Testing For Coronavirus, RSV, Influenza, & Future Pandemics (w/Dr. David Persing)

– [Zubin] Hey guys, Dr. Z. Today I have a returning guest, Dr. David Persing, Dave Persing, DP, Diamond Dave, the chief medical officer and chief technology officer at Cepheid. Welcome back to the show, brother.

– [David] Thank you, Z.

– [Zubin] So now we had you on, it feels like there’s been a pandemic between us, brother. It’s been a minute.

– [David] Maybe a couple.

– [Zubin] A couple. The reason we talk on the show and not, you know, we’re homies off the show, but on the show is because you Cepheid is a major, major, major PCR testing company. Like I will say the PCR testing company for during and prior to COVID and you have a lot of insight and technology to actually bring to bear on the next evolution of this thing. So when you said what you were doing now, I said, “Oh, well, let’s talk again.” And it sounds like you’re doing now a PCR test that’s rapid, that actually covers four things, COVID, RSV, and some sub-types of RSV, flu A and flu B, all in one test. So let’s talk about that.

– [David] Yeah. So we call it affectionately, we call it FluVid, which started out last year, we were all expecting a big sort of onslaught of influenza and COVID last year, which to almost everyone’s surprise didn’t happen.

– [Zubin] Yeah, that was something, right. You and I sat here and we were like, “Okay, the winter’s going to be a nightmare.” And it was yeah, but purely COVID.

– [David] Yeah, exactly. And who knows what the reasons for that are, but you know, probably a combination of social distancing, masks, kids not being in school. Kids are often the incubators of influenza. And so it didn’t have that source of incubation last year, but, you know, worldwide, it was a major phenomenon to not see a flu season.

– [Zubin] Do you think viral interference with COVID was a factor there or no?

– [David] It’s possible. I think, when you look at the way viruses hit the immune system, they activate the innate immune responses that are characterized by interferon production, both systemically and in the airways. And it’s quite possible that by having a previous viral infection that may be induction of those interferon antiviral interferon pathways, that can actually reduce susceptibility to other viruses during a window of time, ill defined at this point. But it’s the concept of viral exclusion is actually based on the concept of innate immune responses and what they might do to protect against other viral infections that might be happening around the same time.

– [Zubin] See, that’s fascinating. We talked about that on the show a while back a few months ago, where did flu go? And I think it is multifactorial. Like you say, schools a big part, so those kids are incubating, but this viral exclusion is fascinating. You throw up an innate, a non-adaptive, nonspecific immunity in the form of interferons, and it has this halo shield effect against other viruses. You wonder if there was an evolutionary give and take with viruses where they’re out trying to out-compete each other.

– [David] Yeah.

– [Zubin] Yeah.

– [David] In a previous previous life, I worked on vaccine adjuvants that would actually induce immune responses. One of the projects we worked on with support from the US government was a nasal vaccine that stimulated the interferon response in the nasal airways and worked as an adjuvant to induce antibody responses to a protein that was delivered at the same time.

– [Zubin] In the nose as well?

– [David] In the nasal spray. But the surprising thing was that within one day of administering that nasal spray, which induced the immune response and well before any antibody responses were detectable against the protein we were delivering, we saw protection against influenza in the mouse model. And then actually was, it stayed on for a couple of weeks after the initial delivery of that nasal vaccine. So it amounted to a fast acting vaccine. You got innate immune protection during the window period of time it took to develop the adaptive response, which provided long-term protection. So it was really pretty interesting stuff, we published on it and it was pretty interesting.

– [Zubin] It seems to me that that is incredibly applicable to our current situation with Delta, where you have a lot of viral replication in the nasal pharynx. But even if you’re vaccinated, you might still get infected because innate defenses in the nares and the nasopharynx are maybe not jazzed up. Is anybody else working on this stuff?

– [David] I think there are several companies that are working on mucosal vaccination, but I think they’re pretty far behind the injectable forms right now.

– [Zubin] That’s what I’ve heard. Okay. So that’s fascinating. We may touch back on that, but I want to go back now to your H1N1 test because there are a lot of people who ask me, like what’s going on with testing? Like first of all, are we going to be able to catch variants that are new, that are different enough genetically that your PCR test, which is taking a piece of genetic material and trying to match it, with what we expect the virus would have. What if it doesn’t match and it’s still COVID, but it’s a new variant?

– [David] That’s an ongoing challenge with any RNA virus, RNA viruses by nature, genetically drift, they’re really prone to doing this as part of their adaptive ability. We didn’t see much variation early on with COVID, but as time has gone on and herd immunity has built up in certain populations, there’s been selection for variants. Immune selection is not the only story though, because we’re seeing variation in the regions of the virus that are not subject to immune selection. We’re actually seeing variation in some genes that where you see genetic changes that don’t affect the protein sequence, where the genetic change occurs in the third position of a codon that doesn’t affect the translation of that codon, still the same amino acid in the protein, but it’s varying. And why would that happen? Well, it may relate to the fact that these viruses are adapting to become more effective replicators. And by changing a codon, they may better adapt to the availability of transfer RNA pools in our cells. So there are different transfer RNA concentrations in cells. And so to maximize their replication, they’re going to pick the transfer RNA pool that’s in highest abundance to really feed their replication within cells. So this is one theory for why we’re seeing a lot of variation. It’s not just immune selection, it’s variation to become maximally productive and to maximize its ability to spread. Because every time you get that advantage that’s propagated further within the population.

– [Zubin] Okay. That’s fascinating. So you’re not just changing spike protein, you’re not just changing other viral proteins. You are changing actually non-expressed parts of that DNA that actually would change how it interacts with transfer RNA and other things within the cell that might confer a selective advantage in reproduction.

– [David] Yeah, these genes are expressed, but the codons that are affected are not always, don’t result in an amino acid change. So the bottom line is we think that it’s really adapting at multiple levels to maximize its ability to replicate and propagate.

– [Zubin] Man, and Delta in particular, is there anything about Delta that does take advantage of that that you know, is there something specific there?

– [David] Yeah. Who knows what the combination of factors is? There’s a lot of spike protein changes that may offer an advantage. There’s probably other changes that offer replication advantage, but the combination of those changes has really allowed it to become the dominant variant right now. So when you talk about variants and you talk about genetic targets, you want to pick for diagnostics, it’s hard to predict which ones are going to vary. And it’s hard to predict how fast they’re going to change. I call it the 1% rule. This is not the 1% that manage to avoid taxation. This is the 1% that manage to avoid detection. So for any given target, single target, there’s roughly 1% of variation within that target that would potentially avoid detection. So we first encountered this with influenza in 2009, where we saw some variation happening within our single target for influenza. And a lot of diagnostic companies had trouble keeping up with the 2009 H1N1 outbreak. A lot of the rapid antigen tests fell to around 40 to 60% sensitivity missing a whole lot of cases of H1N1 2009, because of variation within the protein targets. We were afraid of that happening in our assay, so we just said, you know, to hell with that, we’re going to gang up on this virus. We’re going to put in three targets to cover influenza A and add a fourth target to provide additional avian coverage all within the influence A family. And yes, you might have 1% that could escape detection within any single target. But then you have, if you have four targets, you’ve got 1% of 1% of 1% of 1%. And that ends up to almost nothing.

– [Zubin] Oh, I did the math wrong. I thought that was 1000%. No, that’s exactly right. So how many targets did you have for flu then?

– [David] So now we have four targets for influenza A, which really detects, not just your seasonal influenza strains, but also strains of pandemic concern, H5N1, H7N9, the avian strains that could emerge are covered by this approach of combining targets. And so we’ve done, we’ve now done the same for COVID for SARS-Cov2. We’ve gone from a two target assay now to a three target assay, 1%, 1%, 1%. It really ends up being a very minuscule number of viruses that might escape detection.

– [Zubin] Wow. So now, and just to clarify for people who don’t really know the genetics of this, when you say targets, you’re saying this is the sequence of viral RNA that you’re able to recognize with your test, that’s one target.

– [David] Yeah, that’s right.

– [Zubin] And so here’s a question. So what would a variant need to do to evade your test? Would it have to have enough changes in each of those targets to be in the 1% in each of those targets to then evade the test as a whole?

– [David] So if a variant had all those changes simultaneously, then that would obviously be a problem, but that’s not what we see, we see these targets are unlinked between viral strains. We don’t find viruses that have all three regions affected by mutation. They may occur within one virus at one site at a low level, but we don’t see all three happening at the same time.

– [Zubin] Got it. Okay. Now here’s a followup question to that. Does having more targets increase the rate of false positives?

– [David] No, it doesn’t. All the data shows that all it really does is help avoid false negatives, which is something we like to try to do is to avoid false negatives, especially for sick people, patients showing up at the hospital, showing up at clinics who really need a diagnosis. We want to avoid false negatives.

– [Zubin] Yeah, because then you end up sending them back out with COVID.

– [David] We don’t want to relive the days of 2009 H1N1.

– [Zubin] Right, right, right. You know, relating to that, do you have a sense of what your sensitivity and specificity is for your various?

– [David] Yeah.

– [Zubin] For COVID let’s say.

– [David] It’s comparable to the reference laboratory tests that usually claim in the nobody’s perfect, but in the mid to high-90s for sensitivity and specificity. And these reference lab tests that use PCR are often cited as the gold standard for detection of the virus. So what we’ve done is to take that reference lab tests that needs to be run in a central lab, either in a hospital central lab or in a send out setting where you send a sample to a lab across the country in some cases, we’ve taken that same technology and put it into a cartridge so it’s automated. It can be run close to the patient and on demand. So that’s really the difference is taking that level of sensitivity and specificity and putting it into a point of care, decentralized tests that can be used for managing sick patients.

– [Zubin] Outpatient facilities. You can have, is it gen expert?

– [David] GeneXpert.

– [Zubin] GeneXpert, right. I like gene better than gen, it reminds me of Gen Z, which I just feel bad for Gen Z. They’re so anxious.

– [David] Gen zoom.

– [Zubin] Gen zoom, yeah, really iGen. So, so relating to that, then a follow up question would be, what about, it used to be that you guys were like going right into the brain basically, it’s a swab. Where are you now on that?

– [David] Everybody started off that way. We thought that was the only way to detect it. What we found is that with really sensitive methods, you can actually get away with just a nasal swab. You don’t have to go all the way back to the brain tickle as they called it with the nasopharyngeal swab. Still uncomfortable, but much less uncomfortable than nasopharyngeal swabs. It’s still the gold standard to go all the way back there. But when you have a sensitive test, you don’t lose very much in sensitivity by going to a nasal swab.

– [Zubin] How does your test, because so many people are getting these rapid antigen tests and you talked about antigen test failure in H1N1 during 2009, the protein changes and suddenly the antigen is not recognized. What’s going on between antigen and what you’re doing in PCR?

– [David] It really comes down to viral load. I think that the antigen tests do a good job in symptomatic patients who have high viral loads. And so for influenza, children have higher viral loads than adults. So the antigen tests did better in 2009 for influenza in children than it did for adults, especially elderly adults were the ones getting missed with the antigen tests. It was all based on viral load. So that during that period of peak replication during symptomatic presentations, and maybe just before and just after, you can detect it with the antigen tests. Whereas if you wanted to detect it days earlier or days later, maybe for a patient who is showing up in the hospital after first getting symptomatic a week ago, and has some inflammatory complications.

– [Zubin] But no viral load.

– [David] But hardly any virus onboard, that’s where this technology really comes in handy because antigen tests often miss those cases, those late presenters that would otherwise be detected by a more sensitive method. So I think to give yourself a bigger intervention window to prevent somebody from getting into a transmission pathway, or also to deal with the late presenters who come in with inflammatory complications, molecular methods still are the gold standard for those cases. Now, for school testing and airport testing, and that sort of thing, where you want to, you want to screen out people to prevent transmission over the next four hours during a flight. They’re probably good for that. They’re good if you use them often, test often, so you don’t miss the window. But I think the practicalities of really running the test often enough often forces labs to lean back on molecular methods.

– [Zubin] Molecular methods like yours. One of the interesting things about antigen is since it is so viral load dependent, it is interesting, like you said, for say school screening where you could kind of look at if it’s positive, their viral load is high and they’re probably most transmissible. Is there like a correlation?

– [David] Yeah, I think there is, there’s likely to be a correlation with transmissibility and viral load. And that’s the real value of these is identifying the transmitters within the population who need to be taken out of circulation. But I think for managing the full population of patients who might present in a hospital and clinic setting, I think molecular is probably a better option because you don’t have to choose between test modalities depending on the clinical presentation.

– [Zubin] Right, right. It’s just you know it’s working. So now you have this four in one. So flu A, flu B, within flu, and let’s talk about each of these pieces. So within flu A and flu B, first of all, do you think we’re going to see flu?

– [David] You know, all bets are off. I think the concern this season that’s different from last season is that kids are going back to school in larger numbers. And we know that that correlates with incubation of influenza and broader spread of influenza. Who knows what the impact of social distancing, masking will have on transmission of influenza. But I think most are concerned that we really might see some, at least some flu this year that will confuse the picture.

– And flu A and flu B in your swab, are there any subtypes, you said you’re looking also at avian, all the targets are in it?

– [David] So all the avian strains of concern are in the influenza A category.

– [Zubin] Got it.

– [David] And that’s the most variable influenza subtype. Influenza B is really pretty steady. Just doesn’t vary. And so that’s less of a concern from a genetic drift standpoint. RSV A and B, a little bit of drift, not much. And then, of course COVID with its own drift problem, but they vary a lot depending on the type of virus.

– [Zubin] Got it. But your fourplex type test is pretty good at not missing those.

– [David] The ones that are likely to vary the most.

– [Zubin] Tell me about RSV a little bit. What’s going on? Why are we seeing so much RSV?

– [David] Good question. You know, it’s kind of, it’s out of season for RSV. RSV usually happens a little bit before the flu season and then lasts a little longer than the flu season. Often peaks a little earlier than the flu season, then flu itself, this year, we’re seeing it, you know, it’s out of order. It’s been happening in places all over the country. And it’s been happening during the summer months, which is unusual. So who knows what the factors behind that are? Is it opportunistic? Who knows? But the bottom line is that we’re seeing it in places all over the world really at a time of year when it’s unusual to see it.

– [Zubin] It’s interesting to think about innate immunity and that idea of viral interference that we talked about. If kids are generally hyper clean now and kept apart and masked up and all that, I wonder if they aren’t exposed to the standard cold coronaviruses and so on, and they’re not getting that little shot of interferon and maybe RSV is taken advantage of that.

– [David] That’s not an unreasonable thought.

– [Zubin] Of course that doesn’t mean I’m advocating throw the masks away because COVID is quite a different beast. But relating to that then comes the question, why test for RSV? So in other words, you’ve got flu A, flu B, RSV, COVID. An adult shows up, they’ve got a fever, muscle aches. They feel like they’ve been hit by a train. My top concern in that person would be COVID or flu? Why is RSV important in that?

– [David] RSV can produce flu-like symptoms with fevers and upper respiratory symptoms, prolonged cough in all age groups, more common and much more dangerous in very young children, two years of age or younger. But also as we get older in the nursing home populations, and those above the age of 70 or 75, RSV becomes a bigger problem. It can be a major cause of morbidity and mortality in the elderly. We need a vaccine for RSV, but the bottom line is that it’s in between age groups, it’s less common to produce flu-like symptoms, but it does produce them and it can be in the mix. And a lot of the cases being reported now are in multiple different age groups.

– [Zubin] So that’s important because if someone comes in with those symptoms typically, and they just get a COVID test, you’re going to miss RSV. And, you know, that’s a different category of thing. Flu, same thing, if you miss flu, it’s a whole different category of thing. I know a lot of people now who’ve been testing negative for COVID, but who’ve had symptoms that they sure sound like COVID, and they’re getting molecular tests. I don’t think they’re false negative tests. So could they have part of this RSV kind of little mini pandemic that’s going on?

– [David] Absolutely.

– [Zubin] Interesting. So this test actually solves that question.

– [David] It really helps. Yeah. It doesn’t detect all the other common cold viruses in this one test that don’t typically produce fevers but it really helps with the cases that look flu-like, where you really feel the myalgias, the muscle aches and pains, the fevers, the cytokine-driven symptoms.

– [Zubin] Got it. So, is there anything else about this test that you wanted to let us know about that clinicians should know that patients should know about?

– [David] Well, I think it’s a very sensitive tool. It’s one that they can, I think depend on. They won’t have to question, gee, did I miss that case because I used the less sensitive test? Do I have to reflex test if it’s negative? It’s kind of a one and done approach, so I think that the level of confidence that providers will have from the result will be fairly high, given that it incorporates really sensitive technology. And it’s also reasonably fast. It’s about 30 minutes.

– [Zubin] It’s pretty quick.

– [David] For all that technology, all those targets, all that strain coverage in 30 minutes, it’s pretty impressive. And it also, I think this is technology that we can count on going forward for once we’re out of Delta, there may be other pandemic strains and other variants that come in both for flu and for COVID. And so sort of future-proofing the technology was the goal with this. And we think that that it’ll really prepare us well for future waves of variants and other things that might happen going forward.

– [Zubin] So it makes it future-proofing, present availability. It’s common. It doesn’t take too long. It’s not super expensive beyond what you would expect normal testing. It’s standard of care in many places. So you guys have really, and I’ve talked to a lot of people in the industry who work in large health systems and to one when I mentioned, oh, you know, we’ve done some shows with Cepheid and Dave, they go, “Oh, I love those guys. I love my GeneXpert. I love it.” And you rarely hear that about diagnostics, you know, so whatever you’re doing, you’re doing a great job.

– [David] It’s really gratifying to see that, to see the impact now, that’s what we live for really.

– [Zubin] You know, and I’ve talked with some of your staff too, and they’re like, they’re passionate about this stuff. It’s a little scary. And you guys didn’t ask for COVID, but you stepped in and really it’s been wonderful to see.

– [David] Yeah, it’s really pushed our installed base, our users worldwide to new levels. And I think, we’re going to be better equipped because of that. We’re going to be better equipped for the next pandemic. I think it really is. I think it’s part of our responsibility in the diagnostics industry to sort of future-proof our testing strategies to build in broad range capability so that we don’t miss these things the next time, we’ll we be better prepared to launch testing that at least provides a stop gap measure while we’re developing super specific tests for given outbreak, having something that tells you, I can’t tell you which coronavirus that is, I can’t tell you if it’s SARS-CoV-3 or MERS or V2, that’s a coronavirus. Having that capability, at least on an interim basis in the face of a new outbreak would be really valuable and having it on a widespread basis to be used on multiple systems throughout the world would really offer a lot during the next time we have to encounter this.

– [Zubin] And that’s what you guys are doing.

– [David] Yeah.

– [Zubin] Yeah.

– [David] Yeah, we just started a new project that we announced on with support from BARDA, which is a government agency that’s super focused on pandemic preparedness, and they want us to build a broad range sort of pan-coronavirus cartridge that covers current, seasonal coronaviruses, the big four that have been with us for thousands of years. They also want us to detect all the members of the sarbecovirus family, which is the SARS bat coronavirus complex. To call out specifically, SARS-CoV-1, SARS-CoV-2, but also provide the ability to detect a future SARS-CoV-3 or four built into that cartridge, and then also to provide coverage for the MERS family should that become a more widespread problem. So right now, none of the tests that are designed to pick up SARS-CoV-2 will detect MERS. They are different families of virus. So we need to have, for pandemic preparedness, really need to have the capability to cover the full range of things that we might encounter in the future.

– [Zubin] I really want to emphasize this because if we continue to just be myopic in how our tests actually perceive viral invaders, we are going to miss the resurgence of MERS or a new SARS one type syndrome that’s highly fatal, high case fatality, but maybe is transmitted when you’re asymptomatic, which is the worst possible scenario, right? How are you ever going to catch that if you don’t have something that’s broad enough to detect it, and that’s what you’re working on for the future. So that’s going to be very important and I’d love it if you come up with some new stuff, if you come back and tell us about it, that’d be great.

– [David] Sure, yeah, I’d be happy to.

– [Zubin] Really fabulous.

– [David] But the FluVid test, the fourplex, ’cause we’re not done with the current pandemic.

– [Zubin] I’m already onto the next one.

– [David] And we’re probably not going to be done for a while. We’re going to probably see the seesaw for the next couple of years, but as it kind of builds itself in to become a new endemic virus, it will become the big five, not the big four.

– [Zubin] Can we talk about that? Yeah, because I just did a show on this about “endemifying” COVID. So the big four coronaviruses that have been with us for thousands of years, is it reasonable to assume that it’s when they first hit the human population, it was SARS-ish?

– [David] Probably so. We think so. Some of them came from animal reservoirs that at least based on our molecular clock and evolution, experiments, we think came from animal reservoirs that are known to be associated with human illness after transmission from a zoonotic source. So it’s pretty likely that they did cause havoc when they first hit the population. And the nature of these viruses is that they just adapt over time to become, as you develop increasing amounts of herd immunity, and they continue to vary over time, they adapt to the population to become less pathogenic. And so I think the expectation is, and who knows how long this will take, but that we will see waves of variants and transmission, different parts of the world. Antibody titers will decline. You’ll see some new variants take advantage of that. But each time the infections have become less pathogenic, less severe. And ultimately, maybe hopefully three or four years from now, we’ll be at a point where it’s just like the common cold, like the other coronaviruses that are out there.

– [Zubin] That’s the dream. And it might be that in advance of that, the large majority of the population is safe from severe disease. Having been a combination of natural infected, vaccinated, potentially boosted with vaccine. And one of the questions, I felt this was an interesting thing, because SARS-CoV-2, doesn’t typically kill or injure young kids typically, although there’s always exceptions, the fact that like the big four coronaviruses that already infect us as cold, there may come a time when we don’t need to vaccinate anymore because elders will have natural immunity from the combination of vaccine in the past and natural infection. And every child who’s born will eventually get infected in a common cold type way so that the whole population cycles through and gets immunity against severe disease.

– [David] Yeah, exactly. That’s what I hope happens.

– [Zubin] Right. Right. So there’s hope. And I think people are very frustrated with Delta. Even I was like, starting in the spring, I’m like, this thing’s over! We’ve got the vaccine, it’s great.

– [David] I know, we all were.

– [Zubin] And it’s good that, you know, I think we’re seeing increased vaccination rate. Do you think, and last question, vaccination, you gotta do it, right?

– [David] Absolutely. Please, my friends, get vaccinated. Now more than ever. It’s just really important to protect yourself, protect the population against the emergence of future variants, reduce the overall transmission pressure in the population. Even though the vaccines don’t completely block infection, they still prevent at least a big chunk of them. And they also seem to really suppress severe symptoms. And very likely even among those who experience breakthrough the viral loads are probably pretty low, we’ve heard a lot about, oh, the viral loads are high and it was just as high in vaccinated patients. But I think that’s a very select subset of patients. We’re looking at just a few who got really sick. The viral load correlates with level of severity. We know that, but there’s a ton of people who didn’t get infected and maybe another ton that got infected, but just got a smidge of virus and are probably not transmitting very much. And so we’re much better off getting vaccinated. And I just think, I encourage all of my friends and colleagues to do so.

– [Zubin] That’s really well put. I mean, how do you feel about people with naturally occurring previous infection needing to be vaccinated?

– I think if you look at the data on 20 year old experiments in the UK with natural seasonal coronaviruses that were common cold viruses being used in human inoculation experiments where volunteers got inoculations of one of the common cold coronaviruses and they followed their course for a year, they looked at them get sick and recover as they always did, and then re-challenge them about a year later. And about half of them actually experienced reduced symptoms, but they still got infected with those same strains of virus. So the experience is that very likely you experienced a decline in immunity after natural infection that doesn’t completely block re-infection. And so in order to maintain that level of neutralization, that you would really like to help avoid infection from the outset, you need to have higher antibody titers than natural infections can typically produce. So, and that’s what vaccines do, they produce unnaturally high levels of these neutralizing antibodies. And that’s why I think boosters should be implemented as well, especially in vulnerable populations because they’ll produce unnaturally high levels of antibody that will be better at blocking the virus than even natural infection.

– [Zubin] Right. You know, so the way I like to think of that, all of that is true. I think the way I like to think of that is in our most vulnerable people, even if you’ve been naturally infected, you know, you might get reinfected, but your symptoms might be less, you might be protected against severe disease. But if you really want to put a dent in transmission and be as likely as you can be to have not getting severe disease and even not just getting knocked out for a week, at least one dose of the mRNA vaccines or a J&J is reasonable. Now, if the one thing I will say is, I think there are a lot of people reach out to me going, I don’t want to be mandated to vaccinate when I got naturally infected. I’m a young person, I’m otherwise low risk. And it’s kinda like, we want to be able to have a little nuance in our conversation. I know CDC can’t do that because they’re not allowed to basically they have to give a very monolithic. But I do find that there’s a lot of, when we get too proscriptive, people tend to shut down.

– [David] Yeah, absolutely. I think, you know, there are advantages to natural infection. You’re going to develop T-cell responses to proteins that are not in the vaccine. You’re going to develop T-cell responses to nucleocapsid and other proteins that are going to be effective. You’re going to develop IgA responses in the respiratory tract that may be effective. Who knows how long those will last? But I think all in all, between vaccination, maybe some natural infection on top of vaccination, including all those additional T-cell epitopes and IgA responses and future encounters with future variants, we’re going to develop some pretty solid immunity against this.

– [Zubin] It’s this whole holistic combination of things that I think is going to bring us to endemicity, if that’s a word. Where can people go to learn more about your thing? Cepheid.com?

– [David] They go to our website, cepheid.com And I think, you know, the good news is a lot of their local hospitals and clinics now have the technology and they’re all asking for more stuff and we’re working as fast as we can to make more stuff. But we really do feel responsible for helping to fulfill our part of the diagnostic pathway and really achieve the right level of sensitivity and performance we think will be necessary to really stamp this thing out.

– [Zubin] Love it, man. Science, science, so much science, guys. ZDogg here. Share this video, go to the website if you want to learn more, I’m gonna put links to other shows I’ve done with Diamond Dave. He always teaches us a lot. Let us know in the comments your questions that we can ask him next time he’s on the show or I can do a show on. And I love you guys, we are out. Thank you, brother.

– [David] Thank you, Z.