Jeff Segal, MD, JD
Greetings everyone, and welcome to the podcast. Today, we are thrilled to be joined by Dr. Roger Seheult. And he spells his name a little bit differently than how it’s pronounced. It’s S-E-H-E-U-L-T, but I just learned the correct pronunciation is Dr. Seheult. Who is he? He is the voice and face of a healthcare entrepreneurial entity called MedCram.com. And MedCram has become the voice and face of COVID during this pandemic. It’s been hailed as one of the most informative sources available.
He’s an associate clinical professor at the University of California Riverside School of Medicine, as well as an assistant clinical professor at the School of Medicine and Allied Health at Loma Linda out in California. He takes care of COVID-19 patients. But he’s also a pulmonary and critical care doctor, he’s board certified in internal medicine, pulmonary disease, critical care medicine and sleep medicine. Those are many more boards certifications than I have.
And he’s the co-founder of MedCram. MedCram’s tagline? “Medical lectures explained clearly by world class instructors.” You can get CME credits for EKG, ventilator settings, ABGs and also learn about COVID-19, among other topics.
I’m starting to sound like a commercial, but most importantly, MedCram content has garnered 50 million video views, and their COVID-19 webinars have 800,000 subscribers. So, thanks for taking time to speak with us today, Roger.
I know that you’re still working in the intensive care unit, and we appreciate you being generous with your time. Welcome so much.
Roger Seheult, MD
Thank you so much, Jeff.
Jeff Segal, MD, JD
So, early in this COVID-19 pandemic, I zeroed in on two sites. The first: MedCram. The other one: “This Week in Virology”, a podcast of three or four virologists talking. Initially, they spoke for one hour, but now they speak for about two and a half hours. And they nail down the science. The thing that’s cool about MedCram is that the video presentations are short and just as informative.
And Roger, you have a very soothing voice, in the midst of a pandemic, and you’ve been providing nothing but the facts, supplying exquisite graphics that do an excellent job explaining the science. And as I noted in the introduction, the MedCram videos were cited as reliable and trustworthy, which is important because, in contrast to the news media, I see only two extremes: The world is coming to an end and there won’t be anyone left standing versus this is all a case of the sniffles.
I’m reminded of Mark Twain, who talked about taking a morning paper. He said that if you don’t take a morning paper, you’re uninformed. If you do take a morning paper, you’re misinformed. The news media has done a very poor job in terms of being particularly informative. So, thank you for the work you’ve been doing. Please start by telling us what you do in the hospital.
What is your role there? What type of patients are you seeing?
Roger Seheult, MD
I am a critical care intensivist, so I take care of patients that are critically ill. They’re usually in the intensive care unit and that can be anybody from someone needing a ventilator because they can’t breathe on their own to patients just coming out of the operating room. They’re still on a ventilator. They need to be taken care of because of a critical illness.
They have metabolic problems. So, that’s generally who I’m taking care of. And then I’ll see patients on the regular floor of the hospital who have pulmonary issues. So, they’ve got plural effusions and fluid around the lung or something like that. I also see patients in the clinic. These are patients that are ambulatory. They’re walking around, but they might have a lung nodule or something similar. It’s quite multifaceted.
Jeff Segal, MD, JD
And California was late to be affected by the pandemic, with San Francisco being a notable exception. I don’t think the part of California where you practice was crushed early with COVID. Is that accurate? Or did you see people early on, and your ICUs were filled to the brim initially?
Roger Seheult, MD
No, we were quite lucky in that we were able to prepare. I work in an area of Southern California called the Inland Empire. The Riverside and San Bernardino counties.
We escaped the early wave. It was more Los Angeles and San Francisco, like you said, that were hit early. We had time to prepare.
Jeff Segal, MD, JD
Let’s talk about MedCram. As I was introduced to MedCram and COVID-19, you have produced a number of polished videos explaining to people who have some technical background, but also a general lay audience, what you’re seeing with COVID. How did you get started with MedCram?
What was the kernel of that idea and how did it take off?
Roger Seheult, MD
I am an assistant professor of medicine at Loma Linda in the School of Medicine, and also in the School of Allied Health. I teach physician assistant students, and that’s what I was doing about 10 years ago when one of my students came through – a gentleman by the name of Kyle Allred – who is the co-founder of MedCram. His father had a lot of background in teaching and education, and actually Kyle did, too.
And when he came to my rotation, which was just a four week rotation, he said to me, “Dr. Seheult, people don’t go to the library anymore. They don’t check out books. They don’t check out journals. They go to YouTube, first of all, they go to Google, they go to YouTube, and they find the shortest video they can possibly find on the topic so they can learn it on the fly.”
Jeff Segal, MD, JD
Pretty scary, isn’t it, when you think about it with the benefit of hindsight?
Roger Seheult, MD
Exactly. So, he’s the one that came up with the idea of online medical education. To me, it worked really well because these students were coming every four weeks and I was going over the same issues and I thought that this will work. Why don’t I just record all the lectures that I’m giving these students? When they come out, we’ll put them on YouTube and we’ll do something called “flipping the classroom.”
This is something that Kyle also introduced me to, which is where you allot them time to watch the video on YouTube, and then you meet with them in person after the lecture. That’s when you can answer questions and fine tune things. It’s the opposite of traditional education, where you go to a lecture with a live person, and then you’re supposed to figure it out afterwards. In the style I just described, students watch a video online, they learn about something, and then you talk with them and have an interactive experience.
We started doing these videos on our YouTube channel back in 2012. We’d put a number of videos up talking about, for instance, acid-base balance, acute renal failure, etc. We’ve been doing this for years. Then we finally started our our website, MedCram.com, just a few years later. We started offering courses that provide CME (Continuing Medical Education) credits, which physicians need. And it’s been building ever since, and that’s where we are now.
We were certainly a presence on YouTube. It wasn’t a huge presence, but we were a presence on YouTube. And that led us right up to this coronavirus pandemic.
Jeff Segal, MD, JD
Talk about that for a minute, because COVID-19 put you on the map. It sounds like you had a limited following. Certainly, I could imagine the benefit for those in training, be they medical students, residents, fellows, et cetera. But as you get further and further out into practice, most doctors become very specialized in terms of the types of CMEs that they’re getting. I think COVID changed all of this.
Roger Seheult, MD
We would put videos up that we thought were important to know from a medical standpoint. Maybe not so topical or timely in terms of the news. We did do one on Zika virus when it came out, around the time of the Brazilian Olympics. And it really didn’t go anywhere. Just a few thousand views. No one was really interested. So, in January, things were brewing over in China. We didn’t know exactly how it was going to go, but it started to get a little bit more serious, it was getting in the news.
And my wife said, “Hey, you know, you ought to do a video on coronavirus.” I said, “That’s a good point. Maybe learn about it. A lot of people might not know exactly what a virus is. And we could talk about that.” And so, I did a coronavirus video. We didn’t even call it “Update One”, because I didn’t think I was going to do another one.
Jeff Segal, MD, JD
And you’ve now done a hundred, by the way. So, either yesterday or just two days ago, you hit triple digits with your one-hundredth update.
Roger Seheult, MD
I’ve got this little app on my phone where you can watch what happens to the video over time. My eyes almost fell out of my head when I saw how many views it was getting in just the first twelve hours. And I think it’s probably because we already had a presence on YouTube, so the algorithm already trusted us and pushed the content up when people started searching for it.
And then we just got more and more positive feedback.
Jeff Segal, MD, JD
Did you get a dopamine surge when you saw the app demonstrating acceptance?
Roger Seheult, MD
I had to rub my eyes. I thought I was seeing double.
Jeff Segal, MD, JD
Interesting. My take on COVID-19 is that it’s not the typical flu. Early on, there were some reasonable statistics coming out from the Princess Cruise experience and information from one of the Navy ships that stayed in port. We saw how COVID spread through those entities pretty rapidly. And the lethality rate, to be fair, was probably on the order of about 0.5 – 0.6 percent, even though the statistics on television make it look a bit worse.
But that’s still an ugly statistic. The worst flu in modern times had a lethal lethality rate of about 0.2 percent. So here, you’re looking at something that in a Western country has a lethality rate that’s three times the worst lethality rate that we’ve recorded for influenza. But that horrible influenza was not a pandemic. So, 0.6 percent is not particularly lethal compared to other horrible things that are out there, like avian flu, Ebola, etc.
It’s a combination of that lethality number and the fact that it is a pandemic – that it spreads so easily – that brings on these giant numbers. What are your thoughts? Do you think that because the lethality rate is perceived as not particularly high people have become complacent? The early public health efforts were designed strictly to keep our hospitals from being inundated with difficult to treat patients.
And when we saw videos from Italy where they ran out of ICU space or ran out of ventilators. You had people being triaged in the hallways, and it looked pretty frightening, even with the lethality rate that wasn’t in double digits. What are your thoughts?
Roger Seheult, MD
Yeah, it’s all of those things. You hit on all of them very nicely, Jeff. It’s such a huge denominator, that’s the problem. People look at the death rate. That’s the ratio of the numerator to the denominator. But what we’re dealing with is such a huge denominator that the total deaths can overwhelm the system. And once you overwhelm the system, the death rates for every disease go up.
Why? Because people can’t get the care that they need. And the most misunderstood thing about this pandemic is its potential for exponential growth. People cannot wrap their heads around exponential growth.
And I’ll give you an example that was taught to me many years ago in math class. And it’s an old question: “If you had a choice, I could give you a penny on the first day of the month, and then every day for the rest of that month, I would double the amount of money I gave you. Or I could give you a million dollars.”
And without thinking much about it, you may say, “Give me the million dollars. I’ll take the million dollars.” But exponents work by doubling the amount every day. Every day is a doubling. Day one is a penny. Day two is two pennies. Day three is four pennies, then eight, then sixteen, etc.
In the beginning, you may feel like you’re going nowhere fast. But this is happening right now. Just replace pennies with COVID patients. The health care leaders in our country understand this. We know what’s going to happen at the “end of the month” if this is left unchecked. And so when we start to see this happening, we shut things down. And people are saying, “Why are we shutting down the world over a bunch of pennies?” Well, you must do the math. And that’s they key. You must do the math. Because if you do the math, by the time you reach the end of the month, you’ve got five million dollars.
And most of that disaster is going to manifest on the last two or three days of the month. We don’t want to get to the last two to three days of that month, because once we get there, it’s a disaster. It’s bubonic plague time.
Jeff Segal, MD, JD
What you’re saying is, by that point, it’s too late. The beauty of exponential growth is that there’s a positive flip side. If you cut it off early, you eliminate the downside, and you never see it, which would be a wonderful outcome. The problem is how to get people’s attention and let them know a crisis is coming when we’re not used to this type of crisis. We’re used to thought experiments about a single all or none crisis. A nuclear bomb, or an asteroid hitting the planet.
I know I’m describing crazy examples, but those are either zero or one-hundred percent lethality examples. With COVID, we have something where, over time, you start to see it build and build, but it doesn’t hit your eyes until a lot of damage has been done. And by then, you really are playing an amazing game of catch up.
Roger Seheult, MD
Exactly.
Jeff Segal, MD, JD
The other point that’s interesting is coronavirus is novel. Let’s assume for the moment that this was your run of the mill influenza. We do have experience with the flu. And I know everybody’s talked about how this can be compared in some capacity to influenza. But the thing about influenza is that it’s been around for a while. We have knowledge of it. We have prior exposure to various influenzas and we have some element of immunity.
We also have a vaccine every year. Whether or not it works is another story, but frequently it works “good enough.” We also have therapeutics like Tamiflu. In one sense, influenza is an inappropriate analogy, considering the coronavirus is a novel virus that we have no experience managing, excluding SARS-CoV-1. Let’s talk about that for just a minute.
Roger Seheult, MD
We’ve taken care of influenza for many years. In fact, right before this coronavirus or COVID-19 pandemic, we had a bit of a recurrence of H1N1 2009 flu. I was seeing that in the hospital. And that is notable because that one seems to affect the heart more. Patients get a myocarditis – that’s inflammation of the of the heart tissue. And that can cause cardiac arrest. It can cause conduction abnormalities.
And so, that one is notable for the fact that here’s a virus that tends to affect other organs of the body, in addition to the lungs, which, of course, we all know is the major problem. People get pneumonia, they can’t breathe, and end up on the ventilator. And that’s what we predicted. And I and everybody else are blown away at how this virus affects so much more than just the lungs.
I think the primary way that it’s doing that is through blood clots and thrombosis. This has been seen multiple times in autopsy series. There was an article that was published in the New England Journal of Medicine that showed that there were nine times as many blood clots in coronavirus victims than there were in influenza victims. And that’s mind blowing because this is an endothelial disease. The term “endothelial” refers to the coating of your blood vessels.
Of course, the blood vessels go throughout the entire body. And depending on where the blood clot is, you’re going to get a different symptom. If it’s in the kidneys, you’re going to get kidney failure. If it’s in the brain, you’re going to get a stroke. If it’s in the heart, you’re going to get a heart attack. And that’s why we’re seeing so many different symptoms. If it affects the nerves, you’re going to get burning sensation.
I’ve had patients call me and say, “I have this burning sensation all over my body. What do I need to do?” And that’s the other aspect of this disease. When people recover from the flu, they might feel weak for a while, and then they get better. There are patients self-described as “long haulers.” They can have symptoms that persist for months. In fact, I just saw an article that showed 70 to 80 percent of post COVID patients have some sort of heart dysfunction seen on echocardiography.
This is like a virus we’ve never seen.
Jeff Segal, MD, JD
We can talk about two bookends. You either live or you die, so that’s mortality – or lethality. But then you also have morbidity, an expression of what happens when you get sick. You may live, but you’ll get horribly ill. And even when you recover from the illness, you may have sequelae. This is more than an illness that either does or does not kill you. You’ve got everything in between. A spectrum of outcomes.
We were planning to take a cycling trip to Spain in April of this year.
We made those plans last year and then saw the disease working its way through Italy at the end of January and early February. But we still had a chance to get our money back. And I started thinking, “Well, look. There’s a giant mountain range between the two countries. You have the Alps and the Pyrenees. My guess is it’ll be contained.” And I was still hoping to go until the bitter-end. But one of the people traveling with us, she’s a physician, said, “Look, even if the lethality rate is low, these people are getting really sick. This isn’t your grandmother’s flu. These are people that are spending time in a hospital. And we have no idea what the long-term effects of this will be.” We ended up canceling that trip and we got all of our money back. What a lot of people don’t get is that some of these people get quite sick.
They stay in the hospital for a long period of time. Some of them will linger for two, three, four weeks before passing away. So, that occupies a bed in an intensive care unit that someone else with more conventional illness cannot use. And even if they do recover, recovery means different things to different people. And there may be people who never get back to their full capacity. I know of one high intensity cyclist. This is someone who’s in her 30s or 40s.
She may not be an Olympic level athlete, but she is more than a weekend warrior. Very competitive in terms of being able to do Ironman type competitions. She ended up getting COVID. She recovered at home.
She’s exactly what you described as a long-hauler. She says that it’s been a couple of months. She does not believe she can go out and cycle more than ten miles right now at just a regular pace, much less a competitive pace. Symptoms seem to linger.
What is missed is the morbidity associated with the disease above and beyond the mortality statistics.
Roger Seheult, MD
Everything that you said is well informed. That’s exactly what I’m seeing in the intensive care unit. We have patients in there for weeks. The ones that do get better, they have symptoms that linger. But let’s play devil’s advocate.
Maybe this is exactly what the flu does. The flu also does this in a small percentage of patients. And it could very well be that because so many people are getting it, we’re hearing so many of these stories. It could be a denominator thing, or it could actually be that this is a different virus. I don’t know if it’s both of those, or if it’s one more than the other, but we’re certainly seeing it on a frequent basis.
Jeff Segal, MD, JD
I want to start with your hypothesis because you came to this hypothesis early. Most people suggested early on this was an upper respiratory tract infection. Some people have the misfortune of seeing it turn into a lower respiratory tract infection and or pneumonia.
But you seemed to gravitate to the notion that there’s endothelial involvement with systemic manifestations and this creates a clotting cascade phenomena. Because of that, it cascades very quickly into a systemic manifestation, which makes it very hard to control. Having said that, you positioned it in a way biochemically that made sense to me – and to many people. You don’t have the benefit of a whiteboard here to do it, but I think for the benefit of our listeners, if you could just briefly describe the biochemical cascade you believe is occurring, and describe some of the evidence to support it, that would be valuable.
And then finally, please describe some of the interventions we can do to mitigate this in its tracks. Now, that’s a that’s a mouthful right there, so sorry about that.
Roger Seheult, MD
No, that’s good, Jeff.
There’s really two major parts to this. There’s the “switch” and then there’s the “light bulb” if you will. So, the switch. Let’s talk about the switch. This switch is the ACE2 enzyme. ACE2 is an enzyme that does something very important. It is a balance of a huge system called the renin-angiotensin system, which regulates blood pressure in the body. And its role is to convert something called Angiotensin II into Angiotensin (1-7).
To review: Angiotensin II is a protein and Angiotensin (1-7) is a protein. Angiotensin II is a pro-oxidant molecule. It creates oxidative stress. Angiotensin II creates oxidative stress.
Jeff Segal, MD, JD
And how and why is oxidative stress good or bad for the body?
Roger Seheult, MD
That’s the whole discussion. That’s the light bulb, actually. Oxidative stress, when it builds, can cause inflammation in any cell where it’s happening. In this case, it’s the endothelium. So, ACE2 is converting Angiotensin II into Angiotensin (1-7). Angiotensin (1-7) is the alter ego. It’s the flip side. It’s the Danny DeVito of Arnold Schwarzenegger in Twins. They go together in a pair, but they total opposites, because Angiotensin (1-7) is an antioxidant.
ACE2 is balancing many of the oxidative processes that are going on in the body and counterbalancing them by taking something that’s pro-oxidant and turning it into something that’s an antioxidant. If this were basketball, it would be like stealing the ball from your opponent and coming back and scoring a basket at your own goal. It’s a two-point switch. ACE2 is extremely important in making sure that you don’t have too much oxidative stress.
Jeff Segal, MD, JD
In one sense, it almost sounds like the difference between sugar and blueberries, in terms what each does to your body.
Roger Seheult, MD
Imagine taking sugar and converting it to blueberries. That’s exactly what ACE2 does. Your endothelial lining is lined with ACE2. It’s everywhere. It’s all over the endothelial system. When this virus goes bloodborne, it’s going to attack, bind, and take out of commission a huge proportion of ACE2 enzymes, all of which are responsible for doing exactly what we just described.
At that moment, you lose the ability to convert something that’s a pro-oxidant into an antioxidant. That results in a massive burst of oxidative stress. And that could happen to anybody. And so the question that become critically important is this: What is your oxidative stress balance before the infection? That’s really important because if your oxidative stress balance before the infection is relatively good, then you can survive this kind of a hit because it’s going to be a temporary hit.
But if your oxidative balance before you get this infection is not very good, then this may be, and here comes the euphemism, the straw that breaks the camel’s back. Or the wind that tips you over the edge. So, what are the things that can cause oxidative stress? BMI, cardiovascular disease, obesity, renal insufficiency, renal disease, diabetes type two, etc.
All of these conditions move the scale in the favor of pro-oxidative stress. These are the exact patients that we are seeing in the hospital. Before this pandemic began, I was telling my pulmonary patients, my COPD patients, my asthma patients – these are the patients that are typically susceptible to influenza – we told them in January, February, and March, that they needed to make sure they’re safe. Stay out of the way. Stay home. This virus is coming for you.
Jeff Segal, MD, JD
And what did you learn? Were they actually vulnerable or not?
Roger Seheult, MD
Well, it turns out that they’re not really the ones that are vulnerable. There was some data that came out in JAMA and described New York City patients. It talked about the people that were getting this disease. Who were the kinds of people that ended up in the hospital? The people that were obese, or had cardiovascular disease were over-represented in the New York City hospitals. But patients suffering from COPD or asthma? They were the same as the background New York City population (including those treated as outpatients).
We didn’t see an increase in COPD or asthma, but we did see an increase in diabetics, hypertensives, and patients with cardiovascular disease. It’s because of oxidative stress.
So, why is oxidative stress so bad? Oxidative stress is bad because it will cause inflammation of the cells. When you have inflammation of the cells, they come off the surface. And that’s the other important thing that you have to understand. These endothelial cells are protecting the cell structure below, or the suprastructure of the vessel below.
These vessels have pro-thrombotic agents on them. If they’re not covered, and if these pro-thrombotic agents are exposed to the blood products, the blood will clot.
Jeff Segal, MD, JD
Let me ask you a question. I’m trying to just keep an image in my head. If the endothelial cell comes off, does the body believe somehow there’s now a hole that needs to be walled off?
Roger Seheult, MD
That’s exactly right. And that’s exactly why people get heart attacks. The endothelial surface of the coronary artery underneath it has become so inflamed, that there is a plaque rupture. Immediately you’ll get platelets to that area, and a thrombosis blocking off the vessel, causing a heart attack.
Jeff Segal, MD, JD
It sounds like our American demographics were primed to be exploited by this virus. The number of people who are morbidly obese has skyrocketed over the past couple of decades. The number of people who have prediabetes or diabetes has skyrocketed. And some of those conditions may be well controlled, some not well controlled. Were we just sitting ducks, here in a Western country, because the general health of our population was tuned down?
Put a different way: If we had all been “on the program” and eating well, maintaining a proper weight, etc, would that change in demographics have decreased the morbidity?
Roger Seheult, MD
Yeah, that’s correct. Look at other countries that don’t suffer from obesity. They may be on the other side of the economic system, and so they actually may have deficits in other areas. For instance, if you look at India, they certainly have a mortality rate over there, but it’s not anything close to what we’re seeing over here.
Jeff Segal, MD, JD
And what about people with diabetes? Is it diabetes, in and of itself, that creates the problem? Or does it matter if it’s well controlled or poorly controlled? I’m guessing poorly controlled is worse, but even if your diabetes is well controlled, does that put you in higher risk category than someone else who is in pretty good shape?
Roger Seheult, MD
There is emerging evidence that the person who has the highest risk for mortality and morbidity is, interestingly, somebody with well-controlled diabetes that has huge swings in glucose when they get into the hospital. In other words, they don’t do well under stress. One of the ways that we can measure how well someone’s diabetes is under control is with something called the hemoglobin A1c. It’s basically the average glucose in someone’s body over the last two to three months.
There was a study that showed that the people that you have to be worried about the most when they come into the hospital are those people with normal hemoglobin A1cs, but with huge swings in their glucose when put under stress. I don’t know exactly what that means for the average everyday diabetic, because we want to keep their diabetes under control. But there may be a genetic subset of patients that are just more susceptible to morbidity.
Jeff Segal, MD, JD
We learned this early on in taking care of traumatic brain injuries. When patients with such injuries come in, there’s a lot of cortisol that gets released and you start to see horrific spikes in glucose. What we learned is that if you can cut the peaks and make sure that they don’t become profoundly hyperglycemic, they ended up doing better. But if you lost control and they ended up having high levels of blood sugar, they ended up doing worse.
Which is why some of the researchers started talking about early feeding with lipids. I don’t want to get too much into the weeds, but interestingly enough, the high levels of glucose turns this into a pro inflammatory state and creates all sorts of poor outcomes for all types of conditions.
Roger Seheult, MD
Yeah, that’s what the thinking is. Initially, we didn’t know if the elevated glucose levels were the cause of the worsening outcome, or simply a signal of something else that was the cause.
Jeff Segal, MD, JD
The other thing that makes this virus pretty crafty is that it can spread either in the asymptomatic or pre-symptomatic state. Normally our first barrier of defense is our innate immune system, where the body sees something coming in, doesn’t know what it is, has no experience with it in the past, and just says, “Hey, there’s a fire going on. Let’s send out the fire trucks. We’ll douse the whole body with water to keep this thing from spreading.”
Interferon is one of the compounds used in this response. It’s non-specific. And in fact, the interferon that people release early on in a flu is why they feel so miserable. It causes headaches, photophobia, and all other types of symptoms. We know that’s the case because when you give people interferon to treat conditions like M.S., they describe similar flu-like symptoms.
The thing that’s really crafty about this virus is its mechanism to hijack or intercept the body’s production of interferon until it’s had a chance to go through an exponential reproduction cycle. This mechanism allows it to reproduce quite a bit and spread without the patient even being aware of what’s going on inside of his body. You’ve seen that, I’m sure, with people who are asymptomatic or pre-symptomatic. They spread the virus to many people before the asymptomatic/pre-symptomatic patient knows he is sick.
Roger Seheult, MD
I believe this is at the center of why we’re having so many problems with this virus. It suppresses that very important innate immune system response. Maybe the reason why we’re seeing differences in children versus adults and elderly adults is that as we get older, that innate immune system becomes weaker. And any way that we can boost that innate immune system is going to be helpful in terms of keeping that virus under control.
We think asymptomatic is a good thing. It’s actually a bad thing because it doesn’t tell us when we’re infected. Number two: Symptoms are good in this situation because symptoms tell us that your immune system has detected something. And as you just mentioned, the interferon is coming forth and it’s fighting the virus, and fighting the virus is good in the early stages because if the virus isn’t fought and it spreads, it’s going to trigger a reaction down the line that’s not going to be beneficial at all.
Jeff Segal, MD, JD
The other thing about this particular virus which makes it ugly is that it’s an RNA virus. My understanding is that RNA viruses are more prone to mutating than DNA viruses. But this particular RNA virus has a proofreading gene. So if it does mutate, it’s got a gene that tries to keep it back on track and keep from mutating. Any thoughts on that? It may be too soon to know whether there’s any significance to that, but it seems like function will keep it out there longer as opposed to having it mutating into a less virulent type of a virus.
Roger Seheult, MD
Yeah, I agree. A mutation is good. You know, this may sound counterintuitive, but viruses don’t want to kill their hosts. Viruses want to reproduce. That’s what they “want” to do. Dead bodies don’t produce viruses very well. A successful virus would be like the cold virus. It just causes a bit of inconvenience for the hosts and it spreads and goes on. Those are the successful viruses. Ebola is not a very successful virus because it kills its host pretty quickly and then dies off. Success here is being defined as the amount of copies worldwide.
Jeff Segal, MD, JD
You don’t want to kill the horse you rode in on.
The virus “wants” to spread as much as it can. Being stealthy is a better way to do that than. If you alert the world that you are Ebola, everybody will see Ebola coming a mile away, which is why you can do contact tracing with Ebola. It’s actually doable.
Let’s migrate a little bit in terms of the types of patients you’re seeing. When they come to the hospital, what percent typically require monitoring? O2? Placement in a step-down unit? ICU? Intubation? Describe the life-cycle of this.
If one-hundred people show up at your hospital, help us understand how they get triaged over time and what people can expect. These are only the people that are showing up in the emergency room, not the people who are seeing a doctor in their office, urgent care, or who never show up at all.
Roger Seheult, MD
I work at the San Bernardino County Community Hospital. We’ve set up a little tent outside. We call it the COVID village. People can come in and get tested for COVID and get the results back, depending on how bad the influx is. I don’t work down there, but I’ve heard some of the numbers. They see maybe about 50 or 60 people a day. And how many people get admitted to the hospital on a daily basis for COVID? Of the 50 that come in, we admit maybe two or three people to the medical-surgunit. And of those, how many people get kicked up into the ICU on a regular basis? Maybe one or two. And that may not sound like a lot, but these people, when they come into the intensive care unit, stay there for quite some time.
I would say the low end is at least three to five days if they’re coming in because they need high flow oxygen or they need non-invasive ventilation with a mask or they need to be put on a ventilator. So, at the long end, we’ve had people stay in that intensive care unit literally for months. They’re just not getting better. They’re sort of stuck at a level.
Jeff Segal, MD, JD
I just read about one woman who had COVID and received a double lung transplant. I’m assuming that everything else didn’t work, but she was still viable. And, in fact, it looks like she made a reasonable recovery. Of course, you hate to say that anyone with a lung transplant is out of the woods, but you realize we do have a much better tool kit now than we had at the beginning – with proning, high flow oxygen, antivirals, Decadron, convalescent plasma, hyper immunoglobulin, monoclonal antibodies, and so on. With a smorgasbord of so many things to do, what have you seen work? What have you moved away from? And do you feel like we’re settling in on best practices across the country?
Roger Seheult, MD
I’m hoping so.
Jeff Segal, MD, JD
That’s a loaded question. Thanks for taking a stab at it.
Roger Seheult, MD
Of course. First, anything that I’ve seen is going to be anecdotal, so it’s hard to to generalize. We’re very happy that we saw some evidence that Remdesivir worked and we’ve been getting our weekly allotment of Remdesivir and we’ve had meetings about who gets it, who doesn’t get it, and making sure that we’re not missing anybody. We recently had to put some people on hold because we ran out of Remdesivir and needed to wait until we received our next shipment.
You can’t give it to people with renal insufficiency. It can cause renal insufficiency.
Initially we were using ten days of treatment on ventilated patients, and because of the shortage we are now doing five. There was some data that showed people on the ventilator really don’t respond to Remdesivir. So, that’s Remdesivir. The other one, of course, is Decadron. We have data from the RECOVERY trial that shows that Decadron, more than anything else, helped in these patients who are on oxygen. Specifically those who are on the ventilator, more than those that were just on regular oxygen.
In that study, they were using it for ten days and they did six milligrams a day for ten days. You could do it intravenously or orally – it is bio-available. The pharmacokinetics of that drug are that it lasts for about twenty-four to forty-eight hours. They didn’t see the need to taper that medication. You could just use it for ten days and stop. What I have seen, and we’re trying to get some case studies together to look at this, is a number of patients rebound and become very sick after we quickly stopped the medication.
Jeff Segal, MD, JD
And you’re talking about quitting the medication cold-turkey. Is that correct?
Roger Seheult, MD
Yeah. To give your audience an understanding of what we’re measuring in these patients, we’re looking every day at ferritin levels as a means of looking at inflammation. We’re looking at CRP levels, which is a faster way of measuring inflammation levels in the endothelium and the body on that day.
We’re also looking at d-dimers. That’s sort of a “gross” measure of the clot burden in the body. And, of course, the big end point that we love to see in those patients who are ventilated is the amount of oxygen we have to give as measured by the FiO2. .5 would be 50%, 1.0 would be 100%. And I can tell you in the last week of at least three or four patients within one to two days of stopping their 10-day course of Decadron became significantly worse.
So, we’re looking very carefully at these patients when their 10 days are up. Are these patients clearly out of the woods? Are they off the ventilator and doing better? Or are they still in the thick of it and on the ventilator? And we’ve been making some clinically-based decisions on what we do with that Decadron.
Jeff Segal, MD, JD
In the neurosurgical world, if you put a patient on Decadron for anything other than for a surgical procedure, you ended up tapering over time only because you’d get tired of hearing the phone tell you, “I was fine, fine, fine. And then all of a sudden, everything went to hell in a handbasket!”
Roger Seheult, MD
And that’s exactly what we’re seeing. We’re seeing that bump in CRPs, ferritin, and FiO2.
Jeff Segal, MD, JD
And what about proning. Many of the listeners will be aware of it. They’ve been exposed to it now, but most people had not heard of it and thought it was an unusual or crazy idea during the COVID pandemic. But this is not a new idea. It’s not something that was developed over the past several months. It is an old idea applied to a new problem.
Roger Seheult, MD
The words that we use here are supine, which is lying on your back, and prone, which is lying on your belly. We talked about this in one of our videos called How Coronavirus Kills, which is probably one of our most popular videos. In the video, we talk about the evidence for this technique’s efficacy in treating ARDS. We reasoned acute respiratory distress syndrome is sort of the way that coronavirus kills patients. And it is partially true. That is how the virus does it.
What was the data? What was the evidence behind improved survival in ARDS patients? We talked about low tidal volumes. We talked about the use of paralytics. But the other thing that we talked about was proning, and proning is when you put a patient who’s on a ventilator, or even not on a ventilator, on their belly. If there’s fluid in the lungs, it’s going to shift that fluid gravitationally to a place in the lungs that is going to affect the least amount of the lung volume.
That’s one theory. Another theory is that by proning, instead of the heart laying on the lungs and compressing it (since the heart is in an anterior structure in the chest), the heart is being pushed forward and laying against the chest wall – off the lungs – allowing the lungs to better expand and to oxygenate, at least on that left side. And we’re seeing better oxygenation. There was a study that came out recently in COVID-19 cases specifically, and in that study proning did improve oxygenation and improve the vent endpoints.
In that study, it didn’t prevent eventual intubation in patients, nor did it improve survival. But it’s a tool that we are using right now to stave off intubation in patients who are on the edge. If we have a patient who is on high flow oxygen and they’re saturating in the low 90s or high 80s and doing well for any other reason, we’ll go ahead and put them on their belly.
I’ve seen dramatic improvements in oxygenation. I’ve seen a case where someone had a Pa02, which is the partial pressure of oxygen in the blood go from 60 to 260 just by turning.
Jeff Segal, MD, JD
That’s impressive to see that with just a simple action. That’s very gratifying. You don’t see much of that in medicine. Normally, you have to be patient and wait, but to see an immediate effect, that’s pretty cool.
Are you getting your hands on convalescent plasma or hyper immunoglobulin? I don’t know if monoclonal antibodies have actually cleared through in any capacity, other than in formal clinical trials. Any experience with that?
Roger Seheult, MD
To address that question about monoclonal antibodies, tocilizumab, which is the antibody against IL6, which we have been using, there was a paper that came out a couple of days ago showing it did not meet its endpoints in terms of decreased hospitalization, things of that nature.
So, tocilizumab may be one that we cross off our list in terms of usefulness.
I think there was a trend toward decreased hospitalization, so it wasn’t harmful, but it didn’t meet its statistical endpoint. On the bigger topic that you mentioned, convalescent plasma, as you probably know in the United States, different counties contract specifically with different blood bank companies.
L.A. County goes with the American Red Cross. San Bernardino and Riverside counties here in Southern California, we go with a company called Lifestream. They’re all working together to get convalescent plasma. At our hospital we are able to use it. Sometimes there’s a little bit of a delay. We’ll order it and have to wait. It also depends on the blood type of the patient because there are more types of plasma available for different blood types.
But for all our patients in our COVID village, if they test positive, we always send them a note encouraging them to donate blood after they recover. People are more than willing to do that if they think that it can help others. I should tell you, though, that all of this is being done through a study.
There are a number of studies ongoing. This is still investigational. We don’t know for a fact that it works. We know that in other diseases, antibodies against viruses work, but we just don’t know yet how that treatment works with COVID-19. We hope to get that data soon.
Jeff Segal, MD, JD
This may be a stupid question, but if you’re capturing convalescent plasma, presumably you’re giving all components of plasma to the patient, including the antibodies, which would be a good thing. But one of the things we talked about earlier was that there’s a clotting cascade that just goes horribly wrong. Does convalescent plasma have these clotting factors? And if so, does it move the needle at all in clotting?
Roger Seheult, MD
Theoretically, it shouldn’t. Because the clotting cascades are not exactly the problem. The problem is the activation of these clotting cascades. That gets us back to this oxidative stress thing that we were talking about. It’s this oxidative stress that we believe is inflaming the endothelium, that covering of the vascular wall. What’s stored underneath that endothelium – sub-endothelial – are these factors. And one of the things that we’re looking at is von Willebrand factor (VWF). There were studies that looked at these patients with COVID-19 and they actually tested their VWF activity level. They were up over five hundred percent in these patients.
It’s felt that when these VWF activate, they cause problems. I think of them as Lego blocks. Normally they’re supposed to help you to to plug up things. They go from monomers – which are individual packets – into polymers. And it’s these polymers – they’re like long ropes and strings – that catch and bind platelets.
And then once the platelets get involved, you get this clotting cascade. Those proteins are always available to do this. Now, one of the things I should mention, too, is we’re starting to get evidence that it may not just be a one hit thing. So, yes, there may be more oxidative stress, there may be more endothelium damage. Yes, there may be more VWF. But it’s not like the platelets are normal either.
There was a recent study that looked at RNA expression in platelets, specifically megakaryocytes – the cells that give rise to these platelets. They are abnormally expressing RNA when they are incubated with SARS-CoV-2. These platelets are becoming stickier. So you have more oxidative stress and endothelial damage and exposed VWF, and these platelets are becoming stickier.
And one of these papers said they were pulling out clots that were white. So these are very, very rich in platelets. And then there was another study that backed this up stating they’re seeing megakeryocytes in the clots (these cells give rise to platelets).
So, I don’t think there’s a very eloquent, tight little theory that plays through like a bunch of biochemical arrows in a biochemistry textbook.
Jeff Segal, MD, JD
I think this is hitting multiple areas and it’s like a Rube Goldberg contraption. One of the things you talk about in the MedCram video series is the COVID-19 life cycle; namely prevention, risk mitigation and treatment. In a perfect world, you just prevent this until we come up with vaccines or effective treatments. You also want risk mitigation, which means tuning up the patient as best you can. So, if and when they get hit, it’s a much milder illness.
Prevention is the simplest one. This would include masks, handwashing, physical distancing, the fact that it’s more likely to be transmitted indoors compared to outdoors. If we move on to mitigating the risk, that includes turning people up a bit more. Interestingly enough, you’ve had submissions from some of your listeners related to historic medical documents. What people did 50 or even 100 years ago to treat tough viral conditions. You’ve also talked about more modern techniques that would be considered out of the box.
I’d like to spend a couple of minutes talking about that. The first technique would be the use of heat or hypothermia. The example you gave was fascinating and discussed advanced syphilis. One hundred years ago, we had no real treatments. I believe people used heavy metals at the time to treat it, which is kind of an insane way to do it. It’s like trying to treat people with leeches and bleeding.
But interestingly, we didn’t have any antibiotics back then, but there was a way to treat advanced syphilis. Describe the one-two punch. If I remember correctly, a Nobel Prize was awarded for this clever concoction.
Roger Seheult, MD
So, the irony is that 1927 was the year that penicillin was discovered. That was also the year that Dr. Wagner-Jauregg received the Nobel Prize in Medicine.
Why did he receive that Nobel Prize? Because he noticed in his insane asylum in Austria that patients with neurosyphilis seemed to improve in their symptoms when they had a fever. He had this idea that maybe the fever is so nonspecific that it’s not only fighting whatever the body thinks shouldn’t be there, but it’s fighting stuff that the body can’t fight well enough on its own. In other words, the body’s immune system is not being appropriately jacked up enough to take care of what’s going on.
So, because they had the treatment for malaria at the time, ironically, chloroquine, he purposefully injected his patients with Plasmodium falciparum, and gave them malaria. He did it under very controlled circumstances. He kept these patients in the hospital. They monitored the patients very carefully. Sure enough, the fevers came on. And sure enough, the fevers made the neurosyphilis symptoms go away to the point where the body actually cured itself of the syphilis. And then it was just a simple matter of then curing the malaria with the known medications at the time. These patients were cured.
Jeff Segal, MD, JD
Imagine that this was the pinnacle of science at a time before randomized controlled drug trials. It’s very clever technique, and if I remember one of the MedCram videos, you also talked about exposing people with the 1918 pandemic flu to various types of heat. I think it was called hydrotherapy. Can you talk about that as well?
Roger Seheult, MD
There were a number of sanitariums – as they were called at the time – in the northeast of the United States. This was a time many famous physicians treated patients in such sanitariums. There was John Harvey Kellogg at the Battle Creek Sanitarium in Battle Creek, Michigan. He treated Henry Ford, presidents, all sorts of people. The doctors at sanitariums were the top thinkers of the time.
Jeff Segal, MD, JD
Sidenote about a movie called Road to Wellsville which focuses on Dr. Kellogg. If people haven’t seen it, it’s an excellent movie and it’s about twenty, twenty-five years old. Anyway, sorry to interject. Keep going.
Roger Seheult, MD
Yeah. Thank you. Kellogg published a book – you can get it free online as a pdf – called Rational Hydrotherapy. He went through this technique very methodically. Anyway, there were a number of Adventist-denominational sanitariums in the Northeast that practiced this hydrotherapy. They believed at the time in natural remedies – not using medications.
In the Army hospitals, soldiers were coming back from World War One, bringing back influenza and aspirin was being used, probably overused, in these Army hospitals. In fact, at the time, the saying was that the Germans at the Bayer Company distributing aspirin probably killed more Americans than the German bullets did in WW1.
Dr. Rubel, who was the Medical Director of the New England Sanitarium in Boston, Massachusetts, kept track of the patients being treated and wrote down statistics. And the interesting thing about those statistics were that if you looked at the Army hospital versus what was happening in the sanitarium with the hydrotherapy, the overall mortality rate was one to two percent in the sanitarium versus six percent in the Army hospital.
He looked at the number of people who got pneumonia and then looked at the number of people who died from pneumonia. And the advantage the sanitarium had over the Army hospitals was that they were much better at preventing the pneumonia. But once they got to the clinical phase of pneumonia, the sanitariums really didn’t do much better than the Army hospital.
So, the key was early intervention. They didn’t need a test. There was no biochemical test to determine if someone had influenza. If you had symptoms, that was the test. You were immediately placed in bed. You immediately had bed rest. You were subjected heat treatments two to three times a day. Let me explain that. That’s where they would put you in a bed. They would put hot towels with steam on the bottom. You were separated from that steam by one or two layers of towels.
So, it didn’t burn you. The purpose was to heat the body up. They would put your feet in a very hot bath. They would cover you up. They were basically increasing the temperature of your body and they put a cold towel on your head to try to fool your mind (and hypothalamus) into thinking that you weren’t actually having a fever so they could warm up the temperature. They’d do this about two to three times daily and then you would stay in bed. They made sure you stayed in bed for at least two days after the symptoms resolved.
You know, Jeff, there was a story that was published in another one of those denominational articles where an entire seminary in Minnesota (with students in their 20s) came down with the virus in two days. And the medical director of that seminary did exactly what I was just describing to everybody there. Not a single soul perished in that epidemic in there. I think what was going on there is that they were increasing innate immunity early on.
With use of something like hydrotherapy, you would have to wait for a test to come back and then find out you have coronavirus. You would not have to go to the hospital. There is something to be said for early intervention – when someone feels that they’re ill and starting treatment then. The problem, of course, with coronavirus is that a lot of these people are asymptomatic.
So, it’s something that we have to watch.
Jeff Segal, MD, JD
There seems to be a mechanism of action. You’re saying immunity improves with heat / hydrotherapy. And if I remember your presentation correctly, you can measure that outcome to some degree, perhaps via the number or concentration of Natural Killer (NK) cells.
If we fast forward to more modern days, how do people raise their temperature? Saunas. There are people who swear by them and the question is, do they just feel better after using them, or do they actually help prevent seasonal illnesses?
Roger Seheult, MD
Nobody uses saunas in the world more than the Finns. In fact, I think if we told every single Finn to go inside a sauna at any particular moment, there would be enough saunas for every Finn in Finland. It’s kind of crazy, actually, but scientists have done studies showing all-cause mortality goes down with sauna use. It’s tied to the number of times per week that a sauna is being used.
There is data showing that acute chest infections are reduced. The list goes on and on. So, increasing body temperature, then decreasing prevents and improves outcomes with some infections. They go in the sauna, then they jump into the cold water and they go back in the hot sauna. There’s something to be said for that. The other culture that uses hot baths, let’s give credit where credit is due, is the Japanese.
They use very, very hot baths. One-hundred-and-fifteen degrees. That would be illegal in in the United States. I think the the highest that your spa will go in the United States is one-hundred-and-four. They go to one-hundred-and-fifteen.
Jeff Segal, MD, JD
So, they use it off-label.
There are a couple of things I just want to hit before I let you go. Go back to how you are taking care of your patients. Some of the other interesting things that you’ve talked about on MedCram.com, and you’ve looked deeply at the literature, are treatments specific to what’s called “forest baths.”
Discussion of forest baths addressed “going into nature” and exercising around pine trees. Interestingly enough, it improves their innate immunity. But please don’t take my word for it. Go into the science of that. And whether it’s a real thing that deserves further attention.
Roger Seheult, MD
I think it’s real. You can see it in our MedCram update. Type in “MedCram forest bathing,” you’ll see the whole video on it. Basically, they took select people from the city and took them up into the forest, exposed them to walking through a forest for a couple of hours over the course of several days, and then measured their Natural Killer cells and urinary cortisol. They felt much more relaxed.
They had elevated levels of Natural Killer cells.
They did the same experiments putting them in a hotel room in a city and they aerosolized hinoki oil, which is derived from Japanese Cyprus. They got exactly the same results, except the urinary cortisol was not as reduced. So, there’s something about walking in a forest that relaxes someone and allows their immune system to kick in.
And we know that high cortisol levels are detrimental to your immunity. That’s why longer sleep hours are better. That’s why decreased stress is better. And I’ll just mention this. I’ve discovered that eucalyptus has the same effect, by the way. It’s so amazing when we start to think about what our parents and grandparents used to do. They weren’t so crazy. For example, look at Vicks Vapor Rub. They put eucalyptus oil in Vicks Vapor Rub. Eucalyptus oil has been shown to increase innate immunity as well, exactly at the point where coronavirus tries to suppress it.
So, you have to be careful with eucalyptus. You shouldn’t ingest it, but it’s something that you can put on your skin. There’s good data from 10 years ago that was published showing that there was a significant increase in macrophages. And macrophages clean up the cells with the virus at the very beginning of that phase.
Jeff Segal, MD, JD
Yeah, it is interesting to consider what our parents and grandparents did. My grandparents took vitamin D supplements and cod liver oil.
Let’s go into your regimen. Your statement, which I think was quite powerful, is that you’d rather be taking something that might not work than not taking something that does work, particularly if the risk to benefit ratio is reasonable. And I’ll just go through your laundry list.
You can certainly add and subtract from this list. You’ve talked about zinc, vitamin C, vitamin D and NAC and Quercetin. Is that the list? I know I’m taking them; you’ve certainly persuaded me.
Roger Seheult, MD
Yes, in fact, just before I got on, I downed them with some lemon juice. All of those have good data. Vitamin C, we have great data. Also, we’ve got amazing data on vitamin D. We’ve got data out of the UK that shows that it decreases acute chest infections prospectively. And if you consider COVID-19 as an acute chest infection, well, there you go.
We have all-cause mortality data on vitamin D. We have retrospective data in terms of who is most at-risk of dying from coronavirus based on vitamin D levels. I think vitamin D makes sense.
Now we’ve got data that shows that prospectively in influenza virus that NAC (N-acetyl-cysteine) decreases symptoms. And we also know that NAC acts as an antioxidant, which, according to the hypothesis, should be helpful in COVID.
The cysteine has an S residue – S-H residues cut disulfide bonds. And interestingly, VWF is using disulfide bonds. And so, there are some studies that show that intravenous NAC (we wouldn’t be giving it intravenously at home, but taking it orally) can actually be used as a thrombolytic. There’s some data that intravenous infusion of NAC can actually help break up clots.
And that may be important, especially in COVID-19
Jeff Segal, MD, JD
Quercetin is a zinc ionophore. So is hydroxychloroquine. Those are early data on hydroxychloroquine before it was politicized.
Roger Seheult, MD
We looked at hydroxychloroquine and there’s been many mechanisms proposed for that. One of them was that hydroxychloroquine is a zinc ionophore allowing zinc to get into cells. We’ve got good data that high concentrations of intracellular zinc shuts down the virus, the RNA polymerase of virus. And so, the hypothesis was that if we can get zinc inside the cells, that might be beneficial. One way to do that is Quercetin. Quercetin is also a zinc ionophore found in onions and capers.
But if you take Quercetin as a supplement, it might help. In fact, there is are Canadian and Chinese scientists investigating the use of Quercetin in COVID-19. It had already been tested and found to be successful in Ebola.
Jeff Segal, MD, JD
Interesting, yes. I’d be remiss if I didn’t talk a little bit about hydroxychloroquine. I’m actually reluctant to even bring up the name because I don’t want YouTube to take down this podcast. They tend to censor anyone discussing the topic. So, we’ll use our secret code word, “blueberry” or something like that.
I think you’ve been pretty good in terms of just describing what the literature suggests. I guess the question is, has it been fully tested? Is it safe to say it’s unproven or disproven?
My personal take is that it’s been studied, and we see things on different sides. And I’m not sure it’s been definitively studied in the way that would make the most sense, namely, using it either prophylactically or early, using it in combination with zinc, etc. It may very well be it’s a bust. Some of the early complaints included that it’s an amazingly unsafe compound. People will be dying left and right. So, you’ve got both the safety and the efficacy arguments. Where do you think we are right now? Do you think we have enough to say that it’s been answered definitively? Here’s one other thing I found interesting: In one study, and this is probably the most interesting study to me, even though it was only done on a handful of animals, it used non-human primates.
But the animals were young, they weren’t particularly old or challenged from an oxidative stress standpoint. And they didn’t use zinc either. Still, the scientists found that it didn’t help by giving (hydroxychloroquine) early. It didn’t really have much of an effect in terms of virus load or symptoms. But none of these macaque monkeys (control or experimental group) became particularly ill, partly because they were young and so few were studied – partly because it’s so expensive to do these studies on non-human primates. What do you think is a reasonable conclusion today (about hydroxychloroquine for COVID)? If you care to discuss, then feel free.
Roger Seheult, MD
I just look at the data. The data at first was kind of positive. We had some retrospective studies. I think you could classify the data right now into two camps. A lot of the positive data on hydroxychloroquine are coming from retrospective studies and anecdotal stories. And a lot of the negative stuff is coming from prospective studies – the gold standard of what we use. And so, I’ve become a little bit more disillusioned with the effect of hydroxychloroquine.
We’re certainly not using it now in patients that are coming into the hospital. It was supposed to be used with azithromycin. And we’re not doing that. We’re using Remdesivir, if we have it. If not, we’re trying to do convalescent plasma as an early intervention, but I think more studies are needed. There are actually going to be a lot of studies to review, because when the studies were started, the big thing was hydroxychloroquine.
I think there’s a lot of studies that are going to be coming in over the next month or two that show results one way or the other. And I think it’s going to come down on the side of not working. I wish I was wrong. I wish it did work because it would be great to have that as a tool. But, it seems like the prospective studies that are coming in, the gold standard, are not showing that it’s working. We’ll see.
Jeff Segal, MD, JD
You have to really study it to know whether it works. I was in biotech for five years and it’s just hard to do clinical trials. You have to pick the right compound with the right kinetics for the right patient at the right time. I know it sounds very easy to do. It’s really not. It’s very time consuming. It’s very expensive, particularly when you’re dealing with complex patients who may have a number of underlying comorbid conditions and they’re coming in on multiple medications.
It’s just difficult to do. You would plan a clinical trial up front. You would design a study. But here you’ve got people showing up at the door and not everybody checks the right box in terms of being able to be included in the study.
If you look at what we had previously for viruses, let’s look at Tamiflu for the flu. You’ve got to use it within 48 hours of symptoms. Otherwise it’s not effective. Timing matters. And particularly if you’re talking about zinc. It may very well be that if hydroxychloroquine is effective, it may be effective primarily because it’s helping zinc get into the cell. If you don’t add zinc to it, you may be missing a co-factor, if you will.
Hydroxychloroquine may be necessary, but not sufficient (perhaps zinc must also be used). That’s why this stuff is so complicated.
So, let’s close out with vaccines. Briefly, it looks like we’ve got at least five candidates out there, but there are more and more that are showing up every day. Moderna is the leader, and you’ve got the combination with Biomet and Pfizer. Both of those are RNA type of vaccines focused on the spike protein. AstraZeneca is working with University of Oxford on a chimp adenovirus.
CanSino is doing a similar thing with a human adenovirus.
Then you’ve got J and J. Its vaccine may only require one dose instead of two doses – or more. This is probably the first time in history we’ve seen so many candidates come out at one time. I’m hopeful that we will have a vaccine by the end of this year or Q1 2021.
The primary limiting step is going to be testing it out in the field. On the one hand, you want the fewest number of patients with COVID out there, just from a economic and health burden perspective. On the other hand, the greater the number of people who have COVID in the background, the quicker you’ll be able to get an answer as to whether it’s efficacious. So, it’s a double edged sword.
On the one hand, you’re rooting against COVID just for the country. On the other hand, you’re rooting for it just so you can test the vaccine and get it out sooner rather than later.
Roger Seheult, MD
You’re right, and I think that’s why they’re going to these epidemic centers like Texas, California, Florida, to recruit a lot of their their subjects. They’re supposed to be doing phase three trials now. So, we’ll see how fast they can get that completed. At least that’s what they were announcing, that Moderna was starting phase three trials in late July, early August. So, here we are, already starting.
Jeff Segal, MD, JD
They’ve already injected the first people, or at least they’re lining up people. And I believe Biomet and Pfizer are in the same boat – they’ve started the injections. The other ones are going to be started around the corner. So, you have at least five leaders that are out there. And in parallel, the manufacturing capability has been ramped up. The government is underwriting the risk associated with getting enough of these vaccines manufactured. If they are successful, we won’t have to wait to ramp up manufacturing capability.
If any do fail, we’ll still be able to move to a different vaccine. Manufacturing is being ramped up as we’re having this podcast right now, which is good.
Finally, two things. What are you pessimistic about? What are you optimistic about? And then we’ll close.
Roger Seheult, MD
Wow, optimistic is hard. First pessimism.
Well, the vaccine, I mean, everyone’s sort of waiting. We have high expectations for the vaccine. There are two areas where I’m a little bit pessimistic on the vaccine. That it works too well, and you get an autoimmune response. We actually saw some of that with the H1N1 vaccine in Europe. There was a spike in narcolepsy cases. And I’m not saying that would happen specifically with this, but it’s the kind of thing that you could get from inducing an autoimmune response.
Narcolepsy is a hyper-somnolence that occurs when you don’t have hypocretin in the posterior pituitary secretion or the posterior hypothalamus. That’s because there are antibodies that hit those cells and knock them out. And so, they become narcoleptics. And we think that may be related to the vaccine.
Something else could happen. And we know that we’re getting autoimmune responses with people who are naturally being vaccinated, meaning “vaccinated” by actually getting the the virus. Some children are getting Kawasaki-like diseases. So, that’s what you might get when you come to market that quickly. And you might get some post-marketing analysis showing there may be an increase in autoimmune conditions.
The other pessimism that I have deals with making an error in selecting the vaccine, and that it doesn’t work so well. The problem they’ve had with HIV vaccines is one thing that no one has really talked about much. We think about this very clean ACE2 receptor and a very clean spike protein on the virus. But in fact, that’s not the case at all. There’s something called sialic acids. These are, if you can imagine, proteins that are like Christmas trees with the sialic acids like the little decorations.
There are little ornaments. And they can change making small differences in terms of conformational binding that makes these proteins a little bit different. The HIV virus itself is almost completely covered with sialic acids. So, it makes it really difficult to try to find and reliably target that protein conformation.
And we don’t know how much sialic acids – these are sugar molecules – are going to coat the spike protein in different ways.
And that’s a whole different area of biology. And in fact, if you go to conferences on HIV virus vaccines, the whole conference is about these sialic acids – and glycoproteins – and how to get around those. So, that’s something that hasn’t really been discussed up to this point. But it may be important in terms of getting a good vaccine. We’ll see what happens. Those are my two pessimisms.
Jeff Segal, MD, JD
On the subject of optimism, what about planning ahead? I mean, on the one hand, while COVID is lethal, it’s not as lethal as it could have been.
Do you think that the country has now woken up to the fact that we need to be prepared in the future for more aggressive types of biologic catastrophes?
Roger Seheult, MD
Yeah, it’s true. I would hope that we have now a blueprint. If something else comes out with a completely different binding protein and a completely different cell receptor attachment, we’ve already got some sort of a concerted way of dealing with this from the federal / state and scientific aspect.
Jeff Segal, MD, JD
I just finished a book about existential threats to civilization. It’s actually a very depressing read, although on the other hand, it’s somewhat optimistic because if you think about these issues up front, you can plan for them. But what will humanity do? The book talks about the likelihood of us making it one-hundred years or forever.
The author’s calculation was a one in six chance of making it as a civilization over the next one-hundred years. And a one in two chance of making it long-term with the biggest threats, with those big threats not being the ones you would think about; it’s not an asteroid hitting the planet or or some of the other natural catastrophe. The author says his biggest concerns would be artificial general intelligence that gets out of control, a nuclear catastrophe (mutual assured destruction) and finally an engineered pandemic.
And the last one is the one of greatest concern. And I hear your beeper going off in the background. So, I am going to close. Do you have any final thoughts for our listeners?
Roger Seheult, MD
Well, I was going to say that sounds like the plot to a Terminator movie.
Jeff Segal, MD, JD
The author’s larger point was that if you think about these problems up front and if you invest the appropriate amount of resources into it, we’re clever people. We can probably figure it out. He said that the amount of money we have put into preparing for a biologic catastrophe is less than the annual budget for an individual McDonald’s franchise, which is extremely sobering. My guess is that will change going forward.
Roger Seheult, MD
Yeah, I agree with that. People are starting to wake up and understand what the existential threats are. So there is some optimism that people are starting to think about this.
Jeff Segal, MD, JD
I’ll close with this: What is the difference between an optimist and a pessimist? The optimist believes these are the best of all times. The pessimist is afraid the optimist is right.
Roger, thanks so much. I encourage everyone to go to his site (MedCram.com). Do it now. If you’re not a subscriber, just subscribe to the COVID MedCram videos. We all need CME credits, and MedCram.com is a great resource. It’s a no brainer. Just do it. There’s no more cost-effective way to get CME credits.
I could talk for two or three or four hours on this topic with you. Thanks so much for being generous with your time and hopefully we can do it again soon.
Roger Seheult, MD
Thank you so much, Jeff. Really appreciate being on.
