Episode 41-  John Haller Interview

Brian Kruger:

Welcome to the podcast, the Common Bridge with Richard Helppie. Rich is a successful entrepreneur in the technology, health and finance space. He and his wife Leslie are also philanthropists with interest in civic and artistic endeavors but with a primary focus on medically and educationally under-served children. My name is Brian Kruger and from time to time I’ll be the moderator and host of this podcast.

And welcome to the Common Bridge. We’re in week 10 of the COVID-19 locked down in most parts of the country, and while some states are relaxing their restrictions, we’re still using a virtual studio here at the Common Bridge. So if you can bear with Rich as he welcomes his guest remotely again, and that guest today is Dr. John Heller. Dr Heller is a clinical research scientist who has held faculty positions at Washington University School of Medicine and the University of Iowa College of Medicine. He also served as Health Scientists Administrator at the NIH, the National Institute of Health. Currently, Dr. Heller works as a clinical research program manager for a medical imaging company, managing CT and MRI clinical imaging research programs at Johns Hopkins Hospital in Baltimore. Now just as an all of our podcasts, the views of our guests are their own, and they don’t necessarily reflect those of their employers or their associates. I think you’re going to find this conversation enlightening. And we join Rich and Dr. Heller’s conversation in progress.

Rich Helppie:

John, it’s been a great conversation this morning talking with a real scientist trying to make some sense out of this corona virus pandemic. You and I chatted about this in various forms. We, I think we’d both agree there’s still more that is unknown than known. Not sure where we stand in this nine inning game, but I know our listeners would really appreciate some of your insights. One of the things I’ve been wondering about is this, what do we know about the origins of this virus? I know there’s a theory about it being in a wet market. There is a competing theory about it being manufactured. Have, we reached a degree of certainty at this point about where this thing came from.

John Haller:

As you and I talked about Rich, the wet market in Wuhan is one of the leading theories about where this originated. It jumped from an animal to a human, so probably from a bat to a person, but it could have jumped from a bat to a pig, to a person. A lot of these kinds of viruses start out that way. They start in animals and then jump to humans. So that’s the sort of the leading idea. I would say that there’s really no evidence, at least in the scientific community, there’s really zero evidence that it originated in a lab in China, which is another idea out there.

Rich Haller:

Is there a way that the virus itself can be examined and say, know it doesn’t have the characteristics of a manufactured virus, versus it has the characteristics of one that originated in an animal. And I know I’m going to mangle this terminology, zoonotic, is that the correct way to say…

John Haller:

Zoonotic. I think it’s pronounced, so like a zoo from the zoo. So there’s…it’s been well known that these viruses originate animals. That’s been something that’s been studied for decades. I think, and I’m not a molecular biologist or an epidemiologist, but my understanding is that there are ways of knowing the genetic makeup, for example, of the virus has manipulated, they can know that from certain markers in the RNA or DNA, or something like that. So there’s no scientific evidence, and I think there’s some literature out there in the scientific community that, that reinforces that. And my friends who are molecular biologists or geneticists would, I think, support that. So I think that general consensus is that there is no evidence that this originated in a lab in China. There’s no scientific evidence.

Rich Helppie:

What do we know about the transmission? And one of the things that I was fascinated with is that early on, and I guess it’s debatable what early was…October, November, December, January, but someplace in there, the scientists were real confident, hey, we’ve got something that’s going worldwide. They were right about that. How do they know that? It, to me, it was a fascinating prediction that that proved true.

John Haller:

Well, as you know, Rich, there’s the epidemiologists have been studying epidemics for a very long time, and they’ve actually modeled these kinds of pandemics. As late as six weeks before this pandemic broke out, there was a conference where they modeled or predicted or actually rehearsed an actual outbreak like this and how it would overwhelm the health care system, the simulation that they went through actually at Johns Hopkins University. I think, there were scientists from around the country and from the government as well, who were involved in the conference, modeled this thing and made these predictions. And the predictions, of course, were much worse because they were trying to model the worst case scenario. So they really understood this for a long time and have been thinking about the possibility of a flu pandemic or in this case, a corona virus pandemic, some kind of pandemic that was both airborne and deadly.

Rich Helppie:

That makes a lot of sense to me that if we weren’t in the public health field or we weren’t an epidemiologist, we just may not be thinking about it, but somebody does or many people do. And they looked at this one and they go, uh oh, here it comes. I know that we’ve got a wide range of symptoms, we’ve got infection rates that are still a mystery. We’re still chasing those down. We have treatment protocols that are still being developed, we have vaccines that are in early experimenting, and we still don’t know today just how the antibodies work. In fact, I’ve read just this morning that some of the sailors on one of our aircraft carriers got a second infection, and I know people that have had it that are fine, and then show symptoms again. So it seems that the degree that the disease…

John Haller:

But one thing I wanted to mention that occurred to me is that there are metrics for the spread of the disease. So you’ve probably seen or read about this “R naught”, their R zero measurement. So the epidemiologists talk about this number. If it drops below one, then it’s likely that a virus would stop spreading. If it’s above one, like it often is in a flu season, or with diseases like measles, the number is very high to highly contagious disease, it’s up around 15 I think. In this case, they’ve estimated this R naught, to be around two, which means for every person that gets infected, two people, two more people get infected from that person, from those two people, four people get infected and so on. So that’s kind of the general consensus. It could be higher, it could be lower. It’s certainly not below one because you still see the disease spreading. And I’d also mention that these efforts to mitigate or slow down the spread also reduce that number. So the kind of social distancing efforts actually reduce the number from, if it’s two or higher than two, down to some lower number. So the spread isn’t quite as fast. People talk about flattening the curve, that’s what’s happening there. The spread is less.

Rich Helppie:

That’s been very encouraging to see. It was just a couple of weeks ago that we had case rates rising at an alarming rate. The rate of hospitalization was threatening to consume our capacity. We were short staffing and supplies, and in a few cases threatening to use up all the beds. The testing at that time was, which was only testing symptomatic people, was about 15% positive. And there was little to nothing known about the treatments. If you remember at that time there was a lot of anxiety around whether we were going to have enough ventilators. And now it’s, I guess, becoming conventional wisdom that ventilators are not terribly effective. And in fact, the people that get on the ventilators often don’t get off. So from that point, where are we today? You know, I agree with…you made mention that the social distancing, the hand washing, that has certainly had a positive effect. So good for the policymakers that set that up to flatten that curve. Where are we today? If you could characterize the infection rates and the hospitalizations and the like?

John Haller:

Well, I think we’ve flattened the curve. I think one of the worries was that the healthcare system would not, would hopefully not become overwhelmed because of the fast spread of this disease. We’re at the flat part of the curve in some places, and in some States, in some communities, the number of infections, the number of people who are becoming infected on a daily basis is actually declining from day to day. So we’re either, in some places like where I live in Florida, we’re on sort of the flat part of the curve. In Michigan there’s a rapid decline in the number of cases and number of deaths from this disease. So I guess it really depends on where you’re talking about now, what part of the country or what city you live in, in terms of where we are.

Rich Helppie:

And it seems that there’s vulnerable demographics, vulnerable locations like nursing homes, meat packing plants, prisons. We had a group of Catholic sisters here in Michigan that were all elderly, seven of them that succumbed to the disease, and a Senator from Pennsylvania, his claim that 69% of the deaths in Pennsylvania were in nursing homes. And of course, as you’d expect in any kind of a crisis, some mistakes were made along the way, and the discharging COVID active patients in nursing homes in New York, I believe that has accounted for about 25%. But are we taking the right steps with those vulnerable populations in the prisons and the nursing homes, the meat packing plants, to protect those folks? And what would be the right approach to demographics that perhaps are not at the same level of risk? 

John Haller:

Well, I think I know where you’re going with this Rich, because you and I have talked about this. I think as far as the vulnerable populations or even communities, or people who are at risk, I think one of the key things to mitigate the spread among them is testing. So people talk about testing, testing, testing. So they’re really talking about diagnostic tests that can identify who is infected and then isolate those people from vulnerable populations, in particular in the nursing homes, but also in the workplace, for example. So in meat packing factories or just in the office, you would like to know who among those people are infected so that they could be isolated from, from others. Most of the spread of the disease actually occurs within the home. So among family members or people who live among each other, but of course they may not get the disease at home, bring it home from their work, or from some interaction with others who are infected in various settings. That’s where the vulnerable populations come in. Those who are less vulnerable, as I think that’s where you were going with this are people who are much younger, children seem to be less susceptible to the disease, although even children sometimes are affected. So some kids with are developing this Kawasaki syndrome or some of the features of that syndrome. And then even older people, under 45 years old, can be hospitalized with this disease. And Rich, you may know better than I do, but I think something like 40% of the people in New York may have been in that, who were hospitalized, were in that age bracket, in the 45 years old or less. So it does have an impact on those people, but it’s much less, and it’s probably more like the flu for that age group, 45 and younger. It’s probably, in terms of the spread of the disease, more like a typical flu season, in terms of the R naught measurement of the spread.

Rich Helppie:

I read this professor from Dartmouth, Aaron Bromage, and I’m not sure I’m pronouncing his name correctly, but he had some very good data, and I believe we put a link up on our website, RichardHelppie.com. He goes through each of the settings, and as a nonscientific person, my take away was, it’s kind of a cumulative thing. So that a light amount of exposure over a sustained period of time may result in an infection, or a big dose like a sneeze, a one time event, could get that same kind of exposure. I don’t know if you’ve read any of his stuff, but he concurs about in the home and he says, you’re inside, you’re constantly being exposed to the infected person who more than likely doesn’t know they’re carrying the virus, and you’re breathing the same air, you’re doing it over a period of time, and now the more health compromised person would be getting it, is the way I’m reading it. Again, I’m a not a scientist at all, but that was my lay takeaway up from that.

John Haller:

That’s exactly right. That’s how I read…I’m not sure I read the same paper, but I did read an interesting report. I think you saw this too about the idea that you have to get a thousand virus particles, whether it’s a thousand or 5,000 or some other number. You have to get…there has to be a certain, what you might call a viral load, before you actually get the disease. So being in a confined space where there’s no exchange of air, so being in a confined space in an office or a home, you’re more likely to breathe in a thousand viral particles. You know that the one reason, I think, they talk about the six foot rule for social distancing is if somebody’s breathing in your face and you can actually smell their breath, that’s going to have a lot more viral particles in it. And at some point, as I understand it, you reach a threshold where you’ve been exposed to so many viral particles that you actually become infected. So those cases and those situations, I think you’re at much higher risk. Whereas, in an outside area and well ventilated area, you’re at much less risk for, there’s still people and virus around you, but if you aren’t heavily exposed to it, you’re less likely to become infected.

Rich Helppie:

I would concur. And if you read Dr. Bromage’s paper, it makes a compelling case about probably not quite ready to open bars and restaurants yet, but also made mention that so few of the cases were contracted at the grocery store because, you’re in and out. Also, looking at New York, I think New York is a special case for many reasons. First of all, it’s a very concentrated urban area. And they were also on the front end of the pandemic when we knew a lot less and about what the right policy would be. Manhattan is a place where people take public transport, the subways and such, and they’re walking on crowded sidewalks. So it seems to me that would be pretty easy place to get that thousand particle exposure. And then here in Southeast Michigan, particularly in Detroit, we have, although we don’t do much, public transportation, we do want everybody to buy a car, American made car, thank you very much. But it’s also we’re a hub to Asia because of the automotive industry. And we also saw exposed at the social determinants of health coming into play here. So when you think about people that are in urban areas, lower income that may already have diabetes or obesity or asthma, which is very common in a major industrial city, you can see why the virus found it so friendly. So in looking at the policy responses, I think there were some that were done well, some that were made the best decision they could with the data they had. I know that we’re going to seek to get cures and vaccines, although I don’t believe there’s a magic bullet out there that’s going to solve this. I think it’s, we’re still going to be in this situation where we know something we don’t, and we do have hospital capacity today. I did confirm that earlier this week in a number of places. I also believe that we have the balance between the public health risks of the corona virus with a public health crisis that’s growing: domestic violence, suicides, alcoholism, addiction on the rise. The number of people dying at home is skyrocketing. One of the nearby counties to me last month, eight times the number of people dying at home than in a normal month. And there’s just untreated things from cancers and cardiac cases, diabetes, dentistry, and even appendicitis. So leaving aside the economy, which I think is a false choice in some ways, and we can come back to that, but in understanding that we do have to conquer this virus, at the same time not put ourselves in another public health crisis. Are we at a point right now where some of the more strict stay at home orders might need to be revisited?

John Haller:

You’re asking about opening up the state and not having these stay at home orders. I think that’s happened in a lot of places already

Rich Helppie:

One of the things that our governor points out is that Michigan’s the 10th largest state, but the third most in deaths, so the states that have more population than Michigan, but fewer deaths are California, Texas, Florida, New York, Pennsylvania, Illinois, Ohio, Georgia and North Carolina. And some of those you might look at say Florida, which has twice the population as Michigan, but about a third of the deaths and say, well, maybe there’s something attributable to the climate, but you can look at Ohio, which has about 15% greater population, but fewer deaths. It’s a lot more comparable, in the upper Midwest as a great Lake state. And the approaches are vastly different. I mean, clearly things like masks, hand-washing, distancing, all seem to have a role. Perhaps letting the young and healthy get outside may have a role. And from a scientific point of view, if we want to combat this growing public health crisis and try to find our way through this pandemic, is there any policy changes that you maybe witnessed in Florida that it might be safe to try in Michigan or some of the other places?

John Haller:

I don’t know. I don’t know if I would try the things that are being done here in Florida. I pretty much rely on the guidelines, the different phases of opening up communities, are opening up States. So I think you’ve seen a decline, a rapid decline in cases death from COVID-19 in Michigan. Here in Florida, as I mentioned before, I think the numbers are pretty flat. The question here is, since since the governor has opened up the state, and we’re going into phase one, are we going to see a resurgence? It’s really hard to predict. In fact, I would have predicted, might’ve predicted a resurgence within two weeks of some of the measures that have already been taken in Florida. So we haven’t seen resurgence here, but we haven’t seen a decline either. Places like Texas, they’ve actually seen, after opening up, seen more than a 10% increase in the number of cases. So it’s really, it might, maybe it’s too soon to predict or we don’t know what all the variables are that affect these different places. And in terms of relaxing these social distancing rules.

Rich Helppie:

I think that is an accurate summation. And Florida, they actually closed the freeways coming in from Georgia and Louisiana and were restrictive about the people from the Northeast coming down and who knows.

John, let’s take just a couple of minutes. Let’s look toward the future a little bit. I know there’s a lot of hope about antibodies, and that perhaps a person that has suffered an infection knowingly or unknowingly, that they may have antibodies. What do we know about immunity from future exposure based on the antibodies?

John Haller:

I think you’ve read some more recent reports than I have about this, but based on, on other viruses, that once you have an immunity that you retain that immunity to the virus. So that could last for years, it could last for only two years. For some viruses it might be short lived because the virus can mutate. This particular virus has a very slow mutation rate, which is encouraging because it’s not going to change into a different strain that is suddenly immune to these antibodies. Or if a vaccine comes out, it wouldn’t be immune to that vaccine. So that’s what I know, but you also mentioned there was a sailor and maybe some other case reports where people have become infected a second time. If that were true, I would guess it’s because their antibodies are no longer able to fight this virus if it’s a mutation or whatever reason.

Rich Helppie:

Or the other question is, did it actually clear from the body? And I know that some of these blood plasma infusions that they’re working on here, they show that the patient would get kind of an immediate rebound, but then relapse.

John Haller:

That makes sense. It, in fact, you probably read about this too, in children, it seems like those who are suffering from this Kawasaki syndrome or other maladies that are associated with COVID-19 infections, those things appear very late after exposure to the virus. And in my mind, I think what you’d might be describing is the person’s ability to fight the disease, which really is related to the antibodies in their system and to the immune system itself, how healthy is their immune system. So I guess you could still have the virus present and maybe there would be some kind of rebound like you described. I did read an article that said the viral load in children is very low and I’m guessing that that’s because they are able to fight this virus and it doesn’t reach a level that’s really dangerous as it is in older people.

Rich Helppie:

I’m wondering about  medication and, unless at some point in the future we find a vaccine, but if somebody becomes symptomatic, and I know that there’s experimentation going around with various compounds and some experimental drugs, anything that you’re aware of that looks promising in terms of treating those that have the symptoms?

John Haller:

I don’t know anything off the top of my head. I know that there are a number of drugs in clinical trials. I haven’t been following that literature lately. Remdesivir was one candidate, one leading candidate, but it really isn’t a cure for the disease. It’s not something that even prevents death from corona virus, but it appears that it may have some impact on getting people out of the hospital faster, for example. So the initial reports are that you get out of the hospital four days sooner than somebody not treated with this drug. I would say in general though, from what I’ve heard, and I guess what I’ve read, that there are many drugs in development, various stages of clinical trials. I would not be surprised if they came up with some more effective treatment or treatments in a very short period of time. So that probably that may even happen or probably would happen before we would have a vaccine in place.

Rich Helppie:

The vaccine to me is something that is going to be a long way off. And given how little we know about how this virus behaves, it seems like it’s going to be fraught with risk trying to hit a moving target. And we’ll have to wait and see. And I know that folks have talked about this notion of herd immunity, and if this particular virus is asymptomatic, we may have a lot more people that are carrying it that just aren’t aware. And you wanted to talk a little bit about the testing and contact tracing. So as we wrap up this podcast, I’d like to have you just riff a little bit on, in an ideal world, according to John Heller, what would we be doing policy-wise, and in a nightmare world, what kind of things might we be doing policy wise?

John Haller:

Well, I guess in my view they’re sort of one and the same. In the ideal world where we’re mitigating the spread of the disease. And in a worst case scenario, we’ve fully opened up and going back to normal and the disease spreads very quickly and there’s a huge resurgence of the disease. The only tool that we have right now is what’s broadly referred to as social distancing. There are stay at home orders, but I think we’ve moved beyond that in most places. But there’s no hand washing and social or physical distancing. So staying apart, six feet apart and not congregating in places where there are large crowds, and so on. So that’s the tool that I think can help to contain the disease. But you’re right, the thing I did want to talk about was testing and contact tracing and containing the disease. Really, ultimately, if you can get the number of infections down so low, the number of cases, that you can begin to contain the disease, that would be sort of the ideal situation. Then once you’re back in this containment phase, you can test as many people as are needed. The ideal thing would be to isolate them or quarantine them to keep them from spreading the disease.

Rich Helppie:

How exactly would that work? And let me tell you where some of my confusion around this resides. They’ll say, well, we’re going to take everybody’s temperature. And I said, well, all right, but I understand that I could be shedding virus for 14 days and infecting people without having a fever or any other symptom. And that if you’re going to test me today with the nasal swab, you’re talking eight to ten hours to turn that test around if you have the reagents. And then they’ve got the rapid test, which purports-and I’m holding up air quotes on purports-to be able to register a positive in five minutes and a negative in 13 minutes. And I’m watching workers go into the Ford plant today, going into some kind of testing. I don’t know what they’re doing in there, but I have loved ones that work in the plant. It’s a very close environment. And what protections are they getting so that they’re not bringing it home and infecting households? That’s what I was trying to get my hand around is how are we testing. And I get it if we find a positive case, then we can, by some means figure out who else this person has been around. I don’t think we’re going to do what South Korea did, for example, which is everybody had to wear a wristband that had your temperature and your location and if somebody got infected, there was a digital tracking. They knew exactly who had been exposed. I don’t see that working in this country, and yet I’ve heard that the CDC has hired a lot of contact tracers. So do you have any understanding on how the mechanics of the testing or contact tracing would go?

John Haller:

I don’t know a lot about exactly how the contact tracing is executed, but what I picture is they hire thousands of people to basically call up. There’s a person with a known infection and they know or have some good idea of where they’ve been and who they’ve been in contact with. So they call up everybody that’s been in contact and potentially exposed to that person. And you might even, I think, even if you don’t capture all of those people, all of the people in the Ford plant that they’ve been in contact with, are potentially infected. You’re still gonna stop a lot of the spread of the disease through contact tracing. The testing is pretty well understood that, at least for the sort of the gold standard test, which is a PCR test, as it’s called. So they’re looking at the RNA of the virus. These different tests have a known sensitivity and specificity, meaning they can tell you about false negatives and false positives for a particular test. The point of care tests, well let, let me back up and say that all of the things you mentioned are potential tests, testing someone’s temperature is a way of screening for someone who’s infected. And you can presume, although you don’t know that they have, if they have a high fever, that they have corona virus, that it’s quite likely they’re infected with something. So that’s a test. I learned from a colleague of mine that in Canada, they don’t even do this kind of PCR testing as a first line of tests. They actually go straight to a CT scanner, which I found kind of a remarkable. So they take a picture of their lungs and they see that they’ve got these features of corona virus. So we talk about a ground glass opacities, which are-they look like a ground glass in the lungs that are kind of a foggy spot of texturing alone, a single spot. And they talk about consolidation, which is a feature of pneumonia. The problem with CT testing, because that’s a diagnostic test too, is that that doesn’t tell you what’s causing that pneumonia. But again, you could presume that it’s probably corona virus because there’s so many cases around. It could also be the flu or some other airborne infectious disease that’s causing pneumonia or this kind of consolidation as it’s called. So those are all tests. But the PCR test that I mentioned is the one that is the gold standard. One problem with that is that it takes maybe 24, 48 hours turnaround, maybe even longer in some cases because the cases can become backed up in an overloaded healthcare system, or have in the past. I know that happened in Missouri, in St. Louis. So the PCR test is very accurate, but it’s slow. And then you talked about the rapid point of care tests. Those can be done in 15 minutes, but they’re not, they don’t have the same specificity or sensitivity rather, they can’t…you may miss some cases.

Rich Helppie:

The White House is using one of the more popular versions of the quick test and they’re finding some false negatives. The CT scan, I can’t imagine that would be a permanent policy. Just the radiation exposure alone is going to overwhelm people. And not to mention just the cost and the time to get the CT scan. I mean that’s a pretty heavy duty test, well, it’s a typical diagnostic case, are you going to start with chest where you go to CT, you go to MRI?

John Haller:

There are methods of reducing the radiation down, so they’re trying to get CT exams down to the radiation level of an X Ray, a chest X Ray. But the CT is much more informative and tells you how bad the disease is or perhaps could even predict how bad the disease is going to get. So that can help with the interventions, but you’re right, I don’t think, especially in the United States, that may be done. In fact, the American College of Radiology does not suggest that you use CT. There’s also problems with having to sterilize the scanner once patients have gone through there. And that can take up to an hour or more. So it’s not a practical solution. But my point was that there are many different kinds of tests and something as simple as testing your temperature is one of them. They just have different levels of sensitivity and specificity.

Rich Helppie:

Well, John, this has been a fascinating discussion. I hope to have you back as this pandemic hopefully eases. But certainly in a couple of months I hope we’re having a chat about what the pandemic was like in the past tense. I hope come fall we’re having the discussion that we’re sure glad it hasn’t flared up again, but I do believe that we need, as a society, to be prepared, to have capacities to treat it if it does, and to understand what the policies are.

John Haller:

You sort of talked about the testing and the contact tracing and the, what I referred to as a containment. And that I think is something I mentioned to you earlier, that it’s sort of the elephant in the room that we haven’t talked about quarantine, so really isolating people who are infected. So how are we going to…that seems to me to be a dilemma or a difficult question about how will we do this in the future? How will we contain the disease or how will we mitigate it’s spread. So once people are identified as being infected or suspected of being infected, how will we contain that disease or mitigate the spread? I think that’s a big unanswered question. So as we do lots more testing and identification of people who are infected, how do we keep them from spreading the disease even more? And that’s a critical question I think in terms of the things you’re talking about, in terms of being prepared for resurgence or future infections or those kinds of things.

Rich Helppie:

It’s hard to quarrel with any of that. And I hope that our listeners have found this to be informative. And I hope that if you are in a position in life where you don’t need to go out, that means if you’re employed and you can work at home, that’s a great place to be. If you are retired and out of the workforce, great place to be is at home. And if you do need to go out, please exercise all the cautions relative to hand-washing and social distancing and face masks and God willing, we’ll be back to a semblance of whatever normal is going to look like, as we exit this. So you’ve been listening to the Common Bridge with our special guest, Dr. John Haller. Thanks so much.

John Haller:

Thank you.

Brian Kruger:

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