​COVID-19 AND MULTIPLE SCLEROSIS: Part II - What we think we know

Part II: What we think we know
 
As is often the case, what we think we know in medicine exceeds our grasp of the actual facts. This does not mean we cannot make logical assumptions, better known as educated guesses, based on our prior medical experience with other viral infections. These experiences must guide our advice and recommendations to patients and families until we have a better understanding of COVID-19.
 
First, we do not know how people with multiple sclerosis respond to a COVID-19 infection. When I talk to colleagues in Italy, which is slightly ahead of us in terms of the pandemic, they know their MS patients are getting sick, but they’ve had no time to determine if certain MS patients are more or less susceptible to severe disease. Even my colleagues in the USA are starting to tweet about their anecdotal experience with COVID-19 infections in isolated MS patients. 

These anecdotes are reassuring, but not terribly informative. Since 80-90 % of people with a COVID-19 infection experience relatively mild disease, it is not surprising to hear that individual MS patients on various disease modifying therapies (DMTs) recover well from their COVID-19 infection.

​For the time being we need to pay attention to what we know for sure and not jump to unnecessary conclusions. Here is what we think we know.
 
As pointed out by recent publications from China and in my last blog, there are several risk factors for COVID-19 related pneumonia (severe disease) that apply to everyone, including MS patients.  These known risks include age over 50 (particularly age over 65), male sex, hypertension (treated or untreated), diabetes and cardiovascular disease.  What seems to be unique about COVID-19 infection is the unusual link between the severity of infection (pneumonia) and high blood pressure.

We do not usually see a link between infectious diseases and high blood pressure. Experts on corona viruses tell us that COVID-19 uses a receptor on the surface of cells that line the respiratory system to infect your upper and lower respiratory tract. This receptor, called the angiotensin II receptor, is more numerous (up-regulated in scientific jargon) in people with high blood pressure, apparently making those individuals with high blood pressure wonderful targets for this virus. 

You can think of the angiotensin II receptor as a lock and the COVID-19 virus happens to possess a very good key to that lock, opening the door into your respiratory system.  This seems to be the way that the COVID-19 virus infects all people, not just people with high blood pressure, since we all express the angiotensin II receptor in our respiratory system. However, other factors must be responsible for the increased risk of more severe infections with COVID-19 in people with high blood pressure. 

One possibility is that certain medications taken by people with high blood pressure increase the risk of severe COVID-19 infections by further increasing the number of angiotensin II receptors in the lung or changing other characteristics of the angiotensin II receptor. Stay tuned for more information on this topic that may even be relevant to prevention or treatment. Suffice it to say that most people with high blood pressure with or without treatment will experience mild disease.
 
 
We also know from years of experience and research studies in people with MS and other neurological diseases that there are other factors known to increase the risk of severe respiratory tract infections. These risks include physical disability in any age group defined as anyone spending time in a wheelchair, a prior history of frequent upper respiratory tract infections, pulmonary disease (e.g. asthma, COPD), smoking and immunosuppression. There is no reason to believe that these same characteristics would not also increase the risk of severe COVID-19 infection.  
 
So how do we put all this information together to provide advice to our patients with MS based on, what we think we now?
 

1. Follow the advice of the CDC and your state health officials. We cannot emphasize enough the importance of social distancing, washing and sheltering at home as much as possible.
   
2. We have no reason to believe that relapsing remitting MS patients without physical disability are at any greater risk of severe COVID-19 infections than their healthy peers as long as they do not have any of the risk factors discussed previously (i.e. age > 50, male sex, high blood pressure, diabetes or cardiovascular disease, pulmonary disease, smoking, frequent respiratory infections or immunosuppression)
   
3. It is prudent to avoid or postpone immunosuppression with lymphocyte depleting agents, particularly if you are over age 50, a male or have a diagnosis past or present of hypertension, diabetes or heart disease.  Lymphocyte depleting agents include rituximab, ocrelizumab (Ocrevus), Mavenclad (Cladribine), lemtrada (Alemtuzumab) and chemotherapies used to treat MS (cyclophosphamide is an example). There will definitely be some people with MS, whose disease is so active that it is too risky to postpone treatment, but most people will be able to delay treatment with lymphocyte depleting agents until the risk of COVID 19 infections pass.
   
4. We do not know if Natalizumab (Tysabri) will increase the frequency or severity of COVID-19 infections. Some studies, notably studies of Tysabri in Crohn’s disease, reported a slightly increased risk of respiratory tract infections, but this risk was not the observed in the MS studies. Tysabri alters normal immune cell trafficking and interactions with the extracellular matrix, particularly in the central nervous system and GI tract, but this does not suppress immune cell function, notably. Some MS specialists may increase the interval between infusions to every 6 to 8 weeks during the pandemic to allay this potential concern. It is important not to stop Tysabri altogether, because of the risk of a rebound relapse.
   
5. We have no reason to believe that Beta Interferon treatments (i.e. avonex, betaseron, rebif, extavia and plegridy) will increase the risk or severity of COVID-19 infections. In fact, interferons are being studied as a potential anti-viral treatment for COVID-19 infection.
   
6. We have no reason to believe that Copaxone and glatiramer acetate will increase the risk or severity of COVID-19 infection
   
7. We do not know if Aubagio, tecfidera, gilenya or mayzent will increase the risk or severity of COVID-19 infections. It is possible that people with MS who experience a significant lowering of their lymphocyte counts on any of these DMTs could experience an increased risk of severe COVID-19 infections. Some MS specialists may alter the dose or dose frequency of these medications, if you are considered at increased risk for severe COVID-19 infection. Talk to your MS specialist to see if you fall into this category of people with MS. But remember that people on Gilenya and Mayzent may also experience a rebound relapse if they suddenly stop treatment.

 
What will happen if you do experience a COVID-19 infection?

Perhaps nothing. Some people just experience mild cold symptoms and some experienced only an alteration of taste and/or smell. Most people feel like they have the flu with fever, body aches, fatigue, congestion and cough. People with MS can expect their MS symptoms to worsen with a COVID-19 infection because of fever and/or a general activation of your immune system. If you do get ill, make sure you stay well hydrated and keep your temperature down with Tylenol (acetaminophen). If your MS worsens significantly your MS specialist may even consider treating you with steroids depending on the severity of the COVID-19 infection. But the best thing to do is not to get infected at all
 
Good luck and stay well

Revere P (Rip) Kinkel, MDProfessor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego