Randall Cron, MD, PhD: The Role of Rheumatologists in COVID-19

Rheumatology Network interviewed Randall Cron, MD, PhD, to discuss his lectures entitled, “The Immunology of COVID” and “The Role of Rheumatologists in COVID-19,” which will be presented at the Congress of Clinical Rheumatology. Cron is Director of Pediatric Rheumatology at the University of Alabama at Birmingham. He explains what the immunology of COVID means, pediatric rheumatology, the advantages of telemedicine, and the part rheumatologists play during the COVID-19 pandemic.

Rheumatology Network: Can you tell me a little bit about the immunology of COVID?

Randall Cron, MD, PhD: Yeah, so not a ton of stuff is known quite yet. But there are a few things we know. And that there seems to be, for the most severe patients, the ones who end up requiring oxygen and hospitalization and who sometimes go into multi-organ failure, there seems to be a cytokine storm syndrome taking place. It's not identical to other cytokine storms that as rheumatologists we’re more familiar with, like macrophage activation syndrome, for example. interleukin (IL)-6 levels are elevated in the blood, but not nearly as high as we see in other cytokine storms, particularly in something called cytokine release syndrome, which we can see from chimeric antigen receptor (CAR) T cell therapy, for example, for refractory leukemia. They do have some degree of hyperferritinemia by laboratory bias as well, but it doesn't tend to be as severe for the bulk of the patients compared to, again, other cytokine storms. They do get acute respiratory distress syndrome, for sure, with the oxygen requirement, which tends to be a late finding in other cytokine storms, but as kind of an early finding with this virus having predilection for the lower airways.

RN: How has COVID-19 changed the treatment landscape for rheumatologists?

RC: It's a moving target and we're learning as we go. Early on, there was some suggestion that the drug hydroxychloroquine may have both antiviral and anti-cytokine storm properties, at least in vitro, to help patients with severe COVID-19. And so, there was a scare or kind of run on hydroxychloroquine, early on, which in the end probably doesn’t really help patients all that much when the larger studies were done. But because of that, like the short supply, particularly for patients with lupus, it's not the greatest drug out there, but it does help patients. So patients who come off it, for example, may flare their disease. And there's data from a while back that just being on it with a positive antinuclear antibody (ANA) could delay the onset of lupus. So, it clearly benefits lupus patients. That was one thing that changed. And then with the virus being out there and rheumatology patients in general being more susceptible to viral illnesses, in part based on their disease and in part based on the therapies they're on, then we had to decide as a group, “what do we do about this?” Do we change therapies? Or do we leave patients on what they're on? And for the most part, this is all just kind of consensus-think based on what available data there is, but I think the bulk of the suggestions that have come through places like the American College of Rheumatology papers that have been put out in, for example, arthritis and rheumatology, suggest staying on your current medicines. If you can lower the dose of glucocorticoids, for example, and not flare disease, that it’s recommended if possible, but not to just flat out stop them. And then certain drugs probably put you at higher risk than others if you're exposed and/or get the virus. So, there are different recommendations in general while the virus is out there or if you're exposed or get the disease.

RN: What are your thoughts on telemedicine, including advantages and disadvantages?

RC: I for one, personally, was kind of fighting going to telemedicine before COVID came along, just because I didn't think it was a reasonable alternative for patients where you're trying to examine their joints, for example. And there was some data, at least in pediatric rheumatology, that even though telehealth was becoming more available, that in places like Montana where they might have to drive long distances to find a pediatric rheumatologist, they still prefer driving rather than doing telehealth. So, I kind of was fighting it for a while. Then COVID came along, and now I'm a convert and I really like it. But the advantages are you don't have to come into the office or be exposed during the middle of a pandemic. A lot moreso in pediatric pathology than adult rheumatology, but there as well, there are a lot less of us. Some families have to travel 4, 5, or 6 hours to see a rheumatologist, particularly a pediatric rheumatologist. So, if they're doing well on their current therapies, then it seems reasonable to perhaps do every other visit via telehealth because it's such it's a burden to travel that far. There’s actually an amazing amount of things you can do on a telehealth exam that you'd be surprised. Even a joint exam was, you know, someone holding the phone or the small laptop computer or whatever they're using as their camera. You can see a fair amount, and you can certainly get them to do a variety of ranges of motion and even some strength exams and a skin exam, if that's relevant. It's not nearly as good as in person, obviously, but it's not completely impossible. And maybe one of the benefits that comes out of this is we teach families and our patients how to do joint exams on their loved one who has the disease. And that doesn't only help with telehealth, but in between visits as well. I don't know if that will ultimately be feasible or cause more problems than it's worth. But it seems like it's certainly a possibility for insurance or for the overall system. There's less facility fees, which isn't great for your institution who's charging those facility fees, but it does save money overall and certainly saves travel and time. I mean, there's certainly a lot of advantages to telehealth that are becoming more aware of during this pandemic.

RN: What is the role of rheumatologists during the pandemic?

RC: So, I think there's a lot of roles. Number 1: the cytokine storm aspect. The therapies that are being used to treat the severe forms of COVID-19, for example, are therapies that we're familiar with. We use IL-6 blockade, IL-1 blockade, and glucocorticoids as rheumatologists. We're immunologists in a sense; we understand the immune system pretty well. So, we definitely have a role to play even beyond our own patients and just helping to be part of the treatment decision making team for patients with severe COVID-19. For example, one of the curveballs that this pandemic threw at us was what appears to be post-infectious inflammatory process called multisystem inflammatory syndrome in children (MIS-C). It goes by other names in Europe, but at least in this country, MIS-C, which affects children primarily but young adults can get it too (MIS-A). And it's particularly the younger kids or kids under 5. It's very similar in a lot of ways and shares a lot of features with Kawasaki disease, which is a vasculitis that can affect the coronary arteries and children. And as rheumatologist we're very aware of that. We have treatments for Kawasaki that have been around for quite some time as well as some novel treatments that are for refractory Kawasaki that, again, the rheumatologists have played a role in helping set up the standard therapies that are being used for children and now young adults with MIS-A. With this MIS-C, this post-infection usually occurs about a month after infection or exposure to the virus. So even just from a treatment standpoint, in terms of trying to diagnose a cytokine storm syndrome in the setting of COVID, there have been rheumatologists, including folks at Temple, Roberto Caricchio and colleagues, who have tried to come up with criteria based on their large patient cohort. They're at Temple to define what a cytokine storm syndrome is in the setting of COVID because it's relatively new compared to other cytokine storms. So, I think there's a lot of roles in addition to what we're doing, such as talking with our own patient population, and making sure number 1 that they get vaccinated. Number 2: that there's hydroxychloroquine for those who need it. Number 3: giving them advice on their own meds, whether it's preexposure, post-exposure, or during infection. What needs to be done?

RN: Is there anything else that you'd like to add before we wrap up?

RC: At the end of the day, and this isn't really meant to be political or anything, but I think, as much as we can help in treating patients, it would be really just nice to prevent that. And I think the vaccines have been a homerun in terms of the technology, the speed that which we got there, even though the technology has been around for a while, but actually proven that, for example, the mRNA technology works as well as it does. The safety. Hundreds of millions of people have gotten these things and very small danger signals out there. But incredible benefits, like these things are amazingly good at keeping you out of the hospital and keeping you from dying. And so, if we want to get this off the planet and certainly out of our own country, we need to immunize as many people as we can. I would say that's the primary take home message despite all the immunology of COVID.