The COVID-19 Testing Environment & the Role Testing will Play in “Return to Normalcy”
Insight by Doug Schenkel
Doug Schenkel, Cowen’s Life Science & Diagnostic Tools analyst speaks with Nathan Ledeboer, Ph.D.Professor, Pathology and Medical Director of Microbiology and Molecular Diagnostics Laboratories, Froedtert & the Medical College of Wisconsin. They discuss how COVID-19 testing has evolved over the past several weeks and some current bottlenecks contributing to the inability to test on a wide scale basis. They also speak about the broader use of molecular diagnostics and how diagnostic tests such as serologic tests can be used to reopen the economy.
Press play below to listen to their conversation.
Cowen Host:
Doug Schenkel, Managing Director, Health Care – Life Science & Diagnostic Tools
Guest:
Nathan Ledeboer, Ph.D.
Nathan Ledeboer, Ph.D. is Professor of Pathology and Medical Director of Microbiology and Molecular Diagnostics Laboratories at Froedtert & the Medical College of Wisconsin. Dr. Ledeboer’s primary responsibility is for the medical and technical oversight of the Clinical Microbiology and Molecular Diagnostics Laboratories. In this role he oversees development and implementation of new assays, oversees and sign out all testing performed in these laboratories, and consults with physician colleagues regarding test results and selection. His research interests include the development of rapid molecular techniques for detection of infectious diseases and molecular detection and epidemiology of respiratory viruses.
Transcript
Speaker 1: Welcome to Cowen Insights, a special look at the Coronavirus and its effects on sectors across the economy as well as the policy arena. You will hear the latest insights from leading experts about where things stand and what’s around the corner.
Doug: [00:00:30] Good afternoon, everyone. I’m joined by my colleagues, Ryan Blicker, Chris Mullen, Subbu Nambi from the Cowen Life Science, & Diagnostic team. It’s our pleasure to welcome Dr. Nate Ledeboar. Nate joins us from Froedtert and the Medical College of Wisconsin. His primary responsibility is for medical and technical oversight of the clinical microbiology and molecular diagnostic labs there. Thanks for joining us again, Nate. Just to provide a quick roadmap [00:01:00] for our discussion. Our intent is to discuss where things stand at Nate’s lab today and how that compares to when we spoke with Nate on our last conference call about a month ago. Second thing we want to do is really assess the outlook for broader use of molecular diagnostics. The third thing we want to get at is really just talking through how diagnostic tests such as serologic tests can be used to reopen the economy.
Nate, just to get [00:01:30] into the current state of affairs. Again, we spoke with you actually pretty much a month ago to the day. At that point there were I think under 10 COVID 19 cases known in Wisconsin where you’re based. I believe the state’s now approaching 3000 cases. So the numbers have jumped a lot, but it actually seems like, where we are today is actually a bit better than you might’ve expected based on what we talked about last month. [00:02:00] Would you agree with that?
Dr. Ledeboar: Yeah. I would overall agree with that and I think we’ve really seen it. One of the interesting things that we’ve seen, particularly in the Midwest and similar between say Milwaukee and Detroit is this is a really adversely affected populations quite differently. So among our at-risk underserved populations, particularly our African-American and our Hispanic populations, we’ve seen very, very significant levels of disease. Whereas [00:02:30] our Caucasian populations, we have not seen as severe of disease and we have not seen, the quantity of disease. So it’s been kind of different. So certainly for our overall population we’ve seen it be a little bit less as bad as we had expected it to be. But certainly for some of our at-risk populations it’s been quite a devastating event overall.
Doug: Do you think some of that is a function of density or [00:03:00] certain conditions that are more prevalent in certain demographics, or might it be something other than that?
Dr. Ledeboar: So there’ve been a number of studies that have looked at whether there’s a genetic basis or not to these differences. And what we’ve overall found is that there’s probably not a genetic basis to it. I think a lot of it is number one, communicating and really conveying the information from both public health authorities. Its living conditions, certainly it’s living with multi-generational families, that [00:03:30] could be playing a role. I think there are a number of sociological factors that are probably playing into that. It’s also been in particular lack of access to testing which has really been throughout the country a bit of a challenge.
Doug: Okay. In terms of things coming in a little bit better than expected, how much of this do you think is a function of social distancing having its effect versus maybe the original projection models having some flaws?
Dr. Ledeboar: [00:04:00] So I think it’s really there’s an issue of both quite honestly. I can tell you the social distancing works and it actually has worked quite well. And I can tell you that based upon our flu numbers. So when we spoke a month ago, we were looking at significantly higher proportions of our patients having influenza. We were still at that point about 25% positivity among our cases of influenza. What we saw was as the social distancing was implemented, our [00:04:30] influenza case numbers dropped off dramatically. We went from 25% to 9% to less than 1% positivity in less than two and a half weeks overall. So definitely the social distancing has worked. But I also think that a lot of the original projections were really more worst case scenarios. And we have been able to stem that tide a bit.
Doug: Do you think some of that is [00:05:00] the fact that maybe the original inputs from China, the data integrity really wasn’t there and then also in Italy. In answering a previous question you talked about multi-generational living in Italy you see that pretty broadly, it’s an older population, it’s a denser country. Are those part of the problems with the early model?
Dr. Ledeboar: Correct. I think there’s been a lot of questions around data integrity around what was seen and experienced in China. And I think that there are certainly some unanswered [00:05:30] questions when it comes to that. So, that have may have been a bit of an overly optimistic projection. Whereas, even though many of us share common European backgrounds with the population of Italy, we really do have a quite significantly different population than what Italy does there as you had mentioned. There’s multi-generational housing. There is a significant difference in terms of the overall of the population. And there are significant differences [00:06:00] when it comes to predisposing conditions, particularly as you start to think about age. So I think the Italian numbers were certainly overly worst-case and the Chinese numbers may have been a little bit overly optimistic, leading our projections to be more on the worst case scenario.
Doug: Maybe just one more thing on that, when it comes to the China data, I know folks are trying to sift through this and clean it up a little bit as [00:06:30] best they can. Is it your impression right now that in terms of it being overly optimistic, maybe it wasn’t on a mortality rate basis, but in terms of how infectious the virus is? Is that where most of the optimism was or was it really across the board?
Dr. Ledeboar: I think it was overall number of cases. I think that the mortality was probably somewhat under-reported. We’ve all probably read in the news several reports of examples of, numbers of dissidents that were being released [00:07:00] from mortuaries compared to number of reported deaths. The numbers didn’t match up quite so well. So I think there’s certainly a possibility of both. And we’ll have to kind of see how that starts to shape up as we start to clean that data up a bit more.
Doug: Okay. Bringing it back to your lab and what you’re hearing about domestically more broadly, it seems like the diagnostic vendors have really ramped their capacity, yet we’re still hearing about [00:07:30] diagnostic bottlenecks. What’s the disconnect? What’s holding things up at this point?
Dr. Ledeboar: We’ve definitely seen the vendors respond and they’ve responded very, very well. A month ago when we talked, there was no testing options unless you were one of the large reference laboratories or you were going to bring in an LDP. Today, there are greater than 30 kits that are out and available on the market. I think there really are a couple of different bottlenecks today. I think [00:08:00] the first bottleneck that’s really impacting everybody is we are continuing to see shortages on viral transport media and on swamps. And getting access to those can be a significant challenge and is really contributing to a bit of the inability to be able to perform testing on a much more wide-scale basis. I at least, not probably not everybody reads this but at least I read it over the weekend if you look at the province [00:08:30] of Ontario, as an example in Canada, the province of Ontario attempted to get around the swab issue by going to China sourcing swabs from China.
And there was a very large report in the Toronto Star over the weekend documenting that as they were doing some of their QC testing on those swabs, they found that the swabs were contaminated with mold and it didn’t allow them to use the swab. So I think the swabs and transport media continue to be a very significant challenge for both public health authorities [00:09:00] and clinical laboratories. We are also continuing to see some shortages when it comes to extraction reagents and being put on allocation, that’s still constraining the supply of available tests. I think the other real key thing that we have to consider here is testing still is fragmented based on the type of hospital that you are as well. For large academic medical centers tertiary care centers, they’re able to bring up one or multiple different tests that may [00:09:30] be available.
But if you look at the available options to the 200 bed and less community hospitals, the number of available platforms is still quite small. You have the avid platform, and you have the Sofia Gene expert platform. Those are really the primary drivers of molecular testing in those smaller hospitals. And unless you’re a part of a larger system and have been given an allocation for one of those systems testing still continues to be a challenge, and you’re [00:10:00] probably referring it out. So I think one of the real opportunities that exists when it comes to testing is really pushing it down into those regional medical centers so that timely decisions can be made. Because I’m still hearing that from a number of the larger reference laboratories turnaround time can be five days or longer.
Doug: Okay. Understood. Very interesting and it’s good to hear about the progress, but unfortunately [00:10:30] it’s unfortunate we’re still hearing about some of those bottlenecks. What’s your capacity today? You were just getting rolling last time we did a call. What’s your capacity today for COVID testing?
Dr. Ledeboar: So we have capacity on a daily basis to run about 1,200 a day right now. If we really needed to we could probably ramp that to closer to 2,000, but we’re routinely doing about 500 a day right now. And we’ve spiked to about 750 as our highest. [00:11:00] And we’ve really been able to do that. And the number of laboratories have kind of implemented a similar strategy to what we’re doing, and that is to diversify our supply chain of who we’re getting testing supplies from. And that’s really been very beneficial for us in terms of being able to continue and maintain a very steady supply of testing options.
Doug: Which platforms are running right now?
Dr. Ledeboar: So we’re running four different platforms. We’re running the CDC test, we’re running the Thermo Scientific KingFisher [00:11:30] platform. We’re running the Roche, 6,800 UASA, and then we’re also running the Sofia at UASA. And we really determine who gets what tests based upon our allocations for the different companies as well as the need for rapid turnaround time.
Doug: Okay. What’s the most rapid option of those [crosstalk 00:11:52].
Dr. Ledeboar: Sure. Of ours, the most rapid is the Sofia test because it can be run on demand and it doesn’t need to be batched. Roche has the capability of being able to run [00:12:00] on demand, but we’re trying to be very good stewards of the available essentially supplies for the test. So plastics, that kind of thing. And so we’re trying to optimize our batch sizes to make sure that we’re really being wise in how we use that test.
Doug: Are you noticing any differences that are notable and performance amongst the different assets?
Dr. Ledeboar: So we’ve actually done a comparison study. We looked at the performance and the limits of detection using the CDC as kind of [00:12:30] the gold standard test. And we’ve really seen very, very similar performance all within the limit of detection of 0.5 log or less, so indicating similar levels of performance.
Doug: Okay. So, so all-
Dr. Ledeboar: Which is a really good thing.
Doug: Yeah. So that’s good news for sure. So all of those can be used. It’s just ultimately what you talked about earlier is probably going to dictate what the best test is for the right patient and for the right [00:13:00] site? So if you need something-
Dr. Ledeboar: Correct.
Doug: Or if you’re a lower complexity lab that’s where a specialty Sofia’s going to play a role.
Dr. Ledeboar: That’s exactly correct. That’s exactly correct. So we’re, we’re really trying to triage those that we really need to make effective decisions on. So those that we need to triage, who’s getting PPE or which patients need to go into isolation. So if we’re admitting you, or if we’re going to send you to the OR for a procedure where we’re going to be doing an aerosol generating procedure, [00:13:30] or if you’re already admitted, those are the ones that we really need that rapid result on.
Doug: Okay, Great. So let’s talk a little bit, more about the tasks like we have been specifically on the molecular diagnostic side. We’ll get to serology in a little bit. So if we take a step back, you started to touch upon this with the answer to that last question, which patients get access to COVID-19 [00:14:00] molecular tests today? What are the protocols today? Because that was in a lot of focus a month ago. It sounds like things have got better, but what are the protocols today?
Dr. Ledeboar: So, who gets access to testing is still very dependent upon where you are in the country and what testing options that you have. Most institutions are testing at minimum all their inpatients that have symptoms, ED patients, and those that have comorbidities that may put them at [00:14:30] risk for admission or for a ventilator. Additionally, most institutions are also testing healthcare workers that are symptomatic just for the reason that we need to be able to ensure that our healthcare workers are safe, healthy, and can be available if we need them to treat patients. So in minimum that’s what most people are doing. Through our ramp in capacity what we’ve really been able to do is beyond our inpatients, beyond those that are going to be admitted and [00:15:00] beyond our healthcare workers, we’ve really been able to say, we are willing to test patients in the ambulatory environment, provided that they’re symptomatic. We don’t have any restrictions on comorbidities anymore. So anybody can get a task provided that there’s symptomatic.
So it’s really enabled us the ability to increase the number of patients that we’re offering testing to and to give a diagnosis [00:15:30] to. And that’s really important from a public health perspective, because it allows us to identify who those reservoirs may be, get them into isolation and really prevent them from being out in the community and transmitting the virus within the community.
Doug: Got it. And just to, maybe I’m the only one who isn’t clear on this, so sorry to just belabor this but amongst those that you are testing now, all of them are symptomatic. There’s nobody [00:16:00] in any of those categories that’s asymptomatic. Is that right?
Dr. Ledeboar: That is correct. Yes.
Doug: Okay.
Dr. Ledeboar: Now we have seen, it’s important to point- Oh I’m sorry. It’s important to point out that some medical centers have adopted either universal testing of admissions. Some have adopted universal testing of patients that undergo procedures, all focused really on protection of patients and healthcare workers. So there are those practices that are [00:16:30] out there and they do exist.
Doug: Yeah. That’s where I was going next. And I had just read an article yesterday about, I think it was in New York where a protocol had been implemented where we’re all moms to be heading into maternity wards where were also being tested. So it sounds consistent with what you’ve just described that it’s occurring a little more broadly.
Dr. Ledeboar: Correct. And we also are going to start seeing … So in a patient that’s been diagnosed with COVID, we are going to start seeing [00:17:00] some testing at time of cure to take these patients out of isolation. In other words, we will be potentially testing these patients at day 14, day 18, if they’re going to be seen in healthcare systems, and we want to take them out of isolation so that they don’t have to be masked gowned et cetera, every time they come in to see a provider. So we would expect that we’ll probably start to see a bit more of that moving forward. We may also start to see some more asymptomatic screening again really [00:17:30] as a part of risk assessment at determining who may be at risk of being an asymptomatic carrier and transmitting within the healthcare environment as well.
Doug: Based on what you’ve seen, do you agree with some of the studies that have suggested that the mean time to detection after infection, or I should say median and time to detection after infection is probably around five days?
Dr. Ledeboar: That seems to be at least what we’ve been seeing as well.
Doug: Okay. Okay. And [00:18:00] based on what we talked about earlier with pretty consistent limits of detection, there’s probably not one asset that’s going to be better or worse than others in terms of finding patients earlier.
Dr. Ledeboar: No, but there have been a lot of discussions and rumors around the issue of just how sensitive molecular testing is using an NP swab. And I think that’s going to be very variable based on a number of different contributing factors, including quality of the specimen collection, the state at which the patient’s illness is. We know [00:18:30] that patients begin to shed two to three days before they become symptomatic. Once they’re symptomatic, they’re shedding at fairly high levels, but after the initiation of symptoms we have seen in patients at day four day, five day 67, the amount of virus that’s being shed does drop off. And so there’s concern about sensitivity of the test, and there’s been a lot of reports and there’s been a lot of discussion around just how sensitive is the NP swab, how sensitive is the molecular [00:19:00] test.
There was a study published on medRxiv out of China that largely said, there was another one also published in I believe, JAMA that largely looked at exactly how well do this testing perform. We know that lower respiratory samples tend to be the best. So sputum BAL or bronchoalveolar lavage tend to be the most sensitive samples. And at least based on these studies, NP swabs and throat swabs tended to be a little bit less [00:19:30] sensitive than those lower respiratory samples. Again, there are a lot of things that we could spend an entire call discussing the pluses and minuses of those studies. But there has been a lot of discussion around that particular topic.
Doug: Okay. But one way or the other there’s not going to be probably a better alternative than just optimizing with these approaches, right? I mean, you basically got to deal with these types of samples and the hope is you get the best collection from the best operator you can.
Dr. Ledeboar: And that’s exactly correct. And we may look at opportunities [00:20:00] for host state based diagnostic to look at and identify who is potentially carrying it. That may be an option later down the road. There’s been discussion around can you detect the virus in blood? Less than 1% of patients that are infected actually carry detectable levels of arrhythmias. So it doesn’t seem like that’s necessarily an option either. So really as you said, it does come down to optimizing those respiratory samples.
Doug: Okay. [00:20:30] Just a few more on the molecular side. I refer to it as Alere. We talked about it as Abbott Alere. Really what we’re talking about is the older Alere I which is now called Abbott’s ID NOW platform that’s garnering a lot of attention in part because it is a very easy to use platform and it can give you an answer in 15 minutes or quicker than that. The only thing is prior to the acquisition of Alere by Abbott, that system [00:21:00] was viewed as occasionally being less accurate than some of the other platforms. That was a while ago, so I think the hope is that, that’s got a lot better. Have you heard anything or seen any data on how that platform’s performing?
Dr. Ledeboar: So, that’s a great question. And I’ve been trying to get my hands on data for the better part of two weeks on that platform. What I can tell you is if you look at the package insert data, and if you look at the limits of detection data for that platform, it looks to be on par with what many of the other molecular [00:21:30] platforms, lab based Sofia, et cetera are. So it looks to be on par with everything else. But I don’t have any real world clinical data where these houses have been compared to one another. That will come over time. We just haven’t started to see any of that data quite yet.
Doug: Okay. But that’s good news just based on a package and serve and yeah, that would be great I would think given the ease of use associated with that platform, as well as Danaher’s [crosstalk 00:21:59] expert.
Dr. Ledeboar: [00:22:00] And both of those platforms really offer us the opportunity to take this testing to the next level. And that is before somebody leaves, it offers us the potential to be able to provide a result. So 15 minutes, half hour, whatever these tests take, that’s a whole lot better than when we started this whole thing where we were talking seven to 14 days to getting results. We’re now talking 15 minutes to an hour. That’s a significant improvement in turnaround and does help us to be much more prospective [00:22:30] as we start to think about how do we identify these patients and how do we get those that may be shedding into isolation?
Doug: Would you describe that Nate? One thing that jumps out at me is if somebody comes in with respiratory symptoms, you’re going to test them there. If they’re positive, you’re going to have to test them at least a couple of times before you release them from the hospital and conclude that they’re ready to go home. I mean, [00:23:00] for a patient who’s positive, is it at least three tests per patient or two tests? Do you have a handle on what that number is?
Dr. Ledeboar: It really depends upon what type of patient you are. If you’re somebody like me, I’m relatively healthy. If I got sick, I’m probably looking at one test because they’re going to make a decision to send me home based upon my symptoms, not based upon my negative test. Now I’m a little bit of a unique scenario because I’m also a healthcare worker. [00:23:30] So I might need that, to go back to work or to be able to be released from wearing a mask everywhere I go. But for an average healthy person, it’s probably closer to one to two tests. For the immunocompromised patient for example, that’s coming in that’s being seen fairly routinely, they’re diagnosed on the initial diagnosis, and then they subsequently are followed and have many follow-up appointments to get them out of isolation, you’re probably [00:24:00] looking at at least three tests on that particular patient.
Again, thinking down the line a little bit further, somebody is coming in for a procedure. They may be in order to avoid going into isolation, they may come in the day before, get screened for COVID and based on the negative tests. So there’s potential extra tests on an asymptomatic patient where you may see utilization. And then the third place where we are seeing some degree of repeat testing is around patients that come [00:24:30] into the ER, they go into that ambulatory environment, they get worse, or they have a negative test, but they look and act like a COVID patient. And they’re getting retested. In some of those patients we’re seeing at least two tests, sometimes three tests as well. So I would say an average of two tests probably per patient is not unreasonable.
Doug: One thing we’ve been playing with, it’s easy to do this in Excel where you take what are some pretty [00:25:00] sad numbers in terms of the projected depth totals through August. And then use that as a starting point mathematically to figure out how many people will actually be diagnosed with COVID. And then use data on which percentage of those who test actually test positive versus negative to come up with a total number of tests number. So, probably more detailed than I needed to go through, [00:25:30] but when we go through that exercise, I mean there’s a scenario where we could see mathematically 50 million tests done in the U.S. by the end of August. I mean, does that make any sense to you and is it plausible that the system could even do that many tests?
Dr. Ledeboar: As we’re ramping capacity, we certainly are getting closer to a point where we can support that level of testing. I also think that it is … I mean, I think that’s presumed on the fact that [00:26:00] once we start going to back to work, we’ll see little small spikes around the country based upon just people interacting more with one another and potentially sharing the virus. The other interesting factor, and we’ll also spend some time talking about this when we get into the serology section is we really don’t have a good understanding of just how protective having had this virus may be. In other words, we don’t really have a very good understanding of just how protective having an antibody response [00:26:30] truly is. And there are some reports that say there was a study out of China that looked at recess mechanics, and they saw very high degrees of humidity in the mechanic models.
But if you look some of the human experiences that have been out there, there are studies that are out there that are suggesting up to a third of patients may not have neutralizing antibodies. And so despite the fact that they may have an antibody response, they may not in fact be immune. And so that could really play into [00:27:00] the overall re-infection rate and the need for additional testing as well.
Doug: Understood. Yeah. And I want to unpack that in a little more detail momentarily, just before we get to that.
Dr. Ledeboar: No. I just wanted to add it because it was kind of important as we think about the molecular testing needs as well.
Doug: Yeah. Yeah, absolutely. Yeah, depending on where we come out on that I think that probably dictates whether you need to do more or less testing on both fronts.
Dr. Ledeboar: [00:27:30] Completely agree.
Doug: On one more, I think this was my last one specific to molecular. Yeah, Genmark the company that has a respiratory viral panel, they’re one of a few. There’s BioFire, there’s bioMerieux, Cajun has one that’s, coming to market across all geographies. And that of course, Luminex has an offering. Genmark had a really strong [00:28:00] Q1 volume wise. I think it was driven more frankly by the panel than COVID testing, just based on when that test became available. I guess the question is, as we think about molecular testing moving forward, and the fact that this isn’t going to go away. We hope to be in a better place in a month or two, but that the virus isn’t going to go away. What do you think the role is for these panels as we think about respiratory season next fall?
Dr. Ledeboar: [00:28:30] Sure. So I think there’s a couple of important things to unpack there with that. The first thing is you’re right, they did have a very strong Q1. And we also have to remember that and this also plays into what we talked about a little bit earlier with the swab shortages. We had a fairly big flu year this year as well. It was extended. We had a fairly large number of cases and we saw a fairly broad range of the population be effected. So, that contributed certainly to that aspect. [00:29:00] Then we later layered COVID on top of that, which has only multiplied that. The role of the panels is going to continue to be really important, particularly in the inpatient environment as we start to think about next fall respiratory season, because then you’re going to be looking at viruses like flu, RSV, even human Coronavirus 229. All have syndromes that can include the exact same symptoms that we see with [00:29:30] COVID.
And the only way that you’re going to get to the ideological agents in those cases is we are going to have to be able to use a panel-based approach or a syndromic based in order to identify that. Because based simply on clinical symptoms, we don’t have that ability. Bow in the ambulatory environment where we want to know about COVID because we would have to potentially make admission decisions and closer following decision based upon the test. We’d [00:30:00] want to know about flu because we could make treatment decisions in those particular cases. We may see lower Plex testing be more popular, but I think in the inpatient environment, in the immunocompromised environment, the panels are going to play a very, very important role. And we’ve heard from all of the major manufacturers that they will be incorporating a COVID marker in their panel that will be ready late summer, and will certainly be ready for the [00:30:30] next flu season.
Doug: Got it. Super helpful. I’m going to jump to serology right after this one. I lied, I got one more. I just wanted to get your thoughts on this is one more molecular question. Scott Gottlieb recently indicated that when people return to work, maybe companies should have an onsite molecular platform like the Danaher’s Sofia gene expert. What do you think of that idea?
Dr. Ledeboar: [00:31:00] So this is a really important point, and as we’re starting to see in many states the curve flatten, we’re starting to have the conversations about return to work. There’s going to be a lot of discussions around what is the role of antibody testing? What is the role of molecular testing? What do we need to do in terms of personal protective equipment to protect ourselves? We have not heard a great deal of communication from our public health authorities yet in terms of what people [00:31:30] should do. So they’re starting to kind of think through this on their own. I think the challenge with the benefit of having an on-demand system available would be you could identify those asymptomatic carriers and you could get them out of work quickly to prevent spread within the work environment. The downside of that is that’s all predicated on what level of specimen are we willing to all contribute to walk into work?
I can certainly [00:32:00] tell you having done NP swabs even on myself, that is not a pleasant procedure to go through. And I certainly wouldn’t want to do it every day as I walk into work. Oh, you get to have, we always oftentimes refer to getting an NP as a brain biopsy. Oh, you could to have a brain biopsy every time you walk into work. So I think there’s some logistical challenges with that. I also think that depending upon the turnaround time of the test and [00:32:30] the throughput of the test, that will also be a significant challenge. I think what we’ll likely see, and then we have the supply issues that we’ll continue to play this because we need to be able to get this testing out to be able to test the symptomatic patients.
And we don’t want to be having asymptomatic patients preventing our symptomatic patients from being tested. So we would definitely have to get through the logistical challenges. We would really want to get through the turnaround time challenges as well [00:33:00] because even with a fairly rapid test waiting 15, 20 minutes or an hour before you can get into a baseball game or something like that, it would be a bit of a logistical nightmare as well. So we’d have to work through a number of those logistical issues to get to that point. But certainly there’ve been some discussions around somebody that’s been sick, how do we clear them to be able to come back to work? And how do we ensure that they’re not asymptomatically shutting and infecting their coworkers? [00:33:30] And there’ll certainly be some opportunity there for test utilization and for where we’re going to use these and roll these out.
Doug: Okay. All right. So kind of along the same lines, now let’s pivot to the use of serology tests. So, serology tests, immuno acid, essentially tests where you’re looking for the presence of essentially antibodies that would tell you, “Hey, this person’s not symptomatic anymore, [00:34:00] but they had COVID at some point.” To be clear, there’s not a role on the clinical side, right? This is purely going to play a role in determining exposure and potentially immunity. Correct?
Dr. Ledeboar: So, no, you hit a really important point Doug. In terms of the diagnosis of acute COVID, serological tests really play almost no role. And that’s really based on the fact that there are now at least two studies out that have demonstrated that [00:34:30] to get a detectable total antibody, it takes about seven days post onset of symptoms to get a detectable antibody response. To look for the IgG, which is really that more specific in that protective response 10 to 14 days is what it’s going to take. That really minimizes the role that serology can play in the diagnosis of acute disease. And just to give you an idea, we did a small [00:35:00] little study using a point of care serological test here where we looked at patients ranging from day one of onset of symptoms to day seven of onset of symptoms. And our overall sensitivity was about 45% using a serological test.
Doug: Got it. Okay. So maybe a good segue to how you think about the accuracy of serology tests outside [00:35:30] the purpose of clinical diagnostics. I mean, historically there’ve been tests in this category that have been knocked for their accuracy, for the purpose we’re talking about. Do you have any concerns about these tests?
Dr. Ledeboar: And I think a lot of your concern is rooted on the Oxford article that really cited the UK performance, the Spanish performance of the antibody tests, particularly the point of care test. [00:36:00] And there was reported to have a lot of variation in performance among those tests. In that study in particular, and this has been picked up by the New York times and a number of other papers that have cited 50 to 60% overall accuracy at identifying the correct number of patients. So I want to really point out and distinguish that not all tests are created equal. There are very good tests that are out there that are being developed and that are being evaluated today [00:36:30] that do have specific antibodies that don’t cross react with the human Coronaviruses, that don’t cross-react with influenza, that don’t cross-react with CMV or HSV. And for those tests, in terms of their accuracy, their reporting numbers approaching a 100% specificity.
Doug: Which is what you want for the purpose we’re talking about?
Dr. Ledeboar: Which is really what you want for the purpose of what we’re talking about. Yeah. And that’s [00:37:00] again, the time to generation of immunity for most patients should be within that 14 days. And for almost the entire population that have been exposed or that have been infected with this organism by 28 days you should have a detectable antibody response.
Doug: We’ve seen some data out of Becton, Dickinson through their partner. We saw some very high specificity quoted from Bio-Rad. Are those [00:37:30] amongst the tests you’re referring to and are there other vendors that you feel like should be on the list of folks we should trust based on what you’ve seen thus far?
Dr. Ledeboar: So again, we haven’t seen a lot of independent verification studies yet. So remember this is all package insert or EOA submission data, and those are all really good numbers and that’s very good early data. We’ve seen good numbers also on EUROIMMUN tests. We’ve seen good numbers on COVAX’s test. Beckman Coulter announced within [00:38:00] the last few days that they’re going to be they’re developing a test I would expect there should be fairly good as well. So there are definitely those high quality methods. What we’re kind of seeing at least right now is there are a few rapid diagnostics, including the BD Henry Schein tests that are demonstrating fairly good numbers. A lot of the UIC tests that are being developed, the EUROIMMUN test, the COVAX test, the Beckman Coulter test, all seem to be demonstrating fairly good numbers [00:38:30] and fairly good performance. And that really has to do with how their antigens are generated and how specific those antigens are.
Doug: Got it. Do you as a matter of just at a high level like you can’t say, “Hey lateral flow as a category is going to be better or worse than Kenny luminescence, or whether it’s automated. It’s really just going [00:39:00] to be outside specific, not necessarily category specific. Is that right?
Dr. Ledeboar: It is going to be outside specific. And I think this is one of the places where having some good oversight not inhibitory oversight, but good oversight by FDA is really going to be important. And also getting some of that data published early is going to be really important in helping facilities choose what methodology they’re going to use. And it’s also important to continue to get the voice out there that this should not be used for [00:39:30] the diagnosis of disease. Because I haven’t seen it happening in many locations where people are using it as a point of care test to make the clinical diagnosis, which can absolutely result in false negatives.
Doug: Okay. Got it. So to that point, yeah like these tests aren’t going to be great for the reasons you’ve described in accurately finding patients. And then the risk is you send somebody back into the community who actually has this, which is obviously a big no-no, [00:40:00] but for the purpose of actually trying to find folks as we’ve talked about this, this can play a role. What do you think an acceptable level of sensitivity and specificity is?
Dr. Ledeboar: Well, I think it really depends upon what we’re going to use the test for. And let’s just kind of walk through like a population model on this. So let’s say you have a test. Let’s say we’re going to use this test to determine who can go back to work and who can’t go back to work. And let’s say [00:40:30] our test has a sensitivity of 90%, or a specificity of 90%. So even if we’re going to do it on a large population scale basis, and we test a 100 patients, we’re going to miss. If it’s a test with 90% sensitivity, we’re going to miss 10 people that may have had it. And those are 10 people that may be at risk. Similarly, if we have a 10% false positive rate, we’re going to tell [00:41:00] 10 people that they had it that didn’t have it.
Those people may not use the same mobile precautions that they would if they knew that they didn’t have it. And so those 10 people are at risk that we told were not at risk for reinfection. So as you start to think about testing very, very large numbers of people, particularly among a population that we would expect at least shouldn’t have a great deal of positivity, [00:41:30] specificity and sensitivity to become a really important terms of performance determinants as to how usable that data is and how usable that test is. Does that make sense?
Doug: It does. It does.
Dr. Ledeboar: Okay.
Doug: So a lot of what we’ve talked about have been these rapid tests, when I look at some of the reports in the mainstream media, I’m almost under the impression that people think we should go out and test the whole country. [00:42:00] I guess I’m wondering let’s put aside for now the question of whether this actually tells you whether you have immunity or not. Which is a pretty tough question to answer at this point, but let’s assume we’re moving forward, do we have to test everybody? Do you test a very small number of people in a certain population? I don’t know what, what’s your view on how many tests we need to do to open up the economy?
Dr. Ledeboar: So I think we’re going to see a phased in approach because we all now recognize that there’s variable performance. So people are going to be a little bit cautious [00:42:30] about using this, which is going to somewhat constrain supply. So very similar to how we managed the early molecular diagnosis of this organism. We’ll probably take a very similar approach to the use of these neurological tests. The first group that I think we’re going to see a lot of testing again is going to be our healthcare workers. And this is really going to be done in order to give our healthcare workers really a sense of security. There was an article that was published in the [00:43:00] Washington Post I believe this morning, citing the Beaumont health care system. And I really liked the ID doctor that they quoted there.
And he said, “We’re doing this testing to give our healthcare workers a sense of security, essentially, that additional security blanket that may be available.” So I think that’s going to be one of the major populations that we see tested. I think the second population that we’re going to see tested is in our patients that are getting a lot of healthcare. And we’re going to use that as an important determinant [00:43:30] of who do we think are going to be at risk for getting the disease and what additional precautions do we need to take? And then I think the third group is going to be as we start to move towards going back to work people that just by the necessity of their jobs require them to have close contact. We’re going to be offering them the serological tests as a sense of security again, in terms of you’ve been exposed, you should be protected and we potentially could [00:44:00] be using it that way.
The other place I think we’re going to be using this test fairly routinely, and there’s an evidence basis around it is one of the leading candidates for therapy for COVID-19 has been the use of convalescence serum. So taking the antibodies from somebody who’s recovered, giving it to somebody who’s acutely sick and hoping for a passive immune response, as a result of those antibodies being given to them. In those particular treatment protocols, [00:44:30] a titer of one to 64 or greater has been demonstrated to produce better overall outcomes. Meaning that if you give a patient a higher titer of antibody, it ultimately helps them to fight the virus off a bit better. So, that’s going to be another place that we’re going to see a lot of utility of the serological tests. And what I suspect we’re going to probably-
Doug: Oh, go ahead. Sorry.
Dr. Ledeboar: No, please go ahead.
Doug: Oh I was-
Dr. Ledeboar: No, I was just going to say- [00:45:00] go ahead. I’m sorry.
Doug: I don’t know. More important to hear your opinion, please, please.
Dr. Ledeboar: No. So I was just going to say that I think beyond the serology tests, I think we’re going to really be using as we think about going back to work, I think we’ll be using the serological test to really risk stratify who’s at risk for potential infection or who may be at lower risk. This is going to be done in combination with NAT screening, because it’s only the NAT screen that’s [00:45:30] going to tell us who are our shutters as well. So we’ll probably be thinking about doing a multi-tiered approach to screening, identifying who’s at risk of becoming infected, also identifying who are shutters, maybe.
Doug: Okay. So that would be a test that would be used to find somebody who’s asymptomatic, but currently shedding, is that the right way to think about it?
Dr. Ledeboar: That’s correct.
Doug: Okay. And as we think [00:46:00] about opening schools and folks going to work who might be less at risk because they don’t have comorbidities or they’re younger, is there a role for serology in that population?
Dr. Ledeboar: There definitely could be a role for that, and I think we need some further study in that particular case. Because one of the interesting things that we’re finding is the incidents overall of COVID-19 in our pediatric patients is quite low. So unlike flu which [00:46:30] significantly impacts our pediatric patients, we just don’t see a lot of pediatric patients that are infected with COVID-19 and when they do get it, it’s a very, very mild infection. Now, one of the things we don’t really know is can children be reservoirs? And again, further study is really going to be needed in that particular case. But I do think as we start to think about reopening the schools come fall and really risk stratifying who’s at risk and who may be our shutters, serology could play [00:47:00] an important role there as well.
Doug: So just going back to something I asked before, this idea of like testing everyone, that’s a lot of tests. That’s a lot of people. Do you think the way this could roll out would be in New York or California or some other spots that you could broadly use serology to get a better understanding of what’s going on in the population and the disease and use that as a way to open up the country?
Dr. Ledeboar: [00:47:30] Oh I think a hundred percent that’s going to be used. And I think it’s also going to be even outside of hotspots is going to be, employers are going to want some level of assurance that opening their business is safe because they want to protect their employees and prevent and not put themselves at risk for lawsuits or things like that. So I think employers as well are going to likely mandate to a certain degree testing and the availability of results [00:48:00] in order to really let people come back to work as well. So I think we are talking very, very significant levels of testing. And I will tell you-
Doug: [crosstalk 00:48:10] molecular testing done like two months from now, three months from now is serology eclipsing molecular volumes?
Dr. Ledeboar: Absolutely. I can tell you that we … And just to give you a sense of that, I mean we’re a regional healthcare system, just touching Northern Illinois but really focused in Southeastern Wisconsin. [00:48:30] The overall population of our region is just right around three and a half million. We’re planning for just as our healthcare system testing numbers for serology in the hundreds of thousands over the six month period.
Doug: That’s the projection?
Dr. Ledeboar: That’s what we’re planning for, yes.
Doug: Okay. How do you do that? I know rapids will play a role based on what you described, but ultimately do you need some of the big diagnostic instruments that will [00:49:00] be able to do this in a high throughput automated way?
Dr. Ledeboar: As we started talking about those numbers, the diagnostic instruments are going to be critical to being able to test that kind of those large numbers of patients. I would expect in places like New York, that’s been very hard hit those numbers will be significantly higher. So we’re really talking- we are definitely in the process of evaluating several of the tests and I know a number of the [00:49:30] manufacturers, Roche, Abbott, Beckman Coulter, have all come out very publicly and said, “We’re looking at developing these.” I’m not sure that they’re going to be first to market a lot of those, but they will definitely I think have a solution in the next month or two.
Doug: Okay. You think a month or two is when we can have some EUAs on these high volume systems?
Dr. Ledeboar: I think within the next couple of weeks, we’ll have EUAs on the automated ELISA platforms [00:50:00] like Bio-Rad or the agility or one of those. I think it’s in the next month, we’ll have an EUA on a chemistry line that’s clear. And I think within two months we’ll see a majority of the vendors in the industry have a clear test.
Doug: Okay. And then just [00:50:30] separate from virology and molecular, is there any technology that could be used as an immediate rule out for infection? I think that’s pretty much impossible, but just want to in the lightening round make sure that that’s the case, in your opinion.
Dr. Ledeboar: I think a lot of people are going to try to use simple screens, like fever as a risk assessment tool. A lot of the healthcare institutions have already been doing that for a period of time. [00:51:00] Every time when I walk into work, there’s a medical assistant or a nurse sitting at the door and I get my forehead shot, or I get asked, “Do you have a fever? Do you have a cough?” Or any of the symptoms that you may have. Do you have shortness of breath? So I think that’s going to be very common place moving forward.
Doug: Okay. Where I was going to go next and we’ve got a number of emails with questions along these lines. [00:51:30] Do you think the role of serology as a means of reopening the economy is a bit optimistic based on what’s known about SARS CoV-2 and immunity? I think the answer is maybe yes based on some of what you’ve talked about already.
Dr. Ledeboar: I think the answer is absolutely yes. I think we’re really searching for something that’s going to make us feel better about opening the economy and really make us feel comfortable that we’re [00:52:00] not putting our employees at risk. That being said, I think there’s a lot of things we don’t know. We don’t know what percentage of the patients that develop an antibody response actually get immunity. We don’t know how long that immunity is going to last. I mentioned the Yale paper earlier in our discussion. One of the interesting facts that, that Yale paper cited was that up to a third of patients that have detectable [00:52:30] COVID antibodies, don’t have neutralizing antibodies. In other words, they may not have immunity.
I think that’s a really important thing that we need to better understand, to understand what role the serological tests can play. I think we really have to understand what is the chance and how long is immunity going to last? Because that really plays into, are we going to see this thing in the fall and are we going to see similar numbers of patients? [00:53:00] I think we really don’t have the answer to that quite yet.
Doug: What is the percentage of folks who have antibodies is really low? I think the hope is that it’s 50, 60, some big percentage. What if it were like 10, that’s a problem, right?
Dr. Ledeboar: I think that’s a real problem because that means, and again we’re seeing this a little bit in Singapore right now. Singapore is at least a couple of weeks ahead of us [00:53:30] and they are reopening their economy. As people are starting to more closely interact with one another, they’re starting to see small spikes in number of infected patients, in the number of positive tests. So I think that, that is a real risk if the number of people with immunity is less than 10%.
Doug: Right. Which is either the question would be either the immunity isn’t there or not as many people are as exposed as you think. [00:54:00] One of those two things either one’s not a great outcome.
Dr. Ledeboar: Exactly.
Doug: Another question, which is what do you think the right interval or frequency, however you want to answer it is for testing folks in the workforce using serology?
Dr. Ledeboar: Well, I think again a lot of that really plays to how long we think immunity is going to last for. And it also is going to be determined by [00:54:30] what do we see for development of a vaccine? Again, how long lasting is that vaccine? Those are all going to play very significantly into how often we test patients. For the immediate future. I think once we know somebody has an IgG response and has immunity, we probably won’t retest them right away. But I think if somebody comes back after having been sick or is out [00:55:00] for a period after being sick, I think they’ll absolutely be retested at that point. Again, a lot of that will be determined as we start to do some of these studies on a population basis and understanding what percentage of our population now has immunity. In other words, what percent of our patients asymptomatically had this virus and never really had significant symptoms that caused them to be out of work or school or wherever whatever they may be doing?
Doug: Nate, another question [00:55:30] and I’ll frame this by pointing out that according to covidtracking.com, the current capacity in the U.S. to do molecular tests is around 150,000 per day. So with that in mind, we have a question from the audience about where do you think the serology testing capacity needs to be on a daily basis to start opening the economy?
Dr. Ledeboar: I think that the economic factors [00:56:00] and the need to open our economy fast is going to be a much stronger driver than the presence of serological tests. I mean, think about where we are right now in terms of the developmental scale for serological tests. We have one EUA cleared test, and we sent an email to that company probably a week and a half ago asking them for information about their tests and asking them about using their test. We have yet to have received a response from them. And [00:56:30] our lack of a response is not unique. So I think as we start to see the epi curve drop, we may have an acute need to open the economy that is much faster, much earlier than the availability of good serological tests. So I think that’s going to probably play a bigger role.
We’ll probably be using that as a surrogate [00:57:00] for that, at least in the interim until we get testing capacity ramped up. And just to give you an example, I cited that our needs were going to be over the next six months into the hundreds of thousands. We’ve done some modeling to look at without the ability to use our high volume chemistry testing system, just what can we do or what are we capable of being able to test? And using an ELISA based system, [00:57:30] I’m just going to pull the numbers up here. We’re looking at volumes of like a thousand to 1500 a day if we don’t have access to a large high volume chemistry analyzer. And I think that’s going to be very, very constraining in terms of what we can actually do or the number of people we can actually test. So just to give you an idea-
Doug: [crosstalk 00:57:53].
Dr. Ledeboar: What’s that?
Doug: The 1000 to 1500 that’s [00:58:00] that’s without having access to one of the big chemistry machines?
Dr. Ledeboar: Correct. That’s assuming that we would use an ELISA based test that we can do 90 tests per plate, that we can do six plates per run, and we can do one run per shift. If we make those assumptions, it’s about 540 tests per day. If we run three runs per shift, we do a one shift a day we can get to about 1600 a day. And if [00:58:30] I go to all three shifts maximizing the use of our instrument, or right around 3,500 or so tests per day.
Doug: Okay. And Nate when you say, just to clarify I think I know the answer to this, but when you’re talking about NAT, the nucleic acids, those are you are referring to molecular tests, or are you referring to something else?
Dr. Ledeboar: Yes, that’s correct. Yes.
Doug: Okay. That math you went [00:59:00] through on the ELISA, when you move those over to a big Beckman system or something like that? What does that jump to?
Dr. Ledeboar: I mean, I can run tens of thousands a day through those systems.
Doug: Okay. All right. Another question, I referenced the 150,000 molecular tests per day. How far away do you think we are from being able to do a million of those per day? That’s another question from the audience.
Dr. Ledeboar: Of the molecular tests?
Doug: [00:59:30] Yes.
Dr. Ledeboar: Oh, all right I think we’re probably at least a month- I think we’re probably at least a month, a month and a half away. I mean I think a big part of that is again going to be able to get to those kinds of numbers. You really can’t be doing manual tests or onesy twosy tests. I need to be pushing. If we’re talking about population level screening, I need to be able to use high throughput instruments like [01:00:00] the Abbott M2,000, like the Roche 6,800, like Hologic’s Panther platform. I need to be able to use those kinds of instruments to push through that volume. And ultimately the limiting factor in those particular cases are all of those manufacturers are still on allocation. I still only get X number of tests per day, and we would need to get around those allocation issues to be able to get to that.
And that’s going to [01:00:30] come at the expense of other testing that we still do, the viral load testing and that kind of stuff. And so a lot of it is also a balancing act. So you really have to start if we want to get to that level, manufacturers have to be able to produce that many. Which means they’re either going to have to build capacity, or they’re going to have to take away capacity from other tests and laboratories are going to need additional infrastructure and are going to need additional [01:01:00] reagents as well. I think we can probably based on current available reagents probably pretty easily get to half a million a day. I think getting really pushing in beyond that is going to require some very structural changes to both the manufacturing side and the laboratory side so it’s much longer term. And again, those are best cases at this point.
Doug: Best cases. Yeah. Yeah. Another question, just a couple more, what do you think [01:01:30] the channel is going to be for serology? And I guess this is really just the question of whether you’ve heard anything or you have an opinion on like who’s going to mandate them? Are they going to tell you where to run these? And then importantly, how are these going to get documented? Because that’s what we’re going to need to do to make sure we learn from doing all this testing.
Dr. Ledeboar: I would expect at some point CDC is probably going to mandate, the states are going to mandate that the serological values are going to be publicly [01:02:00] reportable information. So very similar to the molecular tests where positive, negative they’re all reportable. I would expect that as we move to more towards a get back to work strategy, our public health authorities will make those nationally reportable values. In terms of who will be doing it, this is a really being led by the clinical laboratories. I’ve spoken to a number of colleagues in public health, they’re considering it at this point, but the clinical labs [01:02:30] are significantly further ahead. And a lot of that is being driven by the healthcare systems themselves as well as my conversations between the healthcare systems and the employers or the healthcare systems and the insurers.
We’ve heard about many of the Blue Cross insurers and some of the other insurers talking about supporting it and talking about what kind of algorithms we may want to utilize in order to get people back to work. I would expect they’re going to be big drivers of this as well. So I do think that the [01:03:00] clinical laboratories, including Quest and LabCorp are going to be big drivers of this.
Doug: Okay. I got a question about saliva tests. I did not look into this, but Rutgers I guess has a saliva test at least have talked about launching a saliva based test. Is that something that without having looked at it would potentially be, obviously it would be exciting. What do you think [01:03:30] the outlook is for saliva based test?
Dr. Ledeboar: Sure. I saw that announcement I think yesterday I saw that, and I was really hoping to see some data attached to that. I didn’t happen to see any data on it. If saliva is a possible specimen type and it has very good sensitivity, it could be really fairly transformative in terms of how we test and whether and how we sample. A big rate limiting factor today continues to be just the PPE that’s required in order to test somebody and [01:04:00] the level of education that you need to test somebody. If you could do a saliva test, anybody could collect that, pack that specimen up, send it in the mail to the lab and get a result back the next day or two.
So it could be very transformational in terms of how we test and it would be quite a significant advancement for removing barriers to testing as well. But again, I think we really want to see what the data is and how well it performs compared to [01:04:30] NP swabs compared to a lower respiratory sample. I think we’ll have a lot of really interesting findings that come out once the craziness dies down and we can start to look at things in a very evidence-based manner. I think we’re going to have a lot of interesting findings, assumptions that we made that were good and some that we made that were probably bad.
Doug: Okay. I know we’re over time. So I’m going to ask these very last two lightning round. You can be as quick as you want. One [01:05:00] question on based on what you described in terms of when the high throughput chemistry platforms are going to be available for serological testing. Would you say that that probably means, not asking you to play government policy guide, but if those are needed to open up the economy, does that mean the economy is not opening just based on that alone for another month and a half?
Dr. Ledeboar: No, not at all. I think the economy is going to open based upon [01:05:30] the fact that the economy needs to open and the fact that people are already to already seen pockets of this. Where people are already starting to push back and push back fairly hard against a lot of these restrictions. We’ve seen reports out of Michigan, North Carolina over the last two days both sighting people are tired of being locked in their houses, they want to go back to work and they want to be able to earn a living again. I think the population itself wouldn’t accept another month or two [01:06:00] particularly in lower indemnity populations.
Doug: Yep. No, and we’ve heard a lot of that as well I guess, to the extent though, like if we need certain logic to open up-
Dr. Ledeboar: I think if we needed to up
[crosstalk 01:06:21]
.
Doug: Can you hear me now Nate? I think I broke up there.
Dr. Ledeboar: Oh yeah. I think [01:06:30] I can hear you now. I think we’re going to if we need the serology test right now, we will see a big push from the White House and from the COVID-19 task force to really get it out there and get it done quickly and think there’ll be removing a lot of barriers should we need that.
Doug: Okay. And then last one back to molecular, in the fall do you think anybody who shows up with respiratory symptoms, assuming the availability’s there, would you [01:07:00] assume anyone who shows up with respiratory symptoms is getting some sort of a COVID test?
Dr. Ledeboar: I think that’s a very logical assumption to make right now, but I also think that it’s important to point out that if we look at our previous experience with Coronaviruses that jump into the human population, they fairly quickly disappeared again. We don’t talk about MERS a lot anymore, unless you’re in specific geographies, we don’t talk about SARS 1. So I think [01:07:30] there are a number of factors that really support that idea that we would be somebody that needs a respiratory test, we would be screening for COVID. We know that COVID-19 does seem to like to replicate in human cells quite well. And that’s a big distinguishing factor from MERS and SARS 1. But I think it’s a reasonable assumption today, but ultimately we’ll see kind of what the virus chooses to do.
Doug: [01:08:00] Okay. All right. We will leave it there. Thanks for sticking with us for a few extra minutes. As usual just a fantastic job informing us with all of your insight. And I want to make sure before we let you go that we all appreciate the role you’re playing in developing more knowledge about the virus and really being one of the folks that’s out there working on the front lines with others to diagnose and care for folks. So we really appreciate not just the information, but more importantly [01:08:30] all you’re doing. So thanks for joining us Nate.
Dr. Ledeboar: No, thank you Doug. I think that calls like this are really important because it’s also important to determining what are the technologies that we invest in and how do we push this population or how do we push the technology so that we can better serve our overall populations? So thanks for having me today as well.
Doug: Yeah, that was awesome. All right. All right. We’ll talk to you soon Nate, and thanks everybody for joining us.