term sequelae are fatigue, cognitive difficulties, and generalized weakness.

In answering the questions with respect to whether COVID has a pernicious effect over and above what we would see otherwise in the MS population, and whether certain disease-modifying therapies affect the course of the disease, there have been a number of registries created.

I have a list of the registries. I don't know how important it is. The one that we have in North America, the biggest one in North America, is the COViMS registry. There are those that are available at country level. Sweden has one, UK, Germany, Australia, New Zealand, and in addition to those there are other broader registries like, MSBase.

There are a lot of registries that are now looking at patients who have MS, who had been infected with SARS-CoV-2, and trying to analyze whether or not there's significant risks over and above that, which would be otherwise expected. These have been very helpful.

At the University Pennsylvania we have our own registry with probably close to 200 or more patients in it. This has been enormously helpful for us.

What these registries have taught us by and large, and I won't refer to any specific registry, is that MS in and of itself does not increase the risk of morbidity and mortality associated with COVID-19, with the exception of those individuals who are severely affected by their MS.

Individuals that have very high EDSS scores, that are wheelchair bound or bedridden, and individuals that are older, and individuals that have underlying risk factors that would have otherwise put them at risk for COVID-19 morbidity and mortality, such as hypertension, diabetes, obesity, etc., those individuals are at increased risk. The overall population, the overall MS population does not appear to be.

There does not appear to be a very strong signal from any of the disease modifying drugs and increase risk with COVID-19. With perhaps the possible exception of the anti-CD20 monoclonal antibodies, or pertuzumab, or ofatumumab, or rituximab.

In those instances, there may be from some of these registries, not all. We don't find it in our registry at the University of Pennsylvania, where we have over 1,200 patients on these drugs. Some registries have reported a slight increased risk of hospitalization, but there does not appear to be a significant increased risk of death associated with these drugs.

By and large MS does not have a very significant impact on the course of COVID-19. With the exceptions that I've mentioned, that is, being older, being debilitated, and having these other underlying risk factors.

In terms of these drugs that we use for MS, it turns out that some of them may actually have a salutary effect on COVID-19. There is some data that Interferon Beta -- which by the way is an antiviral -- may have a salutary effect. There have been others that have been considered as possibly having a beneficial effect in the setting of COVID-19 though, it remains to be demonstrated.

In part because of the dampening of this aggressive immune response that has in large measured the cause for the morbidity and mortality that we see. Now, another area that is quite important is people's response to vaccines, if they are on one of these disease modifying therapies.

What we find is that certain of the drugs seem to blunt the immune response to vaccines. That appears to be true with the anti-CD20s of varying degrees with each of them, and also appears to be true with the S1P receptor modulators, probably to a lesser extent than with the anti-CD20 monoclonal antibodies.

Now recall that most of these studies have looked only at humoral immune response and humoral immune responses only one side of the coin. There's both a humoral and a cell mediated immune response that is generated by vaccine, and it is believed, although it remains to be studied and unequivocally demonstrated, that the cellular immune response is largely unaffected by the drugs that we administer. The humoral immune response can be blunted.

Perhaps among the best papers, looking at this, has been the study referred to as the Baluchi study of individuals who've received vaccines, three months after a dose of ocrelizumab. Where one sees that when compared to control groups, who've received either no disease modifying therapy or Interferon Beta, there is a blunting of the immune response, the humoral immune response. Although for the most part while attenuated, they are believed to be sufficiently protective against the diseases that the vaccines were developed for, in this case, a Tetanus, influenza, and pneumococcus.

The data so far with respect to vaccine response is still quite preliminary. There is concern that some people may generate little if any antibody, and the course of treatment after that is whether they will require a booster dose or how best to manage it has not been fully developed. My sense is that virtually everybody may need a booster dose at some point in time for COVID-19.

There's certain drugs that we hesitate to initiate until we've gotten somebody vaccinated. It's probably reasonable for drugs such as alemtuzumab, the anti-CD20s, and the S1Ps that if you're about to start, then it's perhaps best to attempt to get the patient vaccinated in advance of that initiation. Although sometimes, it's quite difficult to do that.

That, in essence, is the COVID and MS intersection talk.