What role does antibody testing play in our return to normal society? Stu Akerman, MD joins the GCP to visit with Dr. Ken and they take a dive into what point of care can do and might not do for us. Like and share, and stay safe!
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Hey, what’s up everybody? Here we are on our COVID files 4.5. That means a point five we have our recurring super smart guests, my friend and colleague, Dr. Stuart Ackerman. Dr. Ackerman, would you please introduce yourself?
Sure, Ken. Thanks for having me again. It’s my name’s Stuart Ackerman. I’m a gastroenterologist with digestive health associates of Texas. And we’re glad that I’m here again to discuss more COVID type stuff.
So on Dr. Ackerman and I did a COVID 3.5 Episode three and a half episode where we looked into the role of COVID in the digestive tract. Today, we’re going to look at some journals and discuss the role of COVID-19 testing specifically the role of antibodies, and you’re going to be hearing a lot about this. And so a lot of the shows that we’re doing, we’re a little ahead of the media. So that’s what I’m really happy about is that every time we do a show, and then later the media kind of catches up, so. The one thing I do want to address and if you’re watching this on YouTube, Dr. Ackerman, you’ve changed your look a little bit. I mean, you had this very beautiful luscious beard, you know Wolverine like and it’s a little different is that because you’re getting all the notoriety from the show or what’s going on?
Yeah, some sacrifices have to be made. So, as part of my practice, you know, although there’s some restrictions because of COVID on doing procedures and seeing patients in person, I still I still have a significant number of emergency and urgent procedures that needs to be done and part of the protocol as recommended by all of our societies is that you’ve got to wear PPE these protective equipment and some of that is an N95 mask and an N95 mask when it goes over your your mouth and your nose, it doesn’t fit to securely if you’ve got luscious locks like I did. So sacrifices needed to be made.
So Dr. Ackerman did this really cool video where he’s basically explained the whole process of this, and how certain sacrifices have to be made. So I suggest everybody go to his website. What is your website?
It’s www.stuartakermanmd.com Stuart Akerman dot com
You posted the video on your website, I hope.
Yeah, it’s posted on my blog on the website.
That’s awesome. I love the video. It’s so cool. All right. So when you and I were discussing about doing this, and what I like is that you and I talk all the time. And we discuss journals and we do stuff and we kind of debate a little bit and we poke each other and you were you were discussing that, you know, hey, we should do a show on this. Do you want to do like a point counterpoint kind of thing where we should debate and I laughed because I immediately thought of airplane the movie from 1980 you’re way too young for this but the airplane.
I’ve done I’ve googled it.
They were doing point CounterPoint. And you know, the whole point of the show is to be so obscenely on either end where the one guy so, a CRNA Jack Kerry that I’m not sure if you know him. Have you met jack? So jack would always laugh, he would use that quote whenever something would happen in the in our endoscopy center. If maybe the scopes weren’t ready or a patient showed up late or something got off track, he would always say the same thing which I started thinking about about this. In the point counterpoint in airplane, the CounterPoint guy was like, they bought the ticket, they knew what they were getting into, I say, let him crash. This is not going to be quite like that. Because I think you and I will end up in the same spot ultimately when we’re discussing this. So that’s kind of where I thought where you and I were hoping to have a kind of a point CounterPoint. But I think we’re gonna end up in the same spot. You kind of agree?
Yeah, I agree. I think that it’s, it’s good to sort of flush out both sides of the argument so that you’re more well rounded in your discussion. And I think that’s kind of how we approach it, you know, that, we’re we’re looking at the same data. We’re drawing our own conclusions, and sort of coming out on both sides of the argument. I think that’s, that’s good for any kind of evidence based discussion.
Totally. And what we’re going to talk about today is something that is super important, because it is how do we get the economy back on track? How do we use testing to do it? And we’re going to take a look at the evidence based approach to this. And in fact, this is coming so fast that this morning I woke up, and I saw a couple different articles that that came out this morning. One of them was an article on a homeless shelter in Boston. And what they decided to do is do PCR testing on everyone in the homeless shelter, and what they found was that 36% of the people were positive at that moment, and we’re gonna discuss what that moment means. So 33% were positive, but only 7.5% admitted to having a cough and only .7 even had a fever. The conclusion was in this article was holy cow, we need to do mass testing so that we can see who’s really been infected. And then almost on cue, a New York Times article came out today, where it was a journalist that he opens with a with a classic Mark Moran. I’m a comedy fan Mark Moran line, where the the journalist says, “I know a guy. And because I know a guy and the connections I have, I was able to get my hands on a rapid antibody test. And I took the test, and I was negative. The problem is, I’m not sure it was a valid test.” I’m like, this could not have been in a better time this guy did this. And that’s what we’re going to talk about today. You and I know guys.
Yeah, we know people and this is the national and international discussion. Now if you’ve at all been watching the news, or reading papers or going on Reddit, you know that Italy, Spain, the United States to some degree, they’re all discussing this idea of how do we figure out who has immunity? Is there a way for us to figure out who can safely come out of their homes, go back to work, and sort of jumpstart the economy again and jumpstart life? And it sounds dystopian. It sounds like it could be a great idea, it could be a terrible idea and anything in between. But what we don’t have is we don’t we don’t necessarily know the details yet. And I think that’s, that’s what gets everyone confused, because there’s no shortage of media outlets touting this as you know, the next great idea, but is it? I don’t know.
Well, we’re gonna we’re gonna get into that I there was an article written by I don’t remember who wrote this, but it was just this just happened in the last couple days about ending the lockdown. And they interviewed a Harvard epidemiologist, and he said, well any of the lockdowns are going to be an effort with trial and error. There is no scientific evidence to this, he’s like the best I can say this is we’re all in a life raft. I’m not sure how we get to shore yet. What we’re going to talk about is possibly how to get to shore. Because if you think about it, governments around the world, they need to triangulate the health of the people, the freedom of the population, and there’s no scientific consensus. So what I wanted to do today with you, because you’re a super smart guy, much smarter than me, let’s kick some science. Let’s go over some articles, and then play the pros and cons of each side of it. So I’ll throw it back in your court. Where do you want to start with this?
So I think, you know, we, we have a few articles that we definitely want to discuss as the basis for the arguments about immunity. I think before we jump into it, just to get a better sense for our viewers, we need to explain some of the terminology and the differences between the testing methods to understand what best to use to acutely diagnose someone with COVID-19 versus how do we tell that they’re no longer infected, they’re no longer sick and whether or not or at least to start that discussion of whether or not they have immunity.
Absolutely. So let’s start with what is the standard test being done when somebody shows up with a fever to an emergency room?
So the standard testing when you’re trying to figure out is this person currently infected and sick or…not sick, we know they’re sick they’re there is something called PCR testing. So in PCR testing, we actually will try to replicate the virus, right? The implication being that you gotta have virus in order to replicate it. So a negative test means there’s nothing there to replicate. And therefore, you might have a fever, you might have some chills, you might have a cough, but you don’t have COVID-19. On the flip side to that, if you start replicating virus, the virus has to be there. By definition, if a virus is there, you have viral infection. So PCR testing has been considered the gold standard for diagnosis of COVID-19 at this point.
And let’s talk about the what we did talk about on our last show the kind of pros and cons of that, because what we’re learning. And what is fascinating is we’re here today, what is the date? April, April 16, to April 16 2020. I mean, we may be eating crow tomorrow, because everybody, this is all changing. But what we’re learning now is that a lot of people, I was listening, I don’t remember who the virologist was, but he was describing the actual process. If you’ve had this swab done, it’s not very comfortable, they get in there they try and get the cells that try and do this…it…there is some sampling error issues with this and possibly it’s not in the back of the throat. We discussed how possibly could be in the stool. So there are some limitations to that particular PCR testing, and a lot of the studies we’re going to refer to look at comparison to PCR.
Correct. And so with this study is that in order to mitigate that risk for false negatives, they’ll swab multiple areas and multiple sites to try to decrease that risk of missing a potentially positive person just because of sampling error.
It’s funny you say that because now after our last episode, and I’m pretty sure that they listened to our episode and this is why they did this because…
I can only assume
I can only assume that, that there’s a Chinese doctor that saying that we should probably swab the anus and those that have recovered to determine if they have PCR positive. So before somebody is released from the hospital swab their anus,
Yeah, right, I think fewer people are going to go to the hospital. We probably shouldn’t publicize that.
Um, you know, so the PCR testing now explain what the antibody testing is.
So, when we talk about antibody response, and you might have heard a lot about this, you know, the buzz words are IGM and IGG. These are the two immunoglobulins that we talked about with infection. And once you have an infection in order to mount a response, that’s really what we’re talking about. And IGM is the immunoglobulin that comes up first. That’s kind of the, the acute fighter for you to try to get the infection under control. And then once you’re sort of getting to a point where you’re starting to go towards recovery, you start creating idg and idg are more like your your memory, right? That’s what that’s what reminds your body and how to fight something. So when we talk about vaccinations, where we’re actually providing immunity to people, what we really are doing is either providing directly IGG or giving what’s called a live attenuated virus a small kind of stunted virus so that your body will see it react and create its own IGG. If I have encapsulate this in one sentence so that you remember the difference between IGM and IGG? I would say that IGM is what wins the battle for you. But IGG is what wins the war.
I love that. I’ve never heard it. Did you…did you just, I mean, Is this yours?
Yeah, that’s a shower thought.
I love that. You’re exactly right. So, a lot of people if you’ve ever been checked for epstein barr virus, which is a very common thing. epstein barr virus will usually have an IGM and an IGG and people will realize that most of us are IGG positive, we’ve been exposed, which means you saw the virus and you carry these antibodies throughout your life. That is a I love the battle war thing that is awesome.
I just think it’s an easy way to remember it. And you know, similarly, you know, if you go to have a new patient visit at a primary care doctor and they say to you, well, have you been vaccinated for hep B? Have you been vaccinated for varicella, which is chickenpox. You’re like, I don’t know, I don’t have that little card from when I was five years old. They’re going to run some blood tests. And those blood tests are just checking for the varicella IGG and that and certain Hepatitis B IGG is because if you’ve got them, you’re you’re good. And if you don’t you need either vaccination or boosters, right, because sometimes you might be immune, but that immunity can wane.
We’re seeing that with varicella. So we’re seeing people actually, co host Eric Rieger developed shingles.
And it happens. It’s happening to a lot of 40 year olds, a reoccurrence of varicalla, it’s happening and so that we got into a long discussion about that when him and I were in Hawaii because he were in Hawaii, and he had a bad shingles outbreak which sort of limits going to the beach.
But it was all it was all kind of related to that. So yeah, that is a great explanation IGM wins the war. So basically, your your innate immunity The virus comes in your body reacts to it cytokines, they send white blood cells, they kill whatever, hopefully they kill whatever it is. And then they take it back to memory cells that say, look, next time this guy invades the house, make sure that we kill it before it causes any damage like it did this time. And that is initially they go, okay, we’re going to send out some early troops, IGM, just in case it’s out there, just look for this guy, they get a card, they have a picture, and they go out and then they mobilize the IGG which says you guys are our reserves that you will remember this picture, hopefully for the rest of your life. And if this invader comes back, you go out and handle it.
Yeah. And you know, now that now that we understand that I think we can we can jump into some of these articles. And I think…yeah sorry.
I was thinking…before we get into the deep aspects of these these other articles, I I was very impressed with when I threw out the Macaque study at you, and you’re like, yeah, did you really read it? I’m like I read the abstract. This is a great example of what I did scientifically poorly, which was I read the abstract, and I’ve been quoting this article. And then you’re like, yeah, read the whole article. So in the abstract, and not to sabotage where you were going, but I just want to do this that this is why we need to dive deep into the journals, because in the abstract, they described recently has been reported that discharged patients in China and elsewhere were testing positive after recovering. However, it remains unclear whether the convalescing patients have a risk of relapse or reinfection. So what they did is they gave COVID-19 to Macaque monkeys, they don’t say how many they don’t discuss anything. What they say is after the symptoms were alleviated, and the specific antibody tested positively, that positively the half of the infected monkeys were re-challenged half of the infected notably neither viral loads in nasal pharyngeal and anal swabs along timeline nor viral replication in all primary tissue at five days post infection was found in reexposed monkeys. And then you said to me yesterday, why don’t you read the rest of the article?
Right? Because if you I mean, we’ll get into this in a little more detail in a couple minutes. But, you know, sort of a spoiler. This is the study. This is the study that’s been quoted as the basis for immunity testing and talking about giving people immunity cards because it it’s a it’s a solid proof that immunity exists and you can’t get reinfected. And if you read the abstract and you listen to all the pundits, you would think they they herded every monkey they had in China and created a cohort of thousands. In reality, when you read the study, they had four monkeys.
They reinfected half.
They reinfected two. So, not to say that the data is not valid, but you know, you have to have it with a grain of salt the size of the Rock of Gibraltar, you know?
Yeah. So after I read it, I was like, oh, man, he wasn’t kidding. And then they reinfected the two. And then they sacrificed them. And they call them adult Macaques. So then I went down a rabbit hole, typical Google rabbit hole. As it turns out, Macaques can live 20 to 30 years. The average age of these adults were three to five years. So
Right younger, you know, theoretically healthier,
Theoretically healthier, much younger, preteens or teen style adults. And I get it that we don’t want to sacrifice a whole bunch of macaque monkeys. I’d rather not sacrifice any animal or anything and have some sort of other way to test this. But this is just a great example of the media using this article me using the article and other you know, when Eric and I were talking on another episode I was bringing this up, I’m so thank you for pointing that out to me because that has to be you have to look at the articles and that’s what we’re going to do today is let’s let’s dive so I’m gonna throw it in you wherever you want to go with it, run with it, and I’ll try and keep up.
Alright, so before we hit that study, and we definitely want to talk about that because it’s the it’s the basis for the whole argument. There’s there was a study or data set really published by the Chinese CDC, about the Wuhan experience, and I think it’s good just to just to hear the numbers. So basically…
Is it this one?
Okay, great. Yeah. So this is the viewpoint characteristic of and important lessons from the Coronavirus 2019 outbreak in China is the title of the article.
Yeah. and these and these numbers are current as of February which is at the end of the curve in Wuhan so they are completely valid numbers, you know, that they published. So they had 72,314 cases of COVID-19. And, you know, 62% of those were confirmed with some sort of testing. You know, a lot of those numbers came from people who just had the right clinical syndrome because, you know, much like us, they didn’t have enough testing to go around, they weren’t able to get all the testing at the same time. So, you know, some of those numbers are the people who were admitted and treated and may have been on ventilators but didn’t have a confirmed diagnosis. But it seemed pretty likely that that that they were sick with COVID-19 and 3% of them were in advanced age of over 87. An 87%, though, fell into that 30 to 79 age range, with only 8% of the confirmed cases being younger than 30. So, you know most people fell into that fat part of the age distribution, with a very small percentage of them being on opposite ends of the young or old spectrum. Of the disease and this is where it gets really important. 81% of the cases were mild, right? So you might have had some sniffles, you might have not felt so great. But you didn’t end up right, we get worried, right? We talk about ventilator shortages, we talk about, you know, overrunning the capacity of the hospitals. But the vast majority, four out of five, didn’t really have much symptoms, if any. Severe cases-14% right, those are your hospitalized patients. And critical the ones that are new upper ventilators are 5%. So you know, if you break down the numbers, it’s a very, it’s not insignificant, but I think much like is the case in general we sensationalized the worst cases, and we got to be careful about falling into that trap.
You know, just for that. I mean, right before we hopped on the call here, I had a friend call me because his father is very sick with COVID-19. So when we say that 80% of the people don’t get sick If you’re if you have a personal relationship, or it’s you, that’s 100% of the most important thing that’s going on. And that’s what’s scary is the high infectivity rate of this. And in this in this article, the thing that stuck out to me was COVID-19 rapidly spread from a single city to the entire country in 30 days. And now we have a worldwide pandemic. So even though it’s a small, the majority of people will have mild symptoms. But when you take into the account of the people that do get sick, that’s how come we’re taking it so seriously, but where you’re going is how do we get that 80% back to work?
Right. Right. And and also just having that knowledge that you know, we’d much prefer you don’t get sick, but if you do, don’t panic.
Yeah. Yeah, everything is everything in the media right now is really bad. I’ve been talking to a lot of people. The New York Times article, the thing I didn’t get into Was that the guy actually thought for sure he had COVID. Because a month before he had the classic symptoms, high fever, whole nine yards tested negative for the flu, and his antibody test was negative. So is it a valid test or not? And there’s a lot of people that are like, you know what, I got sick in January, I got sick before we start talking about it here in the US. Has it been around? Has it been, basically, did it come to the US sooner? So who knows where this is all, we’re all gonna sort this out.
Right. And the case fatality rate in Wuhan was 2.3%. So 2.3% of the confirmed cases, you know, passed away, but 50% of those were critically ill patients. So it does sort of pass through that the sicker you are, the more serious it is.
Yeah. And then that’s coming out of China. And we have all this new data showing the people that do do worse, and we’re starting to you know, partion everybody out. We know that the Italians have a much higher death rate. And then if you look at their demographic, they’re older and all this other stuff. It’s, we’re learning. We’re learning that in New Orleans here in the US, we’re having a higher fatality rate higher, sicker rate, because of multiple different reasons. And you can start to predict where you’re going to need more healthcare resources based on these based on these demographics,
right. I mean, there were there were two specific issues that came up in New Orleans that may parallel the Italian subset in that it was a high density area with you know, Mardi Gras going on. And, you know, a lot of the case fatalities happened in a nursing home population, people had advanced disease living in close quarters, you know, so, this this may not be a new paradigm, it may actually be the same paradigm playing out in a specific way. Your audio is out.
Sorry, what’s your what’s your take? What’s your summary of this article then?
So my summary of this article is that there’s a really high number of people who got infected pretty quickly. This is a high infectivity virus. But of those, the vast majority of them did not get that sick, thankfully. But of the ones that did get sick, there are significant number who became critically ill and some who unfortunately even died. So it is serious. We do have to take it seriously and maintain social distancing and do all the things we can to flatten that curve. But if you do get sick, there there for most, you will you will see the other side okay.
Yeah. So the other articles that you chose to talk about how does this play into this one?
So the second article is answering the question of what is the true denominator? Right? How many people actually are infected, right? We’re talking about these rates of infection. But the problem is in just about every spot in the world, we’re choosing to because of limited resources, we’re choosing to test people who are high risk- the patients who come in with significant symptoms, right? It’s not just simply that you show up and say, hey, I’ve been coughing for a few days, I want to get checked for COVID. If you do that, you’re gonna get turned around and told to go home and self quarantine, right? The ones who are sick, having trouble breathing, high fevers, those are the ones that are getting tested. So unfortunately, we’re creating our own sample error. And this is this is playing out the world over so the natural follow up question is, what’s the true denominator how many people actually are infected and they there’s a study called the estimates of undetected rate among SARS CoV2 infected using testing data from Iceland. And they chose to look at Iceland in particular, because they have a sort of a dual phase program. They have the same exact setup as we all do, where they’re testing nationally high risk individuals through their national university hospital system. But most of the population again, so they do throw in there, there still is a little bit of sampling bias, but most of the population is eligible for voluntary testing from a private company called deCODE genetics. So because they have a much larger sampling size, this became a good spot to try and figure out what that true denominator is. You know, like I said, there are some limitations because even though most people did fall into the ability to get or eligibility to get tested through this private company, they didn’t get everybody. But they did get some nice demographic data. 44% of the people who went and got voluntarily tested had some mild sort of cold or flu symptoms. So these were not asymptomatic individuals by and far, many were, but not all. And based on their data, the results of both the national testing and the private testing 88.7 to 93.6% of infections are undetected infections. They’re the ones that we don’t know about.
Say that one more time. Slowly.
Yeah, so they created a range, they didn’t have an exact number, but somewhere between 89 to 94% of all true infections. were being undetected to sort of flip that around the other way-we’re only diagnosing about 6% of the true infections. So we’re, we’re leaving a lot on the table by design.
Yeah. And so and I have to believe these guys. Now I know that your undergraduate degree was in economics, correct?
Yeah, among others,
Among others. Well, I got the biggest kick out of reading this article because looking at the math that they’re doing, this is basically my insecurity nightmare. I’m like, I’m not walking around whenever I’m like really stressed, I don’t have nightmares about being naked. I have nightmares about trying to take a calculus test or something. These stats are stunning. I mean, it almost looks like artwork, what they’re doing, so I have to believe them that they’re right. Because, it’s pretty crazy.
Yeah, it took me a little bit to read it and make sure that I understood what the numbers meant. And that and as we discussed it, the the first time around when we’re talking about this article, I actually overstated what they were trying to say. Because I misunderstood some of the numbers. So after reading it two, three or four times, it made a little more sense to me. So…
Well, I’m glad it made sense to you because it just I just looked at this and it just looks like I’m, I’m, I feel like I’m on goodwill hunting with that chalkboard and trying to solve the, whatever equation it is these things are they did a lot of math on this to extrapolate this to a nationwide thing, which means they had that they had the test. They showed how many people were being missed, and then they extrapolated it to their census.
Right, and just to explain what I mean by numerator and denominator in this situation. So the numerator or the number above the line are the number of people who have COVID infection. The denominator is the population, right? So one point of bias in a study like this, that you have to understand whenever you’re reading this, is you have volunteers by people who said I’m going to go get tested. You might have plenty of people who said, I’m fine. I’m not getting tested. I don’t want to know.
I’m not getting paid. So why should I drive over?
Yeah, exactly. Maybe I’m gonna get exposed because I’m hanging out with all these people. So the true denominator, the population might be underrepresented. So even though we’re saying that 6% of the people are the true and 94% are being undetected, might actually be a smaller number. But I think what you can take away from this is that we’re only seeing the drop in the bucket. The question is, how much is that drop?
So we have to figure out how much of the population has already been exposed. Because what it comes down to is what this study is telling us.
Yeah. So how do we get to the denominator here? What are some different ways to do it?
So probably one way to do it, which hasn’t been done yet, but is under discussion is random testing, right? Because if here you’re saying the selection bias is in that only certain people are coming to you…well, maybe if you go to them, you’ll be able to get a better sense of a smattering or a cross section of the population. And this has been one of the discussions now in the media, about in the United States, in particular about certain counties, getting access to testing, and setting up random testing protocols. And some of the discussion has been about mobile command centers, right, going out to people so that you decrease that selection bias.
So if you’re going to do something like that, it has to be a test that is easy has to be a test that is sensitive and more important to be…
Gotta be cheap.
Gotta be cheap.
It’s gotta be cheap. You have to have a certain level of sensitivity and specificity. Can you explain to everybody what sensitivity and specificity is?
Sure. So harking back to my medical school days, I remember this little, this little memory game that you play to try to remember the difference between sensitivity and specificity. And we call it spin and snout. So when you talk about sensitivity, sensitivity is the number or the percentage of ruling out the disease, whereas specificity is ruling in the disease right, so we want to talk about it. In other words, or another part of that is, if you have a positive test, do you actually have it? What are the chances that that that’s a true positive, and you actually are infected? And on the flip side to that, if you have negative exam, how confident are you that you don’t have it and we didn’t miss the fact that you have it?
Yeah. If you want an update on this, I went to Peter Attia MDs website and he does a whole thing on how to get people back up to speed with this epidemiology and in stats kind of terms, because it is confusing, but bottom line is, if you have a high sensitivity, high specificity, it’s a good test.
Is what it comes down to.
Yeah, any screening test you want to have, you want to know that it’s picking up the right people and casting away the right people and not telling people incorrectly that they have something. And also not letting us lose the ones who truly have who we don’t know.
Yeah, so think about this: if we do a test, and it says that I am positive for the antibody, meaning that i have IGG, and it is a false positive, then I go around the world thinking I’m, I’m bulletproof, and I could be infecting people. And then I put myself at risk. If we take a test, and it is a false negative, then we’re putting people in saying you don’t have this yet, go back in your home, keep quarantine, you can’t go back to work and all this other stuff. And that’s kind of what we’re going to get into right now.
Right. The risk of it is it’s the antithesis of social distancing.
Yeah, yeah. So you pulled up another article, or this is the diagnostic value and dynamic variants of serum antibody, Coronavirus disease. What was your take on this article?
So it’s an interesting article for sure, but I would caution that when you read it, kind of similar to the monkey article, which we’ll discuss next, the numbers are small. And you always have to be careful whenever you’re trying to interpret data in a small data set, because the smaller it is, the higher the risk of bias, the unintentional but but bias in the numbers. So it was the first published data that compared the PCR testing, versus well, rather, they took a bunch of patients who were all being tested for COVID with PCR, and the ones who tested negative and therefore were known to not have COVID right? We might walk around thinking we don’t have COVID. But we don’t know whether we do or don’t since people can be asymptomatic for so long. These are patients who we know don’t have COVID and use them as the control group compared to the PCR positive patients who are known to have COVID. And what they did is they then looked at those patients, and tested IGM and IGG to know who makes it how much and whether or not that can happen in the control group as well, to say it another way: if I’m infected with COVID, and I make IGM and IGG, but somehow someone in the non COVID group does it as well, how valid is that to know that I’m immune?
Right? The idea is that only the people who have been exposed and therefore can protect themselves should generate that immunity or should we should be using that as a marker for the immunity so a couple interesting things are that some people that’s an important point did not make IGG. And on the on the control side, three people did make IGG. However, a big caveat in that is that they made it a much lower titer. So they had a they made some IGG but less IGG than those people who were exposed to or had active viral replication. So another point I’ll make is that this is a it’s a very interesting article, and it’s been discussed a lot. It’s a journal pre proof article. So it does mean that it hasn’t been published yet. But the journal has accepted it for publication. It’s already been through peer review. So this is still a very legitimate publication. So there were in the two in the two sides, there were 43 patients with PCR positive confirmed COVID-19 and compared to their control group of 33 patients who were these rule out patients, patients who came in they, they thought they were sick and potentially had COVID, but the PCRs were never positive. And another good point I would make is, these patients have multiple testing points. They were tested at multiple times. So to decrease…
Multiple times in the same location, though right? Nasopharyngeal swabbing.
Right. So so they’re trying to control for that. Well, what if there, we missed it the first time, right? So then they’re going to repeat it again a few days, which gives you a trend over over time. So but but I agree, the point being that it was all nasopharyngeal swabs, I think oral too nasal and oral, yeah. So limited to one type. So you can still you still have that bias of did you not do it adequately? You would hope it’s only and they don’t mention this, whether it was or not, that’s it only a certain few people who are doing the testing, so that you’re controlling for variables of maybe some who do it better than others. And maybe get better sampling. So they don’t mention that but because it was all done in one site, you have to assume for the moment that there’s only a few people who are doing the testing, so they know what they’re doing. The sensitivity, I’m sorry.
Oh, I was just gonna say what I found interesting in this is this suspected infected patients were discharged from the hospital once the results of two time molecular tests in 24 hours were negative. So basically, in my interpretation of this understanding, now, the limitations of the testing, they may have sent people out that were not PCR positive, that could later develop IGG and IGM. So when you get into the sensitivity and specificity of this, it is this is this is as good as we can get. But it may change as we gather more data.
Right. Right. So the sensitivity specificity for IGM and IGG to diagnose an infection was 48% and 88.9% of sensitivity. So IGM was 48 and IGG was 88.9 and 100% and 90.9% specificity, right? So, in other words, if you had IGM, that meant that you had the infection because it’s an acute marker that would only happen if you’ve been acutely infected. But if you didn’t have IGM, it did not mean that you weren’t infected. Right? So just to sort of wrap your head around that it’s really really good as a marker if you have it, but if you don’t have it doesn’t give you a whole lot of confidence.
I love how we’re doing this because the media just glosses over it and just confuses people. My patients are calling me all day long asking all these questions.
Yeah, it’s important to understand what it is right and the media doesn’t kind of give you a primer to explain the background of what they’re talking about. They just give you a two minute soundbite and you’re sort of left on your own to interpret it.
Exactly. Sorry to interrupt go on.
No no problem at all. So they found that as you would expect, given that IGM comes first and then IGG follows IGM titers would rise and then they’d fall because as you get over the acute infection, you no longer need your IGM. But the IGG titer would rise until they were 100% in those people that produced IGG, right, so the ones that were making IGG made them. It was always higher, for whatever reason, and this, this is not clearly explained, but the titers of IGG were always higher than the titers of IGM. I think it’s just something to sort of keep in the back in your mind just because we don’t yet know what titers means. So it’s just getting all the data you can and trying to figure out what it means going forward is important. The IGG positivity rate was over 90 was up to 90%. And it didn’t really change it once…from the time that you were virus positive with PCR to your post infectious viral negative state. But the titer of IGG was almost double once you pass the infection, which that starts giving you that glimmer of hope about immunity, right. Because as you’re fighting the infection, it’s not as important to remember, you need someone who’s actively on the front line. And that’s where your IGG IGM helps you. But once you’re done, you want to you want to remember that you want to be stone cold, you want to know that if you get any kind of exposure again, your body is ready to jump into action.
I mean, this is just getting back to your analogy, what you have are some special, we’ve got special ops that have a picture of something and they say when this thing shows up, kill it before it does anything. And all they do is wait. That’s what the IGG is doing is waiting for the possibility of seeing that and they just get after it.
Right. So just to sort of talked about the the the sort of underside of this, three of the 33 patients in the control group are IGG positive, right. So that that makes you step back just a little bit in saying that, well, if you got the IGG, you’re good, right? But the important thing is that the titers were lower. So they talk about the the units, the units of positivity for this assay, were 1010 units per milliliter, and those that were in the control group had no one higher than 15. So they were sort of a low kind of weak positive compared to those in the active group, who all had much higher at least twice the normal titers. So that might be an important piece of information, right that not only figuring out who is IGG but how much maybe there’s a threshold value that confers immunity. 27 of the known COVID patients has IGG testing during the infection, three of them didn’t make any IGM or IGG, so whoever didn’t make IGG also didn’t make IGM. It’s interesting because the way I look at this is probably different than almost everybody who reads this article. I’m sure everyone who looks at it and it’s valid is gonna say certain people don’t make it. What I look at it is that’s kind of an amazing thought. 10% of the people didn’t make IGM or IGG and still fought off the virus somehow. So there’s some sort of mechanism of secondary mechanism to be able to successfully defeat the virus beyond this, the typical virology that we know about.
Well, I okay, so point CounterPoint. What if they’re catching this person at a point in time where the IGM is dipped down and the IGG is coming up? So you’re going to have two overlapping…
Right you’re in a window right?
You’re in a window. So did they check them at the wrong time?
Right. That’s a great thought. The catch is they did this at least three times separated over several days, going all the way out to 28 days post infection. So I suppose it’s possible, but given what we know about the curves of IGM and IGG, even if you think maybe you were shifted over in time, you should have caught it somewhere. And maybe you don’t get one maybe maybe you only get one, maybe you don’t get both. We should have seen something.
So what you’re describing is that people that had an innate immunity, but they did not develop the adaptive immunity. In other words, their body’s initial response may have been effective enough, but they did not develop. So those people, the question is, can they be reinfected? Will they have a possibility of the virus, having a resurgence and come back and hit them again? Interesting.
Yeah. So that’s the discussion. The discussion is do these people have immunity now, right? If you’re making the supposition that you need IGG to have immunity, and these people can’t make IGG, are they subject to reinfection? I would argue it goes even deeper. We’re trying to get serum right draw blood from people who have had infection, to look at IGG titers to understand how much is needed for immunity. How much is enough? I would want to know about the serum of these people. What makes it different? Is there something is there a different way that we could be looking at this to confer immunity? Is there something else that maybe can work in concert?
Hmm. So here you have the subset of people which is a significant amount and it’s small study 10%.
So a subset of people that survived did not produce the antibodies, and going forward and some sort of weird society where we have to have immunity passports to go around. Peter Attia was talking about when you get bracelets for people to show I’m this I’m that which is gets a little bit big brother-ish and it gets real scary thinking about that. But there could be a subset of people that will not produce antibodies, but their innate immunity prevents them from getting infected. And we can’t withhold them from going to work. We can’t stop them. That’s a fascinating observation. I did not see it that way. I was I was of everybody else that read this article and just went 10% didn’t produce it. So…
Yeah, but it’s going back to what you said. I mean, this is this is why you gotta analyze articles and you got to have multiple people looking at it because people can read articles and have the same data and draw completely different conclusions.
Much like everything else.
Much like life. Let’s, let’s jump into the sort of article the day before we start talking about the pros and cons of these immunity badges or licenses. The we want to talk about the the Macaque monkey study. And…
What’s the only reason why I threw that out first not to describe it, but it just shows why you have to pay attention and read the articles yourself and have two different people interpreting it differently.
Right. So it’s a very small study. It is pre-publication, and it has not been peer reviewed. So it is being touted as kind of the be all and end all for the discussion about immunity. But it is a very much in the pubescent stages of research.
It’s fascinating because I heard Dr. Fousey on a CNN news thing. We believe that because of the macaque monkey study, and then I heard Dr. Hotez go on Joe Rogan. He said we’re we’re sure that we can develop immunity because there was a macaque monkey study and everybody just keeps saying the macaque monkey study the macaque monkey study. I don’t think there’s another one out there. I tried to look I didn’t find one. This is the one that I found.
Yeah, no, I did the same. And, you know, like I said, it’s it’s fascinating but has to be taken with a big grain of salt. So let’s, let’s jump into it. Yeah. The whole reason why they did this study, it was prompted by reports of patients who have been discharged and considered cleared from virus and then they were coming back with reinfection or raising that question of is this a relapse or reinfection? You know the difference being relapse, that you have the same infection you did and you just got sick again, versus reinfection that you actually got sick a second time. And it implies that there’s no immunity.
So they followed four rhesus monkeys. And they infected all four of them. They actually gave them inoculations of the SARS CoV2 virus and they developed a lot of those typical symptoms that we’re seeing in people around the world. Once they the symptoms were alleviated, and the viral replication as judged by, as you said, respiratory and animal swabs and PCR had all subsided, all appropriate antibodies, so IGM and IGG and there’s actually a whole bunch of other ones we didn’t even touch on. They were all there, right? So they sort of validated the subset of the four monkeys by saying these all created everything appropriately and therefore, we can look at them for some information. They euthanized one of the monkeys from the start. And they basically took various organs and tested the organ tissue to see if they would be PCR positive and they found evidence of viral replication all over the body: nose, pharynx lung, gut, spinal cord, heart, skeletal muscle and bladder all displayed PCR positive COVID at the time of infection. Two of the Monkey so now you’re down to three monkeys. Two of the monkeys were then re challenged, where they inoculated them a second time with SARS CoV2. So again, this is talking about reinfection, not reactivation. All the monkeys. So all three monkeys were then tested for viral load. And none of them were found to be PCR positive. So the one monkey who was left as a control and the two monkeys who were re inoculated, none of them had PCR positive disease at this point. They then took one of those reinfected monkeys euthanized that monkey as well did the same kind of testing, looking at all those different organs and trying to see if they were PCR positive and found that they were negative in the tissue
In all of the tissue and that’s pretty shocking how disseminated that virus was in the first one. So that’s impressive.
Yeah. So very interesting data very interesting information throws out a lot of very positive possibilities here now for infection and the ability to fight off reoccurrence. But, gotta gotta to be very skeptical, right? I mean, for monkeys, you know, they all displayed antibodies. And from the last study we looked at, we know that that’s not true, right? If you have those 43 patients, you know, sort of looking at that and say, if I only took four of them, and looked at those four people, and they all made antibodies, I draw conclusions from the study. Well, I guess everyone makes antibodies, but we know that’s not true.
Yeah, that is a that’s a very interesting analysis on a study that’s being thrown around in the media like crazy. Nobody’s talking about that. And if you read their abstract, I’ll say it one more time, like I did. It seems like they had 1000 monkeys. So great job on interpreting that and getting into the details and you know, having the time during Passover and stuff to go into detail like that, because…
Yeah, I mean I just got a cup of coffee, got some matza just sat down and went through all these studies.
Well, you’re better than me because it’s it’s like drinking out of a firehose, I try to sort through which ones I’m going to take a deep dive in. And I like doing this with you. I like doing these point five episodes where we do do deep dives. And, and you challenged me to look at some of these studies. So I had a long interview yesterday with Matt Atwood, who’s the CEO of a company that has access to rapid point of care IGG, IGM testing, where they actually have the ability to take a finger prick like a glucose stick, and then you can see if you’re IGM positive, IGG positive. And it’s interesting because you had also sent me that study and he sent it to me about the Laredo was it El Paso or Laredo?
Laredo. Yeah. Why don’t you go ahead and tell everybody about what kind of a fiasco that was?
Well, the short version is best intentions for sure. The city of Laredo ordered, I think half a million testing kits to try and stimulate their economy, right? They wanted to…
Just to clarify, it was half a million dollars for 20,000 kits. So they spent half a million dollars.
Oh, thank you. And they basically wanted to go out and test everyone and see if they could figure out who’s IGG positive and say that those people can go back to work and sort of get Main Street running again. And it turned out that the kits were not quite up to snuff. And unfortunately, it was a bit of a loss for the city of Laredo.
So people are asking like, well, how is this happening? And I just want to just clarify this a little bit. It’s what happened in China is exactly what President Trump is doing here. When they realized that they were behind the curve on this, and they needed masks and gloves and testing kits, China went to facilities like toy manufacturers, and they went to different manufacturing companies and said, you’re going to stop production on that. Here’s your parts to make masks, here’s your parts to make test kits. And here’s how you’re going to do it, figure it out. So these were not already pre designed medical locations. They were doing what the government told them to do. And then they made a bunch of these things. They shipped them out, the US bought a bunch. And then we realized…a lot of these things are not effective, and they shipped them back, discussed possibly suing this and so then China had to step it up and be like, well, we can’t just force you to do this. Well, as it turns out, there’s a bunch of that stuff still floating around in the US. And there are some companies that are saying, well, I’ll just repackage it and sell it. And that’s kind of what happened to these guys. So for instance, our group, I got an email from somebody in our group that said, we have access to these IGG kits. And I looked into it and as it turns out, I, we contacted the manufacturered for company and they’re like, yeah, we got a bunch of those kits that are not valid because they’re not certified. So a company out of Houston bought us. And then they contacted our group and offered to sell it for dirt cheap. And it’s, you get what you pay for, I guess.
Yeah, I mean, it definitely was a great deal. They were super cheap, but…couldn’t really do much with them unfortunately.
And then from as doctors, imagine, if we tested people with an unreliable test, and we said look, the we all you and I carry liability all the time, but at least we can say this test was FDA shown to be this the sensitivity specificity, so there is a 95% chance that the information I’m going to give you as correct, you’re going to assume and I’m going to assume that there’s a slight possibility that it could be wrong. If you’re positive, then what we’re going to do is send you for another more distinct test, which costs a lot more money, it’s going to be serum and that’s kind of where I think this needs to go. You do mass screening, like we did with well, quite honestly, HIV, I remember we did the rapid HIV and then you do the the Elisa test or whatever it was afterwards to try and really determine what’s going on. So we have these people that if we can screen them and get the IGG IGM and then do a secondary test and prove that they’re that they have antibody. Then now the next discussion is alright, Dr. Akerman. We’ve got IGG people running around with their badge saying I can work I can do things. What are the limitations of that?
Well, I think there’s there’s some issues that are…and I want to be clear, I, I agree that we need to figure something out. And this opens up a world of possibilities. But we’re in the infancy because there’s a lot of questions that haven’t been answered. So first of all, do we know are there specific titers that confer immunity? Because if there are, a simple little blood test that just says yay or nay might not be enough, right, we have to make sure that all the manufacturers are assessing at the same level to call that positive. Right? If we know that you need titers of 20, let’s say, and you have a test that calls it positive at 10. Right? You’re creating a ton of false positive results. So you got to be really, really careful about that. And, you know, again, we haven’t answered that question just yet. Is there the possibility of reinfection? So what does immunity mean? Right, we have all this data now coming out of South Korea because they’ve had over 100 people come back who were discharged from hospitals being told that they’ve cleared infections and that they’re no longer sick. And they’ve actually come back and have retested positive by PCR. But what does that mean? Does that mean that they’ve gotten the infection again? Does that mean that maybe they were kicked out too quickly? Maybe that their viral loads had dropped? Or they simply had sampling error. Right. When they got tested the day before, maybe they just didn’t pick it up in the right spot.
Exactly. So the other articles that you talked about bringing that up, but it is fascinating, because this is just case reports coming out of South Korea. And everybody that looks at this nobody wants to believe that you can get reinfected like like that is like the the that is a doomsday prediction. So we’re going to say, look, the macaque monkey study which you’ve kind of already said take it with a grain of salt, the size of Gibraltar and then this the IGG so it’s the good news is looking at SARS CoV from 2003…they those people have been looked at years later a decade later, and they’ve maintained their immunity. Now, I challenge that there are some possibilities that these tests, although they’re COVID-19 specific, what if some of these people test positive because they have IGG to SARS CoC? That was right. That was an argument that a PhD brought to me. Because he did…I was on the I was on a zoom call yesterday with a virologist who did the original research on that and he’s like, doing this he’s like, well, we’re seeing that some people can develop antibodies which made a mistake that being said, I don’t know that these fingerpricks there was a article that just came out today, that detection of SARS CoV2. They found the binding protein to be specific so the test you can still do a test specific for SARS CoV2. And I’m not sure if these IGG IGM are can actually do determine that. So more studies are gonna have to be kind of vetted for this.
Yeah. And I think that, you know, it begs the larger question, what do you do with those false positive results, especially if you don’t know that they’re falsely positive? Right? Again, like you mentioned earlier, patient could be walking around thinking that they’re bulletproof. And it turns out, not only are they not bulletproof, they might now get the infection and pass it along to everyone. It becomes part of the larger discussion about herd immunity, right? Because if we’re getting all these people that now are immune, and we’re putting those people out in the population, then the people that they’re coming across are not as at risk. Right, but we don’t know what that critical number is to create that herd immunity.
Yeah, absolutely. There’s a lot to discuss and clearly you and I can get together and try and vet some of this stuff as the literature comes out. I appreciate you taking the time to do that. Unfortunately, it’s starting my telemedicine time right now. But where can people find you Dr. Akerman?
The easiest way is to check out my website. There’s a lot of information about my practice there and I’ve been trying to update my blog with useful information. And that’s at www.stuartakermanmd.com.
Yeah, so clearly this is a super smart guy watch his videos he actually has a pretty good sense of humor and has some pretty interesting stuff and his the videos you’re sending me your kids which we will not discuss today was pretty pretty funny also so quarantine in the Akerman house should be a some sort of big brother type thing where it’s just funny it’s hilarious
Yeah, we’re thinking of pitching it to the networks in the near future.
Alright buddy, I appreciate you taking the time so go to stuartakermanmd.com You can reach me at on Instagram at kbmdhealth and kbmdhealth.com for the website. We are currently oh good news, we now have brought a leak on our website. So BrocElite, Atrantil, and CBD. We’re having some pretty good results with that we can get into that later but today was much more of an academic discussion. Thank you so much, Dr. Akerman for joining now I got to get to the real job.