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Leonard Calabrese, DO, discusses his findings entitled, “Applied Immunology to Autoimmune Diseases: COVID-19 as Immunology,” which was presented at the Rheumatology Nurses Society Conference.
Rheumatology Network sat down with Leonard Calabrese, DO, to discuss his findings entitled, “Applied Immunology to Autoimmune Diseases: COVID-19 as Immunology,” which was presented at the Rheumatology Nurses Society Conference. Calabrese is Professor of Medicine at the Cleveland Clinic. He explains the immune history of COVID-19, immune-based therapies, and the impact this has on patients with rheumatic disease.
Rheumatology Network: What is the immune history of COVID-19?
Leonard Calabrese, DO: Well, I mean, the short answer is that this is an infection that is an exemplar of the collision of an infectious disease and immune disease. And as I discussed in detail in my presentation, like a typical infection, you acquire it, the virus multiplies, and it invades your respiratory tract. And most people are able to beat that back, getting either no symptoms or little symptoms and mild symptoms after a couple of weeks. The vast majority of people recover, but some small percentage, which is influenced by all these risk factors such as age, comorbidities, immune diseases, and immune suppressive drugs. They then go on to a third phase. It is not clear what the major drivers are, but what is clear is that it is a disease characterized by hyper inflammation. Some people have used the term cytokine storm others have called it hyper inflammatory syndrome, but it's the immune system gone awry. And in that stage of the illness, that is what most people will succumb to as they develop progressive respiratory distress and ICU and ventilation, shock, and death. So it is a infectious disease that drives an immune disease.
RN: Can you tell me about the idealized clinical course of COVID-19?
LC: Well, that is kind of the idealized clinical course, we divided into 3 stages. The first stage is when you get this infection, as we just mentioned, and the virus starts to multiply and triggers what we call your innate immune system, that I spent a lot of time talking about. That's the early warning system. Interferons, in particular, are very important. Some people may end the infection right there, but over a course of about a week, as the infection lingers, then the second phase triggers and that is when we recruit our adaptive immune system: T cells, B cells. And that serves the vast majority of people. Well, it's stage three, where this occurs in people with diminished interferon responses. In particular, in older age groups with co-morbidities that we start to see hyper inflammation and that's rising markers like C-reactive protein (CRP) and ferritin. And that leads to immune mediated coagulation defects, respiratory failure, other organ failure, and death. So that's the 3 stages, or 3 acts, of COVID-19.
RN: How does this impact patients with rheumatic disease?
LC: Well, it's a good question. I mean, first of all, we know that most patients with rheumatic diseases do relatively well with COVID-19. And thanks to databases like the COVID-19 Global Rheumatology Alliance, we know that the risk factors for having progressive disease in addition to all the risk factors for regular people, such as obesity, diabetes, and heart disease, those risk factors include having active disease when you get the COVID-19. So, you know, this is no time to stop your medicines. And then secondly, there are certain medications that appear to actually increase the risk of bad outcomes. And those include glucocorticoids at doses of like 10 milligrams of prednisone a day or higher. And in particular, being on B cell depleting agents like rituximab and other drugs, those are big risks. Whether that includes drugs such as Janus kinase inhibitors and anti-cytokine therapy, the data are not clear. In fact, many studies from both rheumatology and dermatology suggests that if you're just on anti-tumor necrosis factor (TNF) or an anti-interleukin (IL)-six, without other drugs, there appears to be no increase in bad outcomes. Methotrexate is a tricky one, because we use it so often. By itself, it doesn't appear to offer much risk. But that brings us into the question of how do all these things affect people on vaccines?
I'll just close by saying that there are hundreds of other drugs in clinical trials where they range from very little data to a lot of data. And we eagerly await those. And then finally, what I'll say is that what we're really waiting for, because most people don't believe that this disease is just going to go away, is for the development and approval of an effective oral antiviral agent, like we use for influenza, that would give us all great comfort and confidence that we could deal with this.