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What do People with Rheumatoid Arthritis Need to Know about COVID-19 in 2024?

8 months ago
53 min read
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Episode Summary:

Cheryl sits down with immunology researcher Dr. Campbell, PhD and Rheumatologist Dr. Dave, MD to learn what people with rheumatic diseases need to know about Covid-19 in 2024.  They answer Cheryl’s burning questions about long COVID, vaccine efficacy and safety for people with autoimmune conditions, and potential links between autoimmunity and long COVID. They also talk about cutting edge research and new therapies including CAR T-cell therapy.

Dr. Campbell encourages participation in research studies to better understand these complex issues. Dr. Dave emphasizes the need for precision medicine approaches in treating autoimmune diseases like RA, where individualized treatment plans can be tailored to each patient’s unique needs. Despite the challenges posed by autoimmune diseases and COVID-19, they express optimism about the future of treatment options and the ongoing medical advancements.

Episode at a glance:

  • COVID-19 and Autoimmune Diseases: The conversation delves into the impact of COVID-19 on individuals with autoimmune diseases, particularly rheumatoid arthritis (RA), and the potential implications for their health.
  • Long COVID: There is discussion on the phenomenon of long COVID, which highlights the need for further research in this area.
  • Vaccine Efficacy and Safety:  Vaccination concerns are addressed, including the efficacy while taking immunomodulating medications for autoimmune conditions.
  • Precision Medicine: Advocating for personalized treatment plans tailored to each patient’s needs.
  • Research Efforts: The conversation explores ongoing research efforts aimed at understanding the relationship between autoimmune diseases and COVID-19, as well as advancements in treatment options such as CAR T-cell therapy and personalized medicine.
  • Optimism for the Future: Despite the challenges posed by autoimmune diseases and COVID-19, there is optimism about the future of treatment options and the potential for continued advancements in medical science.

Medical disclaimer: 

All content found on Arthritis Life public channels was created for generalized informational purposes only. The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment.

Episode Sponsors

Rheum to THRIVE, an online course and support program Cheryl created to help people with rheumatic disease go from overwhelmed, confused and alone to confident, supported and connected. See all the details and join the program or waitlist now! 

Speaker Bios:

Dr Dan Campbell:  BRI Principal Investigator Dan Campbell, PhD, has been an investigator with Benaroya Research Institute since 2003. He currently serves as the Director of BRI’s Center for Fundamental Immunology and leads BRI’s Campbell Lab in working to better understand the role that T cells play in immune system diseases as well as in a healthy immune system. Dr. Campbell is also an affiliate professor in the department of immunology at the University of Washington School of Medicine.

Dr Amish Dave: Amish Dave, MD, MPH, is a board-certified rheumatologist practicing at Virginia Mason Franciscan Health, treating patients with autoimmune diseases such as rheumatoid arthritis, lupus, psoriatic arthritis and vasculitis. Through his work as a physician, he enjoys getting to know his patients — including members of their support systems, what symptoms they are experiencing, what barriers to treatment they’re facing, and what their goals are. Dr. Dave has served as a co-chair of the Arthritis Foundation’s Great West Region Chapter since 2020 and as a clinical instructor in the department of family medicine at the University of Washington Medical Center since 2021.

Cheryl Crow

Cheryl is an occupational therapist who has lived with rheumatoid arthritis for nineteen years. Her life passion is helping others with rheumatoid arthritis figure out how to live a full life despite arthritis, by developing tools to navigate physical, emotional and social challenges. She formed the educational company Arthritis Life in 2019 after seeing a huge need for more engaging, accessible, and (dare I say) FUN patient education and self-management resources.

Full Episode Transcript:

Cheryl:  00:00

Hi, I’m so excited to have not one but two guests today to help answer some of your burning questions about what people with rheumatoid arthritis and similar conditions need to know about COVID-19 in the year 2024. So, I’m really glad to have Dr. Dave and Dr. Campbell who are from the Virginia Mason Franciscan Health Rheumatology Clinic and researchers at Benaroya Research Institute. That’s a mouthful. Dr. Dave, can you start just with a quick introduction, what’s your medical specialty? And what drove you to your work today?

Dr. Dave:  00:36

Yeah, thanks so much, Cheryl, for having me on today. So, I’m a rheumatologist and an internal medicine specialist. So, I take care of adult patients with different autoimmune diseases in our rheumatology clinic at Virginia Mason, and also collaborates with Benaroya Research Institute. I got into rheumatology, really, because of a passion for taking care of people with all sorts of strange and not so strange, very common conditions. I think of rheumatology as, you know, primary care for people with different autoimmune diseases, like lupus and rheumatoid arthritis and spondyloarthropathy. But we also take care of a lot of very common conditions like gout, and tennis elbow, and so many different types of osteoarthritis and other types of arthritis. I think people don’t realize that there’s over 400 different types of arthritis out there, and a lot of other conditions that we take care of in rheumatology. And I also think it’s such an amazing field, that’s seeing huge advances in medications and different treatment options for patients. It’s really just a wonderful thing to help people to get a diagnosis of what they have, and help them find the path towards taking care of any sort of pain or inflammation.

Cheryl:  01:47

That’s so wonderful. And I remember they used to say there’s over 100 types of arthritis now. It’s like over 400. It’s amazing.

Dr. Dave:  01:54

Yeah, all these weird, rare genetic things, a lot of things that Dr. Campbell and people at BRI are looking into.

Cheryl:  02:01

Awesome. Oh, yeah. When we say BRI, it’s short for Benaroya Research Institute here in Seattle. We’re actually all not that far geographically. But I’ve just been in the habit of doing everything virtually since of pandemic. So, we’re talking virtually right now. But thank you so much, Dr. Dave. What about Dr. Campbell, what is your research specialty? And what made you get into what you’re doing today?

Dr. Campbell:  02:22

Hi, thanks, Cheryl. And thanks for having me on and allowing me to talk about our research as well, which is, I think, really exciting. And I got into the field of immunology. So, I’m an immunologist. I have a PhD in molecular and cell biology with a specialty in immunology. And I got into immunology, because I think it’s such a fascinating and complex system, that when it functions correctly, really protects us from such a wide variety of threats. And that was something that was really fascinating to me. 

And it really is a, it requires the coordinated action of so many different types of cells that have to work in harmony, right? It’s like an orchestra and you have to have the flute playing at the right time, and the tuba’s playing at the right time. And they have to all work together to make it sound great and for it to function well. And then, obviously, there are cases where it’s not functioning well. 

And the immune system touches on so many different parts of human health. There are some, some really obvious ones, like in the case of individuals with rheumatic diseases with rheumatoid arthritis and other autoimmune diseases, but it touches on neurological health and, you know, metabolic health of individuals. So, it’s really a fascinating and great time to be an immunologist. Because we’ve sort of come to those recognitions recently. 

So, my research focuses really on trying to understand the cells that keep the immune system in check, actually, and prevent it from responding when it shouldn’t respond. So, that’s my sort of focus within immunology. 

Cheryl:  03:56

That’s perfect, less relevant to my interests as somebody who is immune cells are turning onto the wrong thing with rheumatoid arthritis. So, thank you so much. Yeah, I’m really excited to chat with you all today. Because even though we’re four years in the, into the pandemic, and there’s been a lot of guidelines and things coming out, I think it’s still, you know, in my Rheum to THRIVE support groups, I just observed that a lot of us patients are still confused. What do we do? How immunocompromised are they? 

So, I think, you know, I’m going to preface a tiny bit with my story that, you know, before the current pandemic, I was diagnosed in 2003. And my doctor explained that, yes, since you’re on methotrexate plus a biologic, you’re a little more likely to get — you’re a little immunocompromised, you might be more likely than your friends to get, because like I was 21 at the time, to get the bugs, infections, sinus infections that are going around. But she said, you know, don’t let that stop you from preventing, or from pursuing your interests, like becoming an occupational therapist, working in health care settings, or even in elementary schools where they’re like, germ pits, you know, take your precautions, wash your hand, wash your hands, and you know. 

And over the 17 years before the pandemic, I would say that exactly played out. I would get the little colds and bugs that went around, but I never got hospitalized for an infection. And so, when the pandemic happened, it was a little trickier to know how to proceed, because so much, so little was known about it, and especially little known about, like, the long-term, how contagious is it? And what are the long-term effects of it? 

So, let’s just start with the question of at risk. So, how at risk, if somebody has rheumatoid arthritis and takes these disease modifying medications, this is really for Dr. Dave, how careful — people are asking me, like, how careful should I be? Should I mask all the time? Should I not? I know you can’t give us the crystal ball answer. But what’s your thought process on that?

Dr. Dave:  05:52

Yeah. So, I think this is a question that we get a lot. And I think the reality is that every individual person is an individual and very different in terms of like their particular modifiable risk factors, and how immunosuppressed they are. I think if you look at meta-analyses so far, basically compilations of the data from many different research studies on different biologic and non-biologic medications used to treat, say, rheumatoid arthritis or other autoimmune diseases, they all show a trend, like, a very wide variation in infection risk. But all of them show a trend towards higher infection risk in every immunosuppressive medicine, whether it’s methotrexate, or etanercept, or adalimumab, or abatacept. And so, I generally always tell all of my patients on immunosuppressive medicines that you’re high risk for an infection. Now, that said, you know, I have patients, I have patients who are ICU nurses, who are elementary school teachers, who never get infections. And then, I have, you know, people who are parents of two kids who are in elementary schools who are constantly getting infections. And so, every single person is a little bit different. 

We do know that combining different medicines like, being honest, like you said, Cheryl, about methotrexate and a biologic medicine means that you’re more immunosuppressed than if you were on just one medicine. And so, if you do have different medicines tackling your autoimmune disease in different ways, trying to control your immune system in different ways, it definitely suppresses your immune system. 

That also seems to be like the case where people on prednisone, which really suppresses the immune system, are also at a higher risk. And so, if they’re on higher than 5 or 10 milligrams of prednisone every single day, as a patient, I definitely worry about their infection risk. And so, that’s also something that’s really important. And definitely, if you’re not vaccinated, you’re more at risk for those infections than if you are vaccinated. True for COVID; true for shingles as well.

Cheryl:  07:49

That’s super helpful. I think just the spectrum of individual variants is so fascinating to me. Like you said, you’re looking at maybe five patients that are all the same age, same diagnosis, each of them has two kids, and you’re like, one of you is going to be fine. And when you’re all in that spectrum of you’re gonna be more likely to get infections, but some of you are gonna be — is that what I’m hearing? — some are gonna be more likely than others. 

Dr. Dave:  08:15

Yeah. And I’ll say like, sometimes we’re always, you know, I’m always impressed. Like, you know, like, I think about like this last month, I’ll have a patient who’s 95 who’s, like, never gotten an infection in 30 years of being on a biologic, which I think is fabulous. And then, I’ll have someone who just started a medicine, the same medicine, you know, like five months ago, and has already had three upper respiratory tract infections. So, there’s a lot of variability here.

Cheryl:  08:39

And that, yeah, I say, in my support group, like all roads lead to uncertainty. Like, at some point, we kind of have to cope with that, because we— empower ourselves with knowledge and then say, you just have to wait and see sometimes, right. 

But I’m curious, Dr. Campbell, not from the clinician standpoint, but from the researcher standpoint, what is the immune system research that you’ve been doing? Tell us about the susceptibility to viruses like COVID for people on immunomodulating meds?

Dr. Campbell:  09:08

Yeah, well, first, I’ll echo what Dr. Dave just said, you know, about patient-to-patient variability. We see that when we study people’s immune systems all the time, that no two people have an immune system that looks alike. And there’s a broad spectrum, when we look at people’s immune cells in the blood or immune function and measured in different ways, we see a broad spectrum of immune function within individuals. So, it’s not surprising that those sorts of different baselines interact differently with these medications and cause variations in risks that you see, right? So, from a human immunological researcher, that’s not surprising to me at all. 

And that fits exactly with the type of data that we got. What I would say about the, you know, what we know about how these, how the various, you know, DMARDs and medications interact with what we’re really trying to do, all these great DMARDs have been so helpful in treating RA and other autoimmune diseases, have really come out of basic immunological research, right? We’re trying to understand how the immune system works. And I mentioned sort of the analogy to the orchestra the other day, and with these DMARDs — not the other day, the other minute.

Cheryl:  10:20

It’s been a long day.


Dr. Campbell:  10:22

It is, right, it feels like a day. With these different DMARDs, what we’re trying to do is, is, you know, put the brakes on parts of the immune system that we know are causing pathology in individuals, right? Now, those are, of course, required parts of responding sometimes to an infection or to a particular type of pathogen. And so, it’s, again, not surprising that, you know, interacting within someone’s immune variability or the immune variability of the population that you’re going to, by putting the brakes on, that you’re going to end up being much more susceptible to particular diseases, right, in some individuals. 

The example that really comes to mind we talk about, you hear a lot in the, you know, in talking about over the last years about antibodies and cross reactive antibodies to different SARS-CoV-2 variants, right, and individuals who are on B-cell depleting therapies, like rituximab, of course have almost no antibodies, right, or have almost no B-cells to make the antibodies. Those are the cells that make the antibody. 

So, they’re really deficient in that part of the immune system. However, there are lots of redundancies built into this system. And so, your antibody dependent immunity might be a little bit weaker, but your immunity that is conferred by T-cells might be a little bit stronger then, right? So, it kind of balances back out and it leads to some increase in susceptibility, but not, you know, to a potentially dangerous level.

Cheryl:  11:51

Yeah, I think that is something that people have asked about, is like, the antibodies after you’ve had a COVID infection, like, how — I’m sorry, I didn’t prepare you for this question. But I’m just curious, either one of you, you know, I’ve heard people say that — I’m confused on this, I’ll be honest — that you can go get your antibodies tested, I participated on that COVID research registry where you got it tested. But then, other doctors have said, “Well, those aren’t really that accurate.” How or is there, are they accurate?

Dr. Campbell:  12:23

They’re pretty accurate measures of COVID antibodies. And one thing I will say, you know, from, you know, that this does cause more confusion, right, but from an antibody standpoint, if you have antibodies and go on B-cell depleting therapies, the antibodies that you have generally are fairly stable. It’s really a generation of new antibodies that is impaired in that case. The B-cell depleting therapies actually don’t deplete the existing antibodies. But if you’re going in and got another vaccine while on a B-cell depleting therapy, your antibody response to that would be very diminished. So, if you have the pre-existing antibodies, you’re usually pretty good even on a B-cell depleting therapy.

Cheryl:  13:02

Oh, thank you, that’s helpful to know. And then, back to Dr. Dave, for the just, again, real practical, on the ground, you know, day-to-day life, like I’m thinking about myself, I have a 10-year-old, we just did his birthday party, indoor trampoline park, which I practically had to medicate myself for anxiety knowing the risk of spinal cord injuries and such. But anyway, back to the infection risk.

 You know, a lot of people have been asking me, you know, what, I did a video on myself, you know, going to a roller-skating rink with a mask on because that, to me, it’s kind of like I’m a very cautious in general person, right? Like, I’m the graduate of the DARE program, like DARE to keep kids off drugs. And I was like, I’ll never do drugs. And like, that’s it, check it off. Like, I’m like the person who is very risk averse. 

But other people are like — anyway, long story short, you know, what are you, in general, I know you’re not giving anyone individual medical advice. But, you know, are you recommending these basic precautions like mask wearing and hand washing? Or how do you help your patients work through that?

Dr. Dave:  14:08

Yeah, so, you know, I think there’s a wide variability also in how hesitant people are to reenter life and engage. I think I have some thoughts on this. One is like, if you’ve already had COVID once and you’ve been able to get through it, I think there’s a high chance that you’ll get through another infection. And I often tell people to have the phone number for the nurses, the on-call rheumatologist be able to call in for, say, a prescription for Paxlovid if, you know, if you do happen to test positive for COVID a second or third time. And I think that’s important. 

I think a lot of my patients have been COVID once are like, okay, I can breathe, I don’t want to get it again. Maybe it was horrible. But, you know, I’ll make it through. I think it can be a lot more nerve-racking for people who haven’t had COVID yet, you know, three plus years into the pandemic. And a thing I tell people, you know, there’s no way to know exactly how you’re going to do per se, but we want to make sure that, you know, if you do get COVID, it’s, you know, hopefully you’ll be wearing a mask, therefore you’ll have less COVID that you’ve been exposed to hopefully, then you have a less intense reaction. 

So, I think for those patients, it’s a little bit of hand holding figuratively.  I’m making sure that they feel comfortable getting back into society. I’m often telling them to, you know, start with eating outdoors. Get out there, you know, meet other people. If you’re on a plane, still wear your mask. And I think that’s still good, even if you have had COVID once, and I know we’re going to talk a bit about long COVID and risks of developing them. 

But, you know, I still think if you’re in a crowded place, if you’re going to busy Costco, if you’re in a flight, I still think it’s reasonable to wear a mask. Now, whether it needs to be an N95, or whether just a simple mask, I think the data shows that N95 is better, but it’s also more uncomfortable. And if reducing the amount of respiratory particulate you’re breathing in with just a regular mask, I think that’s reasonable, too. 

And so, I think different rheumatologists are giving different advice at this point in time. There’s not standard advice on how to get back into society. But I’m still recommending that people handwash, try to stay away from people with active symptoms of coughing, and etc. 

I’d also say kind of like, going back to your other question, though, like, I’m definitely always worried about my people on, you know, the data that’s been collected by the COVID-19 Global Rheumatology Alliance really shows that patients on B-cell depleting therapies and rituximab and abatacept in particular, abatacept not necessarily depleting your B-cells but affecting co-stimulatory proteins and therefore, B-cell active activity. Those patients are probably at higher risk of bad outcomes from COVID and seem to have, you know, less response to COVID vaccines. We’re not really — per se, I think the data will come out more over time — but we’re not necessarily seeing people on methotrexate or TNF inhibitors having horrible outcomes like we initially were really fearful of.

And so, I’m really trying to use some of that data to calm people, especially people who are more anxious. And here in the Seattle area, I think we have the highest rates of masking in the country. And so, definitely a lot more anxiety and stress. And so, you know, I think that should hopefully provide some reassurance to most people with autoimmune disease. 

Cheryl:  17:17

Yeah, that’s super, super helpful. And I often think about, you know, for me, when I get anxious or overwhelmed to think about what can I do, my zone of control. Like, what can I control the things right in front of me. I can’t control other people’s actions; I’ve tried. There’s the zone of partial control, right?

And so, you know, and I think there’s a biopsychosocial approach, too, where you say, you know, it’s important for me to have, to be alive. So, I can live life, like, occupational therapy is supposed to be living life to the fullest, that’s our tagline. So, you’re like, you can’t really live life to the fullest if you’re not alive. 

So, but you also, you need to protect your livelihood and protect yourself from severe disease, but also say, you know, my psychosocial experience is important, too. I went to the Taylor Swift concert. I was one of the only people masking there, that was so full of a lot of not-masking people. But, you know, it was like a life, a lifetime, you know, bucket list thing for me. And so, we have to make, just like we do with other health behaviors, smoking, driving an ATV, you know, that kind of thing. People make the decisions based on their own matrix of importance. 

But that’s, it’s helpful that you that you said, look, there’s a line in the sand a little bit where if you’re on rituximab or abatacept, you kind of need to be a little bit more cautious.

 Dr. Campbell, I don’t know if this is the right time to ask this. But do you have any other things that you want to share about how research has influenced the clinical care for people with RA regarding —? Sorry.

Dr. Campbell:  18:51

First, I just want to comment that focusing on the zone of control is great advice for everybody. So, I appreciate that. And it’s actually advice that I use as well. You have to focus on the things you can control in life.

Cheryl:  19:06

I’m a recovering control freak, so that’s why I have to repeat to myself,

Dr. Campbell:  19:08

Just fantastic general life advice, period. So, thank you for that. In terms of what we know about the research informing, you know, clinical care, and the way that individuals with RA who are in different immunosuppressive therapies should think about COVID risk, I think exactly as Dr. Dave said, our research and this is research that, you know, we performed in my group in here at BRI really did show about abatacept and rituximab, in terms of at least the vaccine responses, are associated with the lowest vaccine responses, right. So, if you’re on one of those therapies, even if you’ve been vaccinated, you know, that vaccination probably didn’t protect you as much as it might have protected either somebody who’s not on any therapy or who’s on like a TNF blocker. So, that certainly is a way in which you can inform your risk a little bit more by thinking about those, about those issues. 

There are some other things, you know, the idea of at least discussing with your rheumatologist pausing medication during vaccination, or, you know, certainly making sure that you prioritize getting your vaccination, I think, is extremely important when you are in one of these risk categories, so.

Cheryl:  20:23

That’s super helpful. And I will link to the ACR, American College of Rheumatology, guidelines for the timing of stopping medication. Because that that has been a helpful guide, I followed that for both all of my COVID vaccines and both my shingles vaccines, which I didn’t, you know, I’ve had rheumatoid arthritis now for 21 years. And I’m like, I’m a young person with rheumatoid arthritis. And then, my doctor was like, well, you actually, you know, you’re now 42. So, you have to start being eligible for some of these older people things, like, I thought shingles was only — anyway, and also for, ‘cause I’m on immunosuppressants, I needed the shingles vaccine. 

But, you know, another question for you, Dr. Campbell, is about the relationship between COVID-19 infection and the risk of a the development of autoimmune disease. So, my thought what I thought was the case is that any virus can trigger your immune system to go out of whack. But what do we know about COVID-19 specifically? And am I right to think that a virus can trigger autoimmunity in general? 

Dr. Campbell:  21:23

Well, you’re absolutely — you know, at this point, there are certain autoimmune diseases that have been more definitively linked with particular infectious triggers, right? And just in the last couple of years, for example, development of multiple sclerosis has been much more tightly linked with a particular type of response to Epstein Barr Virus. So, there are examples of this, you know? 

A virus is an immune perturbation, right? Virus comes along, tells your immune system it needs to do something. Your immune system starts doing things. And anytime you perturb the system, it doesn’t always, you know, return to where it was at baseline. So, in terms of specifically COVID-19 and RA, though, there really are no clear data at this point that support a link between COVID infection and development, not only of RA, but of any autoimmune disease. 

You know, these are early days, there’s a lot of anecdotes out there, right. An individual will have gotten COVID and a month later, you know, be diagnosed with RA, or develop type one diabetes, or another type of autoimmune disease and, you know, there’s a temporal link. So, at least in that individual, you know, thinks that there’s probably a causal link between those. And there could be, right, but we just don’t have the data at this point in the pandemic to really support a strong link between COVID-19 and development of any given autoimmune disease yet. I think time will tell us we, you know, have more data on this, you know. Almost everybody’s had COVID now, which is remarkable to think about, right.

Cheryl:  23:03

Not for my own husband. Just, he’s invincible apparently. I’ve had it twice, my son’s had at once, and just like, he’s like, well, I guess I’ll just —

Dr. Campbell:  23:14

I’m back at work for the first day today after being out from my first round with COVID. So, I hadn’t gotten it until two weeks ago,

Cheryl:  23:22

Oh, wow. Well, you get a little badge for making it that long. Yeah. Oh, my gosh, well, no, that’s super, super helpful. And you make a great point about like the correlation versus causation. And I have to introduce this topic in in my one of my educational groups, and it’s, it’s a really hard one to wrap your mind around, even when it comes to symptom tracking. Like, oh, let’s say I want to correlate whether exercise is helping reduce my pain or fatigue, like, obviously, over time, you can establish a causal relationship. But at first, you’re like, you have to not over assume that whatever you’re feeling, you could have just gotten a random flare that day that you happened to exercise. 

And so, you’re saying that people, since a lot of people are getting COVID, and a lot of people, in general with or without COVID, we’re just developing RA over time. What would you – what would you add to that, Dr. Dave?

Dr. Dave:  24:10

Yeah, no, I agree with Dr. Campbell. Well, I would say that, you know, we need to just follow this out longer and just see larger patient populations. Because there have, there was like a study out in the Lancet in September 2023 that suggested from a Chinese group that maybe there might have been some increased risk of autoimmunity in people who were, who developed COVID. But then, it’s unclear, the vaccination rates are a little bit unclear there. And then, it’s unclear what was done to attest that those patients actually had COVID, not another virus, etc. So, again, I think we’ll need to watch over time. 

I think what we are seeing, though, is that people who have had COVID do seem to be at high risk of developing cardiovascular disease, and potentially also diabetes. And so, if they’re not developing, you know, necessarily an autoimmune disease, they might be at higher risk for some of these chronic medical conditions that we really worry about. So, also another reason why we want to encourage vaccination and encourage prompt treatments of COVID infections, particularly if they seem severe. 

Cheryl:  25:12

That’s super helpful. And, you know, we’re going to talk about that a little bit more about vaccines in a minute. 

But I also, since both of you alluded to, like, you know, long COVID, or symptoms, certainly there’s people who have gotten COVID and then had a lot of symptoms that some of which overlap with an autoimmune disease, like rheumatoid arthritis, you know. How do you — first of all, you know, what is long COVID? And how do you distinguish the kind of fatigue from long COVID from maybe pre-existing, if someone has inflammatory arthritis like RA, and they’re starting to, they’ve got COVID, and then they’re feeling a lot more fatigued than usual, is it long COVID or is it —? How do they know if it’s, what’s happening? Dr. Dave, what are your thoughts?

Dr. Dave:  26:01

So, the CDC has a kind of a definition of long COVID and it’s evolving, but essentially, they focus on physical and mental symptoms that develop usually during or right after a COVID infection, and then are persisting for over two months, and impacting a patient’s life. And it’s not explained by an alternative diagnosis, like a pre-existing condition that a person had before getting COVID. 

And they bucket the symptoms in three different areas. One is ongoing respiratory symptoms. So, symptoms are started because of the COVID infection like chest pain, shortness of breath, that feeling of dyspnea or cough; or two, persistent fatigue with or without, like, body aches and discomfort; or three, cognitive problems. And I think it’s important to recognize that, you know, there’s a lot of other symptoms can occur during COVID. Like the classic loss of taste or loss of smell that people were panicked about, that doesn’t seem to be as big of an issue for most people with long COVID. It really seems that cognitive issues, respiratory symptoms, and fatigue are the bigger things that people worry about. And I think those are different than how most people with, say, lupus or rheumatoid arthritis typically feel on a day-to-day basis. These are symptoms that feel like almost you’re still struggling with the virus, and it’s persisting, as opposed to necessarily joint pain or flares or swelling.

Cheryl:  27:24

Yeah, that makes that makes a lot of sense. I mean, and I think something, a little bit of a side note, but I’ve delved a lot into in the last six months has been the relationship between physical activity, strength training, and fatigue, both experimenting on my own body and looking at the literature. And it’s been really, like, I don’t know if you guys, if people saw the EULAR recommendations, the first time, put together clinical recommendations for patients with inflammatory arthritis for fatigue. And the strongest recommendation was physical activity and exercise. 

And so, I have noticed that really strongly in my own body that was not just cardio — that was my theory, was that the cardiovascular would be the bigger ones. I’m thinking –  the blood’s flowing to my brain. But the strength training has even had a more pronounced effect on my cognitive issues. Still have some but, yeah, I remember when I had COVID the first time, I remember — sorry, this is a little anecdote so someone else listening doesn’t feel as alone, or weird. I literally was like, trying to feel better. 

And so, and I went and immediately and got Paxlovid, and got it taken care of. And I was like, okay, I’m gonna check my email. And I remember sitting at this exact desk here, and being like, I opened my email, and I was like, what do I do? Like, how do I, how do I check my email? It was so weird.  I didn’t understand what to do. And I was like, wait, I’m not ready, I’m not actually ready to email, like, but that went away. That was transient, like that was gone in a week or so. So, I also, like, put my car keys in the fridge, like kind of weird cognitive dysfunction. So, you know, that wasn’t long COVID because it didn’t last for a long time. 

And so, I would say, the thing I was gonna get with fatigue is that, I want to tell patients who are concerned that they might also have chronic fatigue syndrome along with their RA is like, if your fatigue gets better with exercise, that’s a symptom, that’s a signal that that’s fatigue is probably from your inflammatory arthritis. Does that make sense? But if your fatigue is persisting after exercise, then maybe it’s something else. I don’t know if you agree with that? And tell me if I’m wrong, I’m always open to be wrong.

Dr. Dave:  29:24

I think that’s a reasonable thing. Yeah. I mean, I think that if the fatigue is really new, and it’s a very different sensation than what you are experiencing before your COVID infection, then I’d worry that it’s related to the COVID. I’d just say that your experience, Cheryl, is actually very common.

I mean, one study in Italy of like 2,600 patients suggested that 42% of unvaccinated patients had post-COVID symptoms. So, this is three months after their COVID infection. That number actually goes down when you have vaccinations. So, if you had at least one vaccine, it was down at 30% of patients. If you’ve had two vaccines, it’s down to just 17%. So, less than 1 in 5 at risk of having these post-COVID symptoms. But also, you know, anecdotally and we’ll have to see over time, there is a suggestion that getting COVID vaccines after you have a COVID infection might help with some of the post-COVID symptoms. And then, they’re also concerned that you might flare up the symptoms if it’s too close, like, first two to three months after having an infection. So, time will tell, you know, on what we, how we decided to treat these post-COVID symptoms, but definitely being vaccinated before your infection seems to be protective.

Cheryl:  30:31

That makes me feel better. I’m vaxed to the max. 

And Dr. Campbell, I know you’re doing some really interesting, or your research area includes long COVID. What are some of the, what do we know about long COVID from your standpoint?

Dr. Campbell:  30:48

Yeah, well, as Dr. Dave just pointed out, long COVID has been a little bit difficult to pin down from a, you know, definition standpoint, and that definition has changed. But I think we are honing in on a definition for long COVID that makes it easier to study. It’s hard to study something you can’t define, or is difficult to define. But now we’re getting to better clinical definitions of long COVID. And with that have come some really interesting insights into that.

 There’s a study that was, in part including BRI researchers here, called the impact study recently that published their results last year. And they found some correlations between what’s happening acutely during acute COVID infection and development of long COVID symptoms. And really consistent with what Dr. Dave was just talking about, one of the factors that is associated with long COVID symptoms is a higher viral burden during acute infection, which really speaks to the importance of vaccination. 


Again, when you’re vaccinated, you’re going to decrease that viral burden. You could still get infected, but you’re not going to get infected to the-  to the degree that you would if you were unprotected, right/ So, getting vaccinated is really important for preventing long COVID.

 We know that immune response in long COVID seems to be somewhat, the immune response to the virus seems to be somewhat disjointed, that the orchestra is not all playing in harmony together, right, that you have some parts of it that are going off, and maybe going in the wrong direction. And that causes some persistent inflammatory symptoms, right, that can translate into the feeling that people get in long COVID. 

And it’s right down to — there’s a really fascinating study published in the middle of last year that was getting to the cognitive and brain fog that’s associated with long COVID. But there is a long-term depletion of serotonin individuals with long COVID. So, this is a really fascinating study was published in the journal Cell last year, that really touches again on how immunity and the immune system interacts with all the other systems in our body, right, and can regulate things as basic as serotonin levels and cognitive function, so.

Cheryl:  33:07

Wow, that’s super, that’s really, really fascinating. And I really was thinking also about, like, and I don’t know a ton about this, but the relationship between gut issues and, and rheumatoid arthritis, and a lot of your serotonin is processed in your gut. And there’s, yeah, there’s all these different — I mean, I’m so glad you’re studying the immune system, because I wouldn’t, I don’t think I’d have the patience to study it as a researcher, because it’s so complex.

Dr. Campbell:  33:37

Yeah, we try to take, you know, a, what’s the word that I’m trying to come up with here? I just had COVID, as I mentioned, so maybe my cognitive function might still be a little bit low. [Laughs]

Cheryl:  33:52

Yeah, no, definitely better than I was. 

Dr. Campbell:  33:55

A systematic approach to things, right, where we can study, you know, parts of it in isolation, and really try to figure out what they’re, you know, how they function individually before we can put the whole thing together. But putting the whole thing together has been a fascinating problem.

Cheryl:  34:10

Yeah, it is. Yeah, I’m reminded of that, I think a lot in memes nowadays, because I’m on social media so much, and there’s this meme that’s like, from The Notebook, the movie The Notebook where Rachel McAdams was like, “It’s not that simple.” And he’s like, “What do you want?” Like, it’s not that simple. It’s like: the immune system. It’s not that simple! 

Dr. Campbell:  34:27

It is not. Like, if it’s a puzzle, I think we know a lot about the individual pieces, but not always about how they all fit together, right? 

Cheryl:  34:33

Yeah. And that’s when we do, I do a lot of education on like countering, you know, misinformation that runs rampant online. So, yeah, if anyone tells you that they’ve got a simple solution to boost your immune system with one small supplement, nope. Dr. Campbell is shaking his head no, for those listening on the audio. 

And so, we kind of talked about vaccines a little bit, but I’m just wondering, so, you know, you already mentioned that if — let me summarize, that if you’re on immunosuppressants for rheumatoid arthritis, are you by nature going to have a worse response to vaccination, Dr. Campbell? Or does it depend on which medicine you’re on? 

Dr. Campbell:  35:11

It really does depend on which medicine. I think we touched on that a bit earlier that some are a little bit more, you know, inhibiting the parts of the immune system that are really responsible for these anti-vaccine responses. And so, the two that Dr. Dave brought up that are consistent with our research are abatacept and rituximab.

Cheryl:  35:30

Is abatacept Orencia?

Dr. Campbell:  35:32

Yes.

Cheryl:  35:33

Okay, okay. Sorry. Wow, that was what I was on at the beginning of the pandemic, actually. Yeah, interesting. And then, I switched to Actemra. But I didn’t get COVID until two years into it. But anyway, so I guess I’m marking myself lucky.

Dr. Campbell:  35:47

Yeah, we think of the vaccine, you know, the thing that we’re doing is we’re training our immune system, right?  And we’re training it through generation of primarily antibodies that will recognize the virus and neutralize the virus and not allow that to go into ourselves. And then, both of those medications, were really targeting parts of the immune system important for that antibody generation. And of course, the antibodies are pathogenic in individuals with rheumatoid arthritis, so.

Cheryl:  36:15

What does that mean to people who don’t know?

Dr. Campbell:  36:20

What that means is people with rheumatoid arthritis have what we call auto antibody. So, they have antibodies that instead of recognizing a virus, like COVID, SARS-CoV-2, or the influenza virus, they have antibodies that recognize their own proteins.

Cheryl:  36:32

And they’re, those are the ones in the synovial lining, right, of your joints? They get way in there.

Dr. Campbell:  36:38

They can bind to those proteins and cause an inflammatory reaction and cause dysfunction of the tissue there because of that induced inflammatory response. So, you want to target those antibodies in RA. But of course, that leaves you more susceptible to viral infections where you’d want to mount a good antibody response.

Cheryl:  37:04

Dr. Dave, would you want to add anything to that?

Dr. Dave:  37:07

No, I think I think that’s all right. The other thing I would just add is that, like, we just don’t have enough data on combinations of medicines. And I’ll say that a lot. Like, you know, like, we don’t know what happens when you add methotrexate with abatacept to your COVID response. I think time will tell. 

I think the other area that’s gonna be really interesting is like, you know, so tocilizumab, which you’d mentioned, Cheryl, Actemra, the brand name. So, tocilizumab, you know, is FDA approved for treating COVID lung disease. But does that mean that it prevents COVID? Do we know enough about it? I don’t know yet. I think time will tell. At least I’ll say that we don’t have enough data on it. But time will tell. 

I’m very curious about these things. And what does that mean for sarilumab and other IL-6 inhibitors? So, time will tell kind of what these medications do and don’t do and who’s more at risk. We do know, like, you know, some things like hydroxychloroquine does not seem to protect you against COVID. Or as our former president —

Cheryl:  38:00

Why would you think that? No, I’m just kidding. 

Dr. Dave:  38:02

Yeah. And nor does it seem to really increase your risk to COVID. So, I think we’re learning over time. There was a lot of research spent on that for nefarious purposes, in my opinion, but like, you know, time will tell about other medicines. 

Cheryl:  38:15

Well, you have an informed opinion. So, your opinion means a lot. And then, did we already — I’m sorry, this is me trying to multitask and maybe not successfully. Did we already talk about hybrid immunity, the previous infection? We did talk about that, right?

Dr. Campbell:  38:28

We’ve not talked about hybrid immunity yet, no. My laboratory here at BRI was involved in a study on hybrid immunity. This was relatively early in the pandemic, where we looked at the difference in the immune response in individuals who were vaccinated versus individuals who had been previously infected and then were vaccinated, right. And what we could see was that the previous infection plus vaccination gave us stronger response in a lot of ways. So, we had — and especially on the T-cell side, we actually had a much stronger T-cell response, which is not those antibody generating cells. They protect you in a different way by directly targeting infected, virally infected cells. And it seemed to have a stronger T-cell mediated immunity to the virus in individuals who had hybrid immunity.

Cheryl:  39:25

Okay, that’s super, that’s super helpful to know. I’m feeling even better about my decision to vaccinate. No, it was not a hard decision. 

Dr. Campbell:  39:32

And then, you know, in individuals, for example, who are on rituximab who maybe don’t have an antibody response or have been on rituximab for a long time and have, you know, been vaccinated but don’t have a strong antibody response, it really is that T-cell response that is protective, right? And taking over then in that case, and it might not be as good as having everything together, but it is strong enough to provide a lot of protection from infection and is still well worth being vaccinated in that situation.

Cheryl:  40:00

And then, I know some people are still worried that maybe vaccinating themselves could lead to them developing an autoimmune disease. What do you say to that?

Dr. Campbell:  40:14

There’s no data. We’ve studied this at BRI as well. And there’s really no data at all to suggest that the vaccine itself is triggering autoimmunity. We’ve looked, we looked for new — we talked about auto antibodies a minute ago, how you have antibodies against your self proteins, we looked for development of new auto antibodies post-vaccination in individuals with RA and other autoimmune diseases, and we saw no evidence that that led to development of new auto antibodies or worsening of auto antibodies that they have. There’s no good — there’s no evidence strong epidemiologic data that links vaccination to development of autoimmunity. So, I think there I will be much more definitive in stating there’s no, like, and highly recommend, as Dr. Dave did, going out and getting vaccinated for SARS-CoV-2, if you haven’t already.

Cheryl:  41:07

Thank you. Is there anything else you’d want to add on this topic, Dr. Dave?

Dr. Dave:  41:11

No, I totally agree. And I’ll just say anecdotally, I’ve seen no patients get vaccinated suddenly developing new autoimmunes or anything like that. So, and I probably have over 95% vaccination rates in my clinic. And so, I feel very comfortable with vaccination.

Cheryl:  41:28

That’s, yeah, that’s super helpful. And the other thing we were going to talk about is, you know, the latest research that’s going on at BRI about COVID. And there’s that – you have, Dr. Campbell, the HIPC-RV study, trying to understand the immune system better. Can you tell us a little bit about that? 

Dr. Campbell:  41:50

Yeah, this is we call it the HIPC-RV study. So, it’s Human Immunology Phenotyping Consortium, and RV is for Respiratory Virus. This is a study that is really specifically designed to understand how respiratory virus infection impacts individuals with RA and other autoimmune diseases. So, we recognize that this is a new and emerging problem, right, that we don’t have all the answers. You could ask a lot of questions, Cheryl, where we don’t have the answers, right?

And we already have started and touched on those, you know, we can tell you what the best data that we have indicate. But we need more data. So, that’s really where the HIPC-RV study, the origins of that come from. And so, we are recruiting research participants, individuals with RA and others with other autoimmune diseases and healthy individuals to participate in this study, where we’re really trying to better understand that intersection between respiratory virus infection and autoimmune disease. 

Cheryl:  42:55

That’s super helpful. Is this something that I know, I know that I had me and my son, my son and I, donated blood to like the bio-repository? Is this, does this involve donating blood? Or what does it involve?

Dr. Campbell:  43:08

I believe there are a number of different ways you can participate. Blood is certainly one of them that we are always — and you mentioned our bio-repositories, we are always recruiting for those as well, right? So, anyone who wants to contribute to the research that we do on RA and other autoimmune diseases, we would encourage them to join the BRI bio-repository here and donate blood for our work. 

Cheryl:  43:39

It’s such an easy thing to do. And then, oh, yeah, I’m looking at the website now. I should have done this before. But that for that particular study, you can also — they said that you’ll visit the clinic a couple of times over two years, and that they’ll collect nasal swabs and blood draws well, so I’ll have to sign up for that one. Yeah, yeah. A

nd so, we’ve already kind of touched on my next question, which was like how — I know a lot of patients are really interested in contributing to research or they’re like what, you know, they want to feel empowered, like they can, in the same way that we participate in legislative advocacy, what are some other ways people could get involved, people with rheumatic disease or autoimmune conditions, can get involved in ongoing research, either with COVID-19 or for anything else?

Dr. Campbell:  44:24

Yeah, well, we already touched on the bio-repositories, right, which is a really big resource that we have here at BRI and it’s one of the drivers that really enable the research that we do, so we couldn’t do it without the patient involvement, and without the willingness to donate blood for our studies, we can better understand that. So, I would really encourage people if they’re interested in that to get in touch with the with us here at BRI and we’ll steer you to the right place to get to get signed up for that.

Cheryl:  44:55

That’s awesome. And I’m going to circle back to — oh, Dr. Dave, did you want to say something else about that? 

Dr. Dave:  45:00

I would also just encourage folks, you know, I always think like when you go to vote, you get that sticker that says, ‘I voted’, like in an election. I think, you know, I wish — I always love it when people who get involved in research let people know about, let other people know about ways to get involved. And so, that’s why I so appreciate you even doing this podcast, Cheryl. I feel like you know, if you post on social media, you let a friend know or you let an interest group, a disease focus group, a part of a same group with rheumatoid arthritis or vasculitis, you know, about opportunities. That’s always so helpful. 

And I often say this is particularly helpful for people with rare diseases who need to know about clinical trials, a lot of times it’s word of mouth, is the best where you can find out about things. 

Cheryl:  45:43

Absolutely, yeah, I’ve learned a lot about what influences human behavior, just through being on social media. It’s been really, really fascinating.

 I meant to ask earlier, I’m going to circle back to long COVID really quickly, and I didn’t prepare you for this question. So, it’s okay to be, like, we don’t know. But some of my social media followers wanted to know, is if you have a rheumatic disease, are you more likely to get long COVID? Do we know this?

Dr. Dave:  46:12

We know — so, so far, the data shows that you’re more likely to get long COVID If you haven’t been vaccinated, if you had a really, if you were hospitalized, and particularly if you have a single hospitalization, say, for example, with a really bad respiratory disease, acute respiratory distress syndrome, ARDS, if you have diabetes, and then if you’re older age, you’re more likely to get long COVID. 

Like, people under 21, a large study in the UK, for example, suggests that people under 20 really did not seem to get long COVID at the same rates. Like many things, kids often can be very resilient, per se, that’s not to mean that some kids don’t get long COVID. Certainly they do. But definitely seems advanced age and more medical problems or medical history seems to put you at higher risk. I don’t — and maybe Dr. Campbell has a different answer — but I don’t necessarily think that people with autoimmune disease per se unless they were hospitalized had really bad outcomes from COVID or more in and of themselves are more likely to get long COVID. 

But certainly, I, as well as everyone in my practice and other rheumatologists are seeing people in our practices who are getting long COVID, whether it’s from the autoimmune disease or other risk factors are just bad luck, per se.

Dr. Campbell:  47:29

Yeah, I would agree with that, except to, you know, the extent that your rheumatologic disease and medications might increase your risk for some of those other risk factors, right, put you into those higher risk groups. But otherwise, there does not seem to be a direct link between, you know, RA or other rheumatological disease and development of long COVID.

Cheryl:  47:52

That’s really helpful. And it does, because you are more likely to get long COVID if you’ve had a very, very severe disease, because that’s one thing, these are my things that I comfort myself with. Well, I know I didn’t have long COVID for my first two COVID infections, because I would know by now, but I was fortunate that, yeah, probably due to the vaccination, and maybe yeah, dose of good luck that, you know, both of them were, they were — I say that they were worse than a sinus infection, but better than the flu. I’ve had, like, done, you know, I have had urgent care verified influenza, where they’re like, “Oh, we haven’t had any case influenza yet this year.” I was like, I know my body pretty well by now. Like, I feel like I have the flu. And they’re like, well, they did the tests. Congratulations. You’re the first case of Influenza A in our county, in King County. That was like 2017 or something. 

Anyway, but yeah, for me, it was not as severe as the flu. And that’s just me. But definitely noticeably worse than a sinus infection just in terms of the congestion and headache and some of those fun cognitive issues. Like, how do I check email? Again, Dr. Campbell, you’re doing great. That’s, you’re better than I was. 

But so, my last question is, I know we only have, you know, six minutes left, and I want to be respectful of your time. But, you know, zooming out to the big picture, what advice do you have, or what words of encouragement or wisdom would you give someone who was just diagnosed with RA? Like, do you have — do you think there’s good reason to be hopeful for the future? I’ll start with Dr. Dave and then end with Dr. Campbell.

Dr. Dave:  49:27

Yeah, so absolutely. I think, you know, seeing patients of different ages in my clinic, you realize how far we’ve come. You know, I’ve had, I have patients who told me about getting gold injections, you know, for the rheumatoid arthritis. And we now have so many different medicines. There’s so many different opportunities for combinations that, really, if you have insurance, which I think is the biggest, the biggest factor if you have insurance and good insurance, you have access to so many different things. I think we are reaching an era where there’s talk about potentially CAR T-cell therapy for rheumatoid arthritis and other autoimmune diseases that might lead to lasting remission for a lot of people, especially with the most severe types of disease manifestations.

 So, and I think we’re also coming to that period of time in which we’re gonna have more personalized therapy, where we’re going to eventually, patients very early on once they’re diagnosed, are going to be we’re going to be able to get lab testing to determine which medicines they’re going to be more responsive to and less responsive to. So, I really think that the way we’re going to practice 5, 10, 15, 20 years from now for rheumatoid arthritis and other autoimmune diseases is going to be very different than how we’re practicing now. And I think it’s going to be for the betterment for patients.

Cheryl:  50:41

So helpful. Thank you. What about you, Dr. Campbell?

Dr. Campbell:  50:44

Yeah, first off, I really agree on a precision medicine type of approach, and that I think this is really coming where we can understand people’s disease a lot better right at the beginning, and identify which drugs are going to work best for them, right? Everybody’s disease is a little bit different. And trying to correlate what aspects of the disease will respond best to this particular medication and make those links much faster, I think, is one area where I’m really hopeful. 

You know, the pace of discovery and science and the pace of data generation that we have is it’s truly exponential. We know so much more than we did 20, 25 years ago, it’s led already to development of a lot of these, you know, medications that have really benefited people with RA. Moving forward, I can only see that pace continuing to accelerate, number one.

 And, you know, one of the things I’m most excited about in RA and other autoimmune diseases is identifying people who are developing this disease before they have a lot of, you know, life altering symptoms, and being able to intervene at earlier and earlier times, right? So, trying to screen people. And that prevention really is — the ultimate cure is, comes in prevention. And if we can screen people for, you know, particular auto antibodies and say this individual is on the road to arthritis, for example, and then intervene appropriately through a precision medicine approach, then we can really impact, you know, the burden of disease in these individuals. So, I think that’s an approach that I’m really excited about taking both RA and range of other autoimmune diseases where we can do this.

Cheryl:  52:33

Thank you. That’s so exciting. It definitely echoes what Dr. Buckner and Dr. Mikacenic, when I interviewed them a few months ago, they had some, they were mentioning that same thing. So, it’s really exciting for me as somebody 20 years, I got diagnosed 21 years ago, and I’m 42. So, it has been amazing even just to see there were only three biologics when I got diagnosed, now there’s, you know, over 10, I think. So, it’s really great. 

And thank you all so much for your time. I know you’re so busy. We’re recording this on a Friday. So, and, you know, you’re probably, brains are full. But I really, really appreciate you taking your time to share the wisdom. And I’m gonna put a bunch of links to you both of your, you know, where people can connect with you and then Benaroya Research Institute, but we’ll just say thank you again, and we’ll talk to you later.

Dr. Campbell:  53:19

Thank you, Cheryl. 

Cheryl:  53:21

Thanks! Bye.

Dr. Dave:  53:23

Bye.

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