This Podcast Will Kill You - COVID-19 Chapter 14: Virology, Take 2

Episode Date: January 5, 2021

The fourteenth installment of our Anatomy of a Pandemic series on COVID-19 dives into what we’ve learned about SARS-CoV-2, the virus that causes COVID-19. Curious about the new strains or variants making headlines lately? Or how exactly tests for COVID-19 actually work? Or perhaps you’ve been wondering about the different routes of transmission that this virus uses. Whatever your virology question, we’ve (hopefully) got you covered. We were fortunate enough to interview virologist Dr. Angela Rasmussen, affiliate at the Georgetown Center for Global Health Science and Security, and whom you may remember from our earlier episode on the virology of SARS-CoV-2, which we released all the way back in March 2020. Dr. Rasmussen was kind enough to sit back down with us to answer all of our many burning virology questions (interview recorded December 30, 2020). As always, we wrap up the episode by discussing the top five things we learned from our expert. If you would like to read Dr. Rasmussen's article in The Guardian about the new SARS-CoV-2 variants, follow this link.To help you get a better idea of the topics covered in this episode, we’ve listed the questions below: Can you tell us a bit about SARS-CoV-2? What kind of virus it is, other viruses it’s related to, and what that tells us about the virus and the disease it causes? Could you tell us a bit more about the B117 strain, like whether this appears to be a new strain and how it is different? Do we have any evidence of any strains that seem to cause more severe disease or affect different populations? Where do these new strains come from? What does this new strain (or multiple new strains) mean for the effectiveness of the vaccines that have been developed? Will these vaccines work against these new strains?  What additional things have we learned about the structure or surface proteins of SARS-CoV-2 that give us more insight into how it causes disease or the widespread effects it has on the body? Is there any indication that the virus can be airborne? Does fecal-oral transmission seem to be playing a role? What are the various ways to test for SARS-CoV-2? Can you walk us through what each experience is like? How do the rapid vs PCR tests work? And can you compare their accuracy? Why does the rapid test have a higher rate of false negatives than the PCR test? What has this pandemic taught us about virology? See omnystudio.com/listener for privacy information.

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Terms and conditions apply. Visit blueapron.com slash terms for more information. I'm Amanda Knox, and in the new podcast, Doubt, the case of Lucy Letby, we unpack the story of an unimaginable tragedy that gripped the UK in 2023. But what if we didn't get the whole story? Evidence has been made to fit. The moment you look at the whole picture, the case collapsed. What if the truth was disguised by a story we chose to book?

Oh, my God, I think she might be innocent. Listen to Doubt, the case of Lucy Lettby, on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts. This is Special Agent Regal, Special Agent Bradley Hall. In 2018, the FBI took down a ring of spies working for China's Ministry of State Security, one of the most mysterious intelligence agencies in the world. The Sixth Bureau podcast is a story of the inner workings of the MSS and how one man's ambition and mistakes opened its fault of secrets. Listen to the sixth bureau on the Iheart radio app, Apple podcasts, or wherever you get your podcasts. My name is Patrick and I live in Orlando, Florida.

In June of 2020, both of my parents were hospitalized with COVID. It started with my mother. My mother was 72, active and in good health. She ran her own cosmetics franchise and practiced yoga on a regular basis. Her only underlying condition was asthma, which was not severe. On June 25th, she walked into the hospital complaining of shortness of breath, a persistent cough, and a fever. She was admitted and began aggressive treatment with high-flow oxygen. Due to COVID precautions, we were not allowed into the hospital and had to communicate with her through the phone. As the days progressed, her condition worsened. When she would cough, she would gas for air as if she was drowning.

We kept her phone calls with her short so she could conserve her oxygen. Eventually, we told her only to use text messages. The hospital gave her convalescent plasma, but the treatment course was limited, and it didn't seem to help. On July 4th, she was intubated. With my mother on a ventilator, any updates regarding her condition and prognosis were dependent upon the nurse or doctor on the other end of the phone. The information regarding my mother's condition would change based on the person observing it. We closely watched her ventilator settings, and our hopes and our own. emotions would rise and fall with the daily reports. However, there was no true guideposts with

which to evaluate her progress. We were frequently surprised by new conditions, such as her being septic, a persistent pneumothorax, and the development of AFIB. On August 6th, after 32 days on a ventilator, the hospital transitioned her to compassionate care and removed her from the ventilator. 34 minutes later, my mother died. Before she died, we saw the x-rays of her lung. And she, Instead of the shadowy outline of two healthy lungs, it looked as if a family of spiders created an impenetrable web that showed as white lines criss-crossed throughout the x-ray. My father was admitted to the hospital two days after my mother. My father has been disabled since 2001 after suffering a stroke which permanently compromised his balance and range of motion. He also suffers from heart disease and has frequent bouts of a-fib.

Despite his medical history, my father's only co-covement of his own condition, my father's only co-consum COVID symptoms were a fever, diarrhea, and extreme exhaustion. After five days in the hospital, he was discharged because he did not need oxygen. However, he was still testing positive for COVID. The convergence of his mobility issues and exhaustion meant that he could not even sit up in bed and could not care for himself. We struggled to take care of him while wearing PPE to avoid exposure to ourselves. The same day my mother was intubated, we had to have my father readmitted to the hospital because the level of care he needed. exceeded our capabilities.

My father spent two more weeks in the hospital and survived. January 2021 would have marked my parents' 50th wedding anniversary. Throughout this process, we struggled to obtain reliable and accurate information regarding my parents' conditions. Before my mother died, we were given the opportunity to come into the ICU and see her. The images from that day in the ICU have stuck with me more than those of my mother herself. The entire ICU was COVID patients. Each patient was on a ventilator and confined to their room.

Outside of the door to each room was the IV pole with no fewer than six IV bags and pumps. The atmosphere was eerily silent. The only sound we heard were a faint beeping in the distance and the stifled sniffling of nurses who took turns sitting at the nurse's station, quietly crying with their heads buried in their hands. It was clear to us that the doctors and nurses were trying to care for all of their patients, but they were continuously confronted by the dim, silent reality that most every person in the ICU would not go home. Kura, my name is Rachel. I'm from Atearo, New Zealand, and my husband and I are both working education in Auckland, and we have two young kids.

I wanted to share the experience that I have at the moment living in a country which is essentially post-COVID. We currently have no community cases of COVID, and only 55 cases in the country. as of the 8th of December, which are all quarantined at the border, and now is the result of people coming back into the country. We went into lockdown with the rest of the world in March, and the lockdown at level four lasted for five weeks, and during that time we had very strict conditions. Only hospitals, pharmacies, petrol stations and supermarkets were open,

and we were only allowed out of our house for one local walk a day, or for our designated shopper to go get groceries from the local supermarket. The idea was that we didn't put ourselves at risk, Anything that we did that might increase our chance of interacting with those outside our bubble, we just didn't do. Then we went to level three where online shopping and takeaways were allowed for another few weeks. And then by May, schools were open, businesses were pretty much back to normal. Our Prime Minister took the scientific advice that she received really seriously and we were rallied as a team of 5 million to protect each other in the night against COVID-19. Ashley Bloomfield was a Director General of Health and he did a press conference at 1pm every day

to update everyone on new cases and which clusters had new cases and even though everyone, not everyone agreed with the lockdown, we had very few cases of people breaking it. People received government support and most people got paid at least 80% of their wage over lockdown. And our borders are still closed except for returning citizens in Pemberton. residents and they have to undergo two weeks isolation in a government-funded facility, which is a five-star hotel until they can return three negative tests. So after that first lockdown, we had 100 days with no new cases, and to be honest, it really felt like that was that.

But then we had one relapse where just in Auckland, the Auckland region went back into lockdown for three weeks when one family tested positive in the community. and they were able to find out that that was somebody from quarantine who had delayed incubation period. So they came up positive once they were back in the community. And so contact tracing is a huge part of New Zealand's response and they now trace all cases genomically to help link the clusters. So COVID is this weird thing right now.

We know it's out there. We did the work to eliminate it from the community and there's this sort of peripheral awareness of it because we wear masks on public transport in case another case comes through quarantine. And we hear stories from overseas. And it's by no means completely rosy. Like it's hard for people with loved ones overseas. And you can't fly into the country unless you have a space booked at the managed isolation.

So there are people that are missing out on coming home for Christmas. But we also go to concerts and have plans to travel with New Zealand over summer and have big family Christmas celebrations. And we see what's going on, but we're not really part of that global narrative. quarantine and the ever-present fear of infection or death for us here in New Zealand. And instead, because of how swiftly the government acts, if there is a community case, we're sort of on edge. But it's very easy to forget in the day-to-day that it's out there because our lives are

back to normal, so to speak. Our kids are at school, we're at work. And apart from not being able to travel overseas, there's not a huge difference to how we live now compared to in February. but we do have that feeling of how lucky we are to be in this situation. So basically all that to say, there's a light at the end of the tunnel. New Zealand is proof that testing, contact tracing, quarantine and science and collective action can prevail and hopefully will and across the rest of the world as well.

Thank you so, so much for sharing your stories with us. And thank you also to everyone else who has written in to share your first-hand account of how COVID-19 has impacted you. We absolutely love hearing from you. And we feel like telling your stories is such an important reminder of how far reaching the effects of this pandemic have been. Yeah. Hi, I'm Erin Welsh. And I'm Aaron Alman Updike. And this is, this podcast will kill you.

Yeah. Welcome to our 14th. I can't believe we've made it this far. Oh my gosh, I know. Installment of our anatomy of a pandemic series on COVID-19. Today we are revisiting the virus itself, SARS-CoV-2, which we visited first many, many months ago. Many, many months. So today we'll refresh you on what exactly this virus is, what new things we've learned about its transmission.

We'll touch on some of the new strains, or rather, variants that you've probably been hearing about. And we'll talk about the different tests for COVID-19 and how those actually work. And honestly, so much more. Yeah, there is a lot of great information in this episode, so get excited. I'm excited. But first, are you also excited that it is quarantini time? I'm always excited for quarantini time. Absolutely. What are we drinking this week? We're drinking quarantine 14. What a surprise. And in Quarantini 14, we have lime juice, lemon juice, rum, and maraschino liqueur.

And we'll post the full version of this quarantini as well as our non-alcoholic placebo rita on our website, this podcast will kill you.com and all of our social media channels. So make sure you follow us there. Absolutely. Okay. Let's see. We've got a little bit more business to cover. So we are still soliciting firsthand accounts for this COVID-19 series.

And if you would like to submit your first-hand account, head to our website. This podcast will kill you.com and click on the COVID-19 firsthand tab on the top of the page. And that'll send you over to a Google forum where you can fill out some of the information for your first-hand account. And once again, thank you so much to everyone who has submitted their first-hand account so far. Yeah. We also are in the process of getting transcripts made. Yay! For all of our episodes.

This is long overdue. We're very excited. They will be available under the transcripts tab on our website, this podcast will kill you.com. So check back there or follow us on social media to know when they're all being released. And then there's just the usual business stuff. So we have a Goodreads list. We have a bookshop affiliate account if you want to read more about any of the subjects that we mentioned and that there happens to be a book about. And we also have tons of incredible, amazing, beautiful, super cool TPWKY.

merch. Yeah, we do. And you can find links to all of those things on our website. This podcast will kill you.com. How many times can we say the name of our website in this episode? My gosh. Oh my gosh. Oh, anyways, let's get into today. Let's get into today, yes. So our guest today is someone that you are likely familiar with because we talked with her all the way back in March for our first virology episode. Also, she's been like all over amazing, you know, up first and tons of other podcasts. She's basically super famous at this point. She's super famous. And we think she's great. We thought she was great way back in the day. We still think she's great. So we wanted to ask her once again all about the virus and what we've learned. Yeah. We recorded this interview on

December 30th, 2020, last year. Last year. A whole year ago. And so here she is. We are so thrilled to have back on virologist Dr. Angie Rasmussen, affiliate at the Georgetown Center for Global Health Science and Security. And she is going to answer all of our questions about SARS-CoV-2, the virus that causes COVID-19. And we will let her introduce herself right after this break. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients so there's no meal planning and no extra grocery trip. There, assemble and bake meals take about five minutes of hands-on prep. Just spread the pre-chopped

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We're offering our listeners 15% off their first order of O'Keefs. Just visit O'Keefscompanion slash this podcast and code this podcast at checkout. I'm Clayton Neckerd and in 2022 I was is the lead of ABC's The Bachelor. Unfortunately, it didn't go according to plan. He became the first Bachelor to ever have his final Rose rejected. The internet turned on him. If I could press a button and rewind it all I would. But what happened to Clayton after the show made even bigger headlines.

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I'm Stephanie Young. This is Love Trapped. This season, an epic battle of He Said She Said, and the search for accountability in a sea of lies. Listen to Love Trapped on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. I'm Angela Rasmussen or Angie. I am an affiliate.

and a virologist at the Georgetown Center for Global Health Science and Security. Soon I will be a research scientist at Vito InterVAC, which is the Vaccine Research Institute at the University of Saskatchewan. Excellent. Thank you so much for coming on again. We're thrilled to speak with you. If you could kind of just help refresh our knowledge and tell us a bit about SARS-CoV-2, the virus that causes COVID-19, like what kind of virus it is, maybe other. viruses it's related to and what that tells us about the virus and the disease it causes? Absolutely. So SARS coronavirus, too, as the name implies, is a coronavirus. It is a beta

coronavirus. So the SARS or the coronavirus family is divided up into three major branches. The alpha coronaviruses, the beta coronaviruses, the gamma coronaviruses. SARS coronavirus too, like SARS Classic is a beta coronavirus and it's also what's called a Sarbeko virus, the SARS-like beta-coronoviruses, which is a subgroup of that particular genus. So it's most similar to SARS-coronavirus classic. It's also related to MERS coronavirus, which is another beta-coronavirus, as well as to two of the common cold coronaviruses, which are also beta-coronoviruses. And the other two common cold coronaviruses that circulating humans are alpha coronaviruses. So it's part of this larger family called coronaviruses. And what all coronaviruses have in common is they have a single-stranded RNA genome. So their genome,

their genetic material is encoded on one single piece of RNA, a single strand. So unlike our genomes, which are double-stranded DNA, is just one strand of RNA. And it's what we call positive sense, meaning that if it gets into a cell, it can be directly translated into protein by the ribosomes, which are the organelles inside your cell that basically make proteins from RNA, and that's their normal function. So that's what coronavirus is have in common with each other. They all evolved at some point from a common ancestor coronavirus

back in ancient times. And now there's a very diverse, they're a very diverse family. We probably only know a handful of the coronavirus coronaviruses that are out there and only a subset of those actually infect people. So people should keep in mind not to scare anybody, but SARS coronavirus too is a Sarbeco virus, as I mentioned. And there are quite a few of those that have been found circulating in wild bat species. And not all of them can probably infect humans, but some of them may be able to.

So there may be other coronaviruses out there floating around in the wild that maybe potentially human pathogens, but we really don't know that much about that. And we, I think, really need to know more about that to prevent future pandemics from happening. Yeah. So now let's talk what has been all over the news lately, and that is strains. So in our earlier episode back in, I think March, where we talked with you about the virology of SARS-CoV-2, we asked a bit about a couple of the different strains that seem to have emerged at the time calling the L and S strain. And we talked about what that might mean in terms of disease outcomes. And lately, A, we have a lot more information about just overall strains of SARS

COB2 in general. And then in particular, there's been a lot of coverage about the one UK strain, as it has been called in the news, that seems to have now popped up in the U.S., for instance, and popped up all over different countries. And there's some medication that it might be more contagious. Could you sort of just walk us through what this UK variant is, whether this appears to be a new strain, how different it is, and whether there are any clinical outcomes that we are seeing in regards to the strain? Absolutely. So before I get started, I'll say that, you know, even the big use of the word strain is somewhat confusing, I think, for people sometimes, because it can be used in a variety of different ways.

So I tend to call the variant a variance because it's not really that different from all the other variants of SARS-Coronavirus 2 that are floating around out there. It has, I think, 23 different nucleotide substitutions or deletions. There are 23 changes, basically, to the genome overall that make up this new variance.

And that basically means that it's genetically different, but we expect all these variants to be circulating around anyways because the one thing about RNA viruses that you can count on is that they mutate every time that they replicate. So this is a normal and expected thing to have different variants with different properties emerge. Whether there are strains or not is a matter of debate, just because sometimes when people say strain, they mean something that's radically different, either genetically, meaning. that a much larger part of its genome is substantially different from the parent virus or that it might be different immunologically, meaning that, you know, your immune system will mount fundamentally different responses, make different antibodies to it. And we don't have any evidence that that's happening for this. So the L&S strains that we talked about, which feels like a million years ago, didn't turn out to be L&S. I think that the L&S stood for, I think, low, low,

disease and or lethal. I can't remember what they stood for, but one was mild and one was more severe. And that didn't turn out to be true. That was probably just an artifact of the population sizes they sampled. But this variant in the UK, which has the extremely catchy name of B117, does appear to be more transmissible. And that's really based on a couple different lines of evidence. One is that it became very prevalent, very, very quickly in the southeastern United Kingdom. And I should note that it didn't really necessarily emerge in the UK, but that's where it was first detected because their genomic surveillance program where they're actually sequencing about 10% of the viruses that they identify in terms of new cases. That made it very easy for

them to track the sort of rapid takeover, if you will, of this particular variance. And it just became, it outcompeted essentially all the other variants that were circulating in that population in about a couple of months. So that's really fast for a single variant to take over. So there was that evidence. They also observed that people who were infected with this particular variant had higher viral loads at the time of diagnosis. And that's a little, trickier because people aren't usually being sampled every day and tested. And, you know, during the course of a viral infection, your viral load will change as the virus is replicating and then as it starts to be cleared. So it's hard to say if that's the mechanism by which

it's more transmissible, meaning that people who are infected with it are shedding more virus. But that's what this preliminary data seems to suggest. And then yesterday I saw that they had release some data, some epidemiologic data about the secondary attack rate. And that basically showed that people who were infected with this were more likely to transmit the virus to others in their households or in their workplaces. So it does appear to be more transmissible. You know, we've now found it in the U.S. in Colorado. It's probably elsewhere in the U.S. It's been found in, I think, 25, 26 other countries so far. So this variant has been a emerging and has been spreading globally for a while now. We just hadn't picked up on it until the

week before Christmas. Gotcha. And so if the mechanism by which it is more transmissible is a higher viral load or shedding more virus, does that have any sort of clinical outcomes as well? Like, do we see more severe disease in people infected with this variant compared to other variants? So that hasn't been observed yet. And it doesn't appear that this variant results in increased pathogenicity or increased disease severity. You know, we don't know the mechanism by which it's more transmissible that that viral load data is suggestive that that might be the case. But other people have shown that one of the mutations in the spike protein, which is in the receptor binding domain, binds ACE2, the receptor for the virus more tightly. It could have some

to do with that. It could have something to do with increased fitness, which basically means that the virus is able to replicate to higher titers. We don't know. But the good news is it doesn't appear to be associated at least observationally with more severe clinical disease. And there is a mutation that inserts a stop codon into the ORP 8 protein. And previously with both SARS coronavirus 2 and SARS classic deletions in ORF8 have been associated with attenuation or making the virus less. virulent. So it may be that this stop codon and ORF8 has something to do with that, might not, but people are investigating this now. But the good news in the bottom line is that it doesn't look like this variant is more pathogenic. That is good news. I guess you mentioned that there are a lot of other variants kind of floating around. And I know that that's something that a lot of people have expressed questions or concerns about. Do we have any evidence of any other variants that do seem to cause more severe disease or even potentially affect different populations differentially than more common variants?

So not really. Initially, this UK variance, it was said that it's infecting children more. And today some data came out in a preprint that showed that maybe not. So it's really hard to say, but to my knowledge, there haven't been any variants described. that are more virulent than others, apart from that L&S paper way back when. That doesn't mean that they're not out there. But right now, at least in the U.S., and in most countries besides the U.K., we just aren't doing enough genomic surveillance overall.

So it's really difficult to associate particular variants with particular disease severities if you're not actually sequencing a big portion of the variance that you're seeing. I mean, in the U.S., if somebody goes in and gets a COVID test, you know, if they're very sick, they'll go to the hospital. But that doesn't necessarily mean that somebody's going to be doing the sequencing that's required to say, okay, this person's infected with this variant versus that one. So it's not to say that there aren't variants out there that are associated with more severe disease. But to my knowledge, we haven't found any yet. There are other variants that have been said to be more transmissible.

There's one currently that was reported right around the same time as the UK. variant in South Africa that also may be more transmissible. They've said that it might also have some impact on virulence, but right now there's not a lot of data about that, or at least I haven't seen any, to indicate whether or not that's the case. So the take-home message for me with this is we would maybe have more information about this if we did more genomic surveillance, so we should really think about finding ways to do that. Yeah. And so, you know, in a general sense, where do all of these new variants come from? They don't come out of thin air. They come from the place where all viral variants come from, and that is evolution. When RNA viruses, like

coronaviruses, replicate their genomes, they usually make mistakes. And that's because the enzyme that replicates or copies their genomes essentially makes typos. It's called the RNA-dependent RNA polymerase or RDRP. Coronavirus has actually have an advantage, probably not from an evolutionary standpoint, but it's good for us. They have a lower mutation rate than many other RNA viruses because even though their RDRPs are still very error prone, they have another enzyme that is an exonuclease that basically can do partial spell checking, essentially.

So it can correct some of the errors that the RDRP makes. it copies the genome, but nonetheless, mutation does occur. And some of those mutants, which occur randomly, will be in a place that results in some sort of competitive advantage to the virus. Either it makes it replicate better, it allows it to enter cells more easily, it allows it to evade the immune system more easily. There's a lot of different ways that a mutation could have that sort of impact on a virus. But if it does give the virus some sort of advantage, it's said to be under positive

selection. So these new variants are the result of basically these mutations being acquired, providing some kind of advantage to the virus, and then getting passed on because they are under that positive evolutionary selection. People ask me a lot, how do we stop the virus from mutating? How do we prevent these variants from emerging? The best way to do that is to keep the virus from replicating, and the best way to do that is to keep it from finding new hosts to replicate in. It all comes back basically to masks and social distancing and staying home and washing your hands and avoiding getting infected in the first place. I have a quick question about going back to B-117 and about the mechanism of transmissibility.

How much do you think behavior could play a role in that? So, for instance, if that variant is less virulent than the other circulating more common variants, and that means that potentially more people who are infected with it are still walking around maybe shedding virus asymptomatically and don't know. So could that be one of the major drivers of this apparently increased transmissibility? Could. And I don't think we have enough data to answer that directly, but I'm going to try to speculate a little on how behavior might be involved. It could be because people are more commonly asymptomatic. and infecting people when they don't know that they're sick. But that happens for normal variants of SARS-2 as well.

It could just be that because it's more transmissible, the UK also relaxed some of their restrictions in preparation for the holidays, which I think is kind of a dumb idea because if Christmas is coming up, the virus doesn't care. It doesn't take the holidays off. So if you relax your restrictions and people think that,

okay, it's safe like I can get to go. with my family, I can go to work, I can go have dinner in a restaurant or a bar or something like that, you're in a situation that's going to be more conducive to transmission anyways. And if you have a variant that's more transmissible, then you're going to see transmission in those riskier circumstances increase. And I think that that could explain it just as well as anything else. We already know that there's a lot of pre-symptomatic transmission. and a lot of the literature doesn't really distinguish asymptomatic from pre-symptomatic.

So there are people who are asymptomatic completely through the entire course of their infection. And then there are people who are diagnosed while they're asymptomatic, but they later become symptomatic. Those people already drive a fair amount of transmission. So if people are, you know, in a situation where they're more relaxed, they're not being as vigilance about these non-pharmaceutical interventions intended to reduce exposure risk, you know, and you have a more transmissible variant added into the equation. And whether they're more asymptomatic or not is probably not as relevant as just the fact that a situation in which you would have maybe had five people get infected now is resulting

in 10 people getting infected. Yeah, that makes sense. So I think one of the big questions that a lot of people are concerned about with all this talk of new variants is what do these new variants mean for the effective of all these new vaccines that have been developed. So could you kind of explain whether these new vaccines will work against these new variants and how? Yeah, so that's really the million dollar question. And the short answer to that right now is that we don't know, but those experiments are in progress. And it's actually fairly easy to assess this. Basically, what you do is you take

plasma or serum, the liquid component of blood, which has antibodies in it. from somebody who was either vaccinated or has recovered from being infected. We call that convalescent plasma or convalescent serum. And you take that and you incubate it with the variance or with another virus that has the spike protein from the variance on top of it. That's called a pseudovirus. You take those antibodies and then you take the virus and you incubate them together and see if the antibodies can still neutralize that virus.

So this variant from the UK has, I believe, seven nucleotide changes specifically in two deletions and the spike protein. And that could change the virus's ability to bind antibodies that were produced for the vaccine. It also might not. And one thing that's important, I think, for people to keep in mind is that it's very unlikely that just a couple of mutations are going to completely evade the overall immune response because what the vaccines are made with are they they direct antibody responses to the full-length pre-fusion spike protein which is the protein that's on the surface of the virus particle that protein is is obviously pretty small to us but it's pretty large to your immune system and different antibodies will bind all over the surface of that spike protein

It's thought that the antibodies that bind to the specific part of the spike protein that binds the receptor, which is called the receptor binding domain, are the most neutralizing, meaning that they will be best able to render the virus non-infectious. But not always. Virus proteins can undergo conformational changes, changes in their shape and structure that occur when an antibody binds to a different part of the protein. So it's unlikely that, you know, unless the mutations themselves are inducing sort of radical structural changes to the entire protein, that a few mutations are going to completely avoid the entire broad repertoire of antibodies that are going to be raised against it by your immune system. However, ultimately, we won't know until we do the experiments to actually find out. To a certain degree, a lot of these mutations that distinguish different variants are just kind of like a fingerprint.

They're just mutations that were acquired. They don't necessarily offer any type of advantage to the virus, but because they're incorporated and then they get replicated, they're preserved. So you can use them sort of as genetic fingerprints to see how a particular variance has evolved if you're doing enough sequencing. but they're not always functionally important. The other thing people should really keep in mind about this is that even if the vaccines are less effective against these variants, these vaccines are synthetic and they're easy to change. You could make new mRNA vaccines very quickly.

And I think that it would be very easy to adjust these to accommodate for new emergent variants. And over the long term, people have asked me, are we going to have to keep getting COVID shots over and over again because it's like the flu? Well, SARS-Coronavirus 2 is not like influenza, fortunately. And there are other reasons why we need to get different flu shots every year, first and foremost, because there are a lot of different influenza viruses, including strains and multiple subtypes that are circulating. And they can all reassort with each other, which makes things even more complicated. But we are aware that we need to make new flu shots every year because of this exact issue. So if we can do that annually with an inactivated influenza

vaccine, we can certainly do that probably less than annually to accommodate for evolving SARS-Coronavirus 2. Yeah. So speaking of the spike protein, what additional things have we learned about the structure or surface proteins of SARS-CoV-2 that maybe have given us some more insight into how it causes disease, or some of the widespread effects that it has on the body? Well, that's a good question. And the short answer is not that much. This is still a very active area of research. But one thing I thought was interesting is that people who have more severe disease

have been seen to have more antibodies to the end protein, which is also another viral protein that's not spike. But it might suggest that maybe they're sort of developed, different immune responses than people who are able to successfully control the infection, in which case many of those antibodies are neutralizing antibodies that are specific for the spike protein. And it's not really clear why that is. I mean, it could be for a variety of reasons. It could be because the antibodies targeting end just aren't as effective at neutralizing the virus. And so people have more widespread infections or it takes them longer to clear the infection.

it could be because that's inducing immune responses that are associated with more disease severity rather than with virus clearance. So T cells in your body can be polarized, they call it, to act in a few different ways. TH1 polarization is thought to be antiviral. So that's basically your T-cells saying, all right, we're going to start telling the B cells to crank out a bunch of neutralizing antibodies. We're going to tell the CD8 T-cells to go out and start killing, infecting. We're going to tell the CD4 cells to start thinking about antiviral immunological memory.

We're going to control inflammation. There are other responses that are associated. Typically, they're supposed to be for clearing your body of parasites, like worms and things like that, TH2 responses that are very heavy on antibodies and these other types of specialized immune cells called granulocytes, including eocinophils and mass cells. And it's thought that airway hyper-reactivity can often be the result of an inappropriate TH2 response to a virus. And that's a very simplified way of putting a really complicated process. But that's just one example of how sometimes the wrong type of immune response can lead to more disease severity rather than the immune system doing what it's supposed to do and clear out the virus.

So those anti-N antibodies have been a hot topic of discussion for that reason, just because it's not clear if that's even important, but it is an observation that's been made. And it maybe explains why some people go on to develop ARDS or acute respiratory distress syndrome that's associated with severe COVID-19 and why some people have very mild infections that they can control and clear and don't have any problems with. And then there's the whole issue, which we still really don't know very much about at all, of long COVID, which is not due to a persistent infection most likely, but due to sort of a reprogramming of inflammatory responses. We don't really know much about what causes that, why some people get that and not, some people don't, why some people get that when they have pretty mild disease. So there's a lot that we need to do here to look at, you know, the types of immune responses.

And I realize this doesn't have a lot to do with your original question, which was, what do we know about antibodies to other viral proteins? But it may be that responses to other viral proteins by your immune system or interactions with the virus can determine outcome. Fascinating. So in terms of kind of transmission, I think there's a lot of discussion about transmission of SARS-CoV-2. At this point, is there indication that the virus is truly airborne in terms of transmission? Do we have any evidence? I know early on there was talk of fecal oral transmission with the diarrhea. Do any of these routes seem to be playing a role? So by inhalation, definitely, short range transmission by droplets and aerosols is clearly an important route of transmission

that really drives transmission. This has been an incredibly frustrating conversation to have in the public domain because the term airborne itself, I think, could be really confusing for people. In the strictest sense means that the virus is born by the air and we get it from breathing it to some people that might mean that, oh, God, it's going to get into the H-FAC system and people are going to be breathing it, like, from long distances away. And, you know, is it safe anywhere because we all need to breathe? And the reality is, like, yes, it's in shared air.

So if you're in a room with a bunch of people, like, say, I don't know, you got together with your extended family for the holidays and you're all having dinner in your poorly ventilated dining room, then, yeah, that's going to be a huge risk of transmission by inhalation. I don't like calling it airborne, though, just because a lot of people, I think, hear that and they think, like, that seed and outbreak where Dustin Hoffman is like, it's gone airborne and, like, looks up at the vents in the hospital. And it's not transmitted that way.

There have been a couple reports of people in stack department buildings that share plumbing lines, having infections. They can't rule out infection. from congregating, for example, in shared spaces in those buildings. But I think that if that were happening all the time, we would have a lot more people infected, especially in New York. Having lived in New York in some terrible apartments,

I can guarantee that we would have seen COVID spreading like wildfire in New York City in apartment buildings that are sharing sewage lines and I'm sure are not perfectly sealed. We would have been seen a lot more of that. So I think that, you know, this is opportunistic airborne in that in certain circumstances, it's very easy to transmit this by inhalation. And that really is thinking about shared air.

So anytime you're in an enclosed space with people who are breathing and putting out respiratory droplets and aerosols into the environment, and you can breathe them, particularly cumulatively, over a period of time, that's going to really increase that risk. And that risk, of course, can be mitigated by doing things like wearing masks to prevent you as source control to prevent you from emitting particles yourself into the environment when you breathe or speak. It can be mitigated by increasing ventilation in those enclosed spaces,

by avoiding them altogether. It can be mitigated by taking it outside. where there's obviously no enclosures anymore. It cannot be mitigated by taking it to like a temporary plastic tent that's totally enclosed. That's not outside. But it's definitely transmitted by inhalation. I just think that the term airborne is not really helping the discussion.

COVID is transmitted through shared air without a doubt. And that's a major mode of transmission, much more than than fomites or contaminated surfaces. Yeah. So now shifting a bit to talk about testing for SARS-CoV-2. Can you walk us through what these various test experiences are like? The testing that we've had since the beginning of the pandemic, the sort of gold standard for diagnostic testing is PCR. And this is basically a technique where you take, you essentially are photocopying part of the virus, biochemically, to see if you have. it. And if you have it, then you will amplify that through the PCR reaction. If you have a lot of it to start out with, then you will develop a signal on that PCR test sooner than later. And that's what

if you've heard people talking about the CT or the cycle threshold value, that's what that refers to. So a lower CT, meaning the sooner you got to identifying a positive signal with the PCR test, the more virus you had to start out with. So that's the gold. standard and that's a very specific test. So there's not a lot of false positives contrary to popular belief. Now the problem with the PCR test is that it's quite sensitive, but it's not perfectly sensitive. So if you don't have very much virus, if you just were infected, you won't necessarily detect that. It'll be a false negative essentially. If you just got over having COVID, you might be shedding viral RNA, which is what the PCR test detects for a long period of time.

And that, I think, is what some people have referred to as a false positive. It's not actually a false positive because you are detecting a real signal from viral RNA. It's just that the PCR test can't test for infectious virus. And so it's really important in that regard to have an understanding of when you were actually infected. because a positive test in somebody who's recovered doesn't mean that you're actually still infectious over a long period of time. And that's been shown by multiple streams of experimental evidence and epidemiological evidence. So that's the PCR test.

There are PCR tests that you get by the nasopharyngeal swab, which is the big long Q-tip. Some people are now doing those tests with the anterior narys, which are the nostrils, basically, only. And some people have also developed PCR tests that use saliva, which are actually more sensitive than the nasopharyngeal swabs. And certainly, I think, probably a more pleasant experience to give a select example than to stick a giant keytip up your nose. So those are all the PCR tests, the so-called high-complexity molecular diagnostics. Now you probably have also heard about the rapid tests or sometimes they're called antigen tests. And these are tests that are looking for the viral proteins, the what are called antigens. So the antigen test detects

the viral proteins. There are a couple different ways that they can do that. There are some other rapid tests in development too, LAMP, which is a rapid nucleic acid amplification method that looks at RNA. It just doesn't go through the whole PCR cycling process. Some people have developed a test that has not been authorized yet, but that uses CRISPR technology to look for viral genetic material. But the main tests that are available now are the PCR test and then these rapid tests that look for antigen in a very short period of time. The main disadvantages to the rapid tests is that they are, for diagnostics anyways, they're less sensitive than the PCR tests, and they're also less specific. They are more likely to give you a false positive. There's been some

controversy about this because some people have proposed using rapid antigen testing daily so that people can monitor their own status. And I think that there is a place for that. And this is where we're getting into just my opinion, but I don't think it replaces molecular diagnostics or PCR testing. I think people should have the ability to test themselves, but they should also have clear guidance for what to do. And that is they should call their doctor, make sure that their case can be reported and then make sure that they have all the information and support that they need to actually isolate themselves and put contact traces in contact with people that they have been in, you know, in close physical proximity with recently to make sure that those people can

quarantine and get access to testing as well. Yeah. So our last question is, is pretty general. And that is, so what do you think this pandemic has taught us about virology, whether that's, you know, virologists working together or communication about virology or anything specific related to SARS-CoV-2. What do you think this pandemic has taught us about the field of virology? Oh, God. Well, it's taught me that there's a lot of people who are non-virologists who think that they are. It's also taught me that people, including very educated people, including some of my colleagues, I mean, it's really been telling, like, it's brought out, I think, in some people the worst in people,

and it's brought out in others the best in people. And it's really taught me that in general, scientists and our society, human beings, keep making the same mistakes over and over again. And I've seen that in so many ways. Like, I keep having to explain the same concepts to people. I keep having to debunk the same misinformation. And I think that's because to some degree, people don't actually want to learn. We live like in a world right now where people, they want facts, they want them immediately.

And if those facts aren't there, which in science is usually the case. You know, we are, as scientists, are trained to say, this is very uncertain. We don't know. It may be this. It may be that. In general, people have very little patience for that now. and it can be very, very difficult to communicate that, you know, we don't know this right now. Here's some of the possibilities.

We're looking into it. We'll let you know as soon as we find out. But people want things now. And it's been very surprising to me to see how that vacuum has been filled. For me, it's certainly taught me that the way that I was trained to do virology through analyzing data, developing hypothesis. and testing them and then if they're wrong, revising my hypotheses and testing those new ones is still the correct way to do that.

But I've learned that I really have a long way to go, as do most of my colleagues, in communicating that uncertainty to people. It's taken me a lot of experimentation, and I still haven't got it right in terms of how I communicate. You know, like we don't know if antibodies are going to work against these new variants that are emerging, for example.

I can tell you how we'll go about looking into that, I can tell you, I can teach you all about the spike protein and antibody binding and how the immune system works, although still the immune system is like the most complicated thing in the world. So I think we've all learned that even though we already knew it. But, you know, it's really, really hard for me to communicate to people that there's still probably going to be a lot of knowledge gaps, even after we do this one critical experiment, even after this one paper comes out in this big elite journal, there's still going to be a lot of things that we don't know. And I think the real challenge that all of us have faced from, you know, an individual like me,

all the way to like the New England Journal of Medicine is that sometimes getting an answer fast is not the same and it's not good, that maybe we should figure out a way to communicate to people like we should slow down. We should take our time with this because it's too important to get wrong. It kind of does matter if that answer is the right one or if it's based in evidence. But for me anyways, the most important thing I've learned, I think, is that we were not only unprepared, grossly unprepared to deal with the generational pandemic, even though we knew it was coming, but we were also grossly unprepared to engage the public in fighting it. And that's something that absolutely has to change.

and that's something that I'm probably going to be thinking about for the entire rest of my career, if not the rest of my life. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's Working Hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions.

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The internet turned on him. If I could press a button and rewind it all I would. But what happened to Clayton after the show made even bigger headlines. It began as a one-night stand and ended in a courtroom with Clayton at the center of a very strange paternity scandal. The media is here. This case has gone viral. The dating contract. Agree to date me, but I'm also suing you. Please search warrant.

This is unlike anything I've ever seen before. I'm Stephanie Young. This is Love Trapped. This season, an epic battle of He Said She Said, and the search for accountability in a sea of lies. Listen to Love Trapped on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. In 2023, a story gripped the UK,

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Thank you so, so much, Angie, Dr. Razmussen, for coming on and talking with us again. I learned so much from this episode. So as always, in this series, we want to go back and cover the top five things that we learned. Erin? Yes, we'll start with number one. All viruses mutate. Basically, random mutations can happen every time a virus replicates, and those mutations are what can lead to new strains or rather new variants. And so it's completely normal and expected that a virus, and especially an RNA virus, will have multiple variants. It's something that we were all expecting. And in the case of coronaviruses like SARS-CoV-2, the mutation rate actually isn't as high as we see in some other RNA viruses like influenza. And that's a good thing. It means that it

doesn't change as quickly or as dramatically. And so while we have seen a number of different variants pop up and spread across the globe, these variants represent very small changes in the virus genome, and they aren't drastically different viruses. Many of these mutations, in fact, mean nothing at all, really, biologically, and have no biological implications. We have, however, seen that at least one variant, the so-called B-117, which is the one currently making headlines, does seem to be more transmissible than other variants, but we still don't know the precise mechanism for this apparent increased transmissibility,

and at least some of its rise in prevalence could be due to the lowering of the lowering of restrictions on things like public gathering and indoor dining and so on that led to just a whole lot more transmission in general. And fortunately, this B-117 variant, and actually other variants so far observed, don't appear to be associated with more severe disease. But the bottom line is that we also probably aren't doing enough surveillance overall to know for sure exactly how many variants there are or whether some are more virulent than others, meaning more likely to cause severe disease. So the big question is, how do we stop this

process of mutation, of new variants emerging? I mean, and we can't stop it, but we can slow it down. We can slow it down by reducing transmission. Fewer new hosts for the virus means less replication, and thus fewer opportunities for new variants to arise and spread. Exactly. Number two, the question of will these new variants affect how effective the vaccines that we have will be? And the truth is, we don't 100% know. However, it is highly unlikely that the small changes in these new variants will mean that the vaccines that we have are not effective. So we learned in our vaccines episode that the mRNA-based vaccines produced by Pfizer and Moderna, as well as the virus, Vector vaccine that's produced by AstraZeneca, all encode the entirety of that spike protein.

That's the protein that SARS-CoV-2 uses to actually enter our cells. So when you get vaccinated and your body starts producing this spike protein, you then start making antibodies against it, a whole bunch of them, which target multiple parts of that protein. And the spike protein, it turns out, is a pretty large protein. It's like over 1,200 amino acids long. And the changes that we're seeing in these viral variants are super small. In the case of B117, we're talking 23 nucleic acids out of their whole genome. Not all of those 23 changes are in that particular spike protein.

So while it is possible that small changes can affect vaccine effectiveness, it is overall unlikely. But that's probably not super reassuring to a lot of people. we do have two other better pieces of news that we learned. People are doing the research to answer this exact question of vaccine effectiveness as we speak. So that's awesome. And now that we have this vaccine technology, it's not going to be difficult in the future to make small changes as necessary to these vaccines going forward to make them effective against new variants. In fact, in the case of MRNA vaccines is actually a lot easier to produce new proteins or new MRNA than it would be to produce a new entire whole-killed viral vaccine like we already do

every year for influenza, for example. Yeah, that's really important and pretty reassuring, I feel. Very reassuring, yeah. Number three, we learned that the term airborne gets confusing, and it's probably not the best term to use in general. But what we do know is that for SARS-CoV-2, inhalation of viral particles is still the driving factor behind transmission. And that means that any place where you are sharing air with other people, like in a restaurant or a bar, on a plane, or at

your Aunt Judy's house, you have a risk of transmission. And ways to mitigate this risk, I mean, we've covered them over and over again, but just to reiterate, that includes wearing a mask, increasing ventilation, being outside, being further apart. But if you are are in shared air, whether inside a building or inside a plastic tent outside at a restaurant, distance alone does not cut it because you are still sharing air. Overall, other forms of transmission, like from surfaces or fomites or fecal-oral transmission, don't seem to be big drivers of virus transmission, which is great news. But that doesn't mean that if you rub your nose and then shake someone else's hand and then they touch their nose that they can't get infected through that route. So that's

why we still have to wash our hands and not touch our faces when we can help it. It's the Swiss cheese approach all over again. The more layers of protection you have, both literally and figuratively, the lower the risk of transmission. Yeah. Also, does anyone shake hands anymore? I feel like that's, we're never going to shake hands again. Yeah, I'm okay with that. I'm okay with it. Yeah. I have a fan of the elbow bump. I don't know. Yeah. I like just the wave. Yeah. Number four. So we learned a lot about the difference between PCR-based tests, which are looking for viral RNA, and then the rapid tests, which are detecting antigen, and are overall less sensitive and specific than the PCR-based tests. We also learned that these at-home tests that have recently been approved are these antigen-based tests. And while they are excellent in a number of ways, we do need to make sure that there's really good communication and guidance around what to do with the information.

that these tests provide. Right now, that guidance is severely lacking. And without it, wide implementation of at-home testing with rapid tests could really backfire. False negatives and false positives are possible with any test. But a positive test really needs to be followed up in some way. And we need to have guidance or some sort of protocol as to exactly how to follow up if we're going to be using these tests at home. Mm-hmm. Yeah. And number five, our last point. And this point seems to be a highly recurring theme in these COVID-19 episodes. The number one theme of these episodes. Yep, I think it's been in every episode so far.

But that just underlines how important this particular theme is. And that is communication. Communication during a pandemic is hard, but it's also essential. In this country, especially in the U.S., but truly around the globe, we need to be able to communicate truthfully and directly among scientists, public health professionals, healthcare workers, and communities. And one of the biggest challenges we've faced in this pandemic is how we communicate uncertainty. So much of this last year has been uncertain. And the scientific process works to wade through uncertainty to find answers, but it takes time. And this pandemic is

one of the first times that a lot of people have gotten a front row seat as to how slowly and incrementally, knowledge can grow and how rarely things in science seem black and white. We don't know all of the answers when we start the process, and jumping to conclusions, either discarding or disseminating information early without evidence, just makes everything more confusing in the long run. It's hopefully something we can learn from moving forward, how to better communicate this process and the uncertainty surrounding it to the wider public. Yeah, big time. Yeah, we're learning as we go. Oh, yes. Thank you again so much Dr. Rasmussen, Angie. Like, we're all friends now, right? We're best friends. We're friends. We're BFS. We're going to go to a Zoom happy hour eventually.

Yes. Thanks again for taking time out of your busy schedule. We love chatting with you and your explanations are so great and like easily understandable. It's fantastic. Yeah. Also, if you want even more detail about the variants of SARS-CoV-2 that have been all over the news, Angie wrote a really awesome article in The Guardian that we will link to in our show notes and on the website that explains these variants in a lot of detail and also talks about why things like travel bands aren't effective in stopping the spread of new variants. It's definitely worth the read. Yeah, absolutely. Thank you to Bloodmobile for providing the music for this episode. and all of our episodes. And thank you to Exactly Right Network, of whom we are proud to be a member. Yes, and thank you to you, listeners, for listening. We appreciate it. Send us your COVID questions, whatever.

We'll keep these things going. We really have a lot more in the works in the pipeline. We do. All right. Well, until next time, wash your hands. You filthy animals. This is Special Agent Regal, Special Agent. Bradley Hull.

In 2018, the FBI took down a ring of spies working for China's Ministry of State Security, one of the most mysterious intelligence agencies in the world. The Sixth Bureau podcast is a story of the inner workings of the MSS and how one man's ambition and mistakes opened its fault of secrets. Listen to the Sixth Bureau on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. I'm Amanda Knox, and in the new podcast, doubt

the case of Lucy Letby, we unpack the story of an unimaginable tragedy that gripped the UK in 23. But what if we didn't get the whole story? The moment you look at the whole picture, the case collapsed. What if the truth was disguised by a story we chose to believe? Oh my God, I think she might be innocent. Listen to doubt the case of Lucy Letby on the Iheart radio app, Apple Podcasts, or wherever you get your podcasts. I'm Clayton Eckerd in 2022.

I was the lead of ABC's The Bachelor. But here's the thing. Bachelor fans hated him. If I could press a button and rewind it all I would. That's when his life took a disturbing turn. A one-night stand would end in a courtroom. The media is here. This case has gone viral.

The dating contract. Agree to date me, but I'm also suing you. This is unlike anything I've ever seen before. I'm Stephanie Young. Listen to Love Trapped on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts.