Transcript of video
Professor Cron, is there a typical clinical case that you could discuss that illustrates some of the topics we discussed today. I wish there were you know, every patient always surprises me, right? You think you’ve been studying this for a while, and part of it is. We just see the tip of the iceberg. So I mean, if there is one, there are probably more than one. However, a silver lining that comes out of this horrific pandemic is what we’re doing now, which is talking about cytokine storm syndrome. It has not been talked about a lot, right. And some maybe some of them, even the physicians who trained a while ago, may not have ever even heard of cytokine storm syndrome. And so not only for physicians. It’s important to educate the lay public about this as well. So, but this is a long way of getting to the point that in addition to patients dying from cytokine storm from COVID-19, there are patients around the world. This doesn’t spare anyone, depending on where you live. All ages from childhood, including infancy up through pretty old individuals who get cytokine storms from a whole slew of causes. And I think a lot of them go undetected. And if you don’t diagnose cytokine storm syndrome and don’t specifically treat that aspect of the disease, that patient is not likely to do well. So if we can start lowering that tip of the iceberg, or lowering the water so that we can see more and more of the iceberg, I think we’re going to recognize more and more of cytokine syndrome cases. And hopefully, if we can come up with some good interventions for these various scenarios, then yeah, we could save lives beyond just this pandemic. I mean, we that’s our focus right now, and it should be. But we should also be aware that many people suffer these worldwide. Dengue, for example, this hemorrhagic fever, there are 500,000 people a year who get severely ill from that. I think a large chunk of those may have a cytokine storm as a component of that, for example. So in one sense, this will be good. And it’s also the reason that Dr. Edward Behrens, my co-editor of our cytokine storm textbook, which just happened to be timely being put out last fall. But we knew it needed to be out there not so excited we saw this pandemic coming but because, you know, like we said. It’s something that we need to educate about, if nothing, and we call it cytokine storm syndrome specifically because of some of these other names like Hemophagocytic lymphohistiocytosis, macrophage activation syndrome. So that’s not going to be necessarily easy for the average person to wrap their head around. Not that cytokine storm is easy, but you know, if you figure out what a cytokine is, is kind of pro-inflammatory protein is the hormone of the immune system signaling other aspects of an immune response, for example. Hopefully, we can simplify it to that degree, not tonight. We’ve covered the fact that these different cytokines storms often have different features. And that kind of gets to your question that I’m taking a long time to get to, which is, you know, a typical case of this. maybe I’ll tell the first patient that flipped my research to study this as well as Dr. Behrens. We were both at the University of Pennsylvania at the time. And we had met this 14-year-old girl who had a rare disease that caused her to have repeated episodes of the cytokine storms and just chronic inflammation in general. She was a very kind of sickly individual and, you know, had a tough life. It’s to the point how we’d met her. But we got called one day when she was in the intensive care unit. And for me, she was probably the sickest child I’ve ever seen, who eventually came out of the ICU essentially unscathed. But she had a fever. She presented with abdominal pain and seizures. So she had central nervous system involvement. She had pan side opinion, that is, her white cells count or red cell count or platelet count. They’re all going down. She had pancreatitis, which is a nasty complication of being very, very ill. Her liver was failing. Her kidneys were failing. Her heart was failing. She had, you know, these inotropic drugs that keep your heart alive when it’s suffering like that. She had ARDS. She had acute respiratory distress syndrome. She was as close to death as anyone I’ve ever seen who eventually came out of it. And at that time, they had called the hematologic oncologist who, for a long time, had been using a chemotherapy based approach, using drug etoposide, vp16, to treat this. And so she was deadly ill. It seemed very appropriate. They gave her etoposide. They also gave her corticosteroids and cyclosporine. So that she was getting pretty good cytokine storm syndrome treatment. But she was not getting better. And around this time, this was back in 2004. We had started using one of these novel targeted therapies that go after individual cytokines. A drug called Anakinra. It’s a protein your own body makes. This protein exists to dampen down excess interleukin one. So it’s a recombinant human interleukin, one receptor antagonist, it blocks the action of interleukin one. And we had started using this in another disease, systemic juvenile idiopathic arthritis where these poor unfortunate children, a subset of them, will get macrophage activation syndrome. It is one of these other cytokine storms repeatedly. And our colleagues were starting to use this for that disease. And we were starting to use this for that disease. And it seemed to be helping not only their overall arthritis. But even it reduced the possibility that they would get macrophage activation syndrome. And so we talked to the other physicians, we talked to the family at length. And we said, you know, we need to try this because otherwise, I don’t think it’s going to go well. We didn’t think it was going to go well. And the other nice thing about this particular drug, anakinra, which isn’t true of all of them, but they all are, in a sense, nice because they target individual cytokines. it’s like I said it’s a protein your own body makes you’re just giving more of it. It’s got a good safety profile because it was thought to be a good drug for rheumatoid arthritis, and it got FDA approval for that. It’s an OK drug for that. But it’s not as well as, for example, the TNF or tumor necrosis factor inhibitors. But anyway, there are many safety data with anakinra. And anakinra got pretty reasonably good safety data. It’s very short-acting. So anakinra half-life is around four to six hours. So even if it was dangerous, it’s gone out of your system if you want it out pretty quickly. Anakinra tends to act quickly. So if it’s going to work, you typically know within 48 hours if it’s helping. And you can either try something else or stop it or do whatever if it’s not giving you the results you want. And it’s got a huge therapeutic window. That means you can give many doses, very high doses without increased side effects. And you can’t say that for very many drugs at all. So for many reasons, anakinra a really attractive drug. Within two days of receiving this. And we were using what we now would consider relatively lower doses of that drug, anakinra. But we used a lower dose the first time we tried it in this scenario. She woke up! Within six days, she was out of the intensive care unit. Within two weeks, she was out of the hospital. And it was nothing short of miraculous. I’ve heard not such harrowing stories but not too dissimilar stories very anecdotally, from some of my colleagues who have resorted to using this in COVID-19 coronavirus treatment.