COVID-19 Update: Antibody Testing vs. PCR Testing—Who to Test and Why?

You. It's great to be with everybody again today. The topic I'm going to talk about today is antibody testing versus PCR testing. That's going to be a big topic over the next one to two weeks, especially as antibody testing gets rolled out across the country. So what I'd like to do is just talk about the two differences in testing, how they are testing, how their modalities differ, some of the numbers you may start hearing about as far as how as accurate they are or not they are, and then just to give you some information with a summary as far as what does this mean, can you actually use this test, etc. So just a few introductory comments as well. The references for all these will be below where this is put up on social media on the video as well. The article I referenced that I published in Lancet back in 2016 will be published there as well, will be put there as well. So anyway, so what's going on right now? Right now there's over 70 companies working on antibody tests, but only one has been FDA approved. So what that means is it's the wild, wild west. We don't know which of these is going to come out first in your local area and how accurate they are. One of the issues with FDA approval of testing is you want to make sure if company number one and company number five and number 20 and 30 and 70 do a test on different people. If they're all positive, you want them all to be the same. You want that test to be reliable and dependable. Right now we don't know and 70 different companies is a whole lot. Now one of the issues with the testing is how antibody testing works, how accurate it is, how reliable it is. I have to think about back to HIV testing. So HIV testing initially, when you get tested, you get tested with an antibody test and that antibody test runs about 99% sensitive, meaning if the test is positive, you have a 99% over 99% chance of having HIV. But, but with HIV, we don't consider that accurate enough. So we do a Western blot test, which is a specialized confirmatory test, which then makes the accurate to see down to 99.999%. And if both tests are positive, we consider that test to be a true positive. So that's kind of what we're dealing with. We're dealing with two different tests of the same thing, the PCR versus the antibody test. So which one's more reliable? The FDA has actually waived all the initial review of the testing. So what that means Is again, there's really not a whole lot of review going on currently to see which tests are reliable, dependable. In Texas There were about 200 to 2,500 tests were set up. There were these fraudulent basically testing centers set up and 2,500 people were tested. And the test was actually a fraud. And so you're going to start seeing stuff and hearing stuff out there. And so you just want to be aware that when someone pops, if something pops up around you, is it an actual test site? Can you just do this with your provider or the doctor, whoever you work with? Because again, it's going to be a little crazy out there. As of yet, there are no home approved test kits. This is, I'm recording this on the 17th of April, so maybe in the next two to three weeks there may be home testing. But if you hear about it really soon, I would just double check because as of the recording of this, there really weren't any home antibody tests being made available. So California has actually launched large scale antibody testing as well. California is an interesting case study because they are a very, very large state, the largest population wise in the country, but yet their number of cases per million is actually equivalent to Virginia. So for a test for state that's pretty big, that covers a large area, the amount of actual COVID 19 cases does not reflect their size versus New York which has tons and tons of those. So, so it's interesting that they're rolling out this antibody test. How will this translate to the rest of the country? These are all great questions we need to figure out. Reverse transcriptase, polymerase chain reaction testing, rt, pcr, or most people just refer to it as pcr. Those are all the different names for it. How's it done? First you have to get a swab of some part or sample from some part of the body. Either a nasal swab up your nose, it can go in your mouth, or you can actually do lung aspirates. We put fluid into the lung and aspirate it out and send that off for a test. So first you have to collect a sample. Once the sample is collected, it has to get sent off to the lab. The lab will then look for the RNA of COVID 19. What they do is they use these little molecules to replicate and create these long chains and break it up. That's called the amplification process. As it's amplified, you get more and more RNA particles or SNPs and eventually you get enough of those that can actually then look to see, do you have DNA that you're looking for and use a probe to figure that out. So you get the sample, you amplify it, you put the probe, and then you visualize the probe and it's positive the person has the disease, they have whatever's going on. The problem is this has a lot of different steps. Whether it's the collection process, which we'll talk about in a second, whether it's the amplification process and every time it's amplified and if there's fake DNA in there, or RNA or different genetic material in there that can actually make the tests false positive or false negative. And then finally you have the probe and the probe has to be reliable. So with the rt, pcr, it's heavily technology dependent. Most of the processes and processing occur outside the human body as compared to antibody testing in a second. As far as accuracy and predictive availability, it's not been systematically evaluated. So we're not 100% sure how reliable this testing is. Initially In China, about 29% of those who initially had a negative test were later evaluated with serial testing being positive. So initially, if someone was really sick in the hospital, et cetera, 29% were. Of the people that eventually tested positive on the first round were negative. So some of the initial stuff with the PCR, a little questionable. Now the other thing with the rt, the PCR is that depends on where you check which part of the body you check. So for example, if you do what's called a bronchiovolar lavage, I.e. stick a tube down your nose, put fluid down there and suck it out, about 95% of those are accurate. If it's positive, you have disease. That's a really good testing thing. But who's going to do it like that? If we check sputum, you're coughing up stuff, okay, you're really super sick. And usually if you're producing sputum, you've got a little later stage of the disease. About 72% of those are positive. Compared to an oropharyngeal, you take a mouse sample, only about 32% of those who are found later to be positive is a test positive. So right now I've been recommending, I've been doing in my office on the patients I've been seeing the nasal swabs. That gives you better sensitivity than the oral swab. It's not going to be as equivalent as the lung swab, but it is doing a better. You're getting more surface area. When you go back, you're hitting more stuff Versus just the back of the throat with the oral swab, you get more mucus. And these RNA type viruses tend to like a little cooler environment, so they have a little more in the nasal passageways versus the oropharynx. So as far as testing, this is something I thought was really, really interesting that if you think back, you heard about these, all these people, all they were negative, then they were positive and all this kind of stuff. Well, why is that? If you test someone on day one to three, their illness, greater than 90% of those who have the disease will be positive. So if you want this test to be really accurate, you have to check, get the person on day one to three of illness. Problem is some people don't even have symptoms until day five to seven. So literally, to get the most accuracy for the the pcr, you got to check the people super, super early. If you do it at day six, it's less than 80% sensitivity and at day 14, it's less than 50%. So this kind of explains to me how you hear a lot. And I actually had a patient like this who had been sick for a while. I saw her in the office about a week and a half ago. Typical high risk person, her test was negative. But her daughter, who had just been sick for a little bit, hers was positive. So that just reminds me that with the pcr, you have to get people checked pretty early for it to be really reliable. If you wait until someone's been sick for a while, the sensitivity after, again after day 14 is less than 50%. At day six, that's less than 80%. On the first one to three days, it's greater than 90%. Okay, we already talked about that. So what does that mean? That means that the PCR has to be done on people early on. They have to have disease. You have to have the DNA, I'm sorry, the RNA of the actual infection. If you don't, then testing's not going to be super accurate. So antibody testing, how does this differ from antibody testing? Well, antibody testing differs in that your body does all the processing for you. So you have these. I've talked about this before. You have this innate immune system where you have macrophages and natural killer cells and they will eat an infected, virally infected cell. They will then take that virally infected cell, process it, take an antigen and put it outside the cell membrane. A T cell will then activate that, hit that, start making cytokines, then signal B cells to make antibodies. Over time, the B cells will initially make IgG antibodies and IgM antibodies, and eventually they'll ramp up production. We do know that with COVID 19, your body tends to make the IGM and IGG about the same time. So you can use either IgG or IgM probe or antibody testing to figure out what's going on. But the difference between these two tests is with the antibody testing, your body is doing most of the processing in the lab. You just pull the blood out and you put a probe looking for the antibodies. If they're positive, you get a number. So most of the processing in this whole immunologic thing is occurring in your body. With antibody testing versus PCR testing, you have to actually replicate the DNA that then you create the probe and the probe, you can think of the probe as being like a synthetic antibody. And actually the probes are antibodies, actually as a synthetic antibody. So it's almost like you're reversing the whole process. And the first one, it's super sensitive. You don't need a whole lot of DNA, I mean, RNA to be accurate. The second one is more for people who've actually already had disease. So one study, and these studies are going to be Posted below, about 93% of people who had a positive IgM were actually truly positive for the COVID 19. So that's a sensitivity of 93%. Now, sensitivity, you'll hear this number. Sensitivity means if the test is positive, you actually have disease. Specificity means if the test is negative, you actually don't have disease. So right now, you know, we're looking at sensitivity. You know, this One study said 93%. I've seen 87%. We'll just round off to 90 because it makes the math a little easier. And specificity being 93%. Now, again, there's no user errors. So again, so we'll talk about it. So one of the issues looking at these numbers is antibody testing is something that's probably gonna be deployed en masse to the people, so to speak, because we're trying to figure out who has already had disease. So one of the issues with that is if you take a large population of a million people and you start testing everybody and let's say everybody's already had the disease, what happens is, out of a million people, there's maybe 100,000, 70,000 people who had disease that you're gonna miss and falsely say you really don't have disease. And if you do this on a million people and they all come back negative, what that means is there's going to be about 70,000 people who stay negative, who really had disease. So the strength of this test is that you can test it easily, quickly, it does not require a lot of technology. It can be put in mass. But if you're checking millions and millions and millions of people to say, is it safe? You're still going to have a significant number of people who either had disease but test falsely negative or did not have disease and tested falsely positive. So the question is, how do we use this test? How do we deploy it? Well, we're talking about deploying just to figure out who's had disease. And Overall, with about 93% accuracy, you can figure out who's already had disease and to put people back out. Would this apply to the sick people? If someone's grandmother tested negative, would you keep them back in? That's usually the kind of issues we're not quite sure. If you're older and you test negative, what do you do? If they're young and they test positive, what do you do? I think based on the data we have, the best way to use this test would be to figure out for most people, healthcare workers, I'm a physician. If I've already been exposed, if I'm positive, I can go back out in the population. If someone's older, high risk individual tests positive, it's most likely the test is actually accurate. The problem is if you test negative, there are people who will actually have had disease. And so the, the point of all we're doing is to protect the vulnerable, to protect the people who have multiple comorbidities, that is overweight, males over 65, multiple health conditions. So those are the people that, if they test negative, probably need to stay isolated until their antibody converts. Now, here's one of the issues as well. I tend to think about chickenpox. We used to, back in the day when I got chicken pox, you know, I got it, I played with my friends, they all got it. And that was what happened. When one kid got it, they go play with all the other kids. And not everybody got chickenpox. Remember that. You know, maybe two brothers got and two sisters didn't. Again, some people got symptoms, some people did not get symptoms, and some people did not get the disease. But if 70, 80% of population gets it, the rest are protected. And that's where with this is the same thing. There are many people who just aren't going to get this. They're going to be people who get it that just aren't going to test positive. And so we need to have some kind of Criteria for reentry, if you're young and healthy, go out there, you know, et cetera, et cetera. But we need to use this mainly for protection of the high risk. And the question is, how do we implement that? We're not quite sure that if someone's older and negative, do we keep on retesting them? If someone's young and negative, do we keep on retesting? Or do we say, you're young and healthy, go back to school, y', all, spread it around and develop immunity. These are all questions we have not answered as a society yet. And then the test, how do we trust the test? You know, we need to get. I think the biggest thing with the antibody testing is to get a true number of how many people have been infected. Because regardless of the false positive and false negative numbers, we're talking about percentages, not multiples. So what I mean by that, we're seeing maybe 5 to 10 times 50 times more people actually have this disease than were being reported. So we talk about multiples of 5 times 10 times 50 times. A few percentage points is not a big deal when you're trying to figure out currently in the society how many people have this disease. So testing California, they come back with the data in New York that maybe 15% of people have this. Then we know this is already widespread. So using this, then if you have a lot of people having this, using the test on young healthy people to say you're okay to go in public can be useful, but it's not super useful. It's probably going to be more useful for the higher risk people that that 3 to 13% error rate becomes a big deal because the error means death. The error does not mean you get a runny nose, you get sick, you get cruddy. The error is a big deal. And that's what we have to think about how to implement this test. So how do we test? We need to get a number of infected people. We need to get a true number for a mortality. That's the other thing. We don't really have a good mortality number yet. We're still saying 0.7, 0.81%. We still have these really high numbers for death rate. And if it's really tenfold, all the epidemiologists have been saying none of the statistics have actually represented that. So it'd be great to get our morbidity numbers to a more accurate rate to, to figure out what the actual lethality of this infection is if it ends up being the 0.4% which is still worse than flu, then we can then focus on the high mortality people, the elderly, the sick, to protect them with face mask, with deployment, et cetera. So anyway, the articles I used for this brief review of the antibiotics versus PCR will be listed. Hopefully it was helpful. If you have questions or comments, please put them below. If you Again, if these have been useful for you, please share with family and friends as well. Please like us and follow us. That lets us know that people are actually engaging. This is useful for people. If there's a topic you'd like to talk about. If a question you'd like me to address, just put that in the comment as well. We do look at those and read those and try to help assess what future items we can talk about. Stay safe, be well. Again, more information you have. 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