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Hydroxychloroquine and BCG vaccine in COVID-19 coronavirus infection. (7)
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You’re a renowned pediatric rheumatologist and immunologist. Several drugs, chloroquine hydroxychloroquine, or by brand name Plaquenil are used in patients with rheumatic diseases, such as systemic lupus erythematosus, SLE, Sjogren’s green syndrome. Now hydroxychloroquine is promoted as potentially helpful in COVID-19 Coronavirus infection. So what is the mechanism of action for hydroxychloroquine in our immune disease? And what is the proposed mechanism of action of chloroquine derivative medications in Coronavirus infections? I am not, you know, I should be more of a hydroxychloroquine expert. It’s not the strongest medicine we have in our armamentarium. I’ll tell you that it does work. Like we know, for example, from some fascinating studies where people got ahold of army members’ blood. when you join the army, a lot of times, you sign away a lot of things, including your blood. And so some bright researchers said, Okay, let’s look at that blood from way back when and they took lupus Patients who, for example, join the army at some point. Maybe they had a positive ANA blood test. And that’s a very nonspecific antibody that you can detect in your blood. But it’s also almost always present in patients with lupus. So the ANA antibody is not very specific, but it’s very sensitive for lupus. And what they found was that when some of those army recruits were identified with a positive ANA antibody, some of their physicians put them on hydroxychloroquine or Plaquenil, and others did not. And it turns out if I’m getting this correct, if I remembered it correctly, that it took a couple for those patients who ended up developing lupus, sided systemic lupus, an autoimmune disease. That those who had been placed on Plaquenil, lupus tended to develop a couple of years later. So which is fascinating to me. But you know, so it has effects. It’s very slow-acting, it takes a long time to act in autoimmune disease. Plaquenil is not going to help you right away necessarily. Maybe months down the road, it’s going to provide you some benefit. Having said that, you know, if you go off of it and you have active lupus, you can feel a lot worse or flare your disease. And so it has hydroxychloroquine has a role in autoimmunity. What its role is, in this viral COVID-19 coronavirus pandemic, is entirely unclear to me. I think some of the original interest rationale based on some, I think, primarily in vitro data is hydroxychloroquine may inhibit some aspects of viral replication. But also people are thinking, well, maybe it’s treating the cytokine storm I’d be personally a little surprised if that’s what it’s doing to help people. But no one knows, but I learned even today from a colleague that one of his patients with a disease very much like lupus had been on Plaquenil. And this is a case of one so very just a small anecdote. But interesting nonetheless. And she developed a pretty severe cytokine storm with the COVID-19 while on Plaquenil. So she got a lot of other potential risk factors that maybe make you more at risk for developing a severe form of coronavirus infection. No one knows. But I’m not convinced that the Plaquenil is going to be the most beneficial drug here. If it helps a little bit, that would be good because it’s generally pretty safe. At least in kids, we don’t see complications with it. If you’re on hydroxychloroquine long term, like 5-6-7 years on a high dose, it can build up in the back of your eye. So we send people to the eye doctor to screen for that. Some of these arrhythmias or prolonged QT intervals on your EKG. I haven’t seen personally in kids, but I know by learning model from COVID-19 and anything that this happens in adults, for example. Still, I’m not sure anyone knows how Plaquenil would work in this setting, and if it will work, and to what degree. Like what’s the relative benefit from hydroxychloroquine. So another hot topic in COVID-19 Coronavirus infection is using a BCG vaccine to prevent or reduce the risk of getting coronavirus infection. BCG vaccine, it’s a century-old vaccine that’s partially effective against TB, tuberculosis. And BCG vaccine stimulates the general activation of the immune system. That likely partially protects against the viral and bacterial respiratory infections other than TB. So it looks like a contradiction. We are saying at the same time that the general stimulation of the immune system by the BCG vaccine helps to protect people potentially from Coronavirus. But we also see at the same time that excessive stimulation of the immune system termed cytokine storm syndrome leads to severe COVID-19 disease and potentially to death. So, could you please help to resolve this seeming contradiction? Yeah, I’ll take a potshot at best at that. I mean, it may be that if you do ramp up your immune system with something like BCG vaccine, that you may be able to control the virus initially. So maybe be less of a trigger to stimulate the aspect of your immune system, which is going out of control. I mean, that’s just pure speculation, but may explain that dichotomy there. So early on, the activation might be good for the immune system. And later on, once it’s triggered by the infectious pathogen, then it’s not good. And therefore, you know, you need to treat the cytokine storm. Right! If it’s similar to some of the other cytokine storms, where a significant percentage of those patients have a defect in the ability to shut that cytokine storm down. They cannot shut a cytokine storm by not killing the target cell and going on to another one instead of talking to each other forever and ramping up these cytokines. Whether it’s IL-1, or gamma interferon, or TNF, for example, or IL-6, then yeah, that makes sense.