Ask Us Anything About… COVID-19 Testing

Despite the fact that we’re many months into the COVID-19 pandemic, questions are still swirling about the various types of testing for the novel coronavirus. With incidence of COVID-19 trending upward in the U.S., the topic is as timely as ever. In this interview, we learn about the various types of tests, who should be tested and much more with Dr. Melissa George, interim chair of the Department of Pathology; and Dr. Catharine Paules, an infectious diseases physician, both at Penn State Health Milton S. Hershey Medical Center.

View full transcript of video


Scott Gilbert – From Penn State Health this is Ask Us Anything About Covid-19 Testing. I’m Scott Gilbert. Well, despite the fact that we’re many months into the COVID-19 pandemic, questions are still swirling about the various types of testing for the novel coronavirus. With incidents of COVID-19 trending upward in the U.S., the topic is as timely as ever. Today, we’re going to talk about the various types of tests, and who should be tested, and much more with two experts on the topic. At this point, I’d like to welcome in Dr. Melissa George. She’s interim chair of the Department of Pathology at the Milton S. Hershey Medical Center. And Dr. Catherine Paules, an infectious diseases physician at the Milton S. Hershey Medical Center. My thanks to both of you for your time today. Um, and of course, throughout this interview as we’re talking about the topic of COVID-19 testing, we welcome your questions in the comment field. So feel free to add those questions. We’ll get to as many of them as we can in today’s interview. And any that we don’t get to we’ll address with a written reply after the fact. So Dr. George, let me start with you. Let’s talk about the different types of tests. I understand there are essentially three main types. Can you talk about those and how they’re performed?

Dr. Melissa George – Absolutely. The first type of test is the molecular test or the PCR. It’s usually called polymerase chain reaction, although there are other types of molecular tests, as well. That looks for specific sequences of genetic material. In the case of the SARS-CoV-2 virus, they’re looking for RNA, as opposed to DNA. It undergoes a series of steps to basically amplify the amount of virus being detected. Then antigen testing is looking for proteins made by the virus or protein pieces of the virus. And then the antibody test looks for our body’s response to the virus to see if we’ve produced antibodies that help fight infection.

Scott Gilbert – So then which of those tests is taken with the nasal swab, for instance? Is that the – which one is that Dr. Paules, the infamous nasal swab test?

Dr. Catherine Paules – The nasal swab test is a molecular test. So it will tell you if you are right now infected with COVID-19.

Scott Gilbert – Okay, and so and some people say that test is invasive. It’s painful and that that swab has to go in really deep. Why does it have to go in so deep to be effective?

Dr. Catherine Paules – The sensitivity of the test, meaning, um, how many of the cases you’ll actually pick up, is much better when you get that deeper specimen. So even though it’s uncomfortable, that’s the best way to get the test done.

Scott Gilbert – Okay, and Dr. George, how are the other tests performed that you mentioned, the antigen test, the antibody test?

Dr. Melissa George – The antigen test can also be either a nasal swab, either anterior nares to the nostril, or possibly all the way to the back of the nasopharynx, or possibly saliva testing. And the antigen testing is usually a smaller instrument that might be point of care, meaning it could be in a doctor’s office, potentially. But unfortunately, they’re not as sensitive, and with the other type of testing, the antibody test, that’s going to be a blood test. So a tube of blood is going to go on an analyzer to look for the antibodies specific to the SARS-CoV-2 antigens.

Scott Gilbert – So some tests are for whether you have the virus now. Some, like the antibody tests, are for whether you ever had it. Dr. Paules, who should get tested and, you know, how do people know what the right type of test is for them?

Dr. Catherine Paules – So if someone is concerned that right now they might have COVID-19, the best type of test is that nasal swab with the molecular testing. Because that’s what will show you if you’re actively infected with the virus. The antibody tests we’re mostly using to help us define, um, clinical syndromes that might occur later after COVID-19. So, for example, you may have heard about MIS in children, which is this post-inflammatory complication of COVID. And one of the ways that we’ve been able to discover that and diagnose patients with that disease is through an antibody test.

Scott Gilbert – And so some people might also say, well, you know, should I get an antibody test to determine whether I’ve had it and therefore would be immune to it down the road. But I guess there’s some disagreement over whether or not having had the illness constitutes immunity in the future, correct?

Dr. Catherine Paules – There’s a lot we still need to learn. Um, We need to learn if infection protects against reinfection down the road and for how long. And if it does, is antibody the way that we measure that protection. So even if I went and had a positive antibody test today, that would not inspire me to change any of my behaviors. I would still wear a mask. I would still social distance and do all the things I’m doing right now despite having that positive test.

Scott Gilbert – You’re watching Ask Us Anything About COVID-19 Testing from Penn State Health. We’re glad to have you this afternoon. We’re talking with Dr. Melissa George. She’s interim chair of the Department of Pathology. And Dr. Catherine Paules, an infectious diseases physician. Both of them at Penn State Health Milton S. Hershey Medical Center. We welcome your questions, your comments. Just add them to the comment field below this Facebook post and we’ll get to as many of those questions as we can. Um, Dr. George I’d like to ask you a bit about saliva tests. Um, what – how do they differ from some of the swab tests and other things we’re discussing and are they as effective?

Dr. Melissa George – Saliva testing has been validated by a few either companies or universities, and basically has to show comparable results to the nasopharyngeal swabs. Nasopharyngeal swabs are still the gold standard because fewer places are actually performing the saliva test. For the saliva test, it’s usually a funnel test tube that someone has to actually collect a saliva sample and with a video oversight. So usually, it’s a medical provider is watching them basically collect the saliva sample to make sure it’s enough. That gets sent off for molecular testing. The results have been somewhat comparable, but there’s still a lot of difficulties in performing saliva testing, just because of the nature of the specimen. It’s a little bit thicker, potentially, could be more viscous and could cause problems on instruments. So many, many centers are working to validate saliva testing on their particular testing platforms.

Scott Gilbert – Dr. Paules, back to the question of who should get tested and when. So beyond being symptomatic, are there any other situations in which I may want to consider having a COVID-19 test?

Dr. Catherine Paules – Yes, certainly if you’ve been in close contact with someone with COVID-19, you may need to get tested. Now I will caveat that by saying that even if your test is negative on a particular day, you might still fall into that quarantine period, meaning you were exposed. You had a negative test, but your test tomorrow could be positive. So it’s important to interpret those results in the context of your medical provider’s recommendations.

Scott Gilbert – And Dr. Paules where can people get tested and where should they get tested? Because we don’t necessarily want everybody with symptoms, for example, running into their doctor’s office or the emergency department, correct?

Dr. Catherine Paules – Correct. So the best way to get a test if you think you need one is to contact your health care provider. And here at the Medical Center, we have a number of ways to get people tested. Some people may want to use our on-demand app where they can actually virtually talk with a provider and help arrange that test. And then we have —

[ Silence ]

Scott Gilbert – I believe we might have just lost Dr. Paules, briefly. It appears that her screen is frozen. So hopefully, she’ll be able to reconnect with us very shortly. But in the meantime, I’m going to pivot to, uh, Dr. George and ask you, um, how long does it take to get results from the different types of tests, you know? Whether it be the molecular test, the antigen, or the antibody test? You know, we also hear the term rapid test. You know, which of those is that?

Dr. Melissa George – So a rapid test is either going to be a point-of-care antigen test or a point-of-care polymerase chain reaction-type test. And they claim as quick as 15 minutes to half an hour, potentially. That being said, they’re usually lower sensitivity. So the testing performed in our laboratories is going to be the highest sensitivity molecular testing. That can take several hours or potentially up to 24 hours because some of the larger instruments that have higher capacity take a little bit longer but they can process more samples.

Scott Gilbert – So then sometimes people will be given a test with a very quick turnaround and sometimes people will be given a test that could take days to turn around. And I think there are a lot of questions out there about why that’s the case, but essentially, that, I guess, goes back to whatever the most appropriate type of test is for the patient, correct?

Dr. Melissa George – Yes, and the reason for taking days, potentially, sometimes that’s for pre-surgical patients who we have a couple days leeway before their procedure. That sometimes gets sent out to another laboratory. So you have to factor in transit time, the time for the patient to actually get the swab, send it back to that other laboratory. And the time for them to receive it, and then run it on their instruments, and then get a result back to that person’s provider either through the computer or through some kind of, you know, fax mechanism.

Scott Gilbert – You’re watching Ask Us Anything About COVID-19 Testing. I’m Scott Gilbert alongside Dr. Melissa George. She is interim chair of the Department of Pathology at Penn State Health Milton S. Hershey Medical Center. Also, Dr. Catherine Paules, an infectious diseases physician from the Medical Center was with us. We think she had an issue with her, uh, Internet connection, but we hope to get her back very shortly. We welcome your questions about COVID-19 testing. Just add them to the comment field below this Facebook post and we’ll get to as many as we can in the time that we have here. Um, so Dr. George, um, with all of these tests, do they come with a likelihood or a possibility of false positives or even false negatives?

Dr. Melissa George – They do, and I’d like to start with the molecular testing, since that’s probably the primary test that we’re using right now. With the molecular test, a false positive is relatively unlikely because there’s a lot of things that factor into getting an accurate test. One is the specimen collection. If you’re in the correct location to obtain a good sample, that gives us our best chance of getting a good result and also within the right timeframe. So most tests are most sensitive within seven days of infection. Now there are chances – the false positive is unlikely because in order to get a false positive, it’s usually contamination from another patient’s specimen. it would have to be someone else who had been positive in order to find those genetic sequences in another patient’s sample. A false negative is a little bit more likely because there’s a chance that the specimen wasn’t collected properly. That maybe it sat out and maybe it wasn’t under the proper storage conditions, or that something got diluted. It could also be the patient was early on in infection and there wasn’t enough virus to detect. So the false negatives are a little bit more common than a false positive, because the false positive, either you have the genetic material or you don’t.

Scott Gilbert – So it sounds like a lot of the same factors, though, that come into processing these tests are probably similar to those they deal with in processing tests for many other types of viruses, correct?

Dr. Melissa George – Absolutely. It’s pretty similar to influenza testing, but the fact is that we’ve known about influenza for years, whereas the SARS-CoV-2 virus is new to us. We’ve had less than really half a year to be looking at this and understanding this virus. But the testing platforms are primarily about the same.

Scott Gilbert – Yeah, so that must be interesting here the fact that it is, uh, new, and that’s why they call it the novel coronavirus. By definition, that means it is a – the newest strain of coronavirus and something we’re still learning very much about. Dr. Paules, good to have you back with us.

Dr. Catherine Paules – Can you hear me?

Scott Gilbert – Loud and clear. I thought I said —

Dr. Catherine Paules – Oh, good. Great.

Scott Gilbert – — something that offended you, so I’m very glad to have you back.

Dr. Catherine Paules – Sorry about that.

Scott Gilbert – No problem at all. We were just talking with Dr. George about processing of tests and the possibility of false positives, and negatives, and that type of thing. One of my questions for you about testing, Dr. Paules, is what should people do after they’ve been tested? Especially, let’s say it’s for a molecular test. Um, what should they do after they’re tested but before they receive the results, especially if there might be some lag time?

Dr. Catherine Paules – Yes, especially if they’re symptomatic or have been in close contact with someone with COVID, they need to be very carefully isolating while they wait for that test to come back. So, for example, if you had some cold-like symptoms, you’re coughing, you have a fever, and you went and got a test. Your next step should be to go home and really keep it to yourself until that test result comes back positive or negative. Because you certainly don’t want to infect anyone else while you’re waiting for those results.

Scott Gilbert – Okay. We do have a few questions in the comment field and we encourage all viewers to add their own. Let’s start with that from Frank. Frank is asking a question of how many COVID viruses are there? He might be asking about coronaviruses because I know that is a rather vast field. Um, Dr. Paules, do you want to give us an idea of exactly what we’re talking about when we say the word coronavirus?

Dr. Catherine Paules – Yes, that’s a great question. Um, so there are four human coronaviruses. So they circulate every year in people and they cause cold-like symptoms. So many of us, almost 90 percent of us, have seen one of those viruses at some point in our life. And then there are three animal coronaviruses that jumped from animals into people. Those coronaviruses cause much more severe illness. The first was SARS. The second MERS, which continues to cause cases mostly in Saudi Arabia. Um, and the third, of course, is SARS-CoV-2 or COVID-19.

Scott Gilbert – And, uh, Dr. Paules, we seem to have lost your video, but your voice is still with us, so stick around. We’ll just keep talking to, uh, the disembodied voice of Dr. Paules, here, as well. Um, Dr. George, if someone was just recently infected with COVID-19, say within the last day or two, will it show up right away on a viral test?

Dr. Melissa George – There’s a chance that it might not, because in the early phases, there may not be enough viral particles to be detected even by sensitive molecular testing. So really within the first seven days, but in that first day shortly after infection, there’s a chance that it may not be detected. And if I could circle back to the other question before about the antigen testing and antibody testing, those are a little bit more likely to have false positives than the molecular testing. Because there’s a chance that the antibodies and antigens may cross react with other similar antigens and antibodies. So when we’re talking about the different strains of coronavirus, there’s a chance if you have antibodies against one of those other strains, that it could cross react with the SARS-CoV-2, as well. Same thing’s true of the antigen testing. Some of the antibodies we use to actually detect the antigens in that test could also possibly cross-react.

Scott Gilbert – And so Dr. Paules, let’s say somebody – if somebody does test positive, how long should they avoid contact with other people? Is it enough to say until you’re not symptomatic, anymore? Because it seems like that wouldn’t be enough since some people never are symptomatic.

Dr. Catherine Paules – That’s a great question. So the Centers for Disease Control and Prevention recommends that somebody waits at least ten days from their positive test result before they come out of isolation. And then that should be coupled with how the person is doing from a clinical standpoint. So if you’re still having fevers, you’re still having a lot of cough, you still need to be isolated. And then there will be some patients that get really sick from COVID or maybe they have some kind of problem with their immune system where they might be infectious longer. So in those cases, usually a doctor will help them decide when it’s safe to come off of isolation.

Scott Gilbert – So then it seems like the main upshot here when it comes to who should get tested, who should be concerned about being tested. It’s definitely a decision that people should make in concert with their provider, correct?

Dr. Catherine Paules – Correct.

Scott Gilbert – Right. Anything else to add from either of you, Dr. George or Dr. Paules?

Dr. Melissa George – Wear a mask and wash your hands.

Dr. Catherine Paules – I second that.

Scott Gilbert – I was going to say, yeah, let’s just it never hurts to reinforce some of those best practices, so let’s expand on those a little bit. Wearing a mask any time you’re in public around people. Using proper hand hygiene, right? Social distancing. Anything else along those lines? Because CDC still recommends all those very highly.

Dr. Catherine Paules – Yes. I think right now, we’re starting to see cases increase in Pennsylvania and we expected that getting into the fall. Um, this winter, keeping those things in place is going to be very important I’m also recommending that people get their flu shot. That’s a vaccine that we can actually give you to protect you against a respiratory virus. And will help decrease the burden on our health care system, and also keep you from having to come into a clinic, or a doctor’s office, or, um, the hospital.

Scott Gilbert – And I know we’re talking about testing mainly today, but Tammy is asking what I feel is an important question. A little bit off topic here, but I think it’s something where I’m sure you could both provide some valuable guidance. Tammy says, “I would like to visit an elderly family member living in her home. What would I need to do to make that visit as safe as possible?” Because let’s face it, it’s been months since we’ve had the all clear to visit with family members, especially elderly ones. Um, do either of you have pointers or anything that you would offer for someone like Tammy?

Dr. Catherine Paules – So nothing we do is zero risk. Um, but there are some things we can do to decrease the risk to our loved ones and still get to see them. I always tell people that outside is better than inside. You have better ventilation that way, um, and there’s some protection of being outdoors. Wearing a mask, both of you, is very important, because that also decreases transmission. And if you do get together, maybe don’t do it for food, you know, because you have to take a mask off to be able to eat. Um, and stay greater than six feet apart, even though I know that can be challenging. We all want to hug our loved ones, but this might be the time to keep some distance when you’re talking and catching up.

Scott Gilbert – And Dr. George, I’d like to address this next question to you. It’s from Debbie. She asks, “What are the statistics on the different tests and their accuracy?” Can you give us a general idea of the accuracy level of those even if you don’t have the exact numbers at your fingertips?

Dr. Melissa George – Sure. That’s a loaded question, because obviously molecular testing is going to be the most accurate in terms of being able to detect the viral particles. So you’re dealing with, you know, sensitivities in the high 90 percents, you know, 95, 98, somewhere thereabouts, and that’s assuming everything’s gone according to plan. That the test was collected properly. There are no problems with the actual specimen itself getting diluted. With the antigen testing, it’s lower sensitivity. So we’re dealing with maybe in the mid to high-80s percents. And for the antibody testing, that all depends. We’re still kind of learning about that because we’re not using it quite as much, yet. Most manufacturers target at least 90%, ideally in the 95 percentile, roughly. But again, we’re not seeing enough antibody testing to really be definitive about that at this point.

Scott Gilbert – And let’s go on to Wayne’s question now, and he says, “Since there are many manufacturers of COVID-19 PCR tests, what do you estimate the false negative rate for the PCR test method?” Maybe we could just talk more in general, and when we say PCR, what exactly is he talking about there, just for the broader context here?

Dr. Melissa George – Very broadly, PCR stands for polymerase chain reaction. So we’re taking viral particles, whether it be your DNA and RNA. We can use it for either type. And basically, there’s a step that requires amplifying to increase the number of viral particles in that sample so we can detect it. Because we’re trying to figure out is it present or is it not present. There are a lot of different platforms and there are a lot of different manufacturers. So it’s a little bit difficult to say that whether or not the false negative rate depends on the different manufacturer types. All of your major companies will have gone through a lot of steps to make sure their test is as good as humanly possible. One of the hardest things for us has been getting test supplies because that’s – there have been supply chain issues throughout the country. So I think it’s really hard to put an exact number on that about false negatives. False negatives can be due to so many things, not just the test. The larger the quality of the sample is a big issue, too.

Scott Gilbert – And I know that, you know, you bring up the issue of supply chain. That’s an important one, but it, uh, you know, I’m sure it has caused – this whole situation has caused some rather creative supply solutions. Uh, and especially in areas for testing such as yours, right, Dr. George?

Dr. Melissa George – Absolutely. Everything from the nasal swabs, to different reagents, to the instruments themselves, have been subject to supply chain problems and possibly reallocation to hot spot areas. Making areas like ours more difficult to obtain some of those supplies. There have been 3D printed swabs. There have been all kinds of creative solutions. We’ve looked at all sorts of technologies that are slightly different and maybe easier to get a hold of. So every option is a possible option right now. It’s plans A through Z instead of plans A through C.

Scott Gilbert – And you mentioned the term reagent. I’ve heard that a lot, actually, and some folks may not understand what that is. Can you talk about what your staff uses a reagent for, what exactly that is?

Dr. Melissa George – Absolutely, any type of instruments. There’s nasal swab, but there’s also chemicals and the reagents, these, you know, chemical compounds that we need to add to actually do the testing, There are tests that, you know, that helps amplify the actual amount of virus. It may help clean up the sample. So there’s certain enzymes that may break down other junk that might be in the sample. For example, especially in saliva, and that actually enables us to put the, um, sample on the instrument, run it, and get an answer. So there’s various liquids that run through an instrument.

Scott Gilbert – Okay. Good information. My thanks to you, both, Dr. Catherine Paules, an infectious diseases physician at the Milton S. Hershey Medical Center. Dr. Melissa George is interim chair of the Department of Pathology at the Milton S. Hershey Medical Center. Thank you, both, for the great information today. Because as we said early on, it’s as timely as ever, so we appreciate your time.

Dr. Melissa George – Thank you.

Dr. Melissa George – Thank you.

Scott Gilbert – And my thanks, as well, to Mike Deiner and Amy Peiffer for their production assistance for Ask Us Anything About COVID-19 Testing from Penn State Health.

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