Educational Webinar: A timely seasonal update on respiratory testing in primary & urgent care

Good day and welcome. Today's conference is being recorded. To ask a question over the web during today's program, please locate the Q&A panel in the lower right corner of your console. Once opened, type in your question and click Send to all panelists. Now I'd like to turn the conference over to Ms. Allison Kiser. Please go ahead. – [Allison] Thank you, operator. And good afternoon, everyone. My name is Allison Kiser, and I'm a marketing manager at McKesson Medical-Surgical. And I'm pleased to welcome you to today's special webinar event, A Timely Seasonal Update on Respiratory Testing in Primary and Urgent Care. Our speaker for today is Dr. Gregory Berry. Dr. Berry received his undergraduate degree in biology from East Stroudsburg University. And his Ph.D. in microbiology and immunology from Pennsylvania State University College of Medicine in Hershey, Pennsylvania. He also completed a fellowship in medical microbiology and public health at University of Texas Medical Branch in Galveston, Texas. Dr. Berry is the director of Molecular Diagnostics and an assistant director of Infectious Disease Diagnostics at Northwell Health Laboratory. And is also the director of Microbiology at Long Island Jewish Medical Center in New York. He is also a diplomate of the American Board of Medical Microbiology, and assistant professor of Pathology and Laboratory Medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell. His interests include the optimization of current methodologies and the development of new technologies for patient-centered clinical testing. Before we begin, a few quick notes. To ask a question over the web, please locate the Q&A panel in the lower right corner of your console. Once opened, type in your question, and click Send to all panelists. We will answer questions at the end of the webinar. A copy of the recording and slides will be sent to you within 24 hours. Thank you very much and please join me in welcoming today's speaker, Dr. Gregory Berry. – [Dr. Berry] Well, thank you so much, Allison, for that kind introduction. And it really is a pleasure to be able to speak to you all today about a topic that obviously is at the forefront of my mind and all of your minds as well. So with that, I would like to just start with a basic disclosure slide. And also, my own… Whoops, sorry about that. And my own speaker's disclosures. And I'd also like to thank you for all that you do every day. And you know, I just want to say I know McKesson wants to thank you but I also want to thank you personally for all the amazing work you've done over this pandemic and the amazing work you do all the time. But it has been particularly trying over the last 10 to 11 months, and you know, we have not had a respite. And so I just want to say that I appreciate that and so do they. So with that, I believe there are a few poll questions that they want to launch. Let's see how that works. There we go. And so if you can see on your right-hand side of your screen in that polling question box, you basically see the poll. So if you look at your practice right now most of your respiratory testing is performed how? Is it either in-house, send out, or not-applicable? And so I'll give you a few minutes to close that poll. And so I think that's good, we'll move on to the next question. Just waiting for it to load up to the next question. So I'm actually still seeing the same question in my box. So what I'm going to do is actually move the slides forward and we can come back to those in a little bit. So the learning objectives today are going to be to basically…there we go. Now the question just popped up. So if you would go back and if you would say what do we like to do in our practice? Would we like to shift more to in-house testing? Would we like to send more out? Would we like to keep more in-house and send out testing as is? Or would the answer be not applicable? So I think we could close that poll. And so we'll just give it a second for the next one to load. And so here's another question. So relative to test method usage, we would like to expand antigen testing, A, expand molecular testing, B, expand both, C, not change, D, or not applicable? And I believe there is one more question in the poll. But you know, as we go through the presentation you know, just want to kind of think about what your answers are before and after. And kind of go back and reflect and see if after the presentation you feel different about one particular issue or another. Or perhaps hopefully, the presentation helps guide you in that decision making by giving you more knowledge to make your decision to kind of figure out which one makes the most sense. So with that, I will move on to the learning objectives for today's talk. So learning objectives are to basically give an update on respiratory season infections and to kind of forecast coming up. I want to also review the latest SARS-CoV-2 molecular and antigen testing methods, their performance, and really their use cases which are super important. And I want to focus primarily on primary urgent care settings. I also want to go over perspectives of multi-test respiratory panels, whether those are larger panels or smaller panels. And some of the test performance and the detection of co-infection. And I also want to go over the value of rapid testing for respiratory illnesses and other diseases. And so really I just want to start with a brief overview of COVID-19 which obviously we've talked about over the last several months. And always goes back, it's always super important to go back to kind of the beginning kind of go over basic concepts again such as the virus itself. So the virus itself is Severe Acute Respiratory Syndrome Coronavirus 2, or SARS-CoV-2. This was first discovered in December 2019 in Wuhan, which is in Hubei province in China. The genus is a Betacoronavirus, subgenus Sarbecovirus. And the clinical disease which you hear all the time is referred to as COVID-19. There's been over 300,000 deaths in the U.S. thus far, I believe it's over 400,000 at this point. So a staggering number of deaths and just you know, what's happened. And over 35,000 of these deaths have been alone in New York. So we're based in New York State actually, right outside of New York City so I a lot of times go to the New York numbers because they're sharp numbers. And so you'll see I'll cover that a bit in the presentation. The first confirmed case was in New York at the beginning of March, but it quickly became apparent to us that SARS-CoV-2 cases were widespread. And you see the virus right here this is a little pictogram of the virus. You basically see that F that spike glycoprotein that we hear so much about, you have the membrane protein, you have the nuclear proteins which are in here. And then you, of course, have the RNA which is the actual viral RNA. And you have the envelope. And you know the interesting thing and I always like to point out is this coronavirus is new to humans as a pathogen, but there are four other common colds causing coronaviruses that circulate each year. You know, NL63, 229E HKU1, and OC43. So these are common coronaviruses that we see every year in our respiratory testing. And in fact, I pulled these numbers before I gave this presentation you know, from previous years. And on average, if we have a positive respiratory panel, these are about 10% of the overall respiratory cases. So it's not a small number of cases that are actually caused by the coronaviruses. And when we think of the clinical symptomology that's associated with SARS-CoV-2 actually the disease being COVID-19, you think of respiratory tract manifestations, and you think of you know, the nose, the mouth, the throat, in general sinusitis. You know, long manifestations for just coughing and chest pain. And then you have more extra respiratory issues such as neurological issues, muscular, digestive issues. And you see a systemic response that shows fatigue, and malaise, and fever. You know, and of course, here in the red are the much more serious issues that you tend to see in the more serious case. So, overall, a pretty wide manifestation of symptoms that can be caused by SARS-CoV-2. And you know, I think this has been confusing for people not as much now, but especially at the beginning. Is it COVID-19 or is it SARS-CoV-2? So they're often used interchangeably. In fact, I use them interchangeably myself quite often especially when I'm in casual conversation. You know, Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2 actually is a virus. And what it causes is it causes the coronavirus disease which is called COVID-19. And the 19, of course, refers to 2019 because we saw those first cases in December of 2019 which is amazing because it feels like it was just yesterday, but you think it's been a year already. And many lab tests or manufacturers are marketed as SARS-CoV-2 tests because of course, that's the virus. And so there are some numbers that I just wanted to go over because I think it kind of shows very clearly, it lays bare what the situation is like. So if we look at just the state of New York, for example, and we look at the total number of people who were positive and who were tested. So I'll give you an example. This was from a random Thursday a couple of weeks ago, on 12/17/2020. This is the total number of people had been tested in New York State up to that point. Now, it's significantly more now. But we almost had 23 million people, approximately a month ago. The total that were tested just on that day alone were almost a quarter of a million people. And the total tests that were positive up to that point from the beginning to the end, had been just over 800,000 tests. But I think the real stark number here was that even that day, there were 12,697 new positives in New York State and city alone. And that's just amazing. And as we've looked at the numbers, I didn't get into all the other nitty-gritty of the numbers but I did want to show this slide in particular because I think it makes a point. If you look right here so March 1st, back in March 1st, was actually…March 2nd was the first case in New York and you saw a drastic increase. So right here yellow is positive, blue is total number of persons tested. So you see obviously, our testing capabilities have gone way up over time, right? At the beginning, we couldn't test that many people but we had a tremendous number of positives. In fact, we hit almost a 70% positivity rate at the beginning of this spread in New York. And then you saw it right here kind of June and July, especially July, August, September, it petered out and went down below 2% positivity, rate. And you basically watch though, as right after Halloween, we see this bump back up. And you see this red box here on the screen it's kind of amazing to think that now these positive cases have bumped back up. So of course, the positivity rate is not nearly as high as it was here because we weren't testing as many people. But the number of cases is actually quite substantial, as I had just shown. And so, you know, studying what I…you know, being a clinical microbiologist and a clinical virologist, as I looked at this I thought…my mind popped to two things. One of the things that I thought of right off the bat was I thought about this whole idea of a second wave. And mainly the reason I thought about this is because I actually gave a talk back in June actually a talk for McKesson where we talked about the potential of a second wave. So this was right around that time when I gave the talk. And so the line was pretty much right here we did not have data going forward. But health modeling had actually shown that a second wave was potentially going to happen beginning of September. And as you can see, they predicted that we were going to see this wave. Well, in fact, it is quite close to what we have seen. Not exactly the model per se, but the fact that we have seen cases tick way back up going into the fall. That was one thing I thought of. The other thing I thought about was intrinsically when you look at coronaviruses, and when you look at the spread of respiratory viruses in the human population, what kind of behaviors do they exhibit over time? What are the natural behaviors of the viruses that we basically have every year that circulate to the population? That made me think of the other coronaviruses those four I discussed, those four seasonal cold viruses. When we look at that data, it was really interesting. So I thought are we going to start to see a seasonality eventually of SARS-CoV-2? Now if you ask me, I don't think we see a seasonality no not yet. I don't think we fall into that pattern. But will we fall into that pattern eventually? I think that that is a question that's worth thinking about. So if you look at this, this is actually a publication from early on in the pandemic in the Swiss rather "Swiss Med Weekly" looking at the other seasonal coronaviruses those four 229E, NL63, HKU1, and OC43. And as you can kind of see when you look at this, you see that here's 2010, here's 2011, here's 2012, here's 2013. How they fall into this seasonal pattern going basically into the wintertime. So you see them drop down through months, you know, and then by month 12 December, you see them spike back up. So it's kind of interesting to watch that happen. And I think the big question is going to be is how long does immunity last for SARS-CoV-2? If immunity or if the vaccine induces a really robust immunity that lasts longer than a year, for example, you may see this fall into some kind of like a biannual kind of pattern. Whereas it's kind of interesting when you look at these two, you look at HKU1 and OC43 immunity after natural infection lasts on average about 40 weeks. So it's kind of of interesting as the other season then progresses and you go into the next cold season, you're kind of at the point now where you're susceptible to reinfection, which is why you start to see these interesting seasonal patterns. So it's going to be absolutely critical to see how long immunity lasts. And also, obviously, effective vaccination is going to be a huge part of that puzzle piece that really needs to be addressed. And so the question, so we know what SARS-CoV-2 is up to. Now what's influenza up to which is our old respiratory foe every year? And so if you take a look at this slide actually, you can see…and I had originally overlaid this slide, but you can see this just as well. This is the 2019/2020 flu season. This is the one before that, you pretty much see that every season…okay the gray one from 2009/2010. And a couple of the other ones as you watch they kind of go for influenza-like illness, you watch them bounce all over the place. But you see this flu season in red here kind of just stabilizes, right way, way low in the 1% range. And when we look at actual flu cases that have been confirmed by laboratories, you see that the number of positive cases is down below 100 actually or right around or down to 50 to 100, which is amazing this time of year for this to be the case. And so flu for all intents and purposes flu is not here and that's been really interesting. And our thought on that and I'm sure your thought on that is the masking strategy is really doing a number on influenza infections. And it's kind of incredible to watch that…you know, I mean, even in the worst flu season almost everybody I mean, if you looked at the population, they weren't wearing masks, right? And the masks have really had what looks to be probably a major influence on influenza this year. And then, of course, you have RSV which has always been around with flu during the respiratory season. And it's one of the most common causes of childhood illness. And really the most common cause of bronchiolitis which is inflammation of the small airways and pneumonia in children less than one year of age in the United States. So still a serious pathogen. And also in the elderly, it tends to cause major issues. And it's a significant cause of respiratory illness in older adults. The issue has always been the symptomology really just heavily overlaps with flu, but the treatment for RSV is different than flu. So it's always been interesting to look at when you go into respiratory season what do you need to test for? What's a nice to have and what's a has to have? And we'll get to that later. And so, when we look at the types of testing for SARS-CoV-2 you're really thinking of…SARS-CoV-2, by the way, and that would be the main one for this. You're thinking of molecular, molecular is for all the respiratory viruses, right? Viral antigen is for the respiratory viruses as well. Serology is definitely important for SARS-CoV-2 with understanding past immunity, much less so for things like influenza. But these are the three buckets of testing falls into when you think about molecular, antigen, or serology. And then when you dig into molecular or dig into viral antigen, then obviously we get to the point of care and other things. I think the most important thing to think about is when are these tests appropriate, when are they not? When are they useful? And I thought this was really nice. This is actually a…this is a chart from "JAMA" actually looking at when certain tests are good during what time course of infection. So this is really important, especially at the beginning when we weren't testing asymptomatic people. And before symptom onset detection was unlikely. And it wasn't unlikely because a PCR wouldn't pick it up as you can see here PCR would have picked it up no problem. Here's the viral exposure basically, the patient feels fine, no test, right so you don't know it's there. Are they spreading? Oh, yes, they are spreading the virus, but they don't know they have it yet. Then after symptom onset, PCR is almost always likely positive if the specimen is collected properly. We'll get into that a little bit too. I mean, obviously, pre-analytical which basically is the point where you collect the specimen, it's so important to collect a good specimen. But if you do collect a good specimen and the proper specimen is sent the PCR is likely positive, right? As time goes on after four weeks the PCR is more likely to be negative than positive. Although if you test somebody out two three months sometimes they're positive which is amazing which is why you really got to adhere to the CDC guidelines for retesting for known cases. And when you get out further antibodies then tend to come up. You see here's your IgM and your IgG for SARS-CoV-2 coming up right here. And as the PCR kind of drops off here, then the antibodies are positive for past exposure. Again, antibodies are not diagnostics, you're not going to diagnose a patient using antibodies with a primary infection that's for molecular testing, right? But the antibodies can do a lot for epidemiology. And also to know if somebody had had…you know, besides EPI, I mean on the individual patient basis to know if a patient had been infected. It's another tool in the tool belt basically. And when we look at molecular testing we're really thinking of nucleic acid amplification tests for viral RNA. And that would be on things like a nasopharyngeal swab, or nasal swab, or sputum, and other sources but those are the main ones. And you're going to measure current infection with SARS-CoV-2. And the value is really that you can inform infection status. And the anticipated course of illness is really understood at that point because we know what the clinical manifestation looks like. You want to inform for patient management and also to prevent transmission so cohorting, quarantine all these types of things. And inform actions needed to prevent transmission, again super important and both the community and in the hospital environment. So molecular testing, in general, molecular methods are the most sensitive and specific types of tests. The point of care molecular advantage is you get a rapid turnaround time instead of waiting to send it to the lab. If you do molecular point of care which are several platforms on the market for flu and a few on the market now coming out to the market for SARS-CoV-2 really the advantage is that you're going to get an answer super quick and be able to move on that answer. And you know, rapid results have potential downstream impact, appropriate therapy, shorten recovery time potentially if you catch it early enough. And obviously, patient satisfaction because they get the answer right away. Traditional molecular tests, when we talk about molecular typically what people always think about is the laboratory, right? And so traditional molecular lab tests are highly sensitive and specific, they're performed by a specialized laboratory personnel, so we're not thinking about point of care. And you're thinking approximately a one to two-hour turnaround time on most of these assays once the specimen is in the lab. But that's if it's not batched if it's a sample to answer platform. Batch testing could take up to 12 to 24 hours depending on how frequently tests are done. Now, just to give you an idea I know from the picture you can't tell. But like this one here is the Panther, these are large platforms. These are like the size of what would be a very wide refrigerator for example, if you were looking at household equipment, right. This is a large benchtop analyzer. These two go together as large analyzers. This is actually sitting on the floor these two. This is on the benchtop. Here's another benchtop analyzer. So these are large complex instruments that allow us in a laboratory to make definitive diagnoses using molecular techniques. Then you have your point of care components which are molecular as well. And I'll dig into that a little more. But just to give you an idea, right? Here's your classic rapid antigen test a bunch of them that are on the market. And here's all your molecular tests that are on the market. And you think about what the value is of being able to amplify a specimen? So okay, let's say take the same exact specimen, right? Let's say you start with this. So basically, you collect that, well, here's your detection threshold right here. Well, what you have is what you have. If there's enough for your test to detect it, it detects it, if not, your test is a false negative. Well, really the power behind the amplification is that as you start to amplify that specimen, even if you potentially if you start with less template, if you start with less RNA or DNA, right, in this case, RNA you're able to amplify that above that detection threshold and still get a positive in the case of a positive but just started with this. And so that really is a huge advantage that molecular has over rapid antigen. And so when we think about antigen tests just to dig into that a little bit, we're thinking about viral antigen tests that could also identify current infection with SARS-CoV-2. But again, you know, amplify you just detect the virus is there. And so I think the value of these tests are you can inform an individual of infection status. And so you can really look at the course of illness and try to manage that. You can inform the patient that they're infected and basically have it affect the decisions as far as cohorting again, and back to that again, back to quarantine decision. And another thing is, it's very specific for the virus. But one important point about viral antigen tests is they're generally not as sensitive as molecular tests. So negative results don't always rule out infection which is an interesting point that has to be considered. And you know, we have tons of experience with rapid antigen tests with both flu and with Group A strep, and with RSV. I mean, they've been available for flu since the 1980s. They're the most common first-line of test at the clinic I'm sure you're all very familiar with these. So immunoassays that detect pathogens-specific antigens. And they're qualitative so you get a yes-no answer, right? Whether it's a dipstick, whether it's a card, whether it's a reader, I mean, you're getting a qualitative yes, no answer. And basically, you're trying to see if there's enough antigen there to have a positive. And sensitivity really varies by platform and by test. So negative flu tests are unreliable, known to be unreliable. The positives are quite reliable, but negatives are not so much. And the same thing with Group A strep which is why especially in the pediatric population, you always need culture confirmation for a negative Group A strep result. And so here was one of the first papers that looked at antigen-based testing for SARS-CoV-2. It's a nice quote from the paper says, "The assay was easy to use and provided results in a timely manner. Hence, it (the antigen test) has the potential to become an important tool for the early diagnosis of SARS-CoV-2. And it was particularly important in situations with limited access to molecular methods." And it's kind of a standard for molecular when molecular wasn't available. And serology testing. So when we think about the type of test this is antibody detection. So is this antibody…what is this antibody, right? Well, this is an actual host or patient immune response to the virus. So you think about that takes a little while, right, your immune system has to see the virus, and it has to actually mount an adaptive, or first an innate and then an adaptive immune response. And then you start making a viral-specific antibody. So it's kind of interesting when you think about this, that this is why you see that lag in antibodies, right? And so this shows past exposure and identifies individuals that have binding antibodies to detect susceptible individuals. Potentially as a thought, right because if you have the antibodies you could be immune, if you don't have the antibodies well, then we know you're definitely not immune. And it can facilitate contact tracing and surveillance. And so now I just want to discuss because obviously, with this group, point of care testing is huge and it's a super important topic. So I want to talk about the value of point of care testing a bit more than we already have. And so when we think about point of care testing and we talk about what's important, well, timing is everything with point of care testing, right? Timing is you look at days post symptom onset, right so day zero is basically when you start to feel ill. Day 10 you're feeling much better. Day 20, you don't even remember you had it hopefully. That's what I hope anyway. So you go back to day zero well, day zero to four is when the patient…three to four are really when the patients are most infectious, right? And you have the higher viral titer, as your titer goes just like this up and then down, right and maybe up higher, right then down, but you get the idea, right? This is also like for flu, for example, when the antiviral drugs are most effective during first two days of viral sickness and symptoms. Of course, there's nothing for SARS-CoV-2 this was previous. This is a really nice slide to kind of just show about viral infection. But again, this is flu, this is not COVID-19 so keep that in mind. So recommended timeframe for sample collection is really this red box here when you think about it. And this is when obviously rapid point of care is going to have its highest sensitivity because you start with more virus you're more likely going to get a positive. You test out here, way less likely. You test all the way out further out, even way less more…even less than. And, of course, clinically, what do you do with the answer over the last 10 days out? I mean you're already feeling better. And in general, you know, unless you're talking about a hospitalized patient who they're trying to identify the cause in the clinic, it's not as useful. And so when we think about point of care tests, these are tests that are performed while patient care is occurring. And really the main advantage, the huge advantage is the time game because you can make therapeutic choices right on the spot, and you can identify what's the cause, what's the pathogen. And then what treatment, how do we treat that right? And so we can avoid going down unnecessary roads because you have the answer right in front of you. And what this absolute requires though, is simple platforms with accurate results, right. I think that one of the main things that sometimes gets missed is point of care is fantastic. I love point of care test. I love sensitive and specific point of care tests, though. I think point of care needs as much regulation of laboratory testing because if point of care is done wrong, you get the wrong answer. And so it's super important that these tests need to perform…if they're going to be used like the laboratory tests are used, they have to perform at the same level as laboratory tests. I mean, there's a reason that tests have stayed in the lab. And certain tests absolutely have stayed in the lab and will continue to stay in the lab because certain tests just can't be simplified enough to actually run at point of care. But the ones that can have offer that huge advantage. So I think that we'll see a trend towards point of care, in any case, where we can make sure that the result is correct. And that it's just as good as in the laboratory which again you know, put certain things like for example, flu and RSV testing, molecular base flu and RSV testing, right? Strep testing molecular strep. I think that these are all really cool opportunities to really improve patient care. But I think that the important thing is we're going to need to give the right resources to point of care at our facilities in order to make that happen and to make it happen the right way. And so I think one interesting thing now just to get back to SARS-CoV-2 and dive into that a little bit. So I think one of the big problems is for COVID-19, we had all of a sudden, a ton of platforms on the market, right. So we had no data, so we didn't even know how they were going to perform. So you know, I think it was super important early on for groups like for example, my group and other groups all over the country to start publishing this work. And so just to give you an idea some of the initial published evidence for point of care molecular tests that came out were really the early ones looking at the platforms that were developing you know, they were developing these point of care platforms for SARS-CoV-2. For example, things like Cepheid, things like the ID NOW, and looking at the performance of these tests, you know, because they would be used at the clinics just to find out how sensitive and specific they were. And so when we looked at those, you know, there's a wealth of knowledge now starting to be generated, and a bunch have already been generated looking at each of the platforms. So as you start to look at any of your platforms that you're considering, start to dig into the literature, literally do a Google search. I mean, you can start to…start with a Google search, you can go into Google Scholar, I mean, you can use "PubMed," too. But I have to say Google sometimes is just as easy, especially Google Scholar to look up a couple of papers on the platform that you're interested in. And also I think looking at some of the antigen tests. Now, this is a little bit older but not too much. I mean, there's not that many papers out yet, but they're starting to come out looking at the initial evidence for rapid antigen tests and basically where their use case is. And so I think that…sorry, this jumped a little ahead. I think point of care is obviously going to be an ever-increasing proportion of SARS-CoV-2 testing strategy. So much so that the CDC even has a page looking at this, and you can see this was basically the guidance page for SARS-CoV-2. And you'll see these are the different platforms now. So we have ID NOW as isothermal amplification. The BD Veritor, and the BinaxNOW is a rapid antigen, right? Cepheid is molecular and etc., right. And really also the question is, what is the role for multiplex testing, right? So okay, SARS-CoV-2 testing since March has been absolutely critical. But as we enter the flu season, right the traditional flu season, you see we got no flu season, right, but it's the respiratory season. The question was okay, well, I still got to test for SARS-CoV-2 what else do I have to test for? Well, obviously, flu didn't disappear it's still a human pathogen, right? Flu A, flu B still a major problem. RSV is still a major problem obviously clinically in kids and in the elderly, but also all the carriers in between. And so this is always the thought like, what do we need to test for? What can we not do with that? What's the nice to have and what's the has to have, right? Well, my opinion, I think that a has to have, at least as far as SARS-CoV-2 flu A, flu B, and RSV, right. So here's this one paper this was actually one that my group participated in a multi-site study with several other institutions looking at the evaluation of Cepheid Xpert Xpress which was a SARS-CoV-2 flu A, flu B, and RSV test. And you know, basically, the question is, you know, clinical microbiology and public health labs really needed a rapid diagnostic assay to look at COVID-19 versus flu versus RSV because it's super important for example, for figuring out epidemiology. But even a little bit more directly clinically focused, it's super important for cohorting and for infection control, and for all of these types of things. And the performance of this…in this particular case, this performance of the Cepheid flu, RSV, COVID was great. And I think a lot of the molecular tests we're going to see really good performance. So stay tuned and they're starting to roll out onto the market and several are already on the market. So it's definitely going to be a hot topic one of which I'm going to definitely stay close to. And so I think this is a super unique respiratory season I mean, as was the end of last right? I mean, but really the end of last right where this is going in, we are in the respiratory season. And this has really been a unique respiratory season with really I think interesting potential challenges. So I think key selection factors for your types of tests for SARS-CoV-2, but also for flu A, B, RSV, which we just talked about you know, what are your needs of your patients and your practice? What kind of performance characteristics do you need in your particular population? Are you talking about an immunosuppressed population, or a particularly, you know, health vulnerable population? Is this…all these types of things need to be thought about. Understanding your test options I think is absolutely critical today and in respiratory season. And when you come out of respiratory season, again, you're going to have to reevaluate every year, you have to reevaluate. And I think a strong consideration for diversification and testing platforms is also really, really important. So I have to go back to that one again and just kind of reiterate that the supply chains have not been great. Tests that you can get ahold of yesterday, you can't get ahold of today. And they've gotten a bit better but it's been very difficult. So I think it shined a very bright light on why just-in-time inventory doesn't work well and especially doesn't work when you get surges and other things. And obviously, in a pandemic, it's really been laid bare that there are major issues with just-in-time inventory. So you want to consider that when you think about how you build your budgets and how much you buy. Because I have over 10 platforms in the health system that I use. I use three major platforms for high-volume testing. And I use five or six small platforms for more close-to-patient testing. So it's been a very interesting year and it's been one where you constantly pull different levers to move things in different spots that you just never had to think about before. So I know we're all experiencing that. And so here are just some lab resources that you can go back to, to look at this. And I think that these are all really nice resources. And you want to stay up-to-date with your various stuff. And McKesson actually has an address here that you can go to keep up with COVID-19 where they boil down some of the most important facts. And with that, I'd like to thank Department of Pathology and Lab Medicine at Northwell Health. Specifically, I'd like to thank my research scientist Wei Zhen who I work so closely with. And Betsy Smith my Ops manager. And Ryhana my Ops supervisor who has just been fantastic and have published me multiple times throughout this, and we've, you know, been able to keep things running. I'd also like to thank my colleagues. Deb Schron and Scott Duong. And absolutely, the biggest round of applause goes to the fantastic members of my laboratory, The Molecular Diagnostics Lab at Northwell because they've kept the patient testing and the clinical care rolling by keeping that patient testing coming out of the lab in real-time. So with that, I would like to take any questions. And thank you so much it was a pleasure speaking with all of you. – Great, thank you. Thank you so much, Dr. Berry. If you wouldn't mind, go ahead and give instructions for how to ask the question over the web. – Certainly, ma'am. At this time, if you'd like to ask a question over the web, locate the Q&A panel on the right hand side of your screen, type in question in the open area, and click Send. – Okay, great. So we do have a few questions in the queue. And we have time to take a few questions. So the first one is from Courtney and it's a good question, one that we're seeing a lot. So it's about antibody testing. How long after the infection do most patients stay antibody-positive? I have a patient with possible downstream COVID complications and we're debating the value of the antibody test three months after symptoms. – Well, you know, that's a great question because the problem with a new human pathogen is we haven't been able to go years and years and actually look at any of these antibody responses. So you know, like in flu, for example, antibodies are pretty much useless and flu testing. I mean part of that is obviously the vaccination strategy. And another part is that just it doesn't seem useful for actually tracking influenza-related diseases just because flu is so widely established in the population. So for COVID, I mean, three months out, you should see a robust antibody response. Sicker patients tend to have a higher antibody index. It's kind of hard to track though because across the platforms, different platforms have different numbers so they're very difficult to compare across. But three months out you should see a robust immune response still. Now a year out I think that's still to be said, you know, to see. – Oh, great, thank you. So another question that we do have a lot is about testing children. So if you wouldn't mind just speaking to that, you know, recommendations to follow. I know that it's difficult to do. So do you have any thoughts or recommendations there for testing small children? – So, you know, overall anecdotally, when I talk to pediatricians, they tend to say that you know, COVID has ended up being a disease mostly of adults, right and has really wreaked havoc in the adult population. But in the pediatric population while it's there, and while it can cause sickness, it's not been a major issue like it has been with adults. So while children can get tested, I mean, I would defer to the local pediatrician because, for example, I have three children, right, I have three young children, one, four, and six. And I've had to bring them in with school closing and with different things multiple times. And you know, each time my one daughter, my oldest one, my six-year-old got tested actually, a couple of times. She was negative both times. But like, the pediatrician was basically saying that when I went in well, I mean, you know, they want everybody to have a test, but we don't tend to see as many…you know, we don't tend to see it in kids as much as we've been seeing in adults. So I'm sure a lot of people are going to argue with me on that one and that's completely anecdotal. But I mean, testing kids hasn't been as intense, nearly as intense as it's been in adults. So I would just defer to whoever your ordering pediatrician is and see if the symptomology actually matches what could be you know, a COVID-19 particular illness and then go with it. I mean, obviously, kids can have a nasopharyngeal swab. I mean, it's just a matter of it's not fun to do it serially. I mean, all of us who have had testing serially know how not-fun it is. And if you have children, you know how not-fun they find it to be. So, I feel I don't just…you know, I definitely sympathize with you but yeah, I would just go with your local guidance and just keep that in mind. – Thank you. So could you now speak to the improvements in accuracy with rapid antigen testing particularly also with asymptomatic patients if you could speak to that as well? – So, yeah, I mean, rapid antigen testing is never going to be as sensitive as molecular testing. And the reason for that is because it doesn't actually amplify the specimen, right. So when you do molecular testing, you actually take the specimen and you amplify the actual RNA in the specimen. So while rapid antigen tests will not necessarily…they obviously won't pick up every infection that will get picked up by molecular. The question is, is it picking up the clinically relevant tests? And I think that's the real question that is very difficult to answer. And I think that the literature really is still quite, you know… there's a positive literature talking about the clinically relevant test. We know the molecular cut-offs, we kind of know where a molecular test will be positive and an antigen test will be negative. But every test has its use case, right? Rapid antigens just like molecular testing has their use case. And it has to be in a particular patient population where you know the risks of potentially getting a false negative. And those risks outweigh…you know, basically, the benefit outweighs the risk. And so you're going to ask yourself that when you do a risk assessment of what that means. So, you know, rapid antigen tests [inaudible] on some cases the question is, if somebody comes in and they have an illness, right a respiratory illness, and you do a COVID-19 rapid antigen test on them, but they still have a respiratory illness, and it's negative. Okay, if it's positive, you know they're positive, you can tell them to go home and they got to quarantine and everything else that goes along with it. But if the test is negative, I think especially as time goes on right, as COVID-19 becomes more run of the mill, which is still quite far down the road. But just like flu, what do you tell somebody if they come in for a flu rapid antigen test and it's negative but they have flu-like symptoms? You tell them you could still have the flu, you need to go home, you need to you know, self isolate. You know, keep a close eye on your health and keep a close eye on your symptomology. And please call immediately if there's any at all adverse…you know, you see things starting to… if you start to do poorly, you need to call immediately and get medical attention. I think if it's with the context of that, I think that it's much easier to understand how you would use a rapid antigen test. [crosstalk] – So you hear about… Sorry. Thank you. We have time for maybe two more questions so here's one more. So you hear about patients with persistent positives that require long quarantine but are those individuals infectious? – Well, you know, that's…I've debated this with people. And it's funny, you can kind of go either way. You say, well, you know that, for example, the molecular test is still positive, therefore, it's picking up something, right. And people will say…I've heard people say, "Well, that's dead RNA it's picking up." First of all, it makes me laugh because what is dead RNA versus live RNA? That's kind of a funny statement. But other than that, other than my own peculiarities being a lab person finding that funny, I think that the practical part of that is well, at what threshold is that specimen infectious, right? And that's a legit question, right? So if it can grow in cell culture, for example, as an infectious…now, we don't do cell culture diagnostically. It's actually because it would need to be done in a highly…it would need to be done above the HEPA filtration everything that we do in a clinical lab which is already quite good, but it's done at a different level for infectious reasons. I think that a lot of those studies still need to be done. So we're not really sure yet which is why you see public health erring on the side of caution when you see that positive. While I said that the verdict is still out on that, it can't be out for much longer because it has huge implications on public health and on society in general. So I think that we don't know the answer yet but I think the answer will need to be addressed quite soon. I hope that was helpful. – Absolutely. So here's another question for you. So you hear about…I'm sorry. Yeah, so really quickly, this one looks like you have already answered it. But you have people that are testing negatives during initial contact tracing, they have symptoms, but test negative then, of course, later test positive. Just, in your opinion, you know, what is the best time to test and which test is the most reliable, in your opinion? – Well, I think if you're worried about that definitely a molecular test is the most reliable any of the laboratory-based molecular tests. I mean, the point of care molecular tests are pretty darn good too. But if you really want to make sure that you that you're getting the best test result what you want to do…especially in those questionable cases because you're already questioning it, right? You want to collect a nasopharyngeal swab. Skip the nasal, get a nasopharyngeal and send that to the laboratory and use you know, a molecular base PCR test in the lab. Because you're just going to get the best sensitivity in one of those tests. And the nasopharyngeal swab needs to be done properly. You know, you need to follow the instructions and actually do a real, actual good nasopharyngeal swab. – Great, thank you. So before we close, just real quick, Dr. Berry, and thank you again for all of this great information today. You have any remaining recommendations for sites that are still managing testing and types of testing, any successes that you've seen? – Well, you know, some of the successes I think have been switching over to some of the molecular tests. But also I say, on the flip side, some of the tests you know, obviously sites have been switching being able to get their hands on some of the rapid antigen tests. And I think as long as they understand the caveats of the test, I think as the testing supply gets better, they're going to have a better opportunity to actually do testing on-site and keep things moving. One thing I did notice in the chat there were a couple questions. I see one from Judy Works, she said that she had a patient that was COVID-19 positive in September. They're planning to go trekking in Nepal in April want to know if there's a way to determine if he still has immunity. And what specific antibody test would I recommend. I wouldn't recommend a specific antibody test. But I mean, obviously, if you order antibodies, you could look at whether they're still positive or not. Now, the question is, even if they have an antibody-positive test does that guarantee that they're going to be immune and not get reinfected? Well, I'd say the chances are quite high, you know, knowing immunology, I'd say it's quite good. But again, you don't have any… there's no dead ringer right now. There's still 100% that you know that that's a perfect you know, match and a correlation where that person is completely protected. Another one, Wendy Brody said you mentioned good samples giving good results. What are your thoughts about take-home tests I know Labcorp and Quest have one but I know there are two more coming on the market soon. So take-home tests I think are a really interesting concept. I think…and there's even that one called Lucira, right that is like a $50 at-home test. Like I even did a…the news interviewed me about that test actually. I think pre-analytical is going to be super important. Do people know how to take a good nasal swab on themselves? I mean, then we'll look at the sensitivity and specificity of the test. But the at-home test the problem is are we sample handling pre-analytical. Do they take it right or don't they? And also there's one more from Wendy, is there a significant difference between a provider collected versus a medically supervised patient collected test? Now, study-wise I am not actually…I can't think of a study off the top of my head that looked at those two variables. I'm not saying there's not one out there because there may be. So I would do a quick lit search, that's what I'm going to do after the call even. But you know, overall, providers obviously know how to collect a nasopharyngeal swab, you know, or a nasal swab because they do it all the time. While medically supervised patient collection, you know, while people are supervised, I mean, they're still using their own hands to do the collection. So I'm actually not sure about that but it'll be interesting to see. And I'm going to do a quick lit search along. So that's all the questions that were in the chat, too. So I wanted to make sure I was all-inclusive. – Thank you so much. Well, that does conclude our call today. So I do want to one more time thank Dr. Berry for all of his great information today, and all of you for attending. And as a reminder, you can find a list of all of our upcoming webinars at mms.mckesson.com. And visit our COVID-19 Resource Center while you're there to learn more about upcoming events. And again, in closing, thank you again, Dr. Berry, for all of this expertise. And we will see you all next time. Thank you. – Thank you. It was a real pleasure. Have a great day. – And this does conclude today's event. You may now disconnect your lines.