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Testing for COVID-19 with Dr. David Brady: Rational Wellness Podcast 157

Dr. David Brady discusses Testing For COVID-19 with Dr. Ben Weitz.

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Podcast Highlights

8:13  People with chronic diseases like obesity, hypertension, coronary artery disease, and a host of chronic conditions fare more poorly with COVID-19.  And in the US we have a lot of people with one or more of these chronic conditions and it would be good if we took this opportunity as a wake up call and to turn our public health policy and our health care system to focus on reducing obesity, diabetes, hypertension and other chronic diseases.

10:50  This virus seems to have a big cardiovascular component that distinguishes it from the seasonal flu.  We are seeing endothelial inflammation, changes in hemoglobin structure, changes in the ability to perfuse tissues with oxygen while still being able to get rid of CO2, the happy hypoxia thing, the COVID toes, and the micro-coagulations. Some of the emergency rooms are prescribing blood thinners routinely to cut down on the clotting that we are seeing in patients with COVID-19. Functional Medicine practitioners are putting many patients on fish oil, nattokinase, and lumbrokinase prophylactically.

12:45  There is some amazing data on the benefits of some natural agents like vitamin D and zinc helping with COVID-19.  Dr. Brady has gotten calls from doctors at ICUs in major hospitals in New York and Massachusetts about the best procedure to a high dose IV vitamin C drip and about blood ozone and UV treatments. And the vitamin D level has turned out to be the best predictor of who has a very bad outcome and who does okay when exposed to SARS-COVID-2.  When there are no effective drugs, doctors and patients have turned to natural agents like vitamin D and botanicals that help to strengthen the immune system. The most effective drug for COVID-19 at this time is Remdesivir, which did not reduce mortality, but reduced the length of the hospital stay by 2-3 days, while zinc when added to hydroxychloroquine and azithromycin reduced mortality by 49%!  And Remdesivir costs around $5000 per month, while zinc will cost you about $20.  We know that nutrients like quercetin, resveratrol, and ECGC from green tea can block viral docking and penetration into the cell. We know that zinc, vitamin D, high dose vitamin C, and botanicals like elderberry, astragalus, and andrographis have antiviral properties. And melatonin can reduce the potential for having a cytokine storm.

18:53  Testing for the SARS-COV-2 virus, which is what causes COVID-19, includes the nasopharygeal swab which is stuck all the way in the back of the nose and then twisted around, which is then analyzed through pcr testing, which amplifies the DNA, which is the gold standard. A number of labs are offering this test, including Diagnostic Solutions, which Dr. Brady works with. There are rapid tests using the np swab and then placing the swabs into an expensive machine from Abbott or several other pharmaceutical companies, which then gives results in 15 minutes, these do not use pcr, so they are less accurate. There are also tests using an oral swab or saliva, including some at-home tests, but these tests are not as good at getting enough viral load and therefore are not as accurate.  The original CDC test didn’t work very well because it only targeted two end proteins on the virus. Diagnostic Solutions Lab (DSL) developed a pcr test that used these two end proteins along with the spike protein and an envelope protein that has now become the standard. The literature coming out of China indicated that you can find the virus in the GI tract for up to 6 weeks after recovering, so DSL has developed a stool test for the virus, which has advantages in that the patients can do it at home and mail it in, so you don’t need a healthcare worker in PPE to get the sample.  In fact, DSL has been running the nasopharyngeal swab tests for the virus, stool tests for the virus, and IgG and IgM antibody testing and they have been correlating these tests to better internally validate their tests and to understand this disease.

30:25  When it comes to the accuracy of testing for the virus, doctors often ask about the sensitivity and the specificity of the testing.  PCR molecular targeting methods used in such testing has virtually 100% sensitivity and specificity, but the limiting factor is getting the proper sample to test as well as the progression of the disease and the level of the virus in the tissue being sampled.  If the person performing the nasal swab doesn’t do it optimally, you may not have virus in the sample. And it depends where the patient is in their disease process. The viral load is highest on symptomatic people in the first five days of symptoms, and then it starts trailing off. So it depends when during their condition that you perform the test. The test may have 100% analytical validity, but the clinical validity may be lower for the reasons just mentioned.

36:06  The difference between the rapid testing and the PCR testing for the virus is that the rapid testing is not amplifying the DNA, so you need a lot more viral load in the sample to see it.  If a rapid test is positive, you can trust it, but there may be a of of false negatives. These rapid tests are meant for point of care diagnosis, like in an ER or an ICU.  Such tests won’t be a good way to say screen NBA players before games because if they are infected but not symptomatic and don’t have a high viral load, you won’t be able to catch most of these cases. And such tests won’t work that well for screening patients coming into work because the machine for testing is expensive, there are few available to buy and you can only load one sample at a time.  And it takes 15 minutes to get results and then you have to wait 5 minutes for the machine to reset before putting another sample in.  This makes it impossible to test 100s of employees in less than many hours, such as at a meat packing plant, or even 10 employees at a restaurant, since even that would take a few hours. If they are not symptomatic and are infected but have a relatively low viral load and they are likely to be a false negative.  Here is a paper discussing PCR vs rapid testing for the virus, as well as the proper technique for performing the nasopharyngeal swab: Laboratory Diagnosis of COVID-19: Current Issues and Challenges

40:04  Antibody testing also has this mix of blood spot, quick tests as compared with a blood draw and using a quality ELISSA antibody kit.  The rapid antibody tests are lateral flow tests and they are almost like a pregnancy test for HCG where you pee on it an it turns a color. It has poor sensitivity and requires a high level of antibodies.  When it comes to antibody testing, there is also a possible issue of cross-reactivity with antibodies formed to other coronaviruses, such as SARS and MERS, and 229E and OC43, which are two of the coronaviruses responsible for the common cold.  On the other hand, the original SARS from 2003 and MERS  are not around any more so you are not likely to see a lot of false positives to them.  The serum PCR molecular testing for antibodies is much more targeted and exact by nature, so it will be more accurate than the rapid testing.  On the other hand, we are still studying this new virus, SARS-COVID-2, and trying to determine what exact level of IgM means that you have an active infection, what exact level of IgG antibodies confer immunity, how long these IgG antibodies will stick around for, etc.  We have pretty good evidence that infection with SARS-COVID-2 does result in antibodies in most patients: Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019.  

47:01  After an infection with SARS-COVID-2 or any virus, IgM antibodies are the first to form usually after the first week of infection, while IgG antibodies will typically form about 2-4 weeks after infection.  The serum or plasma antibody tests are more accurate than the rapid tests using blood spot.  Here’s an article discussing this: Antibody Tests in Detecting SARS-CoV-2 Infection: A Meta-Analysis.  This article from the Journal Of Infection shows the peak of IgM antibodies after 3 weeks and then fading with IgG antibodies peaking after 4 weeks and continuing: Profile of specific antibodies to SARS-CoV-2: The first report.Here is another article showing when IgM and IgG antibodies form after SARS-COV-2 infection: Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020.   

 

 

                             



Dr. David Brady can be contacted at his website https://drdavidbrady.com/ You can check out the website for The Fibrofix book that he wrote at https://www.fibrofix.com/ You can get information on the swab, antibody, and stool tests for COVID-19 from Diagnostic Solutions at https://www.diagnosticsolutionslab.com/tests/covid-19-sars-cov-2

Dr. Ben Weitz is available for nutrition consultations, including remote consults via video or phone, specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111 or go to www.drweitz.com. Phone or video consulting with Dr. Weitz is available.



 

Podcast Transcript

Dr. Weitz:            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. To learn more, check out my website, drweitz.com. Thanks for joining me and let’s jump into the podcast.  Hello, Rational Wellness Podcasters, Dr. Ben Weitz here again today. Thank you so much for joining me.

So today we will be discussing some of the controversies and confusion about testing for COVID-19 with our special guest, Dr. David Brady. So when we talk about testing, we’re referring to both testing for the virus and testing for antibodies to the virus that causes COVID-19, the SARS-COVID-2 virus. There seems to be quite a bit of controversy over how necessary testing is, how accurate it is, what type of testing is most helpful.  And when it comes to antibody testing, whether it’s valuable or not, do antibodies provide protection, how accurate is it, I’ve asked one of the brightest people in the functional medicine world and someone who is involved with developing some of these tests, including I think the only company that has a stool test for the virus, Dr. David Brady. Dr. David Brady is an internationally known speaker, doctor of chiropractic, naturopathic physician.  He’s also a professor at the University of Bridgeport. He’s the chief medical officer for Designs for Health, and also for Diagnostic Solutions Lab. Dr. Brady’s a prolific writer, having published a number of scientific papers. He’s contributed chapters to numerous textbooks. He’s written a number of books, including his latest is the Fibro Fix published in 2016. Dr. Brady, thank you so much for joining me today. 

Dr. Brady:            Hey Ben. Thanks for having me on again. And I think you’ve been trying to lasso me to do this for about four… I don’t know, at least four weeks, maybe six. But with COVID craziness, it’s just been difficult, but here we are.

Dr. Weitz:            Yeah. Good. And by the way, the information on testing seems to be developing by the day. But before we get into our discussion about testing, you have another title. You are the chief myth buster about bogus concepts circulating through social media related the COVID-19 in the functional medicine world. And you’ve recently spoken out about a number of myths including whether immune-strengthening herbs like elderberry can increase the risk of cytokine storm. Are there any myths that you’d like to comment about now, because there are quite a number?

Dr. Brady:            Oh, it’s quite a minefield, as you know, Ben. And I don’t know if I’m the chief myth buster but at some point I’ve-

Dr. Weitz:            I’ve given you that title.

Dr. Brady:            Yeah, thank you. I’ve had enough sometimes and I’ve used a graphic a couple of times with some blog posts I put out there, or some social media posts with some guy pulling his hair out, just because I couldn’t take it anymore, and I couldn’t answer the same question via email 200 times in a day. So I put something out. Yeah. A lot of it started with that, “Stop your elderberry, and vitamin D, and vitamin A. It’ll cause a cytokine storm,” thing. And then, “Don’t take ibuprofen, but this is fine.”   Then the latest thing I kind of flipped out about a little bit was everyone just comparing it to the flu, and the lethality numbers, without contextualization on a whole lot of other ramification and factors of what’s going on with SARS-COVID-2 as compares to seasonal influenza. It’s just staggering to me that even healthcare providers, practitioners who supposedly have had some schooling in epidemiology, and infectious disease, and laboratory diagnosis go off on some of the tangents that they go.  But I know these are strange times and it’s a very charged subject, and there’s a lot of raw emotions. And it’s something none of us have ever lived through before. So we’re all going down our little rabbit holes sometimes.

Dr. Weitz:            It is true and it’s amazing how even discussions about health seem to break down along partisan line, which you wouldn’t think that that would be the one topic which partisanship would have no role to play. 

Dr. Brady:            No, these days nothing’s off the table when it comes to that, unfortunately.

Dr. Weitz:            Yeah. And when you talk about the numbers, you’re hearing recently all the numbers are inflated, and people who really have died of some other cause are being labeled as dying of COVID. And we’re doing that to purposely inflate the numbers. And why would we want-

Dr. Brady:            That goes back to the way Medicare constructed the billing and things like that. But a lot of that is taken out of context. And I don’t know if any of that’s going on. But I’ll tell you one thing, Ben. I live in a small town in Connecticut. We have 80 dead people in my town. They’re not statistics, they’re not made up COVID deaths. I don’t remember the last time 80 people in my little town in Connecticut died in six weeks. Okay? Not through seasonal flu, not through calling the diagnosis something it’s not. I’ll tell you what doesn’t lie. Body bags, they don’t lie. So I’ll just leave it at that. 

Dr. Weitz:            I’d also like to make a comment, which is that it’s easy to say, “Okay, this person who now is being labeled as dying of COVID-19, really died because they had heart attack, or really died of complications related to some other disease, usually a chronic disease.” But it’s never the case that when someone dies, they die of one thing. There’s always complicating factors. And when someone dies, we don’t say, “Well, this person died 40% from coronary artery disease, and 30% from diabetes, and 20% from hypertension.” We give it a diagnosis, the one that makes the most sense. And that’s what’s being done here. And I don’t think there’s anything sinister going on.  I’d also like to say it’s not the case that Bill Gates is not the evil genius along with a number of other well known people in the epidemiological world, who are trying to force us into mandatory vaccines and a bunch of other- 

Dr. Brady:            Well, listen. I don’t pretend to know every potential sinister plan out there because all kinds of organizations with power, regardless of what side of the political spectrum they come from, what their agendas may be, the ones that have been around a long time and are successful probably all follow the same adage, which is never let any crisis go to waste. So I’m sure they’re all trying to further various agendas. But that’s sort of above my pay grade. I just look at the science, I look at the data we have, I look at what’s happening in front of my face, and try not to go off on conspiracy theories, agendas, political bents.  Hey, I’m not saying anybody who has various opinions along those lines are wrong. I’m not saying public authorities have handled this all correctly. We can have reasonable debate on how to respond to a pandemic like this. There’s different approaches, different opinions, but there’s some core things that are reality, and that is that this is a serious condition. There’s lots of dead people. And it’s not the seasonal flu. It’s not the same. It’s not impacting society and the healthcare system in the same way. Who knows about all those other things. We’ll probably know a lot more in retrospect down the line. And then there’s a bunch of stuff that we’ll never hear about because we don’t get told everything. 

Dr. Weitz:            Right. Well, one thing we do know is that people with chronic conditions, like patients who have hypertension, who are overweight, who have diabetes, who have coronary artery disease, who have a whole host of chronic conditions fare much more poorly with this disease. And I think it would be nice if we put some real focus on doing something about our society that has all these chronic diseases, because if we had a healthier society, whatever condition we could frank, whether it be this particular virus or any other situation, we’d be a lot better off if we had a much lower chronic disease burden. And so, I think that that’s something-

Dr. Brady:            Yeah, there’s no doubt about that. And those are some lessons that we better learn from this. I mean, as a modern culture, we tend to have very short memories. But there are some big lessons that come out of this, and I hope it’s not just the functional integrative kind of healthcare providers that have this imprinted or maybe solidified in their mind, because they’ve kind of been in this camp to begin with. But I hope more conventional people, more people with regulatory responsibility, public health care policy and so forth, realized this is a wake up call.  It doesn’t matter what pandemic comes next or what have you, we better get a healthier population. And the obesity and the dysglycemia, and the diabetes, and the hypertension, and the cardiovascular disease. By and large, most people, talking to my colleagues now. I’m not on the front lines in the ICU in critical care medicine, but I have a lot of friends who are, and most of the people… Now, there’s definitely exceptions to this, but most of the people that ended up on ventilators are in those categories I just named. Although there are some that were perfectly healthy athletes who are 30 years old who are now not breathing anymore and they’re dead.

                                Right now we’re trying to mind those genes, find those different constellations of different patterns of snips, and metabolome issues and things like that to try to, in the future at least, be better at predicting who are those odd docs that if they get exposed to SARS-COVID-2 or even a related virus that’s got some of the sinister characteristics of it, are likely to go down that slippery slope and down into a severe immune overreaction, acute respiratory distress syndrome, cytokine storm, and what have you, and be really susceptible of dying of this, because there are certainly those people. We know some of those genes and snips already. We know some general patterns, but there’s a lot more to be harvested and learned.

Dr. Weitz:            Yeah, no, this virus definitely seems to have a cardiovascular component that’s quite different than the seasonal flu.

Dr. Brady:            Oh yeah. I mean it’s not just the respiratory virus. In fact, it has the ability to get into all kinds of cells, and not just cells with ACE-2 receptors. Because of the furin cleavage sites on the spike protein it can get into almost any tissue. It has an affinity for a highly or densely populated ACE-2 receptor tissues in GI mucosa, cardiovascular tissue. But you’re seeing now, the vascular biologists are having a field day with this trying to figure out what’s going on with all this endothelial inflammatory function changes, changes in hemoglobin structure, changes in the ability to perfuse tissues with oxygen while still being able to get rid of CO2, the happy hypoxia thing, the COVID toes, the micro coagulations. I mean, it’s a really nasty player. 

Dr. Weitz:            Yeah. No, blood clotting seems to be a major factor. And I’ve talked to a couple of docs who are working in the emergency rooms, and I know in Los Angeles, and I’m sure in some other areas, they’re using blood thinners as just a normal part of the usual treatment. 

Dr. Brady:            Yeah. Sure. We’re using them as well. We have lots of patients on fish oil, nattokinase, lumbrokinase, baby aspirin a day. I mean, we’re looking at all those things as well, for sure. 

Dr. Weitz:            Yeah. It’d be nice to see if nattokinase or one of the other natural blood thinners could have the beneficial role if used prophylactically. 

Dr. Brady:            Yeah. I don’t think it’s going to hurt. A lot of us with all of these therapies, even the front line therapies, by and large, we’re going on a rational hypothesis, known mechanism of action, what we know about the pathogen, and throwing stuff at it and seeing what happens.

Dr. Weitz:            Certainly we’re seeing some amazing data already on vitamin D and zinc among other nutrients. 

Dr. Brady:            Yeah. And you know what, Ben, I never thought I’d live to see some of the stuff I’ve seen in the last couple of months. And I think we all can say that. But I never thought I’d have doctors from ICUs in New York, major hospitals, calling me, tracking me down on my cell phone to ask me what I thought about the best procedure to do in a high-dose IV vitamin C drip. I have a hospital from Massachusetts call me about learning more about blood ozone and UV treatments, The stuff in the media and all over the place with vitamin D and zinc and elderberry and all this.  It’s kind of interesting, when the proverbial stool matter hit the fan in society, I think people amazingly queued up pretty quickly. Hey, there’s no magic bullet pharma agent to save me here. And they saw the richest country in the world’s healthcare system basically be reduced to, “If you get sick with respiratory symptoms, don’t come here. Don’t come to your doctor’s office. We can’t see you. We’re not going to see you. We may talk to you on the telephone, but you need to stay home and basically live or die. And if you get really bad, call 911 and they’ll bring you to the emergency room. You’ll probably end up in an ICU and die there.”  So they figured out, hey, I’m on my own. We’re back to the old days. I need to figure out how to help myself. And what did they turn to? They turn to all the stuff that supposedly doesn’t really work. Well, you know what? It turns out the data’s showing it does work, okay? So you see this stuff, like you said, in the biggest, most solid predictor we have right now to determine who goes to a very bad outcome and who does okay when they’re exposed to SARS-COVID-2 is their vitamin D level. Imagine that, right?

Dr. Weitz:            Yes.

Dr. Brady:            People I went to high school with, I’ve never heard from since, are emailing me, “Should I stop my elderberry? Might I have a cytokine storm? And what is this thing about zinc ionophores?” I’m like, “Do I live in bizarro land here?” But there’s such an opportunity here for folks like us in the tribe that your podcast goes out to. I think it’s changed people’s perception for the long term. Not everybody. But I think a much larger segment of the US population now is thinking, “You know what? I’d better proactively take care of myself a little bit better, and maybe there is something to taking vitamin D, and maybe there is something to supporting my immune system. Maybe some of these natural agents and botanicals and things like that, which we were told that’s not real serious therapy, maybe they are.” Right?

Dr. Weitz:            Yeah. No, it’s amazing. Couple of days ago I read that study coming out of New York City where they had two groups of patients where they got hydroxychloroquine and z-pack, and one group got 50 milligrams of zinc taken twice a day. And-

Dr. Brady:            Major difference in the outcome.

Dr. Weitz:            49% reduction in mortality. 49% reduction in mortality.

Dr. Brady:            Yeah. Hydrochloroquine and chloroquine, of course, big function is as a zinc ionophore. It transports zinc into the cell, and zinc is very toxic- 

Dr. Weitz:            Without the zinc, they didn’t get that outcome.

Dr. Brady:            Exactly.

Dr. Weitz:            You’re talking about a supplement that’s going to cost you 20 bucks. And in contrast, we have an antiviral drug like remdesivir, which is supposedly the most effective drug we have so far, and its effects for like $5,000 a month are that the hospital stay will be reduced by two or three days, and no improvement in mortality. And we have a natural substance like zinc that’s reducing mortality by almost 50%. That’s pretty amazing.

Dr. Brady:            Yeah. Admittedly, we don’t have great retrospective long term outcome studies on any of the drugs. I mean-

Dr. Weitz:            Sure. Yeah. No, there was no placebo control group, but-

Dr. Brady:            Yeah. But we do have lessons learned from SARS in 2003 from MERS. We have lessons learned from other Corona viruses, like various influenza viruses. And there’s really good data out there. There’s animal data, but there’s human outcome data on things like quercetin and resveratrol, and EGCG on blocking, viral docking, and penetration into the cell on zinc, on vitamin D, on high-dose vitamin C, and right on down the line, on botanicals like elderberry, astragalus, and so forth.  So we are using these things. We’re not saying, “Hey, they’re a cure for COVID-19.” We’re not. But the more we can look at what we know about this virus, what we know in lessons learned from related viruses, and we can use different types of mechanisms of action on top of one another. Some block the virus from docking to the cells. Some block it from penetrating the cells. Some block RNA replication. Some change the pH in the exosomes where the viruses hang out.

                                Some things up-regulate the immune system with better NK cell function, or change cytokine patterns. Or something like melatonin. Who would have thought? Everyone thinks of it as a sleep thing. In functional medicine, we know at higher dose and things, it’s been used as an immune modulator. But even at the low doses, people use it for sleep. It directly targets NLRP3, which is that first domino that falls in cytokine storms.  I have most of my patient base on melatonin at night right now, just like a three milligram dose even if they don’t have sleep problems. Just in case they get exposed to SARS-COVID-2, we’re lessening the likelihood, it appears, that they would have that cascade effect into cytokine storm. So it’s interesting times. 

Dr. Weitz:            Yep. Let’s get into virus testing.

Dr. Brady:            Sure.

Dr. Weitz:            Some of the tests that are available, we have this nasal swab that you have to stick all the way into the back of the nose, and then it’s sent for DNA reverse transcription, polymerase chain reaction testing. We have some rapid tests that require getting a machine from Abbott or a few other companies that can return results in as little as five minutes. And that’s the test being used daily at the White House. We have a new saliva test developed by Rutgers University, that doesn’t require using a swab at all. We have a new home test from LabCorp.  Diagnostic Solutions, which you work with, has a stool test. How accurate are all these tests? What are the relative benefits of one test over the other? 

Dr. Brady:            Yeah. Well, I wrote a pretty detailed article that’s about to publish in the next edition of Townsend Letter, and it will also run an NDNR, Naturopathic Doctor News and Review, where I kind of go through exactly those things you just asked because there’s a lot of details and there’s a lot of nuances. And unfortunately, when a lot of this stuff gets reported in the media, they like to reduce things to 32nd sound bytes that the average lay person can digest. And unfortunately, it’s hard to reduce the very complicated and nuanced subject with immunology, laboratory medicine. I mean, these are not just easy things. So yeah.

                                I mean, the way the tests break down, they break down into two major categories generally. One is diagnostic testing for COVID-19. And to start off, a lot of mixing of terms in the media, COVID-19, a lot of people call it the COVID-19 virus. The virus is in COVID-19. The virus is SARS-COVID-2, novel Corona virus 2, whatever you want to call it. But it’s not COVID-19. COVID-19 is the clinical presentation and syndrome, which is a respiratory dominant disorder, that you see that’s killing people, okay? So-

Dr. Weitz:            COVID-19 is the name of the disease, not the name of the virus.

Dr. Brady:            Exactly. So SARS-COVID-2 could cause, in some people who are exposed to it, COVID-19 but not all. So the first testing bucket we’ll create here is to diagnose COVID-19. These are tests that are generally done in reserve for people who are symptomatic or there’s some clinical suspicion on the part of a healthcare provider that they may have COVID-19, okay? These are samples that are done generally, and according to FDA, the only laboratory diagnostic tests for COVID-19 is on a respiratory sample. So these are generally taken from the respiratory tract somewhere.   The data’s kind of emerging, shifting, and things, but from what we know, the most convenient sample that has the best sensitivity, and reproducibility, and capture viral load is called an NP swab, a nasal pharyngeal swab, which is those really long kind of Q-tips that you have to stick along the septum, nasal floor, all the way back to where it hits the pharynx and twist it around a little bit. So, from the side, you’re going back all the way to about where the ear is.  Patients don’t love it. It kind of feels like someone’s sticking a big Q-tip in your brain. You can’t collect them by yourself because you just won’t let yourself do that, okay? But they are definitely, at least what the literature shows so far, superior to trying to collect and get a viral load on an oral pharyngeal swab through the mouth to the back of the throat and brushing the tonsils, or just an oral swab, or saliva, or a nasal swab. So these at-home tests are not nearly as good because the sample is just not as good at getting enough viral load to be detected in the laboratory.  But these are done on a respiratory sample, and generally, most of them, the very good ones are not the rapid test. These involve PCR, so polymerase chain reaction. So it’s an amplification of the DNA. The limiting factor in these tests is really the collection, is getting enough viral load on the swab, or sometimes if there’s people in ICUs on ventilators… We’re actually doing testing on bronchial alveolar washings, and sputum, and different things like that, direct sampling from the lungs. You get the biological sample. You do a PCR process to greatly amplify the DNA that’s in there, to have a better chance of finding the virus. So it greatly increases the sensitivity on the test. And this is done through genomic sequencing and just normal PCR molecular method.

                                The original CDC tests that had a lot of controversy about it, that didn’t work very well, at least in the initial iteration, the CDC decided not to use the World Health Organization’s developed tests. They developed their own. This test molecularly targeted two nuclear capsid or end proteins on the virus. For whatever reason, it turned out it wasn’t very good at targeting those. I’m not sure where exactly it was in the process. But then, the FDA released a emergency use authorization appealing to the private sector to start developing some tests.   At DSL, we pivoted to this very, very early in the game because we’re a molecular shop. We’re a quantitative molecular. We have a whole really highly skilled team that does just this kind of work. We’ve applied our molecular skills to things like GI map and other types of testing that we do. But we pivoted and we developed a PCR quantitative real-time PCR based test on respiratory samples, to hit four different targets on the novel Coronavirus. So two end proteins, the same as the CDC test, but also a spike protein and an envelope protein.  Many other people followed that line, but there were remarkably few labs in the US that were able to do that very quickly. You had some major US academic medical centers of excellent pathology labs that were able to do it. And then your Quest and LabCorp, and some of the really, really big biotech firms. DSL was in that first group of 30 in the country that got the FDA EUA validations in and cleared to do the testing. So we’ve been doing it from very early for major hospital systems, a lot of the drive through centers for different states and municipalities. So we have a lot of data collected on doing that kind of testing.

                                We very early also applied that to testing stool because we were looking at the literature coming out of China and out of other countries showing that you can actually find the virus through molecular methods in the GI tract, generally before you can find it in the respiratory tract. And if someone does get respiratory COVID-19 and they recover, we can find the virus in the stool for up to six weeks after they’ve recovered and are asymptomatic. So that brings up the idea, are they shedding it intact in the stool and could they be a fecal oral transmitter of this?  So everyone was sort of obsessed with the nasal droplets and the aerosolization and all of that, which they should be in respiratory sick people. But what about these people who never got respiratory symptoms or who have recovered from respiratory symptoms? If they’re shedding it in the fecal matter, we still have a transmission problem with them. So we pivoted, we started doing that, and we were very successful at applying the same quad target to it. And we talked to FDA about it and they were really intrigued by it for community surveillance.  Now, they don’t consider it a diagnostic test for COVID-19 because it’s not on a respiratory sample. But some of the advantages are you don’t need a healthcare provider all garbed up in PPE trying to get a respiratory sample on a symptomatic patient. You can dropship a kit, let’s say, to people, have them collect it without exposing anyone else, to get the data on it. So then we started looking at things and other researchers where.  Is this just viral RNA shedding in the stool? Is it intact virus? Can you do viral cultures on it? Can you actually transmit the virus this way? So really interesting.  Then down the line now, what we’re doing, we’re the only lab in the country, that we know of at least, doing this on stool. So FDA has been actually referring a lot of the groups and units and academic centers doing fecal microbial transplants to us to screen their transplant material before they introduce it into a patient because they don’t want to be introducing SARS-COVID-2 through a fecal microbial transplant. So we’re doing a lot of that, and we’re doing a lot of…    Now that the medical centers are opening back up for elective tests, there are elective procedures and surgeries and things like that, we’re doing a lot of pre-screening of patients that are going in for other surgical procedures, for colonoscopies, and things like that, using stool and using respiratory samples when necessary, and combining with antibody testing because the other bucket of testing is not looking for the virus per se through molecular targeting, but looking for antibodies that the immune system, in someone who has been exposed, has developed to the SARS-COVID-2. 

                                So, as far as I know, we’re the only lab that are doing the molecular PCR diagnostic testing on respiratory samples, plus the antibody testing, plus the stool testing. So we’ve been trying to correlate all this data with clinical information because that’s what’s important in the long term to better understand the testing. And not only the analytical validity, but the clinical validity. So we early on were doing a lot of antibody testing before we even commercialized it, before we released it for doctors to be able to order.  We were very early in diagnostic testing, very earlier, the first in stool. We were not the earliest ones in the game in antibody testing, even though we’d probably been doing it as long as anybody, because we were waiting to get really rock solid validations in data. We were testing antibodies very early on, on hospital staff, medical staff, in these large hospital systems to help the hospital determine who in our medical staff may have been exposed, have developed immunity, who may have active infection, even if they’re not symptomatic, even if they’re negative on swabbing. If they have really spiked high IGMs, we need to maybe pull them off of the service lines.  So we were able to get clinical data, NP swab data, antibody data, and in some cases stool data all on the same subject, to be able to try to at least internally validate some of those things, which has been interesting. We’re continuing to do that, because it’s going to take a lot longer to fully understand, particularly the antibody patterns. 

Dr. Weitz:            Maybe you could speak for a minute about the accuracy of the testing for the virus, and then we’ll get into the antibody testing afterwards.

Dr. Brady:            Sure.

Dr. Weitz:            When it comes to accuracy, people are concerned about, it’s often broken down into sensitivity and specificity. And then, the other way to understand it is, do you have false negatives or false positives? Maybe you could just explain those. And then, what level of accuracy do we have with these tests? 

Dr. Brady:            Well, most PCR, molecular based testing, they’re using now usually two, three, or in our case, four targets. If there’s viral load on the sample, the NP swab, the OP swab, the lung washings, whatever, if you have enough viral load that’s above the lower limit of detection, for whatever the lab process is, those PCR molecular targeting methods are almost bulletproof. They’re 100% virtually on sensitivity and specificity. You can trust a positive call on them, and you can trust a negative call from the standpoint of, there wasn’t viable virus above the lower level of detection in the sample.  The problem though is more difficult than that. The analytical validity is extremely high, but the limiting factor is the collection of the sample, and the progression of the disease. We have a lot of people out there now, because a lot of healthcare providers were thrown into action in things they’re not used to doing. Like someone said, if you think SARS-COVID-2 is a problem, Wait till you get to the ICU and you get intubated by a gynecologist.  So a lot of people are doing stuff they’re not used to doing, including trying to collect these samples when they’re not really good at it. And it’s variable when the virus is in different places in different people. For instance, we know on classic nasal pharyngeal swabbing, the viral load is highest on symptomatic people in the first five days of symptoms, then it starts trailing off. So if you’re doing the NP swab at day three of symptoms, you’re much more likely to get a good viral load on that swab, on the same subject, than if you did it on day 10. So that’s a variable.   Are you getting enough virus on the sample? Because the lab can be 100%, but if the sample doesn’t come in with enough virus, then you have a problem. You can’t find what’s not there, or what is below the lower limit of detection. So it’s a difficult thing to answer, and a lot of doctors immediately we’re throwing out, “What’s the sensitivity and specificity?” I’m not sure they really understood what they were asking, particularly when it comes to antibody testing, because there’s two different answers to that always in any laboratory process. There’s analytical validity and there’s clinical validity.   The analytical validity, like sensitivity and specificity, is if something is there in the sample, what is your likelihood of finding it? Or when you flip it around to specificity, what is your likelihood of not finding it if it’s not there, or what’s your likelihood of identifying it inappropriately? Right? Well, even in antibody testing, which is way more loosey goosey than the PCR molecular testing, most of these different kits that labs are using, the analytical validity of specificity and sensitivity is up in the mid 90s to virtually 100%.

                                So if the antibody that you’re targeting is there, they’ll find it, and if it’s not, they won’t. And if you didn’t have it that way, you would never be able to sell an ELISA kit. It’s just that’s the way they roll. What most practitioners really want to know is clinical validity. What is the likelihood, if the person has what I think they might have, that the test shows positive? And what is the likelihood, if they have it, that it shows negative? Or you can flip it around, that they don’t have it and it shows positive, what have you.  That’s a whole different kettle of fish, with antibody testing in particular, because this is a novel virus. This is a new pathogen. Nobody has studied this out retrospectively. With antibody testing, you really want to know, tightly, in a controlled study, what is the clinical history of each subject? Do they have all the clinical manifestations, let’s say, of COVID 19? It would be nice to know, do they have a positive PCR on a respiratory sample or not? And then, you need to do antibodies, IgG, IgM at different stages, at two days, at seven days, at two weeks, at eight weeks, at six weeks, and do those. Nobody’s had time to do those studies.   Some people are trying to patch that together, but there’s been organized studies that have been able to be done yet to really report true clinical validity numbers. So everyone’s throwing analytical validity at you, and they’re 100%, or they’re 95%. It sounds impressive, but it’s not really that impressive because it’s the only thing it could be if you’re in a CLIA-certified lab, using an ELISA kit that’s valid, and particularly one that has IVD status with FDA. So the clinical, the analytical, very, very different, and the media has no idea what that all means. And then-

Dr. Weitz:            Now, on the virus testing, what about the quick test versus the PCR test?

Dr. Brady:            Yeah. I was just going to get into that.

Dr. Weitz:            Okay.

Dr. Brady:            Let’s take the PCR diagnostic testing first.

Dr. Weitz:            Okay.

Dr. Brady:            We talk about the rapid testing. Rapid testing, by its very nature, and design, and intention, one of the reasons it’s rapid is because it doesn’t involve the PCR step. It doesn’t involve amplification. So since you’re not amplifying the DNA, you need a lot more viral load in the sample to make it pop on the radar of the test. So rapid tests are good, and they have their place, but they’re really meant for point of care diagnosis, like in an ICU or in an emergency room with something very symptomatic, high viral load. You do this rapid test, put it in the machine. And if it tells you it’s positive, you can trust the positive. The problem is there’s a lot of false negatives because if you don’t have enough viral load, it will be negative. The other downside of this test-

Dr. Weitz:            Right now, the way they want to use it is, “Hey, how can we screen these people as they go into work, into the meat-packing plant, into the White House, before they play their NBA game?”

Dr. Brady:            Yeah. Well, if you’re talking about like NBA players and stuff, they’re still subject to false negatives because if they don’t have a high viral load, they’re not very symptomatic, but they’re a carrier. You’re not going to catch them on those tests, likely. But it’s not good for population-wide surveillance for a couple of reasons. One is you need the high viral load. So it doesn’t have the sensitivity of the PCR-based molecular test.  The other downside is the throughput is terrible. You’ve got to put like one sample in at a time, and they say, “Oh, results in 15 minutes.” It’s one sample at a time on the machine, and then you’ve got to wait like five minutes on a reset to put in another sample. So you’re doing one sample every 20 minutes. When we’re doing our PCR tests on these arrays and multiplexers, we’re doing hundreds of tests at a time, same time. So the throughput is just not realistic for now-

Dr. Weitz:            So you’re saying it’s not practical, say, for a meat-packing plant, or even a restaurant with five or 10 employees to test everybody on one of those before they come to work every day.

Dr. Brady:            No, they’re really point of care with really clinically sick people to confirm a diagnosis type of test. And they’re very good for that. But they’re not good for what they’re not good for. The other thing is you need the right piece… You alluded to this before, you need the right piece of equipment with the right kit. So it’s almost like having the right laser jet or the right inkjet printer and have the right cartridge. The wrong cartridge doesn’t play nice in the other person’s machine. So it’s very proprietarized. So you’re in Apple world or you’re in Mac World. You’re an Abbott land, you’re in Roche world, whatever.   And if you don’t have that machinery already, first of all, it’s very expensive, and it’s hard to get your hands on if you don’t already have it because of what’s going on. So there’s a lot of limitations. No one ever talks about this in the media. Same thing with that saliva test. And, hey, listen, I’m a Rutgers guy, alma mater. So [crosstalk 00:39:15]-

Dr. Weitz:            I saw one of the doctors from Rutgers and he said there were more viruses in the saliva than there were in the nasal discharge.

Dr. Brady:            Yeah, I mean, there’s definitely more persistence of it in the GI mucosal cells. I’m not sure about the saliva, but we know inherently in the lab, saliva’s harder to work with and concentrate and target things like viruses than a swab. But that is a useful test.  But again, I think it falls into the same bucket as these rapid tests.  You really need a higher viral load.  I’m not sure of the exact throughput capabilities on that saliva test because it’s a onesy. It was just developed in an academic lab. It’s not really been commercialized in a scaleable way.  Same thing in those antibody tests.  You have different kind of variations and stripes.  A lot of the testing, like where you’re from, remember when they tested LA and they said it was like 4% of the population was IgG

Dr. Weitz:            Yes.

Dr. Brady:            … and New York was 20%, they were using these rapid antibody tests that were basically what are called lateral flow tests. They’re almost like a pregnancy test for HCG where you pee on it and it turns a color. It’s like a reagent test. They have very bad sensitivity. They need high viral load or high antibody load in that. So high viral load translates to high antibody load, particularly early on in the phase with IgM, and then later after seroconversion and IgG. But then IgGs fall as well. So they’re really also these sort of point of care. It will not be a diagnostic test for COVID, but it can help confirm a diagnosis. Let’s say you’re in an ICU-

Dr. Weitz:            These are the tests where you prick your finger, you get blood spot.

Dr. Brady:            Those are blood spot. Those are different. So the blood spot tests are kind of the next stage. And they also suffer from lack of sensitivity. You need much more antibody load for those to be viable.

Dr. Weitz:            Aren’t the blood spot the lateral flow or not?

Dr. Brady:            It depends what methodology they’re using with the blood spot.

Dr. Weitz:            Oh, I see. I see.

Dr. Brady:            They can take a blood spot, solubilize it, and then try to do an ELISA process on it, or they can a lateral flow [crosstalk 00:41:31]-

Dr. Weitz:            Oh, okay. I see.

Dr. Brady:            But just think about it, it’s kind of intuitive. If you poke your finger and put blood on a blotter paper and it dries, the lab’s got to get it back, solubilize it, get enough of that sample, be able to viably test it. You don’t have the pristineness of the sample and the sensitivity that you would if you did traditional phlebotomy into an SST tube, spun it down, separated the serum, and sent it to the lab.   Now we’re doing our antibody tests. You don’t even have to do the spin down. You can pull it into a lavender tube and just do it on plasma. It’s equally as good. But they’re definitely better than the blood spot ones. But I understand why people want the convenience of a finger stick. It’s just, there’s a yin and yang. There’s a price to pay, and that’s sensitivity. So-

Dr. Weitz:            Do we know what the sensitivity accuracy of the blood spot, the rapid flow tests are?

Dr. Brady:            Once again, we’re talking analytical validity versus [crosstalk 00:42:33]-

Dr. Weitz:            Okay. Okay.

Dr. Brady:            So it’s hard to say at this point.

Dr. Weitz:            I’ve heard 50 to 70% thrown around, but-

Dr. Brady:            Well, yeah, but that’s analytical validity. When you’re talking about an ELISA done on a quality kit with a quality kit, with a good internal laboratory validation, you’re talking 95 to 100%-

Dr. Weitz:            I see.

Dr. Brady:            … on those. So it’s different. And then, there’s issues of cross-reactivity with other Corona viruses, other SARS viruses. Let’s say, when ELISA antibody testing, what did they build the kit to find antibodies to? Now, most of the ELISA kits are meant to find antibodies that are made by the human immune system to nuclear cuspid or end proteins on the virus. The reason they build it to that is because that has the most surface presence on the virus. So if you’re targeting something where the virus has more of it on the surface, your sensitivity goes up.  But one of the things that happens on sort of a ubiquitous thing on the surfaces, your sensitivity goes up, but your specificity can go down a little bit. So there is some potential, theoretically, for cross-reactivity on those tests to other common Corona viruses. Well, I shouldn’t say common, relatively common. They’re still not very common, like 229E and I think it’s OC43. I wrote it down here. But when they’ve looked at that, they really haven’t seen that. So most of the published studies, and I pulled some of them here, show a very high specificity using pre COVID blood samples.  We tried to use samples as controls that were available that were collected before we knew SARS-COVID-2 was around, and we’re not getting cross reactivity. Some of the other ELISA kits are built to the spike protein. They have the ability to cross react a little bit more with original SARS from 2003. But we don’t think that’s around. So it’s kind of moot. So I think you’re not going to get a lot of false positives from cross-reactivity to common influenza viruses or the original SARS on the antibody test. But the antibody tests are a little bit dicier in that there’s not as much uniform quality control for a couple of reasons. One, PCR molecular-

Dr. Weitz:            Keep talking. I just have to turn the music down that popped on.

Dr. Brady:            Sure. 

Dr. Weitz:            Yeah. Go ahead.

Dr. Brady:            PCR molecular is just by nature much more honed in and targeted, and exact in its nature. Think about testing, in immunology testing, it’s a little more fuzzy around the edges. And individuals have a great deal of variability in how they react to a pathogen, how much antibody they produce, how much IgM, and when they convert to IgG, how much IgG they maintain around for lengths of time, what their viral load was to begin with.  Ben, if you get exposed once to SARS-COVID-2 and you harbor it in some way, whether you go on to become clinically symptomatic or not, you’ll develop a certain amount of antibody titer to it. But if you’re a healthcare provider in the hospital every day, and you’re getting exposed to this virus repetitively, you’re going to develop a much higher viral load, whether you’re symptomatic or not, and therefore a much higher antibody titer. So to try to answer questions on what exact level of IgG confers immunity, what exact level of IgM means you have an active infection, there’s different kits, there’s different methods, there’s different individuals, there’s different viral loads. It’s impossible.  So, over time, as the methodology coalesces to a gold standard, and then they can follow people over many subjects over many time intervals after exposure, then you can learn these cut points and dial them in like we know about Epstein-BARR virus. This is a brand new virus. So doctors are asking the same questions that they would ask with a virus that we’ve been studying for decades and have all kinds of retrospective data on to a brand new virus. When in many cases labs, immunologists, everybody’s kind of shooting in the dark, doing the best they can, but they haven’t had the benefit of time to answer the kind of questions that the doctors think you should have. I don’t know-

Dr. Weitz:            Generally speaking, what do we know about… IgM are the first antibodies that form, and then they fade away and we get these IgG antibodies, which are generally considered to be the longer term protective ones. So how long after infection, on average, do the IgM antibodies form with SARS-COVID-2 virus? And then, how long did they last for, and when did the IgG antibodies form?

Dr. Brady:            Well, I mean, once again, they’re still trying to dial a lot of this in, but fundamentally-

Dr. Weitz:            Right. But what do we know so far?

Dr. Brady:            Fundamentally, Corona viruses aren’t new, okay? This is a particularly nasty one because of some novel properties of it. But it’s a-

Dr. Weitz:            By the way, 20% of colds are caused by Corona viruses.

Dr. Brady:            Exactly. So we know how Corona viruses operate. We know how our immune systems react to them. We have the benefit of lessons learned from SARS and MERS and things like that. So there’s no reason to think that there will be some really atypical, bizarre reaction of the human immune system that defies what we know about immunology. So basically, if you’re exposed to the virus, and you have a viable viral load, and whether or not you develop overt symptoms or not, you will start to rapidly develop IgM antibodies.  And depending on your level of exposure, your level of viral load, your IGMs will come up to a point that will be easily detectable through any of these type of laboratory methods. Now, over time, over a couple of weeks, you will get serial conversion of IgM to IgG. So your IgM spike first, then they will come down. The IgG titers will go up, and they’ll be much higher in the beginning, and then they’ll gradually trail off. Then they’ll stay at a lower level on a persistent basis, and that’s your learned long-term immunity.  Let’s say the rapid tests or the lateral flow tests, they’re pretty good at finding that initial high IgM spike, and they are probably still pretty decent detecting that initial high IgG after seroconversion is early. But then as you lower down that IgG titer, you need more resolution or sensitivity in the test to find the low levels of elevated IgGs that are characteristic of a long-term sticky immunity, if you will. And that’s what most clinicians want to do. They want to test someone who isn’t sick right now, who thinks they may have been exposed in January, or had a family member exposed. Do I have protection?  You want to find that relatively or comparatively low level of IgG elevation, which the rapid, linear flow, and all those tests, blood spot tests are not nearly as good at finding as the ones that are done on conventional phlebotomy, either plasma or serum, using a really good quality ELISA kit. So it really depends what you’re looking for. I’ve done a million media interviews on news, national news, local news, regional news, all that, particularly when we were…

                                We were one of the first companies in the United States to do broad-based employee testing on the workforce at Designs For Health because we’ve had to keep all of our manufacturing plants running 24/7 during this because we can’t make enough stuff. It just gets ripped through. So we needed a very healthy workforce, and so we turned to DSL to do all the antibody testing. It generated a lot of media, so I was on a lot of interviews about this. And even if you try to explain some of these nuances, they don’t have time for it, and they don’t want to know. It was like, “No, I don’t want to know. We just want easy answers here.” How do you take something that is complex and has all these nuances, and make it like a binary answer and something really simplistic? It’s hard. 

Dr. Weitz:            But essentially, part of what you just said to me was, you hear in the news, “Well, we don’t really know if you develop antibodies. We don’t really know if you do develop antibodies, will you be protective?” Essentially, what you said to me is, and correct me if I’m wrong, that our immune systems generally work similar to the way they do with other viruses. One of the main ways that we fight viruses is to produce antibodies over time. Depends on the person, depends on the infection and everything else. But generally speaking, we develop antibodies, and generally speaking, these antibodies are protective over time. 

Dr. Brady:            There’s no reason to think, when someone has IgG titers to SARS-COVID-2, that they would not have some significant amount of immunity. They would highly be unlikely to be infected again anytime soon with it. We have not seen that. You saw some reports out, like South Korea, something about reinfection. It turns out, in peer review, it was not really the case. We don’t have evidence of that. I can’t tell you a hundred percent that won’t emerge. But we don’t think so. And even with lower levels of persistent IgG to SARS-COVID-2, it’s likely you would have a persistent immunity to it for at least the near future.

                                This is an RNA virus. By nature, they kind of change around a lot. But this has a very complex large genome, and it has a sinister property of a lot of self reparative mechanisms to the genome of the virus, which means, over time, it doesn’t mutate as much and lose virulence. So that’s the bad news. It’s likely to maintain the characteristics it has now. It’s not likely to be burned out by the heat. All those things.

                                On the other hand, if you develop immunity to it, that really means that we’re more likely to have that immunity persist. But we don’t know if a year from now it’s changed enough. Like influenza, even with the vaccine talk, I don’t think… Honestly, I hope I’m wrong, but I don’t think there’s a magic vaccine coming to cure us, because this is an RNA virus. And if they develop a viable vaccine to this that sticks, that’s the same over time, it will be the first time they’ve done it in history.

                                They don’t have a vaccine for AIDS. The vaccine for influenza is not like polio or MM…You have to get it every year because they’re guessing what new variant may come, and they get it wrong sometimes and get it right sometimes. But this is not easy. When they tried to develop a vaccine for SARS1, I’ve talked to some of the researchers. Every time there was several different efforts, highly funded, every one of them failed. And the ones I know of that I talked to people involved in it, every time they gave the vaccine to animals, it killed them all. So they basically stopped trying.

                                Now maybe they know more now. There’s brilliant people. Hopefully they can develop one that’s safe. Who knows? But I’m not holding my breath, honestly. I think it’s a lifesaver that they throw out to the public to feed them. But I’m not sure that it’s really all that viable, at least in the near term. And I don’t think there’s a magic drug coming along that’s just going to eradicate the virus because we’re not good with antiviral drugs to begin with.

Dr. Weitz:            We were talking about the antibodies, and another piece of evidence that the antibodies are protective, is we’ve been using convalescent plasma therapy, which is taking antibodies from patients who were infected, and using it on patients who are sick. And they’ve been getting some pretty good results with that. So that’s more evidence that antibodies are protective. And then, the only problem with that, it’s not really scalable if you take antibodies from one person and give them to one person. You can’t help a lot of people. But they’re trying to develop those antibodies in a lab and- 

Dr. Brady:            That may be helpful. They can have a form of immune modulatory or immune therapy based on this. And, boy, that whole area has progressed so much. That may be the answer, but who knows? But it’s interesting, when I was doing media too, an interesting phenomena, you had a lot of public health authorities, governors, even all the way up to the top saying, “Oh, antibodies are our ticket to understanding this, to knowing what the penetrance is in the population, and to getting people back to work safely.” and all that.  Then all of a sudden, it started having it spin. Oh, we don’t know about this antibody stuff. Oh, a lot of the tests aren’t any good.  And I’m like, “What flipped the public narrative?” And I really do think that public health and regulatory authorities came to grips with the reality. As people started getting antibody testing done, they realized that they were developing two segments of the population, those with IgG antibodies and those without. So what were they to do with the partition population? One set of rules for the people with antibodies and another set of rules for the people without?  What about the people that found out they have IgG antibody titers to SARS-COVID-2? Did they start telling the public health officials, “We’re not following your social distance stuff. We’re not wearing masks, because we have immunity”? Basically, what do you do with the population where… Do you give them immunity cards, non- immunity? I don’t think they even wanted to deal with that complexity. And they started messaging, “Well, we’re not sure we can trust antibody tests.”

                                Listen, we’ve been using antibody testing in medicine forever. This isn’t new. So there’s ways to figure this out. With antibody testing, it was different than PCR, because PCR molecular testing, you had to have a lab with really good molecular talent, really high level of scientific complexity, and you had to be able to take in samples that had a pathogen that’s infectious. So you had to have a BSL-3 lab. Now most of these labs aren’t BSL three labs. They don’t do molecular work, particularly in the integrative functional space. So they were just sitting on the sidelines.  Meanwhile, all their normal testing dried up. At least for a month, nobody was doing all salivary cortisols, and stool tests, and organic acids. No one was doing that. So then when the antibody opportunity came around and they said, “Hey, well maybe we can get back in the testing game and get some revenue coming in. Let’s do SARS-COVID-2 antibodies because, you know what, you didn’t have to develop that in your lab from scratch with the methodology. You just had to buy a kit and follow the instructions.

                                Now, I oversimplify that because when you get the kit, you still have to follow the instructions right. You have to prepare the samples right. You have to have consistency. So you should do your own internal validations on how you work the kit. But the heavy lifting was done by the big biotech firms that make the kits, submit the validations on the kits to FDA, and do that work for you. So, basically, a lot more people can get in the antibody testing game in PCR kit. So that’s where you saw all this explosion of antibody testing.  If a lab didn’t have a lot of experience in antibody testing or immunology testing, didn’t have supply lines created or supply chains to get the good kits, the only kits they were able to get are were the cheap, less quality kits, mainly out of Asian countries. And the labs that were higher complexity, had these other supply chains, were getting the American and German kits, and they’re a little bit different in their quality.  So I understand the argument, “Hey, we’ve got to worry about the antibody quality throughout the labs.” I get that. It’s definitely more of a question than the PCR testing, but I think there wasn’t really much of a choice. They had to turn to the public sector to just turn on the engine to get the testing capacity to be able to really do enough tests to really get an idea of what’s going on in the population.

Dr. Weitz:            I’ve got one more speculative question. We know that this cytokine storm, it happens when things go bad with patients who are infected. Is there any screening test that can give us any idea about the likelihood that somebody is going to have a cytokine storm? And I’m thinking, are there inflammatory markers, tests of antioxidant status, or even measuring cytokines, that can tell us whether we’re more likely to have an inflammatory situation, oxidant storm, a cytokine storm?

Dr. Brady:            No. I get the question. And we thought about that immediately because we have a cytokine test called cytoDX. And it looks at inflammatory and anti-inflammatory cytokines. But we never positioned it as a screening in that way because we are not sure that the ranges in the sensitivities or the normal ranges of the inflammatory cytokines are set in a way that would somehow screen someone to have an event that didn’t occur yet. Like is there just a mildly elevated pattern of some of these inflammatory cytokines, or the ratio of inflammatory to anti-inflammatory cytokines that would be somewhat predictive of who’s going to go down that pathway?  It may be, but we have no way to really test it because we don’t know who’s going to go there. And then once they go there, we don’t have the data on them before they went there. So it’s a really cool thing. The ranges and the normalities were never established or set with that kind of mindset. So when they go into a cytokine storm or when it starts, if you did a cytoDX, the inflammatory cytokines would be off the chart. But we can’t accurately say that before that ever happened or before they were exposed to SARS-COVID-2, that their anti inflammatory cytokines would be above the normal range. So those are things to be worked out.

                                What we’re mining now, we’re trying to get buccal swabs of people that we know in the ICUs went down into respiratory distress syndrome, and through our genomic insights platform in OPUS23, and all the AI and machine learning, we’re trying to pick apart what is the exact pattern in constellation of snips. And we’re looking at ACE-2 receptor snips. We’re looking at cytokine snips. We’re looking at a whole bunch of different snips to find out what is the golden pattern. And maybe it’s not just snips, it’s snips plus metabolome markers.  So we’re looking at some of that stuff, but once again, we don’t have the time and the number of samples in the right sequence with the clinical histories. It’s really hard to put together, but we’re looking at that. I’m having a little bit of brain freeze on his name, but there’s a researcher, I believe he was at Duke or one of the California institutions, that is the go-to expert on cytokine storm, even before COVID happened, right. People tended to go into a cytokine storm, particularly people with certain auto immune disorders and so forth.  His most accurate predictor of cytokine storm are people that have elevated ferritins, like up in the 4, 5, 600s. And we know it’s an acute phase reactant, early reactant. And it’s not really indicative necessarily of their iron status. It’s sort of a lab artifact as an acute phase reactant. But I read some of his work. Even advising some of the ICU physicians to do just a serum ferritin. And if the serum ferritin was really high, really watch this patient and maybe even use TNF alphas or immune modulating medications on them to stop them from going into that.

                                But it’s a very good question, Ben. And I don’t know. I think our life raft here, beyond vaccines and beyond some direct therapeutics, is to get better at predictive using omics, genomics, proteomics, metabolomics, what have you, to be able to find those canaries in the coal mine. Who are the ones that might go down the cytokine storm pathway, and to be more aggressive with them? And on the flip side, just have better understandings of standards of care when they do get there, because there’s a lot of speculation now that they were treating the COVID-19 like any other viral pneumonia and what they knew how to treat it. And it turns out it’s very different, with the happy hypoxia and the CO2 going off, but the oxygen not profusing, they were getting really silly kind of reactions from patients, and they were very, very quick to ventilate them, and now they’re thinking that was a mistake, that they created more lung damage and worse outcomes by putting people early on ventilators when they shouldn’t have.  So maybe they learn more, I’m sure they will. And then drug combos, whether it’s azithromycin and chloroquine, or whether it’s these antiviral cocktails combined with this and that. We’ll see. I’m sure they’re going to figure out better ways to treat it even if it’s not curative.

Dr. Weitz:            Excellent. Thank you so much, David.

Dr. Brady:            Okay. Thanks, Ben. Appreciate the time.

Dr. Weitz:            Any final words? How can people get a hold of, I guess, the practitioners, can find out about the Diagnostic Solutions Lab testing?

Dr. Brady:            Yeah. They can just go to Diagnosticssolutionslab.com and then click on COVID testing, and you get all the different options, whether it’s stool antibodies and what we’re doing with the NP swabs and the diagnostic testing. And then, I put that link on for you to share in your resources for this podcast interview, but I put a link to some other really good resources like the FDA site on serum antibody testing, and the different kits that have been approved, and their different sensitivity and specificity, and coefficients of confidence intervals and all of that if you want to look at it.  I put something up about, everyone’s talking about different strains of COVID or of SARS-COVID-2. There’s no different strains of SARS-COVID-2. There’s different isolates, different isovariants, but there’s yet to be a different strain of SARS-COVID-2. A different strain means there’s something enough different about the virus and its structure that it behaves different functionally. They haven’t had that. We’ve seen variants or differences in some of the genomics, but that’s really an isoform or an isolate, not a strain. So that’s bad nomenclature. So that’s unlikely to affect antibodies, PCR targeting, anything like that. Then I just put a couple of other resources that people may like to see on false positives, false negatives, why they may occur, why they may not. 

Dr. Weitz:            Excellent. And those will be in the show notes, if you go to drweitz.com. Also, if you’d like to see a video version of this podcast, go to my YouTube page. And if you enjoy this podcast, if you could go to Apple podcasts and give us positive ratings and review, I would certainly appreciate that. Thank you, Dr. Brady.

Dr. Brady:            Okay. Thanks. Appreciate it.

 

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