TWiV 597: A lot of immunology and some COVID-19 with Jon Yewdell

April 3, 2020

Immunologist Jon Yewdell joins Vincent and Rich to discuss immune responses in the context of infection with SARS-CoV-2.

Hosts: Vincent Racaniello and Rich Condit

Guest: Jon Yewdell

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Download TWiV 597 (69 MB .mp3, 115 min)
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Intro music is by Ronald Jenkees.

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21 comments on “TWiV 597: A lot of immunology and some COVID-19 with Jon Yewdell

  1. Cameron Rogers Apr 3, 2020

    Hi TWiV team,
    Thanks Jon Yewdell, what you were saying about the fact that SARS-CoV-2 will probably circulate for years and become endemic is what I have been thinking about this coronavirus all along, eventually infecting most of the population (except for a few isolated mountain men perhaps). I had real doubts about developing herd immunity as an effective “solution”. This virus is proving to be highly infectious, which would have pushed up the required herd immunity anyway, if that strategy could have worked.

    There seems to be evidence of poor immune memory to coronaviruses. Something that Ralph Baric has talked about too. Countries hoping to go via rapid infection to develop herd immunity are just running the risk of overwhelming their hospital systems IMHO. Social distancing and public education is really needed to buy time. We will need a vaccine or at least an effective therapeutic regime to limit the damage that this virus will do, and we are going to need time to develop and test those properly.

    Thanks Vincent and Rich for a great podcast (and the rest of the TWiV team),
    Cheers,
    Cam

  2. Tianaho Apr 3, 2020

    You guys need to invite true innate and adaptive immunologists into this podcast to take about virus/host response. I guess they’d like to talk about it too.

    • profvrr Apr 3, 2020

      Excuse me, Yewdell is a T cell immunologist. Don’t criticize if you don’t know what you are talking about.

  3. Luke Westfall Apr 3, 2020

    Having a new episode of TWIV to listen to every few days has really helped to keep me grounded during this difficult time. Thank you for being the voice of science and reason in the midst of the pandemic!

  4. Glenn McLaughlin Apr 4, 2020

    Absolutely mind blowingly good episode!
    Dr. Yewdell you are amazing in the amount of ground you can cover conceptually, with detail, and STILL make it understandable to a layperson like myself.
    At one point in particular (there were many) when my processor was getting bogged down, and the current was taking me downstream….Rick man, you jumped in and threw me a life preserver (@1:42:52 to be precise)
    and dragged me back to bank….and I was back up to speed….incredibly perceptive and prescient of you….Thanks.!

    And of course Vincent…man you have turned into a rock star….an overnight success 12 years in the making!!
    I dont know how you are managing all of this…and Immune also which is excellent.
    Thank You all so much for my continuing education…I am a subscriber and will be a supporter shortly. How people choose to rot their brains with tv when content like this is available is incomprehensible to me….
    Stay Healthy,
    Glenn

  5. One of many things I neglected to mention: how hydroxychloroquine (HC) might be working (if it does work) to treat COVID 19.
    It is devilishly difficult to “know” how drugs work in mice, let alone humans, due to inevitable biological complexities. Hydroxychloroquine is a particularly broadly acting drug, since, among other things, it raises endosomal pH. As endosomes are involved in myriad biological activities, the effect of neutralizing their lumenal contents will have myriad effects. It is assumed that because hydroxychloroquine blocks COV 2 entry by preventing the acid-induced conformational change in S that triggers its membrane fusion activity, this accounts for its possible anti-viral activity in vivo. Indeed, it might.

    But here’s the bit I neglected to mention. It is well established that chloroquine, by raising endosomal pH, enhances cross-priming of CD8 + T cells by limiting immunogen degradation in endosomes, thereby promoting immunogen delivery to the cytosolic MHC class I antigen processing pathway. This was brilliantly shown by Barnaba and colleagues in 2005 (PMID: 16157687), who reported that 6/9 patients given chloroquine with the standard (protein-based) hepatitis B vaccine mounted at CD8+ T cell response, vs. 0/8 patients receiving the vaccine alone. Thus, hydroxychloroquine might ameliorate COVID 19 by boosting T cell immunity, and not through directly interfering with viral entry.

    All this to point out that the devil is in the details, which are central to rational medical intervention.

    • Glenn Apr 5, 2020

      Thank You Jon for this follow up….I hope you can do another/more episode(s) real soon…fascinating to have a front row seat to the machinations with such a dedicated informed tour-guide!

    • Steve Hawkins Apr 8, 2020

      Thank you Jon, for making the immune system a little less daunting to try and follow! A very interesting conversation.

      On this last point about raising the pH in endosomes actually being useful for priming the T-cells: Isn’t this rather counterintuitive? I only really know about MHC from Scientific American articles back in the 1970s, but, isn’t it the point of the endosomes to break proteins into handy length fragments for presentation by MHC? If so, I would have expected raising the pH to at least make the fragments different lengths to what MHC is used to presenting?

      Ah: I’m probably missing a step: the virus is lowering the endosome pH first, and then the chloroquine raises it back again? Yes?

      Fascinating these sort of details can even be discussed now!

  6. Niklas Apr 4, 2020

    Im doing a masters in Immunology but still I learned so much in this Episode! I’m glad to read in the comments that it was understandable for somebody outside the field, because even studying the topic for a while now I fell I’m going to have to listen to it again. Thanks for the episode!

  7. When plotting the Johns-Hopkins confirmed covid-19 case data for the last month on a log-lin graph (which shows exponential functions as a straight line), it is *remarkable* to observe that some large states demonstrate a straight line (single exponential function) over weeks-worth of data. Even more remarkable is that the addition of a second exponential function in some cases, captures nearly entire datasets, over orders-of-magnitude, typically with correlation coefficients in excess of 99%. I feel like this has to be seen to be believed… https://pattimichelle.com/model_prediction.html (note that these data are from large states, e.g., not from New England). A significant observation revolves around the second exponential and its relation to the first. Where a second exponential is indicated, a clear transition occurs between March 23 and March 27 in the direction of lower infection rates. These two observations are very curious. Several possibilities come to mind:
    – A so-called spectrum (linear combination) of exponential functions (SIR multi-exponential model). Although a spectrum is expected, these are evidently two temporally-disjoint, individual exponentials. (Typically in 10 days, the lowered exponential results in over a half-order-magnitude decrease in new confirmed cases.)
    – Washington State and California do not show the second exponential, but it may be buried in early, turbulent days, and they were among the most rapid to adopt strong social measures.
    – Is there a data-collection methodology change consistent with these observations? System-wide, fewer/more tests would decrease/increase the absolute number of confirmed cases, but there have not been fewer tests, and these are not per-capita data. What other reasonable epidemiological or measurement factors could cause the sudden and well-defined decrease in presumably reasonably well-measured infection rates?
    – Data modification for political reasons, especially considering the wildly-varying wordplay between China and the U.S., is a fearful possibility (don’t laugh – there is a strong, well-documented tradition in the U.S. of the politically-motivated silencing of data; see, for example: https://climate.law.columbia.edu/Silencing-Science-Tracker). The JHU data would require scientific collusion to modify it so consistently.
    – Could the abrupt acceptance of self-imposed “social distancing” among various population groups have this observably strong/sudden result? Is there historical precedent for this in the epidemiological community?

    It will be important to scientifically assign the 2-exponential observation – would you consider and discuss your thoughts?

    (Important Note: The indicated normalization used in log-lin plots simply shifts the plots vertically, preserving their shape – this was done for clarity. If numbers-of-confirmed-cases are read from the Y-axis for Pennsylvania, Florida, or California, the readings must be divided by 20, 3, or 0.3, respectively.)

    Balkew, Teshome Mogessie, “The SIR Model When S(t) is a Multi-Exponential Function.” (2010). Electronic Theses and Dissertations 1747 https://dc.etsu.edu/etd/1747

    • Steve Hawkins Apr 8, 2020

      I’m no mathematician, but I would expect to see two different exponentials, because the transmission is in two distinct populations: the regular case population of all persons, and; the special case population of all those who have not self isolated, for whatever reason. There will be fewer of the latter, overall, though many will be in risky concentrations in hospitals and carehomes. If you separated out the hospital and care workers, you would get a third exponential. You would get a new one for every category you removed from the whole population.

      • The key is that these are disjoint exponentials, occurring at different points in time. That does not figure into any model. The SIR Multi Exponential model covers the case you’re referring to and cannot model these (disjoint) results (see plot).

  8. Debby depamer Apr 7, 2020

    Wow did not know our inumme system had a b cell! That is so cool!! Listioning to all you guys talking about this and the virus you guys got me hooked I find learning about the human body and going back and telling someone else what u learned is so fun . Especially when I describe the Corona virus its werid how it takes it self apart and puts it self back together to Duplicate itself

  9. Steve Hawkins Apr 8, 2020

    This is the best immunology–possibly the best cell biology–discussion I’ve yet heard! You must make Prof Yewdell a regular!

  10. Steve Hawkins Apr 8, 2020

    I think this is the Curtis Suttle, Nature, piece mentioned at the beginning of the discussion.

    Unfortunately paywalled :/

    https://www.nature.com/articles/nature04160?proof=true

  11. Andrea Apr 8, 2020

    hello, thank you for making this available to listen to. Respectfully, have you seen the effects of five G on the oxygen molecule? the bind is spun when 5Gee is entacted. please look into this and corona.

  12. Sofia Apr 8, 2020

    This was a great episode! I hope you get Jon back on the show soon. I think he was right on the spot esp. after reading this: https://www.scmp.com/news/china/science/article/3078840/coronavirus-low-antibody-levels-raise-questions-about

  13. Hey guys I was wondering if its plausible for a process of natural varialation, or passive varialation for lack of a better term. If someone comes in contact with a virus perhaps on a fomite while the virus is weakening or in the process of dying and the virus gets into their system, would our immune system treat it as a full strength virus and could our immune response kick in like it has a full blown infection and produce antibodies without a severe disease present? Thanks for sharing your insights and knowledge with everyone!!

  14. Ann Skalka Apr 11, 2020

    This is a fantastic review of virus immunology! Should be required listening for virology students and medical trainees!

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