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COVID-19 Pandemic Update 101: T Cell Immunity vs. Antibodies & Prior Exposure to Other Coronaviruses

[Music] welcome to another medcram update and we are back after a week off i wanted to thank everybody for their kind words on our 100th update and also for tuning in to our interview with dr mina regarding testing and for those of you who would be interested we do have a five-minute version of the information in that video to share with others but let’s recap where we are currently at this time currently the top three places around the world with infection are the united states brazil and india each one is presenting a little bit differently in the united states daily new cases are slowly decreasing while it seems as though daily new deaths may have peaked here in the united states it seems as though the daily new cases in brazil have plateaued as have the daily new deaths in brazil currently in india the daily new cases continue to rise as do the daily deaths however what’s interesting is if we look at the united states brazil and india and we look at the number of cases per million you can see that much higher in the united states and brazil versus that of india and also the deaths per million are substantially lower maybe a number of reasons for that one of which is here with the tests per million being substantially lower in india as well but it’s hard to hide the deaths and one has to remember that even though india here is third on the list it is one of the most populous countries in the world i wanted to switch gears a bit and talk about this article that was published in the washington post over the weekend and the title is 40 of people with coronavirus infections have no symptoms might they be the key to ending the pandemic the question is is what is it about them that we can learn to perhaps end this pandemic and what they bring up in this article is quite interesting and it’s the number of patients that are asymptomatic and if you look at a number of cases we’ve got a boston homeless shelter and out of 147 people 88 of them were asymptomatic then there was an outbreak at a tyson foods warehouse and out of 481 95 percent of these people were asymptomatic then there was a prison system in multiple states that had 3277 and 96 of these patients were asymptomatic currently the cdc says about forty percent of patients who get infected with sars cov2 have an asymptomatic course now remember that forty percent number for later so what is it about being asymptomatic well they’re looking into this and there’s two potential areas of explanation one is with the virus itself and the other is with the host that’s you and me the people that get infected with sars cov2 and what are some of the factors with the virus well it could be genetics it could be the amount of the virus for the host it could be age could be health again it could be genetics let’s delve a little bit more into these aspects to see what it could be and the paper the washington post paper gets into some of this well of course one of the things that we need to look at is the immune system i’m not an immunologist and i don’t pretend to be one but what we can do is we can look very simply at the immune system and up to this point there’s really two types of cells that are involved here that we’re going to talk about and those are the t cells and the b cells now the b cells are important in making eventually antibodies and it’s the antibodies that everyone’s been looking at because the antibodies tells us that there’s been a response against the virus well what they might not have been telling you is that it’s the virus that activates the t cells which then activates the b cells which then makes plasma cells which eventually makes antibodies and these antibodies are proteins that bind viral particles and so it’s sort of the final common pathway if you will or a major pathway that shows that immunity has been established and it’s fairly easy to check because you can check for very specific proteins what’s harder to check for are these t cells but that’s really where a lot of this reaction starts off with it’s the t cells and so what we’ve noticed and we’ve seen this over the last month or two is that in looking for antibodies we see whether or not someone has been exposed to or has become immune to the virus by predominantly looking for antibodies and what we’re noticing is that these antibodies can dwindle over time and maybe even disappear and what we’ve done is we’ve made our hope for a response against a vaccine or against herd immunity by looking for these antibodies when in fact that may not be all of what we need to have in order to have an immune response these t cells may be just as important in an immune response against the virus in fact where the virus starts is with virus being eaten by macrophages that gets presented to t cells which then tell the b cells to make the antibodies and again i may be over simplifying this here from an immunological standpoint but i wanted to sort of get you thinking about these t cells and what they are one of the reasons why this is important is that t cell responses can last for years it seems whereas b-cell and antibody responses seem to last on the order of months remember when they checked populations for instance in new york there was a 20 incidence of finding antibodies against sars cov2 they noticed similar results in stockholm which was about 7.3 percent in barcelona which was about 7.1 but again these are generally lower than what is expected in order to have herd immunity in other words where there is a high proportion of people in a population that have an immune response or antibodies against a particular virus so the question is if it’s around 20 what are we seeing in terms of t cells so we see that we get antibodies in patients who get coveted 19 and are infected with sars cov2 what do we see with t cells well there was an interesting paper that was published titled targets of t-cell responses to sars kov2 coronavirus in humans with covet 19 disease and unexposed individuals and this was published in cell and it was just published in june of this year and what they showed is when they looked at t cells in two different populations they looked at t cells in population one which was patients that were post covered and they looked at patients that were blood donations or blood samples from 2015 to 2018 clearly before covid came along and what they found in the first population should not surprise you they found near 100 reactivity in the t cells but what they found in 2015 to 2018 again this is before the pandemic what they found was that there was a 40 to 60 percent t cell recognition of the sars co cov2 virus now that’s strikingly similar to what the cdc has been telling us about those patients that are asymptomatic so realize that many of the proteins on the surface of the sars cov2 has similar structure to other coronaviruses coronaviruses that have been around for many years that cause the common cold is it possible that patients who have had previous exposure to similar viruses to the sars cov2 have a t cell response already ready to go and that is evident in this blood sample that we see here from 2015 to 2018.

Well it would seem as though the answer to that question is yes i’ll of course let you look at the article yourself but they sum it up here at the end of the discussion they say in sum we measured sars cov2 specific cd4 and cd8 t cell responses in cova 19 cases using multiple experimental approaches sars cov2 specific cd4 positive t cell and antibody responses were observed in all covid 19 cases and cd8 positive t cell responses were observed in most importantly pre-existing sars-cov2 cross-reactive t-cell responses were observed in healthy donors these are the ones where they were donating blood prior to the outbreak of coven 19 they say indicating some potential for pre-existing immunity in the human population and not only in this article did they find this but in other groups for instance in germany they found a 34 percent reactivity to the sars cov2 virus in the netherlands 28 in singapore 50 t cell recognition of sars kovi 2 at the outset even before being exposed to the virus so yes it’s possible that again it could be the host that is having previous viral exposure and that could be prompting these patients to have a much better immune response and therefore be asymptomatic but is it also possible that the virus itself or how the virus gets into the body may be having an effect and i think the answer there is yes and the way to tell that story is through the tale of two cruises which i’ll talk about the first cruise is the diamond princess and the other one was an antarctic bound argentinian cruise ship with the diamond princess there were no masks that were given out but on the antarctic bound argentinian cruise ship there were masks that were given surgical masks to the passengers and n95 masks to the crew and what they found when they looked at those that were asymptomatic there were 47 percent of those on the diamond princess that were asymptomatic whereas on the argentinian cruise ship where they handed out masks 81 of those were asymptomatic and the speculation is that we’ve known for many years that the amount of viral load the amount of virus that is inoculated in a patient can determine the natural history of how that disease runs its course in other words if you are exposed to just a few viral particles you could get a very mild infection that is easily overcome with any type of immune system and you would have immunity with that type of an inoculation however if you were inoculated with an enormous amount millions billions of viral particles that would cause a much worse illness which would still mount an immune system but it might be a situation where you are much more sick and you might not recover and so this idea of the inoculation size causing the degree of symptoms is not a new hypothesis and in fact this has been seen in a number of countries that have used masks for instance singapore vietnam and the czech republic that they still get cases but the number of deaths and the severity of the cases are more mild and much less so here’s an article where they actually looked at putting masks on hamsters that were infected with the coronavirus disease 2019 and this paper was published on the 30th of may 2020 and it was peer reviewed and published in clinical infectious diseases what they showed here is that not only did masks prevent the spread of this disease but what they also found was this non-contact transmission was found in 66.7 percent of exposed naive hamsters surgical mass partition for challenged index or naive hamsters significantly reduced transmission to 25 that was statistically significant surgical mass partition for challenged indexed hamsters significantly reduced transmission to only 16.7 percent of exposed naive hamsters now here’s the key though unlike the severe covet 19 manifestations of challenged hamsters infective naive hamsters had lower clinical scores milder histopathological changes and lower viral nucleocapsid antigen expression in respiratory tract tissues of course this type of study could never be done in humans because it would be unethical to knowingly expose a human being to a virus that could potentially kill them but you can see here that it certainly makes sense that you can at least in theory get a higher amount of asymptomatic infections if you can reduce the amount of inoculate that is given to a naive patient now whether or not that was the issue that was going on on the two cruise ships we’re not sure because there are other differences between these two cruise ships but that was one of them so as you can see this is a little more complicated than the straightforward way of explaining vaccines proteins immune system and their reactivity to each other now i’m sure as we move forward here in the next couple of months we’re going to be talking a lot more about the immune system and the reason is is we’re going to start to get data back on these vaccines as we speak right now we have at least two trials that are in phase three and they are testing people in the public to see whether or not the vaccines can help prevent them from getting coronavirus and we’re already getting information from dr fauci talking about what to expect from a vaccine that would be approved by the fda he says here that scientists are hoping for a coronavirus vaccine that is at least 75 percent effective but 50 or 60 effective would be acceptable too so stay tuned and let’s see what unfolds as we dig deeper into the world of immunology and vaccines please come and see us at medcram.com for clear explanations on over 60 different medical topics and if you’re a medical professional we offer cme and ce credits thanks for joining us

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