Online Breakout Session: NMOSD & COVID-19 Update (Dec 4)

We hope everyone is well and coping with the challenges of the COVID-19 pandemic. With information changing on a daily basis, we are reaching out to the NMOSD community to aid in your navigation of the many questions at hand. While the Foundation does not provide clinical care policies or recommendations, we hope these 10 frequently asked questions assist all NMOSD patients to make informed decisions with their doctors.

Click here to read our NMOSD & COVID-19 FAQs.

 

Full Transcript

Lisa McDaniel:

Hello, and welcome to the Online Breakout Session, NMOSD and COVID-19 Update. I am Lisa McDaniel, advocacy coordinator for the Guthy-Jackson Charitable Foundation. The foundation is proud to be a source of information about NMOSD. We hope everyone is doing well and coping with the challenges of COVID-19 pandemic. With information changing on a daily basis, we are reaching out to the NMOSD community to aid in your navigation of the many questions at hand. While the foundation does not provide clinical care policies or recommendation, we hope today’s Breakout Session will assist all NMOSD patients to make informed decisions with their doctors. For specific information and advice, please consult your personal physician.

Lisa McDaniel:

Joining us today is Dr. Michael Yeaman, chief medical advisor to the Guthy-Jackson Charitable Foundation. Dr. Yeaman?

Dr. Michael Yeaman:

Hi Lisa, thank you. Good morning, good afternoon, good evening everyone. Hope everybody’s doing well. Thanks a lot for making the time to be here today. We wanted to give you some of the latest information about COVID-19 as relates to NMOSD and with a special focus on vaccines. So hopefully this information will be useful as you consider best options for your particular care. So with that, why don’t we jump right into it? And we’ll have some time for questions toward the end.

Dr. Michael Yeaman:

So you probably have all heard of what’s called the R number, which is the number of individuals that a person who is infected can then go on to infect. And when the R number is one, that means one person can infect one other person with COVID-19. So on this slide, it shows what the numbers looked like three months ago. And I’ve just highlighted California just as a reference point. These are all the states in the United States. And you can see that three months ago, the R number was less than one in California, and that means the rate of infection was decreasing. Unfortunately, there were some states that were above one and even more unfortunate is here is the situation as of today.

Dr. Michael Yeaman:

You can see that there are some states that have an R number less than one, but most are well above one. And so, for example, here’s the issue with California just as an example. So we are amidst a surge, as you all know, and the numbers are going up. We just really need to redouble our efforts to take care of ourselves and our families by using best precautions. And you all know what those are, but we’ll touch on them later in the talk. So let’s now talk a little bit about what we’ve learned about COVID-19 over just about one year now.

Dr. Michael Yeaman:

So first, we know that there is what I call a risk equation, and that has to do with ventilation or being indoors versus outdoors, the number and density of people that are around you, whether you’re protecting yourself with a mask, how long you’re in a situation where it’s higher risk and what you’re doing in that situation. For example, we know that singing or shouting or talking at loud volumes can emit more particles from one’s respiratory tract, and that is a much higher risk activity, for example. So being in places where it’s well-ventilated or outdoors reduces risk. Being socially distanced or not having folks around you that are not within your household reduces risks. Masking and protecting yourself with shields, et cetera, reduces risks. Being in risky situations for a short time as possible will reduce your risk. And as I mentioned, trying to limit activities so that they don’t increase your risk.

Dr. Michael Yeaman:

We know that older folks and males and those with co-morbidity have greater disease severity. However, there’s emerging evidence that females have what’s called long COVID, which means the symptoms and consequences last longer. We don’t understand why that is yet, but it’s an interesting difference between men and women. It is true that younger individuals often have no or mild illness. They can even be asymptomatic, but it can also kill young people. And in particular, there is this multi-inflammatory system syndrome in children, particularly those less than 12 years old that we just have to be very careful about. We know there are racial and ethnic and socioeconomic disparities that correlate with severity of disease and we really need to do our best to change that issue.

Dr. Michael Yeaman:

Interestingly, pre-symptomatic individuals, those are folks who are infected but don’t know it, or have not yet experienced symptoms, are about 10% of the population, but they may be accounting for about 80% of the spread. So unfortunately, folks who are infected but don’t know it and not taking precautions are probably doing most of the spreading right now. Also, lastly, while the global mortality percentage rate is going down relative to the number of cases going up, ICU care and total mortality are increasing. So these are really important issues. They’re tragedies. We really need to do everything we can to minimize this loss.

Dr. Michael Yeaman:

Here is a visual of the kinds of things that are low, moderate, and high risk activities. So you can see over here, the kinds of things that are low risk include getting gas at a gas station, getting takeout food, camping outdoors, et cetera. Things like seeing your doctor, relatively low risk. Higher risk activities include things like small dinner parties indoors, working in a shared office space, and then we get to things like going to a movie theater or visiting someone in an elder care home. Airplanes are potentially moderate high risk. And then we get to the very high risk, which are attending weddings or funerals, hugging or shaking hands with someone, indoor parties. And then of course, bars and nightclubs, as well as some religious services that are high density and poorly ventilated indoors can be very high risk.

Dr. Michael Yeaman:

As far as the pathogenesis and the disease, here’s what we’ve learned over about one year now. First, there are variants of the SARS-CoV-2 virus that causes COVID-19. So it’s not a virus that is standing still. It’s mutating just like most viruses do. But fortunately, there haven’t been really any mutants that have become more dangerous. There is one that’s called the D614G variant that may be a little bit more transmissible from one person to another, but it doesn’t look like it causes more severe disease.

Dr. Michael Yeaman:

We know that there’s an incubation period of between five and 12 days. The average is about five or six days. There can be a prodrome of three to five days. A prodrome means the emergence of symptoms early. The illness can last 10 to 30 or more days and then there’s some sort of resolution or outcome. I’ll talk a little bit more about T cells and interferons, but these are now becoming considered by many to be the most important type of immune response that protects you against COVID-19 rather than antibody alone. And we’ll talk a little bit more about that.

Dr. Michael Yeaman:

We know from experience over the last year that there is immune dysfunction in the most severe cases of COVID-19, and particularly really high levels of antibody and high levels of white blood cells, particularly neutrophils that filter into the lung trying to help can actually do more harm than good. And on the other side of the coin, when there’s too low of T cell responses, either these cells that we call CD4 T cells or CD8 T cells, when those numbers are low or they’re not working correctly, that’s when antibody and neutrophils try to compensate and that’s when we get into trouble. We also know that blood coagulation disorders and activation of certain blood proteins can correlate with worsened outcomes. And this has to do with clotting of blood in places where you don’t want it to clot or activating ways that cause fluid to accumulate in the lungs. So we’re learning more about those processes and we’re starting to treat in advance to deal with those issues before they become problems.

Dr. Michael Yeaman:

We also know that antibody durability, how long antibody lasts, correlates with how much exposure one has to the virus and the severity of the disease. So a person who has very mild symptoms but thinks that they now have antibody that protects them is probably not correct. And we’ll talk more about that in just a second.

Dr. Michael Yeaman:

So here is a little figure that I just wanted to put in front of you to give you a little bit of perspective. So this is the average number of deaths caused by infection per day worldwide. And you can see that COVID-19 due to the SARS-CoV-2 coronavirus, we’re now at about 3,475 deaths per day worldwide due to this infection. By comparison, tuberculosis kills about 3,000 people per day, HIV, 2,100, seasonal influenza, about 1,000, et cetera. Interestingly, COVID-19 now kills about as many people as all of these infections down here combined. So that’s a lot of deaths, unfortunately, due to COVID-19. So it’s not fake, it’s not a hoax, it’s really causing problems and serious problems.

Dr. Michael Yeaman:

You could see some of the issues I’ve put aside here. Tuberculosis increasingly resistant. There hasn’t been a vaccine that’s been successful yet against HIV. The seasonal flu constantly mutates. Because of largely unfounded reasons that people are concerned about vaccines for whooping cough or measles, these infections are re-emerging and that’s a problem. And I just want to point out here’s Ebola virus down here. 5.3 deaths per day at its peak. Compare that to 3,500 with coronavirus. So even a very frightening deadly outbreak like Ebola virus is pale in comparison to what’s happening with COVID-19.

Dr. Michael Yeaman:

As far as treatments and vaccines, we’ll talk a lot about vaccines in just a second, but here’s the overview. As far as treatments are concerned, we’ve learned that hydroxychloroquine really does not have efficacy. So it’s really being avoided now. It can actually cause more harm than good. The drug Remdesivir that has been approved looks like it may be effective in about 15% of patients, but really only if used early in the course of infection when the virus is replicated, because this is an antiviral drug. It stops the virus from replicating. On the contrary, Dexamethasone, which has a steroid, looks like it does help some people with severe disease, but only if used late. So it’s not just whether or not to use a drug, but it needs to be used at the right time.

Dr. Michael Yeaman:

We know that monoclonal antibodies that either target the virus or target the cytokine storm are being studied. The results have been equivocal. We haven’t had a clear signal that any of these really work great yet. So we’re still looking for those kinds of results. We do know, and you’ve heard some of the recent reports that vaccines induce protective T cell and B cell immunity. So that’s good news. And now we’re looking at how long this lasts and how protective it is. And we’ll talk more about that. I also wanted to point out that the leading vaccines that we’ve all been hearing about appear to be quite safe. They’ve been used, for example, in over 70,000 people now, and there haven’t really been any major reports of safety issues. But in a couple we’ll talk about this. But basically, they’re now heading for emergency use authorization, which some have already received, or approvals. And you’ve probably heard that in the United Kingdom, the Pfizer-BioNTech vaccine was approved just a few days ago. So a lot going on in the vaccine world.

Dr. Michael Yeaman:

And now let’s talk specifically about the COVID-19 vaccines. And we’ll talk a little bit of immunology first, then we’ll talk about very practical aspects of vaccines and how one might consider their use. So we’ve done simplifying the science a little bit in the past and look forward to more of those in the future, but I wanted to just give you a little bit of a reminder here of how the immune system responds to non-self antigens, including either a virus or a vaccine.

Dr. Michael Yeaman:

So you’ve heard about us talk about antigen detection. And so certain cells see these antigens, they might be monocytes, they might be dendritic cells. B cells can also detect antigens. And any of these cells then present the antigen to T cells. They say, “Hey, look, I found something over there. I wanted you to know about it.” And if both the antigen presenting cell and the T cell agree through these signals here that are the molecular handshakes that we’ve talked about, then this T cell will polarize. It will become activated. And it will polarize into one of several different kinds. I’ve just shown four different kinds here. There’s a Th1 polarization, Th9, Th17 that we’ve talked a lot about, and Th2. And each of these T cells has a different kind of cytokine signature that they respond to and they emit. For example, in NMO, we know that Th17 cells release IL-17, and that activates neutrophils and neutrophils can cause trouble along with B cells and other cells in causing disease.

Dr. Michael Yeaman:

But anyways, each of these types of T cell polarizations have specific kinds of effect or functions that they activate. So with with Th1 cells and interferon gamma, there are macrophages, there are natural killer cells, CD8+ T cells that all do things like kill infected cells that have pathogens within them like virally infected cells. They also help clear cancer cells and repair tissue. I won’t say much about Th9 and Th17. Neutrophils are really important for clearing extracellular pathogens. So these are organisms like staph and strep and other bugs that don’t really get into cells very often but need to be cleared. And then the Th2 axis really is about promoting B cell function so that antibodies are generated. And antibodies, as you know, can function with compliment to neutralize pathogens or antigens. They can also inhibit toxins. So that’s a quick reminder of how the immune system responds.

Dr. Michael Yeaman:

So I want to just focus on interferons and T cells as we talk further. With respect to interferons, one of the things we’ve learned a lot about in COVID-19 is the importance of interferons in protection against bad outcomes in COVID-19. So, because we haven’t talked a lot about interferons in the past, I just wanted to give you a quick crash course in interferon immunology here. So this is a picture, a cartoon of the airway epithelium. That is the layer of cells on the surface of your airway as you breathe in and out. And so the cells are made up of different kinds of… Or types of cells. This is called a ciliated cell. This is called a goblet cell that secretes mucus onto your airway surface, and there’s other kinds of cells.

Dr. Michael Yeaman:

But when you breathe in and a virus adheres to these ciliated cells and then moves into that cell and replicates. So now this is an infected cell, which ultimately will die. Before the cell dies, it will emit molecules that are called interferons. And it’s abbreviated IFN. And there’s three kinds. The one I really want to talk about is a relatively new kind of interferon that’s called interferon lambda. So it’s a Type III interferon. In any case, all of the interferons have very special properties because what they do is they emit from this infected cell and they communicate to cells that have not yet been infected. And they tell those cells, “You know what? There’s a virus here. It’s probably going to come to try to infect you. So I hope you can get ready and defend yourself before that happens.”

Dr. Michael Yeaman:

And that is how interferons work. They trigger very molecular events in the uninfected cell. One stops the generation of protein, that is if it inhibits translation, and this would stop virus proteins from being made in the other cells. Another function that interferons activate is the degradation of viral RNA. So even if a virus got into this cell, the RNases would cleave the virus RNA before it had a chance to properly infect the cell. And then there are other functions that interferons activate as well. So interferons look like they’re really important in defending against COVID-19.

Dr. Michael Yeaman:

Okay, so let’s talk a lot about the vaccines themselves. These are the COVID-19 vaccine platforms. This is a very summary view here. There’s a lot of details that are not included. But for the sake of a review, let’s just think about this together. So there are four kinds of vaccines that are being generated for COVID-19. One is called the genetic type, another, the attenuated, another the recombinant, and lastly, the inactivated type. So you’ve heard a lot about some of these. For example, the genetic vaccines are exemplified by the Moderna-NIH and the Pfizer-BioNTech vaccines that you’ve all heard about recently.

Dr. Michael Yeaman:

So these kinds of vaccines put a little bit of the viral RNA inside of a lipid nanoparticle and then that is administered as the vaccine. There’s also some interesting new vaccines on the horizon that are DNA, not RNA. And you can see a different kind of approach would be to administer DNA, which would then convert to RNA, and then your body would make the vaccine immunogen. And that’s the important thing about the genetic vaccines. Your body makes the immunogen. So it’s not like other vaccines where they’re expressed by yeast or by bacteria and then those proteins are then put into your body. No, the genetic vaccines, your body actually makes the protein that tells the immune system what to do.

Dr. Michael Yeaman:

The attenuated vaccines are where a Trojan horse approach is used by placing the SARS-CoV-2, the COVID-19 viral RNA, within a different kind of virus that is harmless to humans or it’s made harmless to humans but expresses the kinds of antigens that the immune system needs to see to protect you against COVID-19. So, for example, the AstraZeneca vaccine uses what’s called a chimpanzee adenovirus. The Johnson & Johnson vaccine uses a human adenovirus 26. The Merck attenuated vaccine uses an inactivated or an attenuated measles virus, et cetera. There’s a lot of different kinds that are being used. There’s a couple of vaccines that work this way that are already being used, one in China, one in Russia. So there’s a lot of attention being paid to the attenuated vaccines. One point that I’ll make, and I’ll reiterate in just a few minutes, the attenuated vaccines are oftentimes not recommended for people who have been placed on immunosuppressive therapy. And I’ll talk more about that in just a second.

Dr. Michael Yeaman:

The recombinant vaccines are just pieces of protein from the COVID-19 virus capsid or the shell of the protein. And usually, it’s the spike proteins that we’ve been hearing about, but these are made in the laboratory and then put into a vaccine. And many different companies are focusing on the recombinant types of vaccines. Lastly, the inactivated vaccines. These are actual SARS-CoV-2, that is COVID-19 viruses, that have been grown in the laboratory, but then treated chemically to make them non-viable. And that in theory could work well, but there’s always a little bit of chance that some of the viruses did not get killed. And so that’s the potential downside. But there are several of these kinds of viruses being used in the world today.

Dr. Michael Yeaman:

I wanted to really emphasize that there have been no shortcuts to safety in the development of COVID-19 vaccines. So even though the speed has been much greater than has been the case in the past, safety has been really emphasized at every step along the way. And this is just a quick reminder that there are multiple stages in the development of a vaccine. First, the design in the laboratory, then testing and some experimental system, and then phase one, the first inhuman type of studies. And these are usually done in young, healthy individuals, but really the most important step here has to do with safety. But even as the vaccines proceeded to larger studies, phase two and phase three, safety is the most important measure at any point in the development of these vaccines.

Dr. Michael Yeaman:

We’re now at a point where there are several vaccines that have passed phase three with a lot of good results. Their safety signal is good. They look like they protect. And so the paperwork has been filed for either emergency use authorization or potential approval. And I just wanted to mention that even when a vaccine becomes approved, there will still be high degree safety monitoring. So safety is number one with any vaccine development, COVID-19 or otherwise.

Dr. Michael Yeaman:

So here’s just a quick pocket guide that hopefully will help you in thinking about standard vaccinations and then we’ll talk in just a moment about COVID-19 vaccines. So what’s shown here are just examples of the standard kinds of vaccines that most people should have. And I’ve divided them into the viral and bacterial vaccines. So we’ve all heard of MMR, measles, mumps, rubella. Just by example, these are attenuated viruses. So these viruses are live, and in individuals on immunosuppressive therapy, they’re not really recommended for use because they’re live. And when one’s immune system is not at full strength, they can potentially cause some infection that you wouldn’t have otherwise. And you can go down this list. I’ll just point out a couple of things.

Dr. Michael Yeaman:

So the most common influenza vaccine is inactive or recombinant. It’s not live. It can’t give you the flu virus. And therefore, it can be used in people who are on immunosuppressive therapy. There is one kind of flu vaccine that’s not used very much anymore, and it’s the inhaled or what’s called nasal spray influenza vaccine. It’s attenuated and it is live and we don’t recommend it for use in people who have immunosuppression. Likewise, if you’re thinking about a shingles vaccine, there is a shingles vaccine that’s recombinant. That is it’s just proteins. You can’t get the infection from this vaccine. It’s not live, and so you can use it if immunocompromised. However, there’s also one that’s a live virus. It’s attenuated, but it’s recommended that you stay away from that one if you’re on immunosuppressive therapy. And so you can see the kinds of vaccines. Most of them, you can use if you’re on immunosuppressive therapy. There’s a few that you can’t, but there are workarounds for many of those.

Dr. Michael Yeaman:

Now let’s focus a little bit on the COVID-19 vaccines. So here I’ve divided the group into the four types that I just spoke about a few minutes ago, genetic, attenuated, recombinant, inactivated. So you can quickly see that almost all of the ones that are going likely to be potentially available are usable so long as they’re not the live attenuated type. And so you can imagine that we’d want to probably stay away from the attenuated group in people who are on immunosuppressive therapy.

Dr. Michael Yeaman:

However, one of the great, I think, success stories in the COVID-19 vaccination development program is that there are many different kinds of vaccines that have been developed. So that gives a person who’s on immunosuppressive therapy many different options, for example, with respect to the potential to be vaccinated against this pandemic virus. We know that these two, for example, the Pfizer-BioNTech and the Moderna-NIH are both mRNA vaccines. They’re not live and they can be used in immunosuppressive therapy. Okay. So I hope that helps as a quick pocket guide. We’re not making any recommendations. We’re not telling you what to do or not to do, but this is just information for you to consider with your neurologist.

Dr. Michael Yeaman:

I also wanted to mention that timing is important for when to be vaccinated if you are on immunosuppressive therapy. So here’s just a simplified picture. Your immune response status here that is higher and higher, immunity here, and this is just time in terms of months. So you can imagine many of the immunosuppressive therapies will cause some one or more immune markers to decline and then stay down for a while and then ultimately start coming back up once the drug starts wearing off. And for the most part, I just want to make the point that it’s best to vaccinate in advance of beginning these kinds of drugs if possible, or if you’re already on the drug, then think with your neurologist about vaccinating in one of two time windows.

Dr. Michael Yeaman:

The first that I’ll talk about is late in the course of the dosing cycle where your immune system is starting to come back a little bit. That’s when vaccines might work best for protection. There are of course ways to help prevent infections from occurring even if you can’t be vaccinated during these times. And they include antibiotic prophylaxis and therapeutic IVIg. So we’ll leave that for another talk.

Dr. Michael Yeaman:

But keep in mind that several of the vaccines for COVID-19 will take two doses. And so you probably want to plan a couple of months in advance. If you’re going to begin on an immunosuppressive therapy or working with your neurologist, find a good time either during the normal cycle, or the other approach is to consider a dosing pause where you can perhaps move the next dose out a little bit of time, not a long time, but this needs to be done weighing the risks and the benefits of being vaccinated versus the potential modest increased risk of relapse, for example, in NMOSD if you were to wait a month or so to have your next dose. Again, not recommendations, but just concepts that you should really talk carefully with your neurologist.

Dr. Michael Yeaman:

Here is the potential recommendations that are being made for rolling out of the COVID-19 vaccines. We’ve all been carefully watching this. This information comes from the ACIP, which is the Committee for Immunization Practices from the CDC. And they have designated a three-phased approach to rolling out the vaccines. And phase one is based on a limited vaccine supply, phase two, a growing type diversity and supply of different vaccines, phase three is where supply pretty much equals demand, and then beyond phase three is just continuing ongoing supply.

Dr. Michael Yeaman:

Phase one, it is being recommended for use in frontline workers. These would be individuals who are associated with healthcare, law enforcement. Absolutely critical to the health and wellness of others. Also important would be vulnerable persons. These would be elderly individuals in long-term care facilities, et cetera. And many believe that individuals on immunosuppressive therapy might fall into this category. If not in this category, the other group within phase one are folks who are aged 65 or older, particularly those who have comorbidities and those comorbidities may range from cardiovascular disease, to diabetes, to cancer chemotherapy, et cetera. So about 15% of the population is anticipated to be vaccinated in phase one. And that is projected to start as early as this month and really ramp up into next January, which is coming up just in three, four weeks. So there’s going to be a lot happening just in the next few weeks, we believe. And hopefully, a good number of people will start to get vaccinated.

Dr. Michael Yeaman:

Phase two is really going to be focused on essential workers. These are folks that are really critical to keep the opportunities for others to get what they need, be it from food supply to other aspects of living. Also everyone over 65 years of age will be included in this group, as will some special populations, homeless, prisoners, et cetera. This should bring us up to about 50% of the population being vaccinated. We’re hoping this will be emerging in February of next year and increasing as availability grows.

Dr. Michael Yeaman:

Phase three, children and adolescents less than 18 years old and any adult less than 30 years old, as well as individuals who are key to functioning society. And this should bring us up to about 90% of the population being vaccinated beginning around March or April of next year. Certainly, we are hopeful for that. And then finally, anyone who’s not been vaccinated in any of these phases should bring us up to as close as we can to 100% roughly by May of next year. And that’s the goal. So this, I hope helps understand where NMOSD patients might lie. Hopefully, many will be in phase one, but we’ll keep our eyes on how this rollout moves forward.

Dr. Michael Yeaman:

And lastly, I just wanted to give you a quick crystal ball of what the future would look like if we can put in place what I call this three part solution to the COVID-19 pandemic. The first part is behavioral immunity. What that means is things that you can do to protect yourself, distancing, ventilation, meaning staying outdoors or good ventilation if you’re indoors, masking, et cetera, washing your hands. All the things that you can control. There will also be some individuals who have natural immunity. These are the folks who have had bad COVID-19 disease and have relatively long-lasting immunity. And finally, what we call medical immunity. These are individuals who will be vaccinated or will have monoclonal antibody therapy, et cetera. So behavioral, natural, and medical immunity.

Dr. Michael Yeaman:

Here is where we are now. This is December of 2020, okay? In order for us to stop the pandemic, we need about 75% of citizens to be protected, okay? That will lower the risk of the pandemic down, down, down below 25%, which is where we want to be. But here’s where we are right now. Only about 40% or 50% of individuals are actually protecting themselves in a way that is optimal. Unfortunately, there’s still folks who are not masking, who are gathering together without masks, et cetera, and that’s just a problem. There are now about 8% of the population who’ve had sufficient infection by COVID-19 to generate natural immunity. We don’t know how long that will last. And there’s a very low number of individuals who are either vaccinated or have other type of medical immunity.

Dr. Michael Yeaman:

But if we think about where we might be in February, we expect, as I just pointed out in the last slides, we expect a large number of individuals to emerge that are vaccinated by that point. And we’re still below this level where we need to get to to be about 70%, 75% of everyone protected. But just a month or two later, you can see that if vaccines are used, we’re going to get well above that number and the pandemic will be over more or less as the date from April forward rolls ahead. So hopefully by May or June, we’ll be well above the 75% protection rate and we’ll put an end to this difficult challenge in all of our lives.

Dr. Michael Yeaman:

So just a quick summary. Minimizing exposure is still the most effective risk reduction that you can do for yourself and for your family. And I’ll just point out, even if you as a patient are unable to be vaccinated for some reason, individuals around you becoming vaccinated is another great way to protect you. So that’s called micro-herd immunity where individuals around someone who is at risk become vaccinated and thereby protect the person who can’t be vaccinated. But as I mentioned, there’s a lot of good options for vaccines, even in NMOSD patients. The non-live vaccines are the safest in folks who are on immunosuppressive therapy. And we need to be careful about live or attenuated vaccines in people who are receiving therapies that suppress the immune system.

Dr. Michael Yeaman:

The leading vaccines induce protective cell-mediated immunity and antibody response, but I’ll just remind you that antibody is sometimes highest in people who have the worst disease. So antibody by itself is not the answer. It’s probably more about T cells and interferons with some help from antibodies. Some immune suppressive therapies will diminish antibody production and cell-mediated immune responses for vaccines and you’ll need to talk with your neurologist about the drug that you’re on and how you best can protect yourself with vaccination. Ideally, updating your immunizations before you begin an immunosuppressive therapy, but even if you’re already on immunosuppressive therapy, you can be vaccinated. You just have to prospectively find a good plan with your neurologist. And every plan might be a little bit personalized. We want the best vaccine option for the best protection in that person. So it’s really a personalized approach. So please talk carefully with your neurologist.

Dr. Michael Yeaman:

And finally, vaccines are only one tool. And so we really want to put a lot of emphasis on the tools we have in hand. But most importantly, please take care of yourselves and your family. You have more control in this situation than you might think. So, please be mindful of that. And hopefully, this information has been helpful. And now we’ll turn it over for some questions and answers with Lisa.

Lisa McDaniel:

Thank you so much, Dr. Yeaman. I really learned a lot from your presentation and I’m sure that our in NMOSD community did as well. We do have quite a bit of questions that have come in, most of which of course are asking about vaccines. So our first question says, if we can have the COVID-19 vaccine when available, what would be the timing needed to go along with our last rituximab or other preventable NMO treatments?

Dr. Michael Yeaman:

Yeah, thanks for the question. So, as I pointed out, ideally, before you begin that therapy, but if you’re already on it, then talk with your neurologist about the best time window, which is often late in the cycle before you get your next dose, or potentially a dose pause that will allow your immune system to react well to the vaccines for best protection before you start back up on the dosing.

Lisa McDaniel:

Great. Thank you. We have a question. As most know, Guthy-Jackson has been conducting a COVID-19 survey. Some of the patients are wondering if you could share any of that as to how many patients have had COVID and how have the outcomes been for those patients.

Dr. Michael Yeaman:

Yeah, thanks a lot. And I just want to remind those of you who have participated in the COVID-19 survey, first of all, thank you so much. Secondly, if you have done parts one or two and are preparing for part three, please continue to participate. We really appreciate it. Lisa, as far as results, I can share a few initial results with you. So among those who have responded, there have been about 2% who have gotten severe or serious COVID-19 disease. That’s about the same number as folks who don’t have NMO. So it’s not any higher as far as we know than individuals who don’t have NMO. About 21% of patients have changed their schedule of treatment, which hopefully has been done in consultation with their neurologist. That is they’ve changed the timing, maybe they delayed, for example, their next infusion, for instance, because they didn’t want to go into the clinic. But all of the recommendations from both neurology and rheumatology, as well as the broader community are to maintain your usual dosing schedule and regimen. So those were some initial results, Lisa.

Lisa McDaniel:

Thank you. Of those NMO patients that you know of who have contracted COVID-19, how many of those have had an NMO relapse? And is it commonplace to have a relapse after infection with COVID-19 or other viruses?

Dr. Michael Yeaman:

So it’s a great question. The answer is we don’t really have evidence that there is a strong causal relationship between a COVID-19 or really any viral infection and a relapse. There are possible correlations and potential coincidences. But we like to think even if there’s no absolute causal relationship, we want to be a little bit more aware of possibilities for relapses when a person has really any medical issue that’s unusual, be it an infection or trauma or a surgery or what have you. So there’s no hard and fast evidence that says an infection or a vaccine will cause any kind of a relapse, but we’re studying that.

Lisa McDaniel:

We have a patient who writes, “Does low IgG put me at a higher risk of catching the virus?”

Dr. Michael Yeaman:

Okay, good question. So there’s a big difference between being infected and having the disease of COVID-19. As you know, a lot of people are being infected and they don’t even know it. As far as IgG is concerned, as I pointed out, antibody is not the only protective mechanism against COVID-19. In fact, it may be sort of a secondary protective mechanism. T cells and interferons really look like they’re the most important immune responses. So we don’t know how important IgG is. There probably is a neutralizing effect of some IgG. But antibody alone is not the answer. So if you have low IgG, it may or may not make you more susceptible to infection.

Lisa McDaniel:

Thank you for that, Dr. Yeaman. We have several patients who say that they’ve been talking to their neurologists about the COVID vaccines. And one in particular said that her neurologist said that she would have to test her COVID antibody levels after she received the vaccine to see if she had developed enough to provide immunity. And that would be because she is on Rituxan, which depletes the B cells. She’s asking… He said he may have to do additional doses of the vaccine until the body produces enough COVID antibodies for immunity. Do you agree with this concern and think that those of us on Rituxan should have their levels checked after we’ve received the vaccine?

Dr. Michael Yeaman:

Yeah, great question. So Rituxan and other B cell depleting agents as well as some other immunosuppressive therapies are known to interfere with antibody production, but again, that may or may not be bad in context of COVID-19 either natural immunity or immune response to vaccines. And that’s because antibody, as I mentioned, is not necessarily the first frontline response that protects you against COVID-19. Now, some neurologists will test for antibody response after vaccination just to see how well the immune system responded. It doesn’t mean the antibody level will tell you whether you’re protected or not, but antibody can be a measure of how well your overall immune response occurred following a vaccination. So some neurologists will test you after several weeks or a couple of months after a vaccination.

Dr. Michael Yeaman:

Keep in mind that one of the reasons that most of these vaccines will be two doses is to do what’s called a prime and a boost. And it’s the boost part that really helps your immune system learn about COVID-19 virus before you are infected so that it really gives you a good chance of being prevented from having any issues with that virus.

Lisa McDaniel:

Thank you. We have heard from a lot of patients who of course have some concerns and fears according to safety. And I know you touched on safety. Can you explain why we should trust a new type of vaccine? Have there been enough studies with this type of RNA vaccine for us to really know the long-term side effects, especially given the short timeframe of COVID with these trials?

Dr. Michael Yeaman:

Yeah, thanks for that question. There’s a couple of ways to consider this. First, even the newest technology of vaccines, like the mRNA vaccines, they have now been tested in about 75,000 people around the world, all races, ethnicities, individuals who are older than 18 years of age. So far, no serious signals of safety concern that have emanated from those studies. So there’s already been 75,000 people who’ve been vaccinated and they appear to be quite safe.

Dr. Michael Yeaman:

As far as being worried about the new technology, keep in mind that the mRNA vaccine technology has been used experimentally in the past, including to test for prevention of Ebola and some other types of viruses. And so there’s experience there. And finally, one of the major upsides to the mRNA vaccines is that your body makes the immunogen. Compare that with the classical vaccines where the immunogen is made in the laboratory and then provided to you pre-made. And oftentimes, those vaccines are made by a fungi that is released or expressed by bacteria, and whether or not those are as safe, if you will, remains a question. But the new technology in and of itself should not be a cause of fear. In fact, there might be reasons that those were even safer than some of the traditional vaccines.

Lisa McDaniel:

Thank you, Dr. Yeaman. That’s actually reassuring and very good to know. I’m sure it will be a comfort to many of our patient community. The next question is from a mom. She says, “My 19 year old daughter is MOG positive and is on rituximab. If she qualifies to be vaccinated in Phase 1-B, should she, or should she wait to see if there are side effects in others? She would like to return to in-person classes in college. So there is some desire to get immunized before school resumes in the fall of 2021.”

Dr. Michael Yeaman:

Yeah, this is a great question because it really emphasizes the balance of putting all kinds of factors together in one’s decision. So a young woman who wants to go back to college is probably on an immunosuppressive therapy. There are going to be vaccines that are usable in a person who’s on immunosuppressive therapy. So I would not be surprised if she is eligible. Again, my sense is there will be a lot and there has been a lot of experience in using these vaccines in a lot of people already. And by the time February comes around, for example, there’s going to be probably hundreds of thousands of people who have taken these vaccines and we’ll have even a better experience.

Dr. Michael Yeaman:

So let’s say February, for example, or early spring, there should be plenty of information that should reassure people as to the safety of these vaccines and you would want to consider that. But if all of it lines up, then you might want to consider being vaccinated and that will give your daughter all kinds of options for social activity, returning to school, et cetera.

Lisa McDaniel:

Thank you, Dr. Yeaman. You touched earlier on flu and pneumonia vaccinations. One patient routes in and said, “Should NMOSD patients on immune suppressants receive the flu and pneumonia vaccinations?”

Dr. Michael Yeaman:

In a word, yes. Again, there are different kinds of flu vaccines. Stay away from the live ones. Those are very rarely used in the United States in adults. But as far as the Pneumovax or Prevnar, et cetera, the pneumonia vaccines, again, there’s no reason not to use them because, A, they are not live, and B, they protect against infections that are not uncommon in immunosuppressive therapy. So you want to protect yourself against pneumonia. I think timing of the vaccines is the key, and that’s really when you want to talk with your neurologist, find the best plan for when to become vaccinated in light of your immune suppressive therapy cycle.

Lisa McDaniel:

Thank you. Most NMO patients are on some type of immune suppressing medication. Does that mean that we are potentially less likely to have what I’ve heard called the cytokine storm?

Dr. Michael Yeaman:

Not necessarily. Some of the immunosuppressive drugs inhibit certain types of cytokines and other drugs inhibit other cytokines. I don’t think you should think about being more protected, if you will, by being on an immunosuppressive therapy because the other side of the coin is if you are infected and get COVID-19 disease, then there’s a risk of other secondary infections that would be at higher risk if you were on immunosuppressive therapy like pneumonia or fungal infections of the lung, for example. So best plan is to protect yourself against COVID-19 and not worry about whether your immunosuppressive therapy would keep you from a bad outcome. You want to protect yourself against any bad outcome.

Lisa McDaniel:

Thank you, Dr. Yeaman. I think we have time for one more question. And as usual, I want you to think about any closing remarks that you may have to go along with this question. Someone writes, “I’ve been told and read that since we are on immune suppressants, we are not capable of building antibodies. So doesn’t that make taking any vaccination pointless?”

Dr. Michael Yeaman:

Good question. Antibody is only one part of the immune response to COVID-19 or any microorganism. And it’s looking more and more like T cell responses and interferons and innate immunity are probably all more important than antibody in determining good versus bad outcomes. So just because a person might be on immunosuppressive therapy that reduces antibody response, that’s really not a reason to think that a vaccine would be pointless. In fact, most of these vaccines have been shown to activate T cells and induce good interferon responses, and that will probably be more helpful ultimately than the antibodies. So I wouldn’t let antibody worry you too much.

Dr. Michael Yeaman:

And I guess, Lisa, just in closing, we’re going to all have a lot of different experiences and options with vaccines. Overall, they have been safe. There have been one or two cases in the world of vaccines being associated with adverse events that are very familiar to people who have NMO. There was one case of a transverse myelitis. Just want to emphasize that was determined not to be associated with the vaccine. So you’re talking about 75,000 plus individuals, no real safety signals. There will probably be some very mild vaccine-related symptoms like pain at the injection site, for example, or maybe a little bit of malaise or something like that, but those are normal kinds of issues that are mild and resolved very, very quickly.

Dr. Michael Yeaman:

So in light of the bigger picture of the pandemic, most of us will probably want to strongly consider using a vaccine for COVID-19. It’s very important to know that there are different kinds of vaccines and that there should be a plan that works for you. And that plan will involve very careful discussions with your neurologist, knowing which vaccines are usable in your case and which should be avoided in your case and then trying to find a good timing for when to be vaccinated.

Dr. Michael Yeaman:

I think big picture, we’re all trying to figure this out together as we go forward. The new technology vaccines obviously have a lot of promise based on their degree of protection. It looks like the protection is going to last long enough to be protective in a way that creates what’s called a herd immunity. But even if a person ultimately decides that as an NMO patient, you cannot or do not want to be vaccinated, the individuals who live with you and who are around you should strongly consider being vaccinated to protect you.

Dr. Michael Yeaman:

So infection is really one of the only medical conditions where how each of us acts can affect everyone else. I can’t give somebody else high blood pressure, but I can give somebody else a viral infection. And so we really just need to think about that in a way that we take care of each other. So I’ll stop there, Lisa, and see if there’s any final thoughts you might have.

Lisa McDaniel:

Thank you so much for your very informative presentation, Dr. Yeaman, and for taking the time out of your day to answer questions for our community. I’m sure it’s very much appreciated by everyone. As a closing, I want to remind those that have taken the Guthy-Jackson COVID-19 survey that you will need to log back in to take the second and third parts as they are released. And those parts are only on a limited basis. You can find the survey at our website at guthyjacksonfoundation.org, and you can also find the survey link on our Facebook page. Thank you so much for joining us today. And I hope that your day is lovely and this has been helpful for you.

Dr. Michael Yeaman:

Thanks everyone. Happy holidays.