TWiV 657: Shane Crotty on SARS-CoV-2 immunity

this week in virology the podcast about viruses the kind that make you sick [Music] from microbetv this is twiv this week in virology episode 657 recorded on august 26 2020 i'm vincent draconiello and you're listening to the podcast all about viruses joining me today from austin texas rich condit howdy vincent uh we got uh 84 degrees headed for 95. we still got another you know week and a half at least of temperatures up around 100 and then the phony two-week forecast suggests that maybe it's going to start to cool off but we're almost out of this yeah for you cool off is like 85 right oh 95.95 also joining us from madison new jersey brienne barker hi it's great to be here um it is actually sunny and 71 here um pretty nice from southeastern michigan kathy spindler everybody i'm just checking because um the temperature in the thermometer in my window said 68 but the one on my phone says 78 wow the difference between those two and um i think the one on in my window is closer to being right anyway uh one of those would correspond to 25 celsius uh probably the 78 one but you know your video went away you know that i know because i was checking the window okay you uh remind me you remind me of a story late in my mother's life when uh her neurons weren't uh totally together when she called me up one time in the middle of the night and she says uh one of my clocks says it's three o'clock and the other says it's 301 which is correct and i said it's three in the morning [Laughter] all right we have a guest today from a place where i might actually rather be at this point la jolla california he's at the la jolla institute for immunology shane crotty welcome to twiv thanks for having me uh vincent and uh and all uh it was 70 degrees on my bike ride this morning which is which is warmer than usual i have to still i i'm impressed you got the it's eight o'clock uh your time and you're there and raring to go so you're an early guy oh i i i i get here at six wow wow where do you bike from uh it's about a half hour bike ride from my house so up north i used to live i was asking specifically but apologies uh carmel valley got it okay where did you go i i don't i don't bike past the ocean because it would add three extra miles in a giant hill that i just can't quite stomach uh early morning it would be beautiful to see the ocean yeah no i lived in uh del mar la jolla and i have some friends who had a nice place in carmel valley so nice yeah it's pretty nice out there at least by the coast beautiful i love it all right shane uh we're going to talk about immune responses to sars ko vitula but i want to first tell people a little bit about your history now are you a californian to begin with uh my my dad was in the military so i lived about 11 different places before i uh made it to college so still yes but it's also yes for a bunch of places okay but i've lived here for 17 years now it's by far the longest i've ever lived anywhere in my life so yes i'm a californian at this point where did you go to college uh mit okay what years what years were you there uh 92-95 so uh which is which is where i started coming across david baltimore for example right yeah wow he's a he's a youngster this is you know that was that was yesterday yeah i was gonna keep my mouth shut i was there for i was there from 79 to 82 so not even close to you uh and that was undergrad at mit is that right yeah yeah and then then after that you went off to do a phd at the ucsf with royal endino right which is probably where you came on my radar i guess since uh it's it's a polio lab and i know well and then a postdoc was where with rafi ahmed down at emory university studying vaccine immunology t cells b cells all the stuff in between really my phd was on molecular virology and but there was a vaccine project in rose lab that i helped out on and that was when i saw that wait a minute vaccines are just phenomenal medicine and when when we took our data to an immunologist and said you know what does it mean how can we make it better they said we don't know that's vaccinology not immunology um nobody knows that stuff and i was like wait a minute this is a big this is a big problem um and so that's when i switched directions to try and uh yeah help fill that gap which a lot of people have done now in the past so wait a minute i i would not have made a distinction between vaccinology and immunology i don't think uh how are they distinguished or maybe they aren't well yeah uh so yeah so now they're a lot more connected but uh yeah 20 years ago it was pretty straightforward to say almost every vaccine that had been developed to date had been developed with minimal knowledge of immunology and certainly minimal knowledge of modern immunology and there'd been this huge right amount of discovery in immunology uh certainly from now over the past 30 years and those generally weren't those connections were not being made those fields basically grew up as separate fields because vaccinology existed way before anybody knew immunology and somehow they really stayed quite uh quite separate um such that vaccinology largely stayed um as sort of tried-and-true approaches and empirical approaches just you know you try things until they work and you say wait a minute we know a ton of immunology can't we can't really make those connections and turn it into more of an engineering problem because that's really always been the big problem of vaccine development is that if you try one and it works it's phenomenal right i mean the impacts are just extraordinary but 99 of the time it fails and then and then there's really almost nothing learned from most of those failures in the past it was just you went back to square one because the the immune responses to that to that failure weren't particularly interpretable as to why it was a failure was your actual fundamental vaccine concept wrong or did you just have one piece of the puzzle wrong you know and there was one bit of the immune system that wasn't quite being brought in for example um that was the case when i was in graduate school um and i was sort of a unique person immunology graduate student in this vaccinal vaccine lab it was very strange um so it's gone on for a while so uh shane we're acquainted have been acquainted for some time because you spent some time with vaccinia uh how did that happen yeah so that was really when i joined rafi ahmed's lab as a postdoc and said look i'm you know i'm really obsessed with vaccines in the vaccine immunology what what are things [Music] we can do and rafi agreed that uh one good path was to study licensed human vaccines um because the immunology of licensed vaccines just wasn't understood basically because you have a successful vaccine it works nobody wanted to study it anymore the problem was solved and so with something like vaccinia it gave us an opportunity to ask well there were two things really that we went after one was it was a fantastic opportunity to ask about immune memory um because here you've got a vaccine that there was there was no virus around right smallpox had been eradicated for 30 years the most people didn't get the vaccine and and so we could go find people who definitely hadn't seen this virus or anything like it in 30 years did their immune system still have any memory of it or not and it eliminated a lot of the problems of trying to understand memory and other other contexts and sure enough people had a pretty fantastic memory um even after like 60 years you know from their childhood vaccinations and so that was a really nice study to be able to do both in terms of memory b cells and underneath um and then the other thing i think that you ended up being more acquainted with that we struggled to understand was when people say okay this is a fantastic vaccine why is it fantastic and i think the operating idea of a lot of people was that it's neutralizing antibodies those are important um and then it's probably a fantastic antibody response to like one thing it's like this really great response to the key thing and our take after a bunch of studies was that no that probably wasn't the way it worked actually is it was that there were a bunch of neutralizing antibody targets there were a bunch of good antibody targets and that the vaccine was so good it was that in most people it elicits let's say five to seven different good antibody responses so so that there's a lot of backup plans basically it's a vaccine with a lot of safety nets it's not working for one reason it's working for a number of reasons so even people on the outliers of instead of having five good responses you've got a person with just one or two good responses that's still good enough um and sort of the way we interpret it so there's a lot to learn from did you study t-cell responses as well yes and did you get yeah did you get a sense for their role and the success of the smallpox vaccine so i'd say the best data on on the roles of t cells and the smallpox vaccine uh come from a human longevity study by mark zlifka's group that found that the t cell memory did decline over decades where we found that the memory b-cell the b-cell memory didn't decline over decades so there was a difference in the biology there and then actually a monkey study by a french genie's group where they could really do a rigorous protection experiment and split up the immunological components so they did they basically said you've really got three parts of the adaptive immune system right you've got you've got antibodies helper t cells and killer t cells and so what they did was they immunized monkeys with the small clocks vaccine and as you know rich you can then challenge the monkeys with monkey pox and that's a good um uh that's a good uh model of the severity of smallpox in in monkeys and the vaccine does work against smallpox and they could ask they could have monkeys that they separately tested the role of the antibodies the helper t cells and the killer t cells by by essentially depleting any of the three or transferring them to other monkeys and what they found was that in that case it was really all about the antibodies but if the monkeys had neutralizing antibodies they did well but if they had a really good t cell response they still got a lot of talks they didn't die but they really got severe illness the caveat to the study is your classic uh animal model protective immunity study which is you pretty much you almost always go with a really high dose challenge because the monkeys are really expensive so you really want to make sure all of them get severe disease so i think the answer is if you really got a massive dose right of of smallpox the only way you were going to stay healthy is if neutralizing antibodies stop it at the front door but if you had a more normal right somebody coughed on you it's a respiratory pathogen frequently right so if somebody coughed on you and you got and you got a little infection in your lung and normally right when you get that disease you don't get sick that quick you get sick 10 to 14 days later or something that's a pretty good amount of time for those t cells to actually respond and do something helpful which wasn't really being tested so well in that model system which are which are aspects of protective immunity that come up for coronavirus biology as well so this is a general problem with non-human primates you have to use a lot of virus because as you say you don't have a lot of animals we came across that in some of the sars kofi 2 experiments already you know in fact one set of experiments they they challenged by multiple roots just to make sure you get them infected you know oral mucosal and intramuscularly intrarectal and so forth so yeah it's it's what you're finding out is not always is going to be exactly the same as in people sean i wanted to ask you um i wanted to remind or tell our listeners that you've you've written a book you've written a biography of david baltimore called the head of the curve uh you did that while you were with raul landino right uh i i mostly did it in college um and i had yep i finished it up and and i finished it up in real life yeah it's a wonderful book uh a story of his life if you're interested in it um it's really good and actually have a chapter devoted to my work which is a a chapter with very few words it's called interlude and it's the sequence of the poliovirus rna genome which i thought was really funny remember peter palazzi showing it to me because look you're famous now in a book did you like doing that was that a lot of fun uh no i wouldn't call it fun there's definitely a labor of love i mean if you think about writing a scientific paper it's like that but yeah 40 times longer basically it's hard to wrap your head around you can't just you can't just do it in the evening sort of thing you know it really has to take a lot of your uh a lot of your your time i'm certainly proud of it and and and definitely lots of people told me that they they like it i still have people write me and you know yeah uh want to get an autograph on it or or whatever um which is which is wonderful um i wrote it really to write science for non-scientists um and and and use baltimore's life as a prism to be able to talk about a bunch of interesting and science interesting and important science you know so by talking about a single individual it was possible to talk about molecular biology and cancer and genetic engineering and whatnot so that was that was what was uh fun about it um and he was generous enough to give me access to his four archives at mit so it was really um as a historical project it was it was great because there was all of this old interview material you know because uh as you guys all know your recollections of events change as time goes on so so having a record of event that's much closer you know when it actually happened is much more valuable anyways yeah so that was the that was the project it took quite a few years so writing was actually uh formally part of your college degree is that right training yes nice uh it's a great book i recommend it to listeners uh ahead of the curve really nice biography a lot of the insight behind david baltimore of course so were you always lots of fun virology in it lots of fun biology in it but i recommend you read the chapter called interlude and very very american so uh were you uh when did you decide figure out that you were a scientist and were you sort of uh struggling with am i a scientist or am i a writer in college or was that even an issue no it wasn't i was definitely i went to mit to do biology and research i specifically um wanted to go to mit because one of uh just a couple of places in the country where it was very clear that undergrads could could again get into real research and so the writing came afterwards because of a recognition that uh for me personally a recognition that lots of non-scientists non-scientists in general have to make all these decisions about science that they don't uh have the opportunity to understand right so so they're being asked to vote on genetically engineered foods or just recombinant dna technology in general or cloning animals and whatnot and so what are the things to help communicate that i i always tell people i got tricked into uh interlacing science there was there was an nsf young scholar i went to high school in the california desert far outside of los angeles and there was an nsf young scholars program centered in los angeles and so i was still officially in la county even though i was like two hours outside of la and and i got uh essentially bullied by my high school chemistry teacher into applying to to that program and those innovative young scholar programs are incredible and i wish they had more of them for high school students because the whole mantra of the thing is to take a high school student and pair them with a researcher somewhere at a college nearby and just have them be in a lab and do something and get together every couple months to go visit a college or hear a scientist or whatever and at the end of the year present something and it wasn't there weren't high expectations but it was about exposure as you guys all know science you learn a textbook really has nothing to do with actually doing experimental science and loving one you know isn't it isn't loving the other the only way to really know if you're interested in being a scientist is actually like try it out and for biology that's kind of hard to come across so in my case there were no colleges anywhere near me so they accept i think they accepted me to the program and then they basically went oh wait what do we do with this kid there's no um so they they assigned me to the furthest possible place from my house which is catalina island off the coast of of los angeles and so every friday i would get out of school and drive hours all the way across los angeles to the port and then catch a boat across to the ucla usc marine biology lab on catalina island where they have this protected cove and all this kelp forest and you know sea lions and stuff and frankly mostly i i hung around and i was like wow marine biology this is this is science sign me up nice cool all right shane uh let's talk about uh soros cov2 i want to kind of broadly talk about b and t cell responses if you will and i know you've done a lot of work on t cell responses but i wanted to first get your view of the antibody response to source cov2 in fact you know there's been a bunch of studies and in my view a lot of them are confusing they seem to disagree what's what is your take what's the antibody response and i guess you know a mildly infected patient and a seriously infected patient um so i think that the short answer is it's uh it's great that there have been studies of i mean essentially thousands of patients at this point right on on quite a few comments um i think uh uh people pretty consistently seroconvert uh fairly rapidly against the virus um and um i'd say almost everybody who gets infected makes uh an antibody response against spike and a neutralizing antibody against spike which is almost all the neutralizing antibodies are against uh rbd and that people with severe infections do have higher neutralizing antibody titers than people who have um uh mild or moderate uh uh antibiotic responses um uh yeah what are what are the things that you think are more of the conundrums there i thought for a while some people were saying that a good fraction of patients didn't make antibodies which seemed counterintuitive but that sounds like you don't that's no longer the the feeling in the field right yeah so you're right vincent that was out there and it does still get uh debated uh some but i would say if you talk to labs who look at lots of patients and who um are basically experts in serology you know in the sense that they have sensitive assays set up it's almost everybody seroconverts now it's definitely a reality that that a significant fraction of people have what i think would everybody would agree is low antibody titers and so if you if you don't run particularly sensitive assays um you can have people show up as negative and that happened with mers for sure um as well that low responses were a thing and so then then it becomes all right do the low responses um uh matter or not um and and to me the answer is that they as far as i can tell they matter a lot because to me the the key is how much antibody do you need for protective immunity right and if the answer is it only matters if you have a huge antibody response then then fine you know sensitivity at the low end isn't a big deal um but to me the monkey protection experiments you know indicate that that if you've got a neutralizing antibody titer and sort of the one to 20 range that's still generally protected from disease and therefore low antibody titers are relevant which can be different for other diseases right like i said where um low antibody titers can may be totally irrelevant so you know only being able to attack high amounts matter but but for this i think it does matter to be able to pay attention to to those low to those low tides and most people become positive there are some people who don't become positive but that's anybody who tells you something always happens in immunology is is either lying or wrong and that's just not the way human immunology works it's diverse by design essentially so is there any uh correlation between the uh how good the antibody response is and how good the memory response the memory is or do we even quantify that uh so it's a great question and it's um i'd say it's essentially ongoing um and uh so in the in the general scheme of things um there is no clear-cut early marker for memory on either the the b cell helper t cell killer t cell or or ant body uh side in in humans we would we would love for that right to be able to say all right you know 14 days into a disease we can tell what a person is going to look like a year out the rule of thumb is that the bigger the insult or the bigger the injury the more likely it is your immune system is going to remember it because it's uh um you know just like brain memory it's you know if if you were at an intersection where you almost got hit and killed by a truck you're gonna you're gonna remember that intersection for a long time you're gonna be careful about it right whereas some minor thing you just don't bother to to remember and to a decent degree the immune system behaves that way if if the initial infection was really trivial it's less likely the immune system is going to put significant energy into memory because the memory does cost energy right but if it was a serious disease usually the immune system is going to remember that significantly but you know this is always an interplay between the immune system and the pathogen right and so does the pathogen try and short-circuit that in some way right and so those are things you have to learn so i guess then the answer becomes we just have to wait um and so right now waiting means people have data about 90 days out from from people um more than that serologically they have like 120 days out zoologically but on the cellular side mary and pepper put a pre-print uh up um that's the best uh data today um for looking at uh a first look at memory and it's basically 90 days out which is not long enough to really tell what's going on but it's it's a really helpful step along the way and it's very good to see that they were seeing memory b cells memory helper t cells and memory t cells uh in most people at that 90 day obviously if it was already gone at 90 days you're not going to be seeing it in six months but i i would say six months would be the benchmark we'd really like to see yeah it's a common feature of the common cold coronas that memory wanes i guess within a year or so would are we expecting a similar thing to happen with sarsko v2 so uh i'm a little bit of an outlier in that argument um so so i i disagree with that statement actually fundamentally um and and and to me it it pretty much all ties back to that the the one clear paper on this right which is the english common cold unit study where they they infected people with a common cold coronavirus and they got infected and sick and then they had been come back a year later and they rechallenged them and the abstract of that paper says they weren't they weren't protected they got they got reinfected and you take a look at the data and the date is zero people got sick nobody got a cold again and so yes they had at least some something that they could pcr amplify from the back of somebody's throat you know 24 hours after the challenge um so it was not perfect sterilizing immunity but none of those people got got sick so i think there's a lot of uncertainty there because common colds haven't actually been studied right that much over the decades um there is definitely a decline in antibody titers between like a re-challenge like that and a year later but all those people are still positive for antibodies i mean if you go out right now and do a cereal survey of of the place you live right you would find that over 90 of people are are positive for antibodies to at least three of the four if not all four of those common cold coronaviruses and in fact i mean data i've seen indicate that people stay pretty stable at those levels for long periods of time um and so there then i think to me you get into more sophisticated arguments about right protective immunity from disease versus protective immunity from any detectable virus and what are the two mean for what are you trying to discuss right protection from disease or or any detectable virus and does that affect uh transmission or not which are more complicated um so i yeah i'm actually of the opinion that it's it's not that uh immunity just disappears in a year from common i'm not convinced by the available data yeah i mean many people in their papers say that right and maybe it's an assumption that's made and that shouldn't be you could be right i i just don't know how about how about it essentially all comes from that one paper really oh yeah it's all literally from that one paper and now one paper shows none of those people got colds a year later yeah how about antibody titers to sars ko v2 are they pretty stable do they decline and what's the significance so that's uh that's a debate right now there are there are preprints um and papers um on on both sides of it my assessment so far of the totality of the data are that uh the kinetics of the antibody response look pretty normal in your average uh covet 19 case and that is that people make a response and if you look 90 days after the after the peak of the response nine days after the acute infection uh the titers are probably somewhere between stable and like a four-fold decline from that from that peak which is all very much in the normal range of what you see to uh most viral infections um there's a range of of outcomes and so it's unclear if uh uh from different studies and so it's it's unclear if some patients are you know significantly different from other but to me the totality of the data largely looked like that it looks it looks mostly normal to me um and again to me it what matters is uh how much do you really need for protective immunity right and if the answer at the end of the day is you you need a lot then then a couple full decline becomes a really big deal but if if it if it's actually you only need you know a new tide or something like 1-20 to prevent disease not necessarily infection then then those declines aren't as worrisome um i think the clearest data on on poor responses other things at the low end or this nature of medicine paper from china where they had a pretty clearly defined group of asymptomatic people which in their study was was a pretty small fraction right of the total people who got who got tested it was maybe 15 of people fulfilled that criteria and when they compared those people to other people they said okay those people in general became serial positive um but whatever it was something like 60 90 days later um i think 40 of them were were negative for detectable antibody at that point and so the conclusions that have been made from that are that uh are that asymptomatic people lose antibodies faster and i don't think the data wasn't showing that in my opinion the data was showing they started lower so they became negative faster because they just they didn't have much to start with um but that's of the subgroup of people who were asymptomatic and so yeah maybe it was just such a small exposure and response it just didn't it just didn't trigger much of a fight by the by the immune system so so you mentioned that um you know 90 days is sort of as far out as we know right now um and you know my ex my impression would be that we need to look a little longer um to sort of fully understand some of this um i was really interested in the germinal center paper um that just came out um showing the lack of germinal centers um and so how long do you think we should look i think uh so really the vaccine literature is a good place to look for that so when people um you know do like their their clinical trials of vaccines and they say ah see we got an antibody response at 30 days that's basically not predictive of what they're going to see at six months or a year but in general what you see at six months is predictive of what you're going to see at a year longer and essentially a decent amount of that is is just built into the nature of the kinetics of antibody responses you need you need at least three time points okay because when you initially make a whole lot of antibody if you then stop making a bunch of that those antibodies are going to decline with a half-life of about 21 days right so you get have half as much three weeks later and then half again as much three weeks after that and so um you have to kind of let that go away to then be able to see what's the what's the steady state amount of production that your body is making that's going to remain so if you just have two time points from peak and then some late you're gonna see you might see some really extreme slope right but you need an intermediate time point to see oh actually it was coming down pretty fast and then it was flattening or not and so it's yeah i think the best data will be when people have six month time points and it's you have three time points some uh some early time points some intermediate time point that's six months to see are you just constantly losing the response or or do you really have something that looks like it's going to be some memory up to a year or longer and for sars for classisars it looked like there were responses out you know say five years or so so go ahead rich um uh do you make uh do people make antibodies to viral uh proteins other than spike and are those responses important they they certainly make responses to other viral proteins i mean my rule of thumb for talking to people about that is that you know to um generally speaking the immune system is blind to which parts of the virus are going to be neutralizing antibody targets it it it can't tell right all i can tell is that there are these foreign proteins and so essentially then the immune response needs to try and make antibody responses to as many different uh proteins of the virus as possible um to give the best chance of of getting a neutralizing antibody response and and frequently those responses correlate to the magnitude of the viral protein that was around and so it's really common that things like nucleocapsid right or core proteins are are really strong antibody responses whether we're talking about our coronavirus or hiv gag or you know or whatnot which is why those are frequently quite good diagnostic antibodies is because they're frequently high level responses they're not generally considered to be uh relevant for for protective immunity um the bar is higher for showing that i mean you basically need to take show that you can take a monoclonal antibody against a non-neutralizing target and inject it in a mouse or a or a monkey and show that it that it has some uh positive benefit otherwise really neutralizing antibodies are are generally at the benchmark if you can show neutralization in vitro it's probably helpful [Music] so let me ask you and and again i might be wrong on this so correct me so i've i've read some of stan perlman's work on sars the original source he says if you look 15 years after these people have no memory b cells but they have plenty of memory t cells so do you think that's correct and if so what are the implications for sars kovi ii uh that's correct vincent um and and definitely stan has a pro-men has a a very good sense of the literature of course as being you know one of the main people who has really been studying coronavirus immunology all all along there were two different studies that looked for memory b cells greater than 10 years out two classic stars and neither of them really saw um saw anything um the the the exception of that is there have been people who've tried to see if they could find neutralizing antibodies in a classic sars case right that would be a cross-reactive neutralizing antibody and if they look deep enough and hard enough in those people they could pull out a few cells but those are pretty you know intensive uh searches and i don't recall seeing any evidence of circulating antibodies in in know so yeah so that's that's correct and can we make any uh predictions about sarsko v2 based on that or we just have to see yeah we have to wait and see um it's fair sorry to put you on the spot but no that's a i mean it's a legit question um uh but i would say that while they are related viruses they are different enough such that i wouldn't uh yeah like if you told me if you told me what the memory b cells were for one of the common cold coronaviruses and asked if i thought for one of the other common cold coronal viruses would it look similar i'd say yeah but since the pathogenesis of classic stars was so lethal and spread so differently i i think the memory may in fact be yeah okay i wouldn't make the assumption that the memory will be the same i'm afraid we have to move on to t cells because we only have 15 minutes i'm sorry um and i know you i know you've done a lot of work on tiso so why don't you you have two main papers can you summarize them for us then we'll chat about them a bit yeah sure um so so really going back to march there were lots of uncertainties about and lots of fear people had about just were people making immune responses at all to to this virus or was it really strange and then obviously there was a huge amount of effort to try and get vaccine development going as quickly as possible and alex seti here at belgian and i both realized that it would be very valuable to have a benchmark study of of what's what's an immune response look like in average cases of coca-19 both for understanding the clinical disease and or understanding what was the likelihood of being able to develop a vaccine and so for us that comes down to um measuring all three arms of the adaptive immune response right and it's to me it's really key to measure all three at the same time the the antibodies the helper g cells and the killer g sounds and and we felt it was key to do that in average cases of covet 19 first which is to say people who had something like flu-like symptoms and recovered pretty quickly without having hospitalization first of all because those are average cases so it really makes sense that that should be your your starting point as a benchmark for understanding the immune response to this virus but also those cases probably reflect development of protective immunity or a good immune response right because the virus infected got ahead of them they they were sick but uh the fact that they weren't sick for very long and they got better probably meant that the immune response caught up to the virus and cleared the virus and that's a good immune response now we're having to make some assumptions there right assumptions that we wouldn't make if it wasn't 2020 but there were reasonable assumptions given uh given the time um and we wanted to look for t still responses across the entire virus which is a hard thing to do but alex said he's really probably the number one person in the world at predicting t-cell epitopes and so he had already gotten going on that so we felt like we could do this rigorously because part of the problem with t is our response is it's pretty easy to miss them that you could detect them in one person and not another because you're looking at the wrong thing um so we did that and basically the bottom line was we took 20 convalescent cases right so people had recovered from the disease um something like 30 days out of average cases and just said what what's it look like and basically we saw we considered it good news that they they all made uh igg responses to spike they all made helper t-cell responses and uh most of them made detectable killer t7 responses and the helper t some responses were also against spike um and the t cell responses were well distributed across the genome and the t-cell responses looked like functionally they did the things we would expect a good antiviral immune response to do and the antibody response design and t cell responses were of a reasonable magnitude basically so like all those things pretty across much across the board um would be considered good news and good signs that this was largely the way to expect a person if you just told me there was a new respiratory virus right and just told me no more information than that what type of immune response would i expect if it was a good immune response it's basically what we saw um and so that has helped inform studies of in people who got very bad disease right people are hospitalized is there something strange that goes on immune response is there and we can talk about that and it's also informed a lot of the vaccine studies i mean that the paper has been very widely cited in the vaccine field for saying okay it looks like an antibodies important antibiotic response is important but it looks like it's also normal to elicit a t cell response so do you get do you get a decent t cell response to a vaccine x or or y and our biggest concern going into it would be that there would be a terrible diesel response to spike and all of the vaccines were really focused on spike and so that would be a huge red flag but what we saw was that there really were reasonable t-cell responses to spike so so while i don't think uh you know a single protein vaccine is necessarily perfect it seems like an entirely reasonable approach in 2020. so i guess you would expect cd4 t cell responses because you're getting antibodies right you need those but the cd8s is anyone looking at their function because as you know they have to kill infected cells and we don't know if they're doing that or not correct and so what um and so what you normally do is is you look at surrogates um so do they make enzymes which are what are the the poor forming proteins that'll uh that'll kill the target cell or do they make interference gamma which is just a good general surrogate for them being functional at all and they generally looked fine by by those metrics yeah yeah good question you know i was raised in the era where rafi and um others would fill cells with chromium and look at cd8s pop them open which people don't seem to do anymore it's a really messy essay well there are other ways to do the same thing right but the point is that i understand the surrogates but i'd love to see killing of virus-infected cells at some point right or maybe you don't think that's necessary i don't know yeah it'd be yeah it'd be nice to see um it's it in general the molecular markers um do correlate very well um and that way what you see is is you can run into cases where you don't have those molecular markers and then definitely a killing function is is not okay yeah if a if a cd8 expresses perforin and grand time okay now in that in your first paper you sh you made the suggestion that there might be some uh cross-reactive t-cell epitopes with common cold coronaviruses and then in a subsequent paper you extended that to to actually showing that there are memory t t-cells these are in people who are have never seen sars cov2 yet they seem to have memory t-cells that recognize t-cell peptides so what does that mean yeah so that was uh uh that was definitely the biggest surprise um that we came across was when we when we looked at our control donors our healthy control people we could see some measurable t cells there and that was um uh hard to decipher or be convinced of initially you know and so we definitely ran the experiments a bunch of times and luckily the way we had set it up was that we were using healthy control donors from basically 2015 and so these are people who we knew for sure there was no way they'd ever seen stars ii and yet we could detect t cell responses from them and what was interesting was that that indicated that those people already had memory t cells that could recognize sarge ii even though serologically right people really don't have cross-reactive neutralizing antibodies and most people really don't have antibodies they can for example see sars2 spike protein but here we were saying about 50 of people seem to have memory t sounds that could recognize um sars2 epitopes and the reason that that was interesting and we wanted to get that out there as quickly as possible was really uh well it was really two things one is that just based on general immunological principles and things we know about flu if you already have memory t cells at the time you get infected those memory t cells those helper t cells should help you get a better faster stronger antibody response than you would if you didn't have those memory t cells as well as those membrane t cells may directly have antiviral functioning and so um that we speculated that that uh that could mean that if you have those memory cells you would have less severe disease than somebody who didn't have uh those memory t cells you would still get infected um uh but instead of your immune response taking you know let's say seven days to get up to speed and start controlling the virus um maybe you're controlling the virus after three four days and you never even noticed that you got sick right so instead of having flu-like symptoms you have an asymptomatic disease or instead of having a fatal infection you may still have a hospitalized infection but you still did better you don't you don't die that might be what we would speculate having memory t cells of that type would would do for you and so then the follow-up paper in science which was very much led by by alex seti and junior faculty member uh danielle weiskopf here um at lji showed that yes these are indeed direct confirmation that they remember in t cells and direct confirmation that at least a lot of them are from common cold coronal virus infections so as we're talking about there are four common called coronal viruses that circulate widely and it looks like what happens is that something like 50 of people happen to make t-cell responses to those common cold coronal viruses that can cross-react against stars too and the other 50 people um uh don't or it's a timing difference um that has been reproduced on multiple continents now so that's not something special about people in san diego um and so there definitely are memory t cells they definitely are cross-reactive from exposures to common colds but what we don't know is that they have any functional relevance so there's no direct evidence that we have or anybody else has that these memory t cells are actually doing something um so again just based on general immunological principles and some things we know about flu which i can give you specifics of uh we would hope or speculate that they would be a positive but it is entirely possible that they have no impact on the disease at all um or that they have a negative impact on the disease that they could be screwy in some way because the the immune system uh is complicated um i will quickly mention the second thing the reason we put it out quickly and then i'm happy to open it up to discuss because it's it's really a fascinating topic the second thing reason we wanted to put it out quickly is that in phase one clinical trials for vaccines you're frequently looking at like 20 people okay and asking did your vaccine work or not and clearly there were a lot of phases on clinical trials going on in different parts of the country with different vaccines and we said well wait a minute if these memory t cells actually are functional you could just happen to get 20 people who have those memory cells or don't or predominantly do and get you get a good response to one vaccine you get a lousy response to another vaccine actually just because of the composition of the people you looked at and so we we started telling vaccine people very quickly look you really want to look at those baseline responses like check the people before you immunize them and see if they have any t-cells because the expectation was nobody needed to look at them because nobody nobody's ever had sars before it starts too before so of course any response you would see would be de novo and we said well it looks like it might be more complicated than that and so and so those studies are going on as well okay so so they listen to you they basically listen to you right yeah as far as we can tell they're doing they're doing those studies okay yeah it seems like in one of the papers you said that that was important for phase one trials but wouldn't it also be important for phase two and phase three when you're getting more efficacy data over time to to no i mean it seems like you with more numbers you might have better data right so it's a really good question kathy at the end of the day the the phase three trials the end point is do do you get protection or not right and so um it needs to protect overall in the population um uh whether or not the people had pre-existing uh memories though scientifically it'll be totally interesting to study that in in in the larger clinical trials and understand can it explain uh are there differences between people that can be explained by whether they had uh cross-reactive memory to common cold a big concern from us was in the phase one trials when people would make making decisions about which vaccine candidates to go forward you could be misled by simply the small number of people involved and some randomness to who might have some memory right so i have two questions um in your uh paper about cross-reactive t-cells um you define cross-reactivity as sort of 67 percent um in terms of similarity um and i wondered what uh was the rationale for that 67 percent right really good question um so essentially there wasn't a rationale that was that was basically um uh a guess an observation and then and then a feedback loop and i think uh alex uh we tried to be clear about that in a paper but obviously those papers are really short and so we probably weren't um t cells yeah how much similarity would would a t-cell would an epidural have to have to be cross-reactive between two different viruses and the answer's been we don't we don't know the study lab did a nice flavy virus study where you guys know there's there's been a lot of interest in different dengue viruses and then zika which is related to the dengue viruses and well how much relationship matters and so on the t-cell side they were trying to get at that and and they saw that something in that 67 that two-thirds range seemed to be an indicator of an epitope that was more likely to be cross-reactive than not and so in in this study we first made some pools that just had anything with homology and then we stratified them into pools that had high homology or low homology but but really we did the the experiments were done by daniella to just look at everything and then when looking at the t cell lines for which ones were cross-reactive um if they were lower than 67 percent uh homologous almost none of them were cross-reactive and um other cross-attractive ones uh i think all but one had greater homology than 67 percent and so then it could sort of feedback and say okay that looks like a reasonable benchmark that uh got it so then i guess bigger picture um it seems like i think you mentioned before that pretty much everyone is infected with one of these common cold coronaviruses and so how do you think um we we're seeing you know differences in t-cell responses and how might that influence what we're seeing with heterogeneity and covid right so the um this is one of those this is one of those situations in science where you have an observation that could basically explain everything um or it could literally explain nothing um and and we honestly do not know we we do not have the data uh the the it could explain everything scenario that lots of people have been interested in speculating on and again it's fine to speculate on it and the problem is some people have really declared it knowledge and made some really dramatic claims saying that that this is known um that's a huge problem and we can come back to that in a second but um the it could explain everything scenario would be to say oh yeah well it's been interesting that that the covet 19 has had such a broad spectrum in terms of disease severity right why are there so many people who get very mild they're asymptomatic and some other people get really severe infections you know okay maybe maybe it's people who have some cross-reactive memory that give them just a little bit of a head start in that immune response and that's enough to just blunt the infection not not to stop everything um or that why is it different in kids and somebody like well of course kids are filthy they're getting common colds all the time so did they just have more of these responses so i mean those speculations can go sort of add into an item right and and some people say like oh in southeast asia maybe there are more coronal virus infections that are different or related and so maybe you actually see milder diseases because of that again no data to support any of that but those are each questions worth exploring right and you've got to start somewhere um the the biggest problem has come from there's been prominent public figures who have uh misunderstood or mistaken the immunology to say oh these guys saw 50 immunity in people and so therefore 50 of people are already immune so if you get hurt if you need 70 to get hurt immunity the 50 are already taken care of so you just got to get to 20 which is new york city right and then you've totally hit herd immunity um and that's just a fundamental misunderstanding of of the data there is no way those fifty percent of people who have memory t styles are uh are protected from getting infected and generally what t-cells do right is once you are infected they can help control the infection quicker or blunted and we even said you know one very good scenario would be that those t cells would blunt the infection but they would do it so slow that it really wouldn't affect the viral loads at all right it may keep you from from feeling bad but it really might not in terms from an epidemiological standpoint you know it might not change people's viral loads at all and again it might help explain stuff but it would change anyway i'll pause that i'm glad you and i will have to go into a minute it's okay i want i want to ask two basic questions because as a uh not so much of an immunologist i have wondered about two aspects of this and having an expert now on it how are these epitope pools designed if you could just give us a simple explanation of the algorithms for how you predict those epitopes that would be great sure um so this is absolutely what alex said he has devoted like his entire life to um and he's amazing at it and so like i said he's the old expert in this and that's what made it possible for for me to help out on these studies because he was already so far ahead with predicting epitopes right desires too that these experiments were were possible the way it works is um so t cells are uh hla restricted and each person expresses potentially like six different h2a molecules all right so these are the major history compatibility complex genes this is right simply put right this is why you and i can't swap kidneys right it's not the kidneys are totally functional but your immune system sees them as different because they express these different molecules um and so there are lots of different molecules of those and and those are the things that that present the epitopes and so different people will present different epitopes and those epitopes have different sequence motifs that will bind to different hbla molecules so what people like alex said they do is they they say okay actually a bunch of these hla molecules are similar they find similar things and if you take everybody in the world how many different hla molecules do you have to look at to represent things that would cover like 98 of people okay to simplify it down from having to look at the hundreds of different uh hlas and so they do that and then frankly it's a it's a data driven algorithm you just try lots and lots of different peptide sequences and do they bind and with what affinity and then you just line up all those sequences and you you ask a computer algorithm to say okay given this baseline and data set what's the likelihood that this new peptide would would fit that uh so it's so humans there's a huge data set okay so it's based on some empirical data of things that are already known and then refined from that okay that helps a lot okay and then thousands of them yeah maybe tens of thousands of this one okay and then uh secondly um if you could describe the t cell assay that you do i mean so vincent alluded to um the older types of functional assays but the ones that you actually did in this paper or these papers yeah that's a really good question and that was actually a key decision we made um so i'd say that the classic cell assay um is really uh a cytokine assay um and and really it's the intracellular cytokine assays that are uh uh have really been the benchmark where t-cells when they see their target they will make cytokines and then if you put a plug in the t-cells they make the cytokines but they can't secrete them their job normally is to secrete the cytokines but you basically put a plug in them and they they can't secrete it so then they build up the cytokines and then you then you identify the t cells they physically have the cytokines inside them and those are the ones that are virus specific okay wonderful assay been used for 20 years the problem is with the helper t cells um they frequently don't make your favorite cytokine uh and they frequently don't make your favorite cytokine very quickly and so um when you look for cytokines generally you have to you have to bring some of your own expectations to the assay and on the killer t-cell side it's not such a big problem because they'll basically all make interfering gamma but on the helper t cell sign it it becomes a problem where you miss a lot of things and so instead we used uh what we call cytokine agnostic assay we tend to call them a massage for activation-induced marker assays so that the t cells will always do something when they see the viral antigen but they don't necessarily make cytokine or your favorite cyclic kind so could we capture a broader pool um and so that's where we look for basically surface markers that the that the cells will upregulate and a lot of different labs use these assays now over the past few years and they're quite helpful to look in a more agnostic way um they're also a live cell assay to just get to a technical aspect of it if you do an intracellular cytokine essay you've defined what that cell is but now you can't do anything else with it because you had to kill it to plug it okay but these instead are live cell essays so you can actually sort the live cells and ask okay what's the whole gene expression profile right of that cell which has a huge value so that that was the nature of the approach that we we took um and we find it to be more sensitive than cytokine assays but but t cell t cell your personal experience may vary essays definitely vary from from lab to lab because they're live cell assays there's the uh yeah and then it it seems like you then did assay some cytokine production at least yeah first yeah yeah we did because we definitely want to know um those functionalities and we did it two ways we both we felt it was important to compare those sort of aim assays versus conventional intracellular cytokine assays and basically our experience was the a message were more sensitive than the cytokine acids but told the same thing and then we did more general cytokine assay so that the t cells if you don't mess with them they'll just secrete the cytokines into the culture supernatant and you can measure them there and so we did that and the cytokines involved largely looked like antiviral cytokines now we're doing all of that again we've been doing all that again with hospitalized patients to try and understand um because there's been a lot of debate about immune immune responses and hospitalized cases are they are they good or bad um and and to make that understanding you really have to be able to distinguish innate immune responses from adaptive immune responses and for us to be able to measure to make decisions about make conclusions about adaptive immune responses you really need to measure the antigen specific uh t cells and there's there's not uh there's not much data out there currently with hospitalized patients that have measured uh the antibodies antigen-specific helper t cells and antigen specific actual actual virus specific helper t cells and killer t cells there have been a number of studies that have used surrogates or sort of bulk measurements and then that can get confusing because people would just say oh yeah we looked at the t cells and they were doing this you're like well did you look at the ones that are actually specific and the answers you know frequently been no so far so we're trying to help phil fill that gap shane karate la jolla institute for immunology thanks so much for joining us appreciate it thanks it was a real pleasure uh excellent questions uh across the board uh take care you guys are doing great stuff and a really valuable service thank you bye-bye thanks jane thanks shane all right let's let's summarize that another winner yes no that's not what i meant but yeah so everybody seems every s cov2 infected patient seems to make some kind of antibody yeah we know i know how long they last because it's too soon our assumptions about common cold corona viruses may not be correct is that all fair in that in that responses go away right yeah in yeah or but that maybe nobody gets sick i don't know the sick part i don't know but the antibodies may not go away completely i mean so many papers say they go away after within a year and then you get reinfected you know i think ralph said that the first twiv he was on this year and then many other people said so maybe that's not correct and according to according to shane that's all based on this uh one study uh in england uh that that gave evidence that uh individuals uh could uh get reinfected but yeah uh hidden there was uh none of them were getting sick and this strikes me as a people don't readily distinguish between uh whether you're getting infected and whether you're getting sick okay and this shows up i think most damagingly in this idea that since kids don't get sick you can send them all back to school and everything's okay that's right because they must not be getting infected right yeah right which is nonsense yeah i feel like that's one place where uh immunologists could do a lot to communicate better um that issue all right so then t-cells um these these mildly infected patients which is all that he's looked at so far be interesting to see his other study with the seriously ill patient mildly infected patients they make a range of cd4 and cd8s against um viral protein but peptides in viral proteins and the interesting observation is that some of those seem to cross react with common cold coronas but what that means is anybody's guess and as he said right and i think people are wanting are going to want to find out if that means anything and the experiments need to be done and i think the other thing that he mentioned that's really important is that we know that those cells are present but we don't know necessarily that those cells are actually having any kind of function in protection or anything like that so the function part of this is not really well understood so the funny thing is and he mentioned this you know there were some there was one doctor on twitter who said this oh we got 50 immunity already and i'm like what are you talking about i'm often astounded when people completely misinterpret things but i guess i shouldn't be anymore right uh another take-home message that i got from shane is that the um i don't know that it's the major maybe it is the major the immunodominant antibody response is to spike okay and certainly that's the major neutralizing response uh and that uh that may be sufficient well that's that's driving the vaccine development right that's right it's all the spikes yeah right he didn't see he yeah i i didn't hear him saying uh you know these uh spike only vaccines are a disaster okay you seem to think that that was not in not an unreasonable way but you know what the spike decision was made before we knew that the immune response was spike focused right right i'd rather be lucky than good that's fine one thing one thing that that i liked um is that i've always divided the adaptive immune response into two and he consistently divided it into three and that was interesting to see so the antibody response the helper t cell response and the killer t cell response uh i'm feeling a little bad about sucking up so much time on vaccinia but that's okay actually so interesting because uh i think uh an important lesson that i keep having to relearn is that uh you know facts and vacs vaccination and vaccinology up until very recently was entirely an empirical discipline and when he started working on vaccinia i meant to i meant to ask him whether i'll bet you some of that was biodefense stimulated right because fox viruses for 10 years or so after 9 11. got a got a bio biodefense bump uh but um uh you know uh we had we'd eradicated the disease and we didn't know why okay we didn't know what the immune response was or what its relevance was and it's interesting that he finds that it's a basically an aggregation of different antibody responses in the uh in vaccinia but i wouldn't necessarily extrapolate that to another virus because vaccinia is complicated okay and has many different ways of attaching to cells and being uh taken up rather than just this one thing that attaches and and gets sucked up so it's not i don't think you can extrapolate from the experience with vaccinia to necessarily to another virus but it's interesting that also that has about a gazillion genes right yeah and a gazillion targets so that that what he talked about there is interesting because he said you know if you give non-human primates a lot of virus you need to have antibody but it could be that you know in a normal infection t cells might be enough to limit infection right because it would make sense that if you've got a few cells infected the ctl's go and kill them boom that's the end but if you're putting so much virus in there's no way that that can happen so really another uh caveat for animal models right when we have to give them so much virus because they're precious and i like that a lot i think that was so in that sense rich no question is really on the side it's all intertwined i like it all it's all good i uh uh i'm i'm astonished that i can have these conversations about immunology that's hard i i've learned so much from this yeah but rich when they leave when they leave they laugh at us about you and me you and me anyway what are these guys questions anyway i'd like to hear the result of the serious uh infected patients it's quite interesting you know the thing is that in an evolving pandemic the first few months it's a mess because every paper and they're too many papers coming out uh they're slightly different and people get confused and say oh it can't be and now it's starting to sort out so that's good well you know what it's only been six months no wait it's been longer than that where are we end of august yeah eight months seven years yeah okay one thing that's a little bit different to me is that it seemed with zika that early on there were way more review articles than there were primary papers because this there's lots and lots of primary papers and you know maybe a relevant number of review articles but yeah that kind of drove me crazy with zika right it says every new outbreak that's crazy yeah lots of stuff just pouring out and not all of it good unfortunately i think that the fraction of of work that's not as rigorously done goes up because i think it's done quickly and people think that it's important just to get done but yeah you know i think it's better to get it right definitely that's okay they have to all these people have to go through the twit filter uh eventually okay where p where the peer review us and twitter right right i don't know about i don't know about twitter i think twitter can be a big problem you know uh speaking of twitter so amy and i were discussing the other day you know as we talked about previously on twitter i think with daniel the convalescent serum trials didn't look good and so fda was considering issuing an eua and fauci and collins said no we don't think there's enough data and then the next day the fda issues in the ua okay and then a few days later the head says i made a mistake and where does he announce this he announces it on twitter instead of doing a press conference would be widely picked up he announces it on twitter which i think i agree is just not the place to do that if you're serious about something do a press conference because if you do the original eua in your normal fashion you should reverse it too but i think well he's taking a a hint from how the president does yeah yes but not that i don't think it's necessarily a good you can have your conversations but if you want to make policy i don't think it's the place to do it right but more broadly is that this intersection of politics and science right i mean obviously we the administration has an agenda to push vaccines and anti viral therapies to make them look good but that shouldn't drive it it should be the science that's driving it unfortunately and i know that we have an intersection between society and science and you know science has its own view and society has an agenda obviously but i don't see why an administration can tell the fda or anyone nih cdc what to do it doesn't make any sense to me there needs to be a collaboration between society and science rather than a conflict yeah i i was really um sort of taken um when daniel talked last time about the issues with randomized control trials um when different treatments were thought to be the best or terrible um he couldn't get people to enroll in the trial that he needed to have great data um and so when i saw some of these convalescent serum um announcements i i thought back to that conversation um because there is no randomized control tile data on convalescent serum um and i would assume this will make it much more challenging in a similar way so also the things that daniel said about the dangers of that type of therapy where the coagulation factors are a real problem that's a great point especially this is a disease where colloidal collage clotting is an issue right yeah yeah maybe i mean he made that point so clear yeah yes coagulopathy very good davidson you gotta slow down and you can get it all right let's uh let's do some email claudia writes hello twiv people regarding those never-ending ongoing stories like the florida sheriff and so many others of people not wanting to follow common sense rules for political or whatever reasons it reminds me of some long ago wartime stories in world war ii when germans started bombing london when the alarm went off at night people were supposed to shut down their lights a total dark city would obviously make it more difficult for the enemy to spot their neighborhood and hence to bomb them if you for any stupid reason would be the person to say or even think about something like quote i have the right to keep my lights on unquote well you can imagine what would happen so like vincent says this is war people it's a really great analogy i like that very much she is from brazil it's a great point i like that very much i wonder if that's my there's probably lots of claudio's in brazil but i know a couple of claudio's in brazil i never know the last one you got right uh yeah yeah that one guy you said uh bradley from gainesville uh who with whom i have now reconnected as with a few others in uh twiv and it's been very nice brianne can you take the next one sure charles writes hello twivers just a pissed off human living in chapel hill where the weather is nice at 85 fahrenheit 29 celsius with a chance of rain later today i did listen to all of 654 as i'm sure most of your listeners did i just sent the following and to the point course short and to the point correspondence to my congress critters i hope to get a more meaningful response this time around my first response from senator tom tillis talked about what a great job we have done in other words pure bs senator burr was not much better he talked about how much ppe we produced representative david price was a bit better but not good enough thanks charles p.s about the ignorant sheriff and chief of police i have lived in some diverse places lexington and murray kentucky burlingame and san francisco california durham and chapel hill north carolina and ocala marion county florida just south of gainesville i would live in any of them again except for ocala the sheriff banning masks and the chief of police deciding which laws to enforce without being fired should tell you all you need to know about that area pps because of the language in this email dr brian barker may want to read this one if that is a microaggression sorry ppps a question for twig salt hay had me baffled i assumed it was hay that had salt added to it to keep seeds from sprouting turns out i think it is salt marsh hay which needs salt to sprout is that correct do you mean spartina so that's actually dixon adding in do you mean spartina and that was enough to put me on send me off on the spartina trail so salt marsh grass is partina patens it's also known as salt metal cord grass and also known as salt hay it's found from newfoundland all along the coast of the eastern united states to the caribbean and northeast mexico and so as to his question about it needing salt to sprout from at least some species that i saw salt is not necessary for the sprouting the plants are salt tolerant and in fact if they have too much salt it can make them stubby so this is because i went on this week in gardening yeah twig we went and bought some salt hay to put on top of the the beds so that it would suppress the um weeds but one year we bought hay from home depot and it was full of seeds and they all sprouted so right it defeated the whole purpose so um we found out that there's this salt i don't know how it is all i know it was 25 bucks a a bale which seems to me a lot for a bale of hay any i don't know if it's spartina or salt treated hay but it's expensive well if it's spartina it sounds like the the only uh issue with the salt is that it grows in a marsh it's not as if it's got salt in it when you spread it out but maybe since it grows in a marsh it's not going to bring into your garden the sorts of wheat maybe otherwise i'm totally making stuff up there no i think it's probably just a good solid mulch and doesn't have a bunch of seeds in it and it's expensive because they drug it into your new jersey garden from a salt marsh right maybe maybe well i it does work because it's still there and it pretty much suppresses the weeds and nothing grew in this in the hay itself so that's good and charles seems to have given us uh his letter to his congress critters um to go on our letter page okay we'll put that it has a cup yeah and it has a couple of he said short but sweet he's got a couple of all caps uh things to um to make his points okay yeah kathy can you go next sure essa pekka writes dear to uh twiv i have a fairly simple question that came to me while listening to 652 about transmission of sars covi2 is it possible that the incubation time for the onset of symptoms and for transmissibility are decoupled in sars cov2 i suppose with my limited understanding of sars kobe 2 biology that there may be a component that suppresses the immune response which causes a period of asymptomatic transmission could the level of immune suppression and therefore the delay from peak transistibility to symptom onset be a significant indicator of disease severity i'm a humble non-viral structural biologist so i might be overlooking some obvious facts here regarding home testing i hope the pre-print below has caught your eye in it they describe an open source application to produce a lamp-based test that can also be used at home and this test is a test from a group in vienna and with respect respect to the questions about decoupling symptoms and transmissibility and suppression of the immune response i think it may be making it more complicated necessary i finally found using the the right link to rapidtests.org a really good diagram that they have there that shows uh rapid tests uh versus pcr but uh for the purposes of this discussion i don't know vincent if you can put this figure in the show notes but um there's a gray line that shows the viral load and and where it peaks and then there's a shading of where the virus is transmissible and in terms of uh decoupling the onset of symptoms and transmissibility i think that the gist of it is that the uh symptoms start to arise around the time when there's peak viral loads or even shortly thereafter correct so um i i don't think there's any kind of real decoupling it's going to be different for every virus and that's why it's taken us a while to figure out what this timeline looks like yep exactly and i don't think we understand why it's different for different viruses you know why why in this case is there a uh does the viral load peak before symptom onset on average uh whereas even in something as closely related as uh sars one that was not the case uh right that you had you were transmissible uh and symptomatic uh at the peak um so i don't i don't think we understand why there are those differences certainly i don't no right not either i agree but um that the test that is in the preprint it's interesting um doesn't seem to require any uh instrumentation this is a let's call it a pipet free version for home testing with open source enzymes so i mean it's so it could be okay but i just i do think a um you know what are they called the the lick lick the strip or something oh she called it lick a stick lick a stick yeah that's what she called it i like to lick a stick like a stick all right um rich can you take suzanne writes propublica usually does a pretty good job of investigating things but this really seems like a scare mongering to me i believe they're well-meaning and they may have a point but the lack of transparency about the lack of transparency but the rest sounds uh more to me like things are working the way they should i was wondering what you all thought and she links to an article in propublica that's entitled here are uh six accidents unc researchers had with lab-created coronaviruses uh and i looked through this uh it was a while ago now but i looked through this and i think suzanne you've got it absolutely right i accept i'm not sure that they were well-meaning okay in publishing this article the way they did i think they're i think it's you know some version of click bait in a way uh uh because it is uh it's it's nuts they're um i i don't i don't even think there's a an issue with lack of transparency okay things happen in laboratories there are accidents that happen okay nobody ever said that we weren't ever going to have any access that's why we have eye containment laboratories right so that when there's an accident it's contained and this describes uh some mishaps by and large pretty minor dropping a sample on the floor okay in uh mostly bsl3 labs i think yeah and in these i've never worked in a bsl3 lab but my understanding is that there's a standard procedure where there's an accident to not only clean up but also report it and have the accident reviewed by the appropriate people and that's all public record okay it's not a it's not an it's not an issue okay and so this is just routine reporting of lab accidents and the bottom line is that they're doing their job okay there was there was an accident they cleaned up they did the appropriate uh reporting and surveillance and everything's okay and nobody got hurt yeah so this is this is business as usual exactly all of these stories then talk about well then they reported it and this is the these are the health things that were done by occupational health and this seems like exactly what we want people to do when there's an accident is report it and go through these procedures and so yes this is great the headline calling them lab-created coronaviruses these are mostly all the mouse-adapted coronaviruses and so yes they're lab created but that's by passaging these viruses in such a way that they can now grow in the animal model mice and some of the accidents were mice you know escaping and running around on the floor fighting people fighting people whatever and again in terms of you know reporting everything that happens i know the case where um you know for these uh breathing apparatuses there's a big battery pack um and in one case the person was in the process of uh doffing their ppe taking off all their ppe and the battery pack fell on the floor of the lab and they reported that yeah so you know this is just what is supposed to happen so i agree with the uh suzanne that uh things here are working the way they should it's fear-mongering it's true and and i i appreciate actually this letter to give an opportunity to point out uh how what is really business as usual can be misrepresented as some horrible thing going on we had ron fuschia on twitter at an asv i think it was fort collins and he said you know if our computer crashes in the bso3 we have to report it we have to report everything so the fact that there are reports should not make you think that things are going wrong it's just what we have to do okay let's see where are we paula right everyone's gone everyone has gone once right yes i'm a new twiv listener in minnesota usa currently sunny 67 f 19.4 c where i am humidity 66 percent with calm winds i am a 50 year old stay-at-home mom who started college at michigan tech ages ago majoring in med tech with an eye toward vet school before getting married and working to get my husband through his school i did not finish my degree yes we are still married 29 years this coming november and raised three wonderful kids and have two sweet grandsons now regarding the sudden spike in new zealand cases many are saying that the virus isn't likely to be transmitted on surfaces including frozen food which they think might be the source for these new cases but i haven't found any story that mentioned anything about the phenomena of sublimation of the frost crystals on the surface of frozen items if you're handling frozen food and some of it is contaminated with coronavirus from other workers breathing coughing or sneezing on it then every time air passes over those packages especially as they pass into a slightly warmer environment during shipment you can get you get some sublimation and you are likely to inhale some of the sublimated vapor wouldn't you think thanks for helping to oil my rusty brain lots of the discussion is going over my head but it sure makes me feel more intelligent sublimation so i think of sublimation as uh basically well okay so this is my my lab stuff creeping in i think of it like lyophilization or freeze drying right and in that case uh if we're going to get technical about this i don't think the new zealanders got their virus from frozen food but from a strictly technical point of view i would figure that the vapor coming off of some sort of mixture of stuff frozen on a surface would be water and would leave most of the other material behind okay i have this vivid memory of the first time i ever saw something lyophilized it was a solution it was in harry dollar's lab and it was a solution of ribosomes okay so it's a clear fluid and he stuck it in on the lyophilizer and it's in a this round glass thing and then you freeze it you freeze it and you stick it connect it to the vacuum and all the water comes off and there was this lacy stuff left behind that's all the protein and rna from the ribosomes that's the residue okay that stuff doesn't evaporate sublimation i think is the same thing it's like a distillation in a way i think you lose the vapor i don't think you lose the material so that's that's my spin right i agree i don't think that the virus on frozen food is the cause of the spike in new zealand cases but i did look up sublimate and it is to be transformed directly from solid to gas or from gas to solid without being liquid so i wasn't aware that it could use it could refer to going from gas back to solid but uh so if you go if you go from solid to gas let's say you go from ice to gas there's some coronavirus on the ice it's as as rich said it's going to remain behind the gas will not have coronavirus in it correct or is that wrong assumption that seems to make sense when my snowman sublimates he leaves his uh eyes and his carrot nose behind how many of those do you have in austin not a lot but i've been lusting after sun river thinking about him i think last week we got a letter explaining the new zealand outbreak where people coming in and the quarantine wasn't done right and so forth yes we talked all about that was not frozen food for sure all right uh brienne john writes dear twivers as a jesuit priest and a huge doctor who fan i felt the need to write in response to episode 654 i teach parasitology at creighton university and have been an avid listener of twip which i recommend to all of your listeners although i have listened to a few twiv episodes sporadically in the past i have listened to all of this year's episodes and have thoroughly enjoyed them episode 540 brought me a great deal of hope and so i want to thank you for countering a miasma of desolation i also want to thank daniel griffin who not only has good taste in sci-fi but generally gives his time to share critical first-hand clinical knowledge on covid19 i also love his case studies on twit and use them in my class until we get this pandemic under control stay grumpy and keep up the great work sincerely john who is in omaha nebraska where it has been sunny and in the mid 80s and i think he referred to episode 640 i think so too which is yeah yes the michael mina episode gosh what is 540 it was pre corona virus yeah is it was there such a time lastly irises yeah wow long time ago yes i i recognize you from twip for sending in uh letters um who's next brienne did brian who i just read that kathy all rights dear vincent and other twiv hosts i'm sure you've seen this article by now but since it's so clearly and persuasively echoes what twiv has advocated since the michael min episode 12640 i couldn't resist sending along a copy keep twitting regards earl and it's the atlantic article that i think i pointed out to you because i had read ahead in the listener email and found this one uh so i mentioned it last week it's a really good one yeah and it's nice that they're making them available outside of the paywall right which is normally i never read the atlantic because i don't have a subscription but it's a good article yes very good uh rich and they have a term in there that i really like which is the uh contagiousness test that uh that these rapid tests should be thought of as contagiousness tests yes exactly yes that's absolutely right all right uh rich maria writes dear twin team i am a quality assurance lead for a diagnostics company i learned about twiv from a grad professor of mine i want to thank you all for keeping me sane and informed during this crazy time a couple of weeks ago my 17 year old nephew started feeling ill and soon thereafter lost his sense of taste and smell he had access to an abbott id test and his results came back positive he has spent the summer working in a restaurant and three of his co-workers were also diagnosed positive soon thereafter all of his friends and family who have had exposure to him have since been tested using lab pcr all of their tests came back negative including those of his immediate family and of his girlfriend who he was swapping spit with the day before his positive test result do you have any explanation for this my brother is now convinced that there is a quote different strain unquote of sarge kov2 in our hometown that is less transmissible i ineloquently told him that he was wrong but couldn't explain how my nephew did not infect any of his friends and family keep up the excellent work my gratitude is expressed in the following haiku and here's the haiku so many false facts nowhere to turn so confused then twiv cleared the fog excellent um i you know uh i can't necessarily explain this phenomena except that it's a it is an anecdote of one person's experience in a group of people and so it is a data point transmission isn't necessarily a hundred percent uh you just because you're just because you've uh got virus and you're shedding virus doesn't mean that everybody you're gonna be in contact with gets infected even if you're swapping spit with him who knows maybe his girlfriend um first of all maybe he was swapping spit when he was uh down on the downside of his infection maybe he didn't have a real high titer yeah uh maybe she had just gotten over um a cold or in the recent past it has been infected with all four human coronaviruses and has a little t-cell background or something i don't know okay wildly speculating there i'm wildly speculating yeah okay but i don't i don't think it's a big issue and certainly the notion that there's a different strain is nonsense yeah right absolutely um the word that popped into my mind was stochastic and then i was thinking well that's maybe a little bit uh beyond some people's vocabulary uh and you can just use the word random so it's random that the other people around him did not become infected this reminds me of a uh some correspondence i had with i now get independent correspondence with 12 listeners who you know send me stuff fine okay and this was about uh i guess uh what is the in we had this discussion what's the infectious dose of a virus and um or i forget what the vocabulary was because uh there was that what's the infectivity or something and you guys said it's it's one okay any given particle or any given active particle is potentially infectious but the infectious dose is a different story okay on average how many infectious viruses does it take to infect somebody and in fact this the paper that this person uh uh enlightened me to said that the was the measurements had been done for sarge one and i think there was i kind of forget that there were some uh at least some modeling for sarge two and it's around they came up with the id 50 the on average the dose required to infect 50 of people who were in an encounter was about 250 280 uh infectious particles okay so it's not one okay and that's a statistical measure sometimes maybe you get 500 or a thousand you don't get sick i just thought of another example and that is one that uh really uh befuddled some uh faculty colleague of mine if we're working with genetically identical mice and we infect them all with the same dose of virus why don't they all behave the same way with respect to how sick they get or do they die and we just had to tell them it's biology it's random that you know it that's just the way it is it reminds me of a phrase uh the biological correlate of murphy's law under carefully controlled environmental conditions the organism does what it pleases that's good oh that's another good rich conduit quote i like that i like that yes a friend of mine mentioned that perhaps if we put together all of these excellent uh twiv uh haikus and limericks and other poetry we could call it twiv verse [Music] as you note here i have a note saying i should set up a page um of haiku limerick's poetry if you didn't have enough to do yeah right but you need to somehow you need to somehow highlight these things or something so that you can get back to them or or harvest them in real time this is a good one i like this one okay can writes sends us a ucsf press release makes this sound like potentially a real game changer it references this preprint would be great to hear what the twiv team thinks psraney17c near oxford england not unusual so i this came across my radar a couple of weeks ago uh and they call this aeronabs so what did they do at ucsf they made they identified single chain antibodies against the virus that neutralize infectivity and they they identified a bunch and they're some of them are very potent okay but the the twist here is that they say why don't we spray this into people's noses and prevent infection and the only experiment in the preprint that they do to address that is to show that if you make an aerosol out of these monoclonal antibodies that they still block infectivity so there's no there's no experiment done in an animal although i think there are some ongoing to address this so it's possible that it might work i mean i would think you'd probably have to spray it in your nose pretty frequently and i'm not sure that would be a good thing to have be spraying antibodies in your nose on a daily basis we'd have to find out in a phase one well we'd have to do a lot of preclinical studies first of course but you know the idea of spraying monoclonals into your nose and then you'd you'd be prevent you'd be protected against infection i don't know is that a good idea uh yeah i read this uh i actually got interested in this paper and i read it pretty closely because the technology is is quite interesting um there are these that as i understand it brian maybe you know more about this than i do and you can correct me but as i understand it they start off with a a yeast library uh where individual yeast in the library express uh what are basically um um binding domains from single chain antibodies they aren't even the whole single chain antibody they're binding domains and they can then use an antigen like spike in this case to select out of that library yeast cells that express uh a a binding domain that bind a spike and these are you know like 150 or 200 amino acids long uh and so they screen a bunch of these and they get some that bind the spike in a particular way that is neutralizing and they even have structural data that shows uh how it binds and then they do two things one they do mutagenesis on them and select amongst the mutagenized guys for guys that do that job better and the other thing they do prompted by their structural data is to multimerize so they come up with uh an affinity mature a mutation and affinity matured antibody multimer that is really good and uh among other things these generally have the characteristic that they're very stable which is why you can aerosolize them or heat them up or whatever and they remain stable the idea of using this as a nasal spray aside from the fact that they're stable they is discussed in one sentence in the discussion that has a reference to a paper from 2015 where somebody uh used a monoclonal antibody to respiratory sensational virus and sprayed it in the nose of cotton rats and showed that it helped diminish or prevent a lung infection with rsv and that animal virus one paper different virus animal models i'm not buying stock in this yet right okay brienne you're next all right lori writes um i'm a pediatrician in san francisco and i received an mph in epidemiology at uc berkeley my sister who is a microbiologist turned me on to twiv and i started with the michael minute episode and i was an immediate convert i have told anyone and everyone from colleagues to friends to patient families to watch it and i have been shocked that it this has not hit the front page of every major newspaper however over the last week i have heard more references to it on the radio and from colleagues michael minnow was featured on the ucsf town hall last week and that created a local buzz i think this is starting to happen please do not stop do not discourage you guys are amazing you are going to change the world thank you i would love to do something to move the quick spit test forward i have two sons who are in college and this is no way to learn they need to get back into the classroom but of course they also need to be safe please let me know if there is anything me or my colleagues can do to fan this fire thanks again i am such a fan um so all right thanks laurie i'm glad it's getting momentum uh i want to uh very briefly revisit that previous thing and make the note that uh the i really like the paper from ucsf and the point of the paper is not that they're making uh some sort of vaccine as a matter of fact it just describes the antibody it's titled an ultra high affinity synthetic nanobody blocks sars cov2 infection by locking spike into an inactive confirmation which is absolutely true with uh what uh five or six equally contributing first officers uh uh uh authors shoot faust sanders sanguan and wrestled yet i can't pronounce that properly with the senior author manglik from ucsf it's a great paper i think these antibodies could have a lot of utility for various purposes i think of them as putting them on what are we calling it uh lick a stick they might be great for that okay because they're really stable could be and they bind really hard so i think this technology's fantastic and these guys it's the press release that's twisting this into some some some amazing therapy yeah it's totally the press release press pick this up in multiple places basically on a nose spray which as you say is not really the focus that's not the point of the paper but how would they know otherwise to interpret it right another thing that laurie mentions uh in her email is about something on the rockefeller foundation site where she saw a background photograph where a person is wearing their mask below their nose and i see a cartoon type of diagram there where that's the case um but i'm not sure if that's what she's referring to but basically wanted us to call it out and maybe the rockefeller foundation could fix their website to not show improper mask wearing yep it's ridiculous kathy can you take the next one lizzy writes dear twiv in episode 654 you read my email about convincing friends and family not to tell their congress critters to buy the russian vaccine an important part of my question however was how to communicate that vaccines coming out of operation work speed will be fully tested for safety and efficacy by spending money and resources instead of time fast expensive safe and effective the russians did a combined phase 1-2 trial and declared victory fast being the only shared virtue how do i explain the difference without putting people off vaccines altogether and then i'm not sure who had this that this parenthetical remark 74 patients is not a proper phase one two trial oh that's from vincent okay um so i think that you just have to keep saying that our system based on past experience will give us a safe efficacious vaccine and working fast by spending more money and more resources uh is not to the detriment hopefully of the resulting vaccines no the the numbers alone the phase one two of the russians 74 patients is ridiculous we are doing properly populated phase one two and three trials it's just that we're accelerating it as tony fauci said to us the only thing we're gonna lose is money we're doing everything the same way we're just accelerating it so that's the key the russians didn't even really do a proper phase one trial and i don't know if you all have seen this but have you seen any of the data from that um because i think that the fact that you know we're seeing data and there's some transparency on our trials of course is another big difference i think uh one thing that um lizzie could do to convince her friends is to uh remind them of the thalidomide uh era where uh countries outside the u.s approved this drug and the fda refused to approve it because it didn't meet their uh criteria and it turned out to be when taken in pregnant women have devastating consequences and so the u.s historically at least is capable of making judgments on these things that are different than other countries and turn out to be correct judgments and i have no reason to believe or very little reason to believe that at this point in time it will be any different and in fact this whole thing with this whole dust up recently with the convalescent serum is kind of a warning shot in that regard okay and i hope people are listening uh rich can you take the next one daniel daniel writes uh i've started following your podcast after hearing uh about episode 640 with michael minna that really got a lot of listeners i wanted to get your thoughts on covet transmission among young children and implications for sending them back to school we have a five-year-old and are contemplating sending him to uh to a school that only has very young children ages two to six the school will be practicing social distancing and mask wearing hand washing and holding 75 percent of the class uh class time outside class side is limited to 13 kids and two teachers we had felt pretty good about sending our child there in light of news we heard about studies that young children under 10 are much less likely to catch and spread the virus so those are two different things there catch and spread okay that need to be segregated that's my own little editorial we'll come back to it that children under 10 are much less less likely to catch and spread the virus although we understand that can still happen and when they do become infected at much milder systems the symptoms we were particularly encouraged by news regarding a study from south korea showing much lower rates of infection in younger children but sanjay gupta on cnn today pointed out that the south korean study only had a very small cohort in the under age 10 group so he said he was disregarding his study and keeping his kids home from school although i found his study and she gives links to both of these although i found this study from iceland gives another link which used uh larger samples of children under 10 and found much lower rates of infection than in the rest of the population i'm a trial attorney and while i'm accustomed to diving into new complex areas to learn them quickly i don't have a scientific background and it's a bit difficult to decipher the various incomplete data out there so my questions are do you believe that there is a substantially lower infection and transmission rates among young children number one number two given the school setup described in my email would you send your child to school i should add that i presume this calculus will change if the michael minute type testing is made available i saw over the weekend that yale and the nba have developed something similar and i've already made inquiries to see if the school can use those on staff and kids thanks for all your work dan so uh first of all um once again i want to emphasize uh over and over and over again that catching and spreading uh the virus are not uh let's see they say this the sentence was that young children are much less likely to catch and spread the virus i see no they those aren't necessarily two different things i misspoke okay uh if you catch the virus and you're there's no evidence that children spread it any differently than anybody else so my answer to my answer to question number one do you believe there's a substantially lower infection and transmission rates among young children no i do not believe that okay i've not seen any data that can although i'm not an expert at this i've seen nothing that convinces me that kids uh are infected or transmit any less and and i think there is a lot of confusion about out there uh based on the fact that children do uh uh are less susceptible to when they are infected they less frequently get disease they have a seem to have milder disease more insulin symptomatic asymptomatic infections that does not mean that there's a lower infection rate it does not mean that they transmit any less so unless i see some huge study that convinces me otherwise my assumption is that they get infected because everything i've seen said that there's a lot of infection in children we did one paper that says they cook up even more virus and kids lay less less than five there are not a lot of transmission studies but there's no reason to believe that if you're cooking up that much virus you aren't transmitting it so i would treat kids exactly the same way as adults would i send my child to that school i don't know i really want them to have a testing program in place it's really uh i i don't worry about the kids so much because they you know they don't get sick very much what i worry about is the transmission if they're go go to school and get sick they're going to bring it home to me how do i feel about me they're going to spread it around they're going to spread it around to the rest of their contacts okay or their grand grandparents involved what to what extent are you going to contact trace your kids and quarantine them these are all factors in that decision i think also the the rate of uh positivity in the community is important yes right if it's high forget it you know if it's over a percent or two no but if it's less than one percent then it bodes better at least for not triggering another outbreak then contract tracing is going to be much more possible as well yeah that's right but i would really like to be have testing a part of it i think that's really important um brienne can you take the next one sure steve writes thanks for being a maybe the voice of reason in these chaotic times i am an internist and hospitalist caring for covid19 patients on a regular basis your podcast has been a great source of information and reasonable opinion for me and my group i suspect this question asks for an opinion because i think that it is something that cannot be known yet to what degree do you believe the improvements in morbidity and mortality among covid19 patients can be attributed to the natural selection of the virus towards a less lethal phenotype versus versus the changes in how we are managing them medically is what we are doing medically really helping the patients that much or are we just watching the natural course of a viral pandemic as it evolves thanks for any insights you can offer steve um i would say steve that um we have not seen any evidence that we are seeing a lot of change in this virus or natural selection towards a less lethal phenotype i think that it really probably is about what is you guys are doing managing them medically i would lean much more towards the medical management than anything about natural selection i agree and i think daniel's very interesting on this topic i'd love to hear him talk about this and it makes me think i was going to comment on this last time but it makes me think about uh procedures in a laboratory okay i think i've commented on this before if you have a procedure that you do in a laboratory that you know you do some a series of steps that leads to an experiment typically first couple of times you do it the outcome it's just messy it's mirror it's it's awful okay and if you're paying attention you do it over and over and over again it gets better okay if you're paying attention and you never know why you look back and say what am i doing differently and you don't know okay but you're probably doing lots of things differently because you're paying attention okay and i get the impression from from daniel that while there are some obvious things that they're doing differently and how they're managing their patients that i i have to wonder if there aren't a lot of subtle things that uh that go on that just improves the patient management i think if you were to go back and listen to some of the early twins when daniel came on and gave his clinical reports about uh what we knew and what they were doing and just the one from last week where he again outlined you know what happens each week and how we know so much more about it and what are the things to do as a clinician at each of those different stages definitely improvements in the medical treatment and as brienne said no evidence toward selection of a virus with a less lethal phenotype in particular daniel talks about throwing the kitchen sink at him i have a feeling that you know when you're presented with this kind of stuff i get the impression that as a physician when you're presented with this kind of stuff you try everything you got and over time you find out that uh many of those things were doing more harm than good ventilator is a good example of that you put that off as long as you possibly can because people apparently crash when you put them on a ventilator in the end you don't i guess have any choice but you put it off as long as possible kathy can you take the next one sure dahlia writes dear twiv team hello from berlin germany where things feel relatively normal in fact if you go to the lakes and beer gardens which are packed you can easily forget there's a global pandemic going on groups of people are meeting people are hugging going to routine doctor's appointments and the subways are getting crowded though everyone wears a mask the biggest news item recently was a naked bather who chased a wild boar around a lake in berlin yes there are pictures and uh natalia sent the link to the guardian and it's hilarious so you should stop watching or listening now go to the show notes find this letter and watch this video pull over your car don't hit your embankment no yeah no embankments okay but i think everyone is bracing themselves for the fall so it feels a bit like the calm before the storm infection numbers have been on the rise for the past few weeks yesterday with over 1700 cases registered in the past 24 hours was the highest it has been in germany since the end of april my husband and i traveled here from newark new jersey in early june it was not the most pleasant experience we wore our n95 masks for 15 hours straight and our flight from newark to frankfurt was completely full but somehow we survived without getting infected and are now happily drinking beer in beer gardens and dodging wild boars i don't have any sophisticated virus questions but i did have two puns i wanted to share with you they came to me the other day in a rare moment of inspiration when i was listening to your interview with adam kucharski i think they would make fun logos for twitter merchandise maybe t-shirts viruses are zero oh it should be viruses are not alive so read the zero as a not viruses are not alive or viruses are naughty all the best from germany where it is currently 78 degrees fahrenheit valia wow 15 hours whoa yeah that's a long time and this is the thalia who did that wonderful yeah it is a podcast of her own on uh on twitter it's really great well next week we will have is it next week or the week after christian drastic to give us a german update good das coronavirus is it next week because that's uh your little mini holiday vacation when i you know when i hear that in various locations they're going back to business as usual i go i'm not so sure about that though you know it could be that if everybody is actually maintaining a social distance and everybody is wearing a mask maybe maybe that has a very very significant mitigating effect i don't know let me just give you some numbers uh from a washington post article yesterday uh covet 19 deaths reported the previous day italy 3 france 9 japan 14 canada 7 uk 18 germany 3. united states 974. so all those we're crushing this yeah we're crushing it all under control disaster all right last one from mj don had recently asked about the need for many to avoid complying with any reasonable actions or standard of care in the address of protecting others from infection now with covet 19 and presumably for any other bad infection or pandemic if i may suggest the old freudian defense mechanism of denial is the best solution to don's query the inability to face some bad past event or some potential harm or one's own potential responsibility or the potential for such responsibility is met by the inability to either acknowledge the risk or the situation behind the risk itself yes so this was a letter who someone wrote i don't understand how people can deny these things and do these things in the face of what's going on in a manner analogous to holocaust denial denial that covet 19 can exist as severe the business is no more than a simple case of flu or that it exists trump's use of it's a democratic host or that it is transient trump's use here of it will just go away or the lack of need to respond to it as the person speaking believes that he or she or they could not harbor the virus and would not likely transmit it due to a lack of contact or lack of symptoms or both all of these are patently false but the need to maintain one's own ego gratification while acting in a possibly juvenile and self-centered manner overrides any concept of responsibility all of this jives with freud's mechanism of a person is faced with a fact that is too uncomfortable to accept and rejects it instead insisting that it is not true despite what may be overwhelming evidence and then provides a link to an article called defenses uh november third page construction currently rewritten by richard niolan on april 8 2011 but documented uh on another page keep up your wonderful work well thank you that's a i always like hearing explanations for these blatant ignorant ignor ignoring of science right and it's denial it has it's i think that's this is one of the reasons that i enjoy doing this with you guys so much and probably the reason that people like listening to it because i feel like i'm constantly awash in you know the news which is just insane uh and and this is an island of sanity and all that you know i don't mean to politicize this outbreak i try not to however uh the other day was it cbs news yes did a survey of 2000 registered voters and they asked has the number of u.s deaths from coronavirus been acceptable or unacceptable 57 percent of republicans said the number of deaths was acceptable ten percent of democrats said the number of deaths was acceptable and 33 of independence so tell me in what world does it matter what party you ascribe yourself to to decide that a death of any kind is acceptable or not i just don't understand it maybe i need more explanations from mj that i'm not getting this yeah i think mj has some insights into this it's a there's a kind of a denialism involved yeah but i mean just to say that a death is acceptable on top of it it's crazy right i mean it's crazy no death is acceptable human beings are amazing well they can be oh even when they aren't they are actually what i mean is biologically and you know as as an organism they're amazing right well you know i mean even crazy is amazing right i suppose it's all the human condition right well it's getting twisted now i don't i don't want to go any further let's let's say that is 12657 and i am just amazed that we are 57 episodes past number 600 wow it went fast microbe tv slash twiv is where you will find the show notes i have the unusual situation of having an insect buzzing around which i never do in my office at columbia micro dot tv slash dwive send your comments questions to twitter microwave.tv if you like what we do consider supporting us microbe.tv slash contribute brian barker is at drew university on twitter she is bioprof barker thank you brianne thanks it was great to be here kathy spindlers at the university of michigan in ann arbor thank you kathy thanks this is a lot of fun and last time i did wait until the end and i heard the announcement about uh chat with a virologist the thing that you can do by going to asv.org scroll down and you'll find the link to chat with a virologist if you want to have someone come to your educational zoom or whatever type of meeting and talk to you about viruses rich condition emeritus professor university of florida gainesville currently residing in austin texas thank you rich sure and thank you thank you brianne kathy listeners this is an island of sanity for me i enjoy it i'm vincent dracanello you can find me at virology.blog i'd like to thank the american society for virology and the american society for microbiology for their support of twiv and ronald jenkies for the music this episode of twiv was recorded edited and posted by me vincent bracaniello you've been listening to this week in virology thanks for joining us we'll be back next week another 12 is viral [Music] you

Channel: Vincent Racaniello

Views: 16,912

Keywords: virus, viruses, viral, virology, pandemic, SARS-CoV-2, COVID-19, immunology, B cells, T cells, antibody, peptide, immune memory, vaccine

Id: xGW2IhFBlt8

Length: 134min 54sec (8094 seconds)

Published: Wed Aug 26 2020