Pandemic: Coronavirus Edition

Is herd immunity really possible in light of the new evidence?

July 15, 2020 Dr. Stephen Kissler, Dr. Mark Kissler and Matt Boettger Season 1 Episode 34
Pandemic: Coronavirus Edition
Is herd immunity really possible in light of the new evidence?
Pandemic: Coronavirus Edition
Is herd immunity really possible in light of the new evidence?
Jul 15, 2020 Season 1 Episode 34
Dr. Stephen Kissler, Dr. Mark Kissler and Matt Boettger

Stephen, Mark, and Matt's longest episode yet and NOT because we are getting long-winded! Lot's to cover this week: COVID cases rising but mortality rates decreasing, the effectivity of masks, airborne particles, horseshoe crabs, fall semester fears, smell checks vs. temperature checks, and distinguishing between science and para-science. Man alive! Enjoy this one!

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Show Notes Transcript

Stephen, Mark, and Matt's longest episode yet and NOT because we are getting long-winded! Lot's to cover this week: COVID cases rising but mortality rates decreasing, the effectivity of masks, airborne particles, horseshoe crabs, fall semester fears, smell checks vs. temperature checks, and distinguishing between science and para-science. Man alive! Enjoy this one!

We offer transcription now! Caution, it is AI transcription so please excuse AI errors.

  • Download here -
  • See it on the podcast website here -

Can you Rate and Give us a Review in Apple Podcasts?

Please consider supporting us to help upgrade our equipment and offload our editing responsibilities:

  • Give monthly (as little as $5 a month) on our Patreon Page -
  • Give a one time gift through Venmo at @mattboettger
  • Give a one time gift through PayPal here:

Check Out Stephen on Matt's  "Living the Real" Podcast:

  • Subscribe/Listen to Matt's Living the Real Podcast:
  • Download Matt's visual map of his conversation with Stephen here -

Things Discussed on Episode:

Support the show (

[00:00:00] Matt Boettger: [00:00:00] You were listening to the Ben Demmick podcast. We equip you to live the most real life possible. And the face to these crises. My name is Matt  and I am not joined with either my friends, dr. Steven Kissler and epidemiologist at the Harvard school of public health. Neither my join with dr. Mark Kissler, who was a doctor at university of Colorado hospital.

[00:00:17]we, had a tough time getting together this week. I am on a staycation, which my time was limited and getting altogether was just proven to be difficult, but don't worry. We have you in consideration, we have two recordings, so this is how we're going to do it. I propose a number of questions, just like I normally do.

[00:00:34] To Steven and Mark and they answer them. So we're going to have them individually on little monologues before we get started a few things really helpful. We always need reviews written 96. Love to get to a hundred reviews before the end of this week. If you can leave the stars that you think that is worthy.

[00:00:50] Of our podcast. And if you have a couple extra minutes to maybe just leave a couple of notes, we'd love to read them, to read them to the audience as receive them as well. We also need support [00:01:00] to financial support that is still trying to pay off a number of things we bought to make things easier.

[00:01:06] Having full time jobs. We're trying to streamline, automate things. We can get these. These episodes to you as quickly as possible. So we have a number of things so we could use your help. Either. One time gift is it would be a wonderful, opportunity for us, to pay some stuff off you do that, that PayPal or Venmo all the show notes, or if you want to give a monthly, small recurring donation at podcasts again on the show notes, check it out.

[00:01:28]what else? So, Oh, one great thing. my living the real podcast, new episode drops, I think for our audience here is particularly beneficial. Stephen came on. Let's talk about what it means for him to live in the real, to live the most real life possible in his profession, his personal life. A lot of really fascinating things came about from our conversation, much more heartfelt, deep philosophical, going beyond the scope of just a COVID-19.

[00:01:54] So check it out. It drops today, living the You can go to the episode again in the show [00:02:00] notes, we have also an extra bonus that if you go to the Kissler, Living in the Kissler. I mapped out our conversation with him is really beneficial for me. I do a lot of my conversations to really understand the connective tissue between the conversation.

[00:02:18] I did this for about an hour, even more came out of the episode with Steven that really I took to heart and a few things I'm going to change my own life because of it. So I hope you find it beneficial living in the Kissler. Get it for free. Download it. It's pretty awesome. It goes along well with the actual episode.

[00:02:35]one more Bruce from Australia just emailed us. Thanks so much, Bruce. He was telling me that, things are starting to spike again in Australia, but 250 per day, they're going back into a lockdown. I know this is not uncommon. our thoughts and prayers are further for our country and for the rest of the world.

[00:02:51] So we want a vaccine as soon as can be possible. So, let's get in. So a few things I propose to Steven. Just so, you know, [00:03:00] I asked about COVID confirmations, they're increasing, increasing, but deaths continue not to increase as of maybe a couple of days ago, that story has changed and ask him if he still is set on what he thought last week about why death are not increasing.

[00:03:13] Also there's more information about airborne corner virus and what that means for us. Steven talks about that as well. There's one episode or one article I saw about the Chinese super spreader where this one girl, in fact, it's 71 people in a single elevator trips. So Steven talks in detail about that, what it really means and how that actually is a little bit misleading.

[00:03:34]the article as well. We talk about herd immunity, a lot of stuff going on with that about whether it's even possible, whether we can receive herd immunity at 20%, this is another new hot topic that Steven spends a lot of time helping us navigate that train, understanding what it really means for us.

[00:03:49] And if it really is possible. At all. Finally, Steven talks about the good old, another pig, swine flu potential pandemic, or you probably seen these in the news the past couple of [00:04:00] weeks. Didn't know if this is something to really, to be concerned about or whether this is just something kind of like hysteria news, because we're already freaked out about COBIT.

[00:04:07] So he talks about that as well. Finally, we have Mark come on. He spends most of the time talking about hydroxy chloroquine. We talked about it last week, about how there was a study showing that it actually has benefit. And we mentioned a few weeks ago that there was research that it was not beneficial.

[00:04:22] So he dove deep into this, this, a new research to see what's really going on and helping us to navigate that. And what's true. What's not true. What's uncertain. So I hope you enjoy my conversation or our monologue with Steven Kissler. We'll start with that. Right. This very second. 

[00:04:42] Stephen Kissler: [00:04:42] Hey guys, I'm excited to be trying out this podcast, remote edition with you all.

[00:04:47] Yeah. Sorry that we can't all be together today, but I think that there's a lot of really interesting things to talk about. So I think first of all, you know, it really feels like things are beginning to shift a little bit. It really seems like, you [00:05:00] know, there's, there's a lot more news today and over the past week about increasing cases and questions about whether the death rate is beginning to increase as well or not.

[00:05:08] And, and those are all things we can dive into a little bit more. Over the course of what I'll be talking about today, mean, I just kind of wanted to give a little bit of background and just how things are feeling right now. You know, it's really interesting from the beginning, we've talked about how geographically variable this epidemic is.

[00:05:25] And I think that that continues to be the case now, right? Like we're, we're hearing a lot of reports from different parts of the country where cases are increasing and, you know, some places are really rising quickly. And today there were a number of, sort of reversals of the reopening procedures that were, were announced in a couple of States and even in a couple of different countries.

[00:05:41] Whereas other places, you know, I'm living in the Northeast right now. And, and for now it seems like cases sort of are continuing there to be pretty steady at low levels. So, so, you know, once again, there's just very different things happening in different parts of the country. And I just wanted to say that, you know, my, my, my heart goes out to everybody who's, you know, [00:06:00] who's concerned or anxious or in a place right now where, you know, there were really reckoning with.

[00:06:04] With this rise in cases again. And you know, I'll definitely say, you know, over the last two weeks, I've talked a little bit about how it has felt like, you know, is that the genealogist we've been sort of breathing this night had definitely not a sigh of relief, but sort of taking a few moments to sort of take stock and where it's felt like things are slowing down a little bit.

[00:06:22] And I think that that has changed too. You know, it really feels like we're starting to gear up for something again. And so, so I've been reckoning with that myself as well, you know, really trying to pay close attention to what it's happening and try to think about, you know, how, how we can contribute in the next few weeks.

[00:06:38] Because I think that, you know, it's things were picking up again and, and we're going to have to learn from the lessons that we learned this spring about how to reduce transmission and, and just sort of what to do in our communities. As cases start to rise again. And so, you know, it would look different than the spring for sure.

[00:06:54] In part, because we know a lot more about the virus. We know a lot more about the things that can interrupt its spread, but [00:07:00] nevertheless, you know, there's, there's still sort of the psychological and emotional side of all of this, which, you know, it's just really unfortunate to sort of start to see things creeping up again.

[00:07:08] And so I think that, you know, my hope is that we can all just sort of take care of each other, both in terms of preventing the spread of the virus, but also just sort of dealing with the. With the other impacts that are, that are very important as well, you know, with everything, from coping, with isolation, to, dealing with anxiety and all of that.

[00:07:23] So, so definitely just wanted to, to set the stage with that, to start things off. Now in that one of the questions that you sent me was if there are any updates on the covert confirmations, increasing a bit deaths, not increasing, you know, is that the same as what we talked about last week? Is there really, you know, is that.

[00:07:38] Most likely due to a delay between these metrics or is there something else going on? And I do think that the delay between reported cases and fatalities is, is, is still the most likely scenario. And unfortunately we have started to see the number of deaths starting to increase both across the country as a whole and in a number of the most effected States.

[00:07:59] And so I, it, [00:08:00] and it sort of falls right into that range of. Three or so weeks that we sort of expected to see between the number of cases that were rising and the deaths. So that right in line with both our previous experience and with the epidemiological modeling that we had done, I do definitely want to reiterate that, that we are getting better at treating COVID we're getting better at recognizing it.

[00:08:17] We're getting better at identifying it early. And, and so I think that all of these things are helping for sure, but it really seems like this delay is probably the most likely thing that's contributing to what we were seeing. And so I think that, that, that, you know, unfortunately that means we're going to sort of have to brace ourselves as well.

[00:08:31] And it's really important to sort of not read too much into the fact that deaths are low right now, because you know, that, that, that doesn't mean that this virus is fundamentally different than something that we've, that then the thing that we saw circulating earlier this year, so, you know, I'm hopeful that this next wave will, will.

[00:08:46] You know, it may not be as bad as the first, but it's really just hard to say right now. It just depends a lot on the sorts of responses that we have in the coming weeks. So, so we'll just have to see, there's also been a lot of talk about, and I think we touched on this last week as well, [00:09:00] but yeah, the question of airborne and coronavirus transmission versus droplet transmission.

[00:09:04] And there's a lot of questions that have sort of been raised as a result of this, about like what constitutes exposure, what does it actually mean for me to be exposed to COVID or not? And, and I think this is a really complex question because it's, it's this multi-variable thing. It's it's, there are a lot of different inputs which include X the amount of time that you are close to someone of whether or not the person was symptomatic and how symptomatic, what type of contact you had with them.

[00:09:29] Whether it was indoors or outdoors, whether that indoor space, if it was endorsed, had good ventilation, all of these sorts of things. And then just, you know, the fact that also, there's just an awful lot of randomness in the spread of COVID. Anyway, we don't really know how much virus you need in order to be infected.

[00:09:43] And that probably depends also on sort of your own immune status, you know, just how your immune system functions and how much virus the other person is shedding. So there all of these sorts of things that. Lead to the possibility is that that COVID could be transmitted. And so w you know, we would really like [00:10:00] to say like, well, it does does a 15 minute exposure constitute exposure or a five minute exposure.

[00:10:05] And, you know, the fact is that, like, anytime you're in any sort of proximity with somebody with COVID, there's some risk of transmission and that risk increases. According to all of these different variables. I think that, you know, that that sort of gets us into this weird gray zone where, where we're all sort of assessing our risk in different ways, based on the different sorts of information that we've heard.

[00:10:23] And so it's really hard to draw these hard cutoffs between what's an exposure of what isn't. And so, and so I think that it's, it's really difficult. I think that really what this underscores is. Yeah. One of the, one of the key questions about, you know, is this center exposure or not comes in terms of contact triggers.

[00:10:38] And so one of the key key ways of limiting the spread of the virus is by, is by contacting or is by tracing the contacts with people who have been infected and to whom they've been exposed. And, and so then that, that again raises the question of what does it mean it'd be exposed. And so I think that this, this falls into the remit of what is a good contact tracer.

[00:10:56] It's very similar to what constitutes a good. Like what, what's a good doctor, you [00:11:00] know, we can all sort of read lists of symptoms and go into, to web MD and sort of see what our different symptoms say. And you know, how likely is it that we haven't given illness, but a good doctor will be able to hear an entire narrative and say like, well, you know, this is what I've been feeling.

[00:11:11] This is where I've been. And the doctor will be able to say, you know, just sort of taking this whole sort of, Constellation of factors and be able to make a good diagnosis that really no, no individual assessment of, you know, of separating risks. We'll be able to do a, because it's really built on their expertise in there having seen many different cases across their entire practice.

[00:11:31] And I think that's true of contact tracers too. You know, if you have somebody who's, you know, a person who's doing contact tracing, they'll be able to ask you about where you've been and what sorts of exposures have you had. And if. If they know well enough how this disease spreads, then they'll be able to really be able to say like, what was a significant contact or not.

[00:11:49] And I think that that's something that really requires a fair amount of experience and expertise. And so, so it's difficult, but I think that really the best thing we can do is to just learn about the principles of how this virus spreads, which are [00:12:00] things that we know well about. And that there's a lot of information on, about indoor spread and about, about proximity and duration.

[00:12:06] And so I think it's, you know, besides, you know, keeping in track of like what constitutes a contact, I think it's worth just sort of keeping all of these different. Variables in mind and recognizing that they all contribute in some way. Now that also raises the question that you asked about super spreading.

[00:12:19] And we know that with, with SARS Kofi too, and also with the original SARS virus in 2003, that it seems like super spreading is really a key factor in the transmission of Corona viruses. And in particular of COVID. Yeah, there was this article, I think that was published yesterday, that, that says that this super spreader from China gave a COVID-19 to 71 people in a single elevator trip.

[00:12:40] No, that's, that's a little bit misleading because I'm reading the actual, sort of report that came out. So it seems like this person was infected and probably spread Krone virus to a couple of people potentially during an elevator ride. And, and it was not people weren't in the same elevator. They basically probably.

[00:12:56] Infected the elevator buttons or something like that. And then that [00:13:00] spreads to a couple of other people and then those people spread infection onto others. So even though this sort of cluster of cases could all be traced back to a single person, it's not like the single person gave COVID to 71 people, all of whom wrote the same elevator and it was all due to this elevator trip.

[00:13:14] So I think that's a little bit misleading. It, you know, it's very sensational to say that a single person gave it to 71 others, but there, it seems like there were probably intermediate. Transmissions in between that caused sort of this large number of transmissions from a single person. I think that that's worth keeping in mind, but nevertheless, it does seem like these, these events in which a single person can spread infection to lots of others are important for spread.

[00:13:36] And the most important thing we can do right now is to limit that possibility. And this is something we've talked about before, I think, but you know, the, the, the reproduction number for SARS Kofi two seems to be right around two to three. So that means that over an infectious period, over the time that a person is infectious, our best estimate is that they might spread it to three other people on average.

[00:13:54] And so a super spreading event would constitute, you know, if you spread it to more than that expected number of people, [00:14:00] but it's impossible to have a super spreading event. If you don't have contact with more than. You know, three people over the course of any, any two week period or so. So I think that's really what we should be focusing on is reducing the possibility of these large spreading events.

[00:14:13] And I think that that, that then gets into the next question that you were asking about herd immunity. So there's been a lot of questions about herd immunity and what we need to do to get there. Is it possible to even get there because there have been some studies recently that suggests that. Maybe immunity to Corona virus.

[00:14:27] Doesn't actually last that long, which is, which is something that we've anticipated since beginning of the outbreak. But now there's, there's beginning to be laboratory data that suggests that that, that might actually be true at least to some extent. So, right. So there's, this is really nice article in the Atlantic that was talking about how hurt and unity happens and, and really underscores the fact that that herd immunity to some extent is something that is that in our hands, that we can adjust the amount of herd immunity, the basically the amount of immunity that we need in the population to reduce transmission.

[00:14:59] And there are a couple [00:15:00] of ways that this can happen. You know, the first is. Is is not so much a choice that we make, but it's just the fact of how disease spreads. So if you can imagine that that certain people are more likely to be infected and more likely to spread infection to others, just because of where they are, the number of contacts that they have.

[00:15:15] Then, then you can imagine that those people are more likely to get infected early in the outbreak, but then once they become a unit they're less. Likely to spread infection to others as the outbreak continues. So it's essentially like the epidemic sort of preferentially infects the people who are most likely to spread infection, and that can actually reduce the amount of the population that needs to be infected in order for the, for transmission to stop.

[00:15:35] Because you've basically, basically we've taken the people who are the best spreaders of infection and infected them early so that they can't continue to spread infection to others. So that's one way that the herd immunity threshold that's sort of what is often quoted to be around. You know, maybe 60% of the population could be reduced to some extent, but also herd immunity is related to just how transmissible the virus is.

[00:15:56] And the transmissibility of the virus depends on the virus itself, but [00:16:00] also on our behavior, right? Like if we're not spreading the virus, then, then that means that there's fewer opportunities for it to spread. And that reduces the total number of people in the population who need to be infected to sort of bring transmission.

[00:16:11] To a stop. And so I think that's, that's really what the article was getting at was that, that, you know, if, if we sort of change our behavior in this sort of longer term sense, so that transmission is no longer as likely, then that could reduce the total number of people in the population who need to be infected to bring the epidemic to an end, which I think is really something worth keeping in mind.

[00:16:29] I think, you know, what this, what this really is getting at is that we need to continue making this transition into thinking about this epidemic as a longterm thing. That's something that could be with us for a very long time and as something that could cause us to need to adjust our behavior for fairly long periods of time.

[00:16:45] And just think about new ways of doing things that reduce the probability of spread. No, of course, you know, as I mentioned, it seems like immunity might not last forever. And so, so thinking about herd immunity could also sort of be this false narrative to some extent. And I think [00:17:00] that that's really the place that I want to sort of conclude this.

[00:17:02] There's there's one other point that we might want to get to, you know, there's, I think that. One of the things that's really struck me most about this pandemic is, is that we all seem to have this implicit narrative that we're telling ourselves about how it's going to unfold. And that narrative has shifted over time.

[00:17:18] You know, if we think back to the beginning of the epidemic, it was basically that we're going to have a wave of, of transmission and then it's going to be over. And then there was this notion of, well, we have some choice over that. Let's try to flatten the curve. So, so maybe we can adjust our behavior and flatten the curve.

[00:17:32] And then maybe the epidemic will last a little bit longer, but fewer people will be infected and then we'll be done. But then there was another shift in the narrative that said, well, No previous pandemics there've been multiple waves. So maybe there's a second wave that we need to be thinking about. So maybe we can flatten the curve, but we also need to be preparing for a second wave and, and you can see that this narrative is sort of growing longer and more complex.

[00:17:52] And, and, and I think that implicit in all of these narratives is, is this notion of herd immunity. It's like, well, we're going to have a wave and [00:18:00] then it's going to be over, or we're going to flatten the curve. And then it's going to be over. We're going to have a wave and then a second wave, and then it's going to be over.

[00:18:05]but all of these are sort of these implicit narratives. And, and the fact is that the narrative is still. A little bit uncertain. And even from the beginning, it seemed like actually the most likely narrative is that we'll be able to reduce transmission, but there will be multiple waves of transmission.

[00:18:17] And in fact, it's, the sink will probably be with us for quite a long time until we have a vaccine. And maybe even after we have a vaccine, you know, flu stuff breads from year to year as well. And so I think that really what we're getting at with, with these questions of, of, you know, is their herd immunity, is there not, is, is really what we're trying to do is like ask ourself as like, what.

[00:18:34] What's the right narrative. What's what is the way in which this pandemic is going to play out? And I think that's a huge importance if only because of the psychological effect, you know, we, by placing ourselves in a narrative, that's sort of one way of, of coping with reality. And I don't mean coping in a, in a bad sense.

[00:18:49] It's, it's not a weak thing. I think it's a necessary thing. I think that. Yeah. The, the stories that we tell ourselves, the ways that we construct sort of our notions of what's going on in our lives and our world around us are of [00:19:00] fundamental importance. And we need to be continuing to construct those narratives.

[00:19:03] But I think with the pandemic, we need to realize that that narrative is a very flexible thing. And, and so, so we're beginning to enter, I think, into another sort of shift of the narrative where we're thinking about, about covert sort of as, as this, this chronic thing, not necessarily chronic in an individual sense, although that seems to be potentially possible to.

[00:19:21] What sort of chronic in a, in a social sense, in a societal sense that that COVID is not necessarily going to be this one and done sort of thing, but it's something that we're going to be contending with for a very long time. And so I think that that, that some of this, this debate that's going on about herd immunity or not, and how much, and for how long is really rooted in this sort of restructuring of an area.

[00:19:40] Heard of that. I think we're going to see sort of evolving and taking shape over the next couple of weeks. So I think I'll leave that there there's the last thing that you mentioned, and there was this question about how concerned we should be with this new swine flu that's been reported in pigs. So the short answer is it's not terribly, you know, there are, there's, there's a whole lot of different flu strains in both birds and pigs and [00:20:00] various other animals.

[00:20:01] That spread and that sometimes cross over into humans and that once in a while, cause a very limited human to human transmission. Now it doesn't seem like this swine swine flu strain that has been detected is really capable of human to human transmission. Or if it is, it's not really capable of much human to human transmission, basically the reproduction number seems to be well below one.

[00:20:21] And these, you know, these are things that, that, that, that happen relatively frequently. I'm actually on an email list that every week basically sends out an update. Of any new identified transmission of flu in humans. And it's not terribly uncommon for, for there to be cases of these types of flu to spread over into humans, but, but they, they die out pretty quickly.

[00:20:44] And so, you know, certainly, you know, there were saying that that the, the spread of the strain is increasing among pigs. And so that means that there's going to be more and more human exposers to this strain, which again, just sort of, again, sort of we're, we're working in the realms of probabilities and possibilities and, and, and, and it could be that the strain crosses.

[00:21:00] [00:21:00] Into humans. And then with, with another couple of rounds of evolution could potentially be possible to transmit among humans. But this is a reality that we've been living with for a very long time. And histories, you know, according to history, you know, we were not very good at sort of predicting where the next pandemic flu strain is going to come from.

[00:21:17] In 2009, we were pretty sure that it was going to be a flu strain that emerged from birds probably somewhere in Southeast Asia. And it turns out that it was probably a flu strain that emerged from pigs somewhere in the Mexican peninsula. So, you know, is it just. It didn't really align with our, with, with what we thought.

[00:21:33] And so I think it's very good to be continuing the surveillance, but really what I think this is as a cautionary tale that basically says, you know, covert, isn't the only thing that's circulating. We do know that flu pandemics tend to happen a couple of times, each century. And it's been a little while since our last one.

[00:21:47] So, you know, there's, there is always a chance as there always has been that another flu pandemic could arise too. That's certainly something that I've been thinking about, even from the beginning of the covert pandemic, because I thought that the next pandemic would be a flu pandemic, [00:22:00] not a coronavirus pandemic.

[00:22:01] And so, but the fact that we're having a coronavirus pandemic, it doesn't really change the possibility that we're going to have a flu pandemic. Yeah, it would be, it would be an incredible turn of bad luck if it were to happen, you know, while we were still dealing with, COVID certainly not an impossibility, but, but, you know, I think that, that these reports are probably really just rising to the surface because COVID is happening.

[00:22:23] And, you know, it's where our ears are very attuned to, to the possibility of pandemic viruses spreading. And so this is sort of like, you know, it's just, just like this awful thing. It's like, you mean to tell me that there's a possibility of another pandemic happening right on the heels, or even during this one.

[00:22:37] And, you know, the fact is the possibility is there, but you know, this, this, this virus is not sort of an imminent threat to human health at the moment. And so I think that it's not something that we really need to be concerned at the moment is, is the sort of the longer version of that story. So. All right.

[00:22:51] Well, that went on a little bit longer than I expected, but yeah. Thanks for hanging in. And I hope our listeners didn't mind a little, a little bit of monologuing there, [00:23:00] but looking forward to seeing you guys again very soon, hopefully next week and otherwise hope you all are taking good care of yourselves and we'll talk to you again soon.

[00:23:10] Matt Boettger: [00:23:10] Okay, so now let's get right into dr. Mark Kissler. When he talks about with the updates on the hydroxy chloroquine, 

[00:23:19] Mark Kissler: [00:23:19] everybody happy Wednesday server can be with you this week in conversation, but looking forward to covering a couple of quick clinical updates, you know, I think the big thing on a lot of people's minds right now is the increase in cases across the country.

[00:23:32] We've definitely seen an increase here in Colorado as well, both amongst hospitalized patients in. The Metro area, hospitals. And then also the statistics that the state is keeping seem to indicate the, both the rate of confirmed cases and the rate of rise of those cases have both increased this week. you know, it's hard to know for sure what that means.

[00:23:52] I think we've had some conversations and Stephen's been doing a lot of interesting work on the way that this may wax and wane and that [00:24:00] we are to expect different peaks and troughs over the course of the fall. And so. Where we're at in the peak. I know a lot of people have been asking Steven that, and hopefully he'll, he'll talk a little bit about that and, and sort of the meaning of that question, you know, I think we're trying to get a grip of where, where are we, or what time he used the, he used the phrase when we were talking, what time is it?

[00:24:18] You know, everybody wants to know. Where in the pandemic we are. And I think I certainly do too. And it's something we've been talking about at the hospital. And I think, you know, we have to use caution and using several days or even a week's worth of data and then extrapolating and saying, that's how things are going to be going forward.

[00:24:37] But at the same time, it's worth paying attention to, and continuing just as we have been to do our best to stay safe, I wanted to talk this week about. Something that we opened up last week a little bit, which was this new hydroxy chloroquine study that was published in the international journal of infectious diseases.

[00:24:54]and I said that I do a little bit more of a deep dive and get a better understanding of the methods. And then we could talk [00:25:00] about how this is situated in our clinical knowledge about the therapies that we can use for COVID-19. And of course, as you know, as everybody listening knows. We've had a lot of conversations, a lot of really interesting conversations about what we can do to help patients with COVID-19.

[00:25:15] What are the right therapies to use? And hydro chloroquine has been one of those that's come up and had some of the, the most spotlight on it. I think because of the way that it's been, you know, initially should. Apparently very promising data that in some later scrutiny wasn't as promising and then other studies haven't borne that out.

[00:25:34] And then now there's this bigger study that seems to say that there is a big effect size potentially to using hydroxy cork when, so we're going back and forth and it's, it's a highly kind of contentious and politicized intervention. And, you know, everybody's hoping, I think. I'm in this as with any of the other drugs to have a really definitive answer.

[00:25:53] And unfortunately, I think this study is far from a definitive answer. It does add a little bit to our body of knowledge, [00:26:00] which is always important, but we can talk a little bit about the ways in which it doesn't. It's not the clincher in the hydroxy chloroquine argument. We talked last week about observational studies and the way that a randomized prospective controlled trial is the gold standard for the production of evidence for causation and with a retrospective study or an observational study, we can only at best say that the outcome is correlated with.

[00:26:25] The difference between the two treatment groups and you know, why is that important? You might say, well, what is causation correlation? That's all just kind of statistical. Semantics, what we're really interested in as an effect size. And we can all just kind of draw conclusions based on the effect size.

[00:26:42] The difficulty is with observational studies in particular, or that there's other things that can enter in and contribute to that effect size. And we call those confounders now in a prospective randomized controlled trial, we do the best that we can at the outset to randomize the groups and make. All of the [00:27:00] patient characteristics, those that we can anticipate and those that we might not be able to anticipate at the beginning the same, and that helps to minimize it.

[00:27:07] Doesn't take away, but it helps to minimize some of the confounders that can influence the data in an observational or a retrospective in which we. Take a group of patients and we go backwards and we look, you know, we didn't assign at a certain patient. We didn't randomize a patient to treatment with hydroxy chloroquine, or no.

[00:27:24] Instead we say of the patients during the study period who received the drug, what's the mortality rate there versus the group who did not receive the drug. And what's the mortality rate. There, but the difficulty is that there's other things that can intervene and can contribute to the patients who got the drug and who didn't.

[00:27:42] So an example, kind of a blunt example, but I think useful in this context, let's say that there's a disease and there's a drug called a drug X and it's in moderately limited supply. And we don't know if drug X really works. But there's been some preliminary data that it may help the [00:28:00] sickest of patients.

[00:28:00] And so, because the hospital supply is short clinicians who have patients in front of them are deciding who is going to benefit from this drug. What's the most ethically appropriate way. To allocate this resource, this limited resource of this drug, let's give it to the sickest patients. Let's give it to the patients who are in the ICU who are so sick, that they might end up in the ICU.

[00:28:22] And this may be the thing that keeps them from needing that high level of care. Well, if you take that retrospectively and you say, okay, of the patients who received a group X, the mortality rate was much, much higher than those who didn't receive it and then make the next. Link, which is, Oh, drug X must cause a higher rate of mortality.

[00:28:41] Well, that may not actually be the case because the groups were so different. Now, there are statistical ways that you can try and correct for some of these confounders. After the fact in a lot of observational studies, including this one, use some of those statistical methods, but you can't really control for everything and you can't [00:29:00] control.

[00:29:00] Necessarily for the precise effect size that everything has. And so we run into some issues with that and that's worth keeping in mind. So let's talk a little bit about this study, particularly some strengths that it has. Again, it was relatively large group of patients, a little over 2,500 patients. Is it multiple hospitals?

[00:29:17] There was all in the same healthcare system in Michigan and. The reason that it's important to note whether or not something happens at a single institution or at multiple institutions or at multiple geographic sites, it's just that people in places vary. And if we want to make the results most generalizable to the most number of people, it's helpful to have people included in the study from lots and lots of different demographics.

[00:29:41] The study did include individuals who have lower socioeconomic status, more at risk groups or socially vulnerable group. And ethnically diverse patients. So that's also good that helps to extrapolate the findings to those populations as well. They also used some regression, so some statistical methods [00:30:00] that correct for certain can possible confounders.

[00:30:03] And so that was also a good method that they used. Now, some of the things that may have been. Confounders are some of the things that may make this data a little bit harder to extrapolate. And I'm getting a lot of this information from a really good editorial that was also published in the international journal of infectious diseases.

[00:30:21] A publication date, July two and first author was tough. Lee, well, send it to Matt so we can put it in the show notes as well. So one of the things that wasn't controlled for in this particular study was when in time the patient was treated. And so one of the, we've seen a lot of changes in our understanding of the illness and the way that we treat the disease from sort of the first cases we were getting into February, beginning of March til now.

[00:30:47] One of the examples that stands out to me is the way that we've dealt with anticoagulation in the inpatient setting. So yeah, we've realized over the course of our experience with the coronavirus cases that we're seeing, that there's a higher [00:31:00] incidence of blood clots, and we've instituted some measures in the hospital to be.

[00:31:05] Pretty aggressive about anticoagulation and making sure that people are on or cold blood thinners or anticoagulants, we're using an OXA parent usually to prevent those complications and that wasn't going on as much at the beginning of the case time, as it is now. Similarly there's other maybe and Alation management or fluid management strategies, we just have a little more nuance and how we care for these patients.

[00:31:28] And I do think our care has improved, you know, week to week just as we. All understand the disease process better, but so to have the interventions that we've been using. And so it's important to notice that. The way that we were using hydroxy chloroquine early in the pandemic may have differed from the way that we've been using it more recently.

[00:31:48] And so to lump all those patients together who have all these other treatment advances are these things that are changing to is just going to add a little bit of confusion to whether the signal we're seeing in this [00:32:00] data is really from hydroxy chloroquine, or if it's from some of these other things that are going on.

[00:32:04] Another thing that they mentioned in this study was that the group. The who didn't receive hydroxy chloric. When the non-treatment group had a higher mortality rate. Then it had a rate of individuals who were transferred to the ICU. So meaning that used to take all the people who didn't get hydroxy chloroquine in this study, 20 about 26% of them died and only 15% of that whole group were sent to the ICU that was switched in the other group.

[00:32:30] So there was a higher group of patients in the hydroxychloroquine treatment group who were sent to the ICU. Then who died. And so what does that mean? That's a little bit confusing. It's hard to know exactly what that means, but it does suggest that there was something missing, purely different about the patients who didn't receive hydroxychloroquine than the ones who did.

[00:32:50] And perhaps one of the differences where it shows up in the fact that more of those patients died without going to the ICU. So who are the patients [00:33:00] in, in the hospital setting who might pass away in the hospital? A little bit, not in the ICU. Very often. Those are individuals who come in and say, I don't want ICU level care.

[00:33:10] They have established goals of care or advanced directives coming into the hospital. I don't want to be intubated and I don't want CPR or vasopressors or those sorts of things. This is often done, not exclusively, but it's often a sicker group of patients who have more things going on. Who are generally medically more frail and who may elect not to have that high level of intervention.

[00:33:33] And so it's a little window into a potentially is a big difference between these two groups of treatment and non-treatment, and it might make sense, you know, if someone comes into the hospital and who's in it, goals of care are not for aggressive treatment, that they also might not have been started on drugs that were deemed experimental at the time that they may have gotten.

[00:33:51] You know, more standard care related to comfort oxygenation in a kind of more basic level things. And that it may have been this other group [00:34:00] of patients who are very, very aggressively treated who got some of these drugs at different points during the pandemic. So that can just also influence the results.

[00:34:08] And I think the most, most important thing to note is that the steroid use in the patients who got hydroxy chloroquine in this study, It was more than twice as high as those who didn't get hydroxy chloroquine. So, so take all the patients who got hydroxy chloroquine more than double. The number of those patients got steroids than did the ones in the non treatment group.

[00:34:29] And we know from the recovery trial that we just talked about a couple of weeks ago that dexamethazone showed a very significant mortality benefit. And so. Is some of the effect that we're seeing from the hydroxyl Corcoran group actually actually attributable to the steroids. And that's a big question.

[00:34:45] That's, that's left open by this study. So all that to say, just kind of to, to summarize, you know, thoughts on this study. I think it adds to our understanding of hydroxychloroquine, but we're going to have to look. Two randomized prospective trials that are coming out to [00:35:00] really have a clear sense of the causation.

[00:35:02] I think there's a couple of more studies that are in the pipeline and that'll help to contribute to our knowledge here. I wouldn't say this is as practice changing as the recovery trial. I wouldn't expect, you know, big, big shifts in the way that we're using. Hydroxychloroquine currently. I I'm open to the possibility that there may be a subgroup of patients or a certain time point within the illness, in which this would be really beneficial.

[00:35:24] And I'm hopeful that the evidence will, will bear that out if that's the case so that we can use it appropriately. The other thing that I wanted to mention about this editorial that I thought was really fascinating just from a clinical standpoint, is where they bring their conclusion. So they do a good job of, you know, praising the evidence and talking about the strengths and the.

[00:35:41] The vulnerabilities of this particular study. And then they also say something that I think is important for all of us who are in healthcare, who have ties to healthcare, because what they say is that it's, it's interesting that it's very easy or relatively easy for a hospital system to protocolize something.

[00:35:59] And what they mean by that [00:36:00] is to, you know, to Institute a, kind of a provisional standards of care to say, like these. When the patient comes in with coronavirus, these are the treatments that we offer and, or these are the criteria for which you get hydroxychloroquine or Ramdev, severe or steroids. It's relatively easy for a hospital to put a protocol like that into place, but there's a lot more barriers to enrolling patients.

[00:36:21] Into very robust randomized clinical trials. And so a lot of the data we're getting from this pandemic is of the retrospective sort, where we're doing these interventions, we're doing the best that we can. We're kind of guessing which patients we think might benefit. And of course our, you know, our responsibility as clinicians is to the patient in front of us, that we want to help this individual person.

[00:36:42] And I always am trying to think of what is the thing I can do. It's going to help this person in front of me. but what that doesn't. Do in that instance is generate or is, is participate in sort of the generation of this robust, scientific knowledge. And so we've got to have both ethically sound ways to [00:37:00] protocolize our treatments so that we are gathering data while we're treating the patients in front of us.

[00:37:05] So while we're doing the best for our patients, we're also participating in the, the generation of the scientific knowledge. You know, it'd be great. If at this point in the pandemic we had. More really robust randomized trials that could tell us exactly which drugs we should be using right now. We have some of that data.

[00:37:22] We don't have all of it, and it's just the nature of how things have been progressing. But I think it's, it's an interesting place to bring, you know, the, the editorial and an interesting thing to think about is, you know, how, how do we. How do we respond and be, be responsive and dynamic in an, in a rapidly changing scenario and still be attentive to the ways that we can produce robust scientific evidence.

[00:37:46] And so those are some of the things that I've been thinking about this week. Looking forward to catching up with you guys before too long. All right. Take care. Bye. 

[00:37:54] Matt Boettger: [00:37:54] Thanks for listening to this unusual episode of pandemic, and we'll be back to you hopefully next [00:38:00] week with a real authentic, genuine conversation.

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[00:38:26] Listen to it. You can go to live in the to check it out. Also in the show notes, you get the link subscribe, please. Otherwise we will see you next week. Take care. Bye bye.