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New Data on T Cells and the Coronavirus

Well, I was writing just the other day about what we don’t know about the T-cell response to coronavirus infection, and as of today we know quite a bit more. And from what I can see, we have encouraging news, mixed with some things that we’re going to need to keep an eye on.

Here’s a post from May on a paper in Cell that looked at T cell responses in recovering SARS CoV-2 patients and compared them to reports of people who had been infected with “original SARS” back in 2003, and to people who had never encountered either. It also has some background on T cells in general, which might be useful if you don’t have that info right at the top of your brain’s queue. That’s the paper that showed that the T-cell response to this virus is less “Spike-o-centric” than it was to SARS. It also showed that there are, in fact, people who have both CD4+ and CD8+ T cells that recognize protein antigens from the new coronavirus even though they have never been exposed to SARS, MERS, or the new virus. The paper speculated that this might be due to cross-reactivity with proteins from the “common cold” coronaviruses”, and raised the possibility that there might be a part of the population that has at least some existing protection against the current pandemic.

Now comes a new paper in press at Nature. It confirms that convalescent patients from the current epidemic show T-cell responses (mostly CD4+ but some CD8+ as well) to various epitopes of the N (nucleocapsid) protein, which the earlier paper had identified as one of the main antigens as well (along with the Spike and M proteins, among others, with differences between the CD4+ and CD8+ responses as well). Turning to patients who had caught SARS back in 2003 and recovered, it is already known (and worried about) that their antibody responses faded within two or three years. But this paper shows that these patients still have (17 years later!) a robust T-cell response to the original SARS coronavirus’s N protein, which extends an earlier report of such responses going out to 11 years. This new work finds that these cross-react with the new SARS CoV-2 N protein as well. This makes one think, as many have been wondering, that T-cell driven immunity is perhaps the way to reconcile the apparent paradox between (1) antibody responses that seem to be dropping week by week in convalescent patients but (2) few (if any) reliable reports of actual re-infection. That would be good news indeed.

And turning to patients who have never been exposed to either SARS or the latest SARS CoV-2, this new work confirms that there are people who nonetheless have T cells that are reactive to protein antigens from the new virus. As in the earlier paper, these cells have a different pattern of reactivity compared to people who have recovered from the current pandemic (which also serves to confirm that they truly have not been infected this time around). Recognition of the nsp7 and nsp13 proteins is prominent, as well as the N protein. And when they looked at that nsp7 response, it turns out that the T cells are recognizing particular protein regions that have low homology to those found in the “common cold” coronaviruses – but do have very high homology to various animal coronaviruses.

Very interesting indeed! That would argue that there has been past zoonotic coronavirus transmission in humans, unknown viruses that apparently did not lead to serious disease, which have provided some people with a level of T-cell based protection to the current pandemic. This could potentially help to resolve another gap in our knowledge, as mentioned in that recent post: when antibody surveys come back saying that (say) 95% of a given population does not appear to have been exposed to the current virus, does that mean that all 95% of them are vulnerable – or not? I’ll reiterate the point of that post here: antibody profiling (while very important) is not the whole story, and we need to know what we’re missing.

There are still major gaps in our knowledge: how many people have such unknown-coronavirus-induced T-cells? How protective are they? How long-lasting is the T-cell response in people who have been infected with the current SARS CoV-2 virus, and how protective is it in the declining-antibody situation that seems to be common? What sorts of T cell responses will be induced by the various vaccine candidates? We just don’t know yet. But we’re going to find out.

128 comments on “New Data on T Cells and the Coronavirus”

  1. Alia says:

    Well, there has been a theory going on that cat owners may have milder SARS CoV-2 infections due to their contact with feline coronaviruses, for example here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215164/ (yeah, I know, Medical Hypotheses is not a very respectable journal). I would be very happy if it were true, being a cat owner myself, but I’m not relying on that.

    1. Kitty Wittkower says:

      Yes, alpha corona1 the cat enteric corona virus crossed from pigs to cats when cataxwere mostly barn cats in the pre 1950’s.

    2. Mark Wills says:

      According to the CDC out of the supposed death of 151,000 from Corona, less than 750 of them are under 18. So there is that! Not many under 55 have died from Corona either, I think less than 5,000, it is all on the CDC web site!!

  2. A Nonny Mouse says:

    ………..I am hearing there will be positive news soon (perhaps tomorrow) on initial trials of the Oxford Covid-19 vaccine that is backed by AstraZeneca and supported by tens of millions of pounds of government money.

    The first data is due be published in the Lancet.

    Apparently the vaccine is generating the kind of antibody and T-cell (killer cell) response that the researchers would hope to see………

    Journalist blog from ITV UK (Robert Peston)

    Let’s see, then!

    1. Calvin says:

      I will wait and see on that. Adrian Hill’s group have a long long history of delivering vaccines that are less immunogenic than hoped and require multiple doses or special adjuvants to even get close to being effective. If AZ have managed to get the “right” T-Cell response described above it’s a fluke (and a good one). More likely is that they are saying that they got poor antibody levels and they are using the T-cell response as a way of saying “all is fine”. They likely had no knowledge of the paper above. Most people think the Oxford vaccine will be a dud. Looks like we’ll have some kind of idea tomorrow.

  3. Brian Suarez says:

    In Colombia, we have almost 43% recovery rate. There is, I’m guessing, some genetic, environmental, immunological or even microbiome background persistent in our population that aids in the C19 healing process. I do not know about the prevalence of others CoV in our territory but, certainly, we have a few other viral infections with high incidence. As you said those are great news!

    1. Mark Brophy says:

      Colombia is near the equator so people make plenty of Vitamin D, bolstering their immune systems. People who have plenty of Vitamin D in their blood don’t get sick from Covid-19. People in Thailand don’t get sick, either, and they’re also near the equator.

      1. Webej says:

        A lot of people close to the equator are getting it. If it were respiratory the high absolute humidity would be dampening it. Not sure your comment explains very much.
        People near the equator are on average younger and less obese, two variables highly correlated with less morbidity. Countries near the equator use more hcq than Pharma controlled countries in the OECD.

      2. Define “plenty”. Define “don’t”.

      3. Riah says:

        I agree- I think the involvement of vitamin D in the immune response is highly underrated. You might find this interesting:
        https://doi.org/10.31232/osf.io/73whx

  4. Oudeis says:

    I confess, with the replicability crisis and various politicizing trends I’ve seen at universities, I’ve had my doubts about the state of science.

    Work like this helps remind me that there are a lot of good people doing a lot of good work, and they might yet get us out of this mess despite everything. Hooray for them.

  5. Frank says:

    Does this suggest that the N protein might be a better vaccine target, in terms of generating longer-term immunity, than the Spike protein?

    1. Calvin says:

      I’d agree with that. I might have mentioned that before. N looks better than S. Fusion protein antibodies/vaccines frequently suck.

    2. Alan Goldhammer says:

      There is a group that has taken this approach to vaccine construction and it may be a better approach than just the Spike protein.

    3. Barry says:

      ‘N’ protein antigens will only be exposed for immune surveillance after the virus has infected a cell and fragments are displayed on MHC. Spike protein antigens are exposed to IgA on the respiratory mucosa before any cell has been infected. It might be wise to elicit immunity to both, but it would be silly to discard the Spike antigen approaches.

  6. simva says:

    This is a dumb question, but I haven’t taken Immunology in a while. But just because antibodies in plasma wane over time doesn’t mean that individual’s aren’t protected right, Derek? What’s really important is Memory B-Cells, which can rapidly reproduce antibodies if the antigen is seen again? Have peoeple tested individuals with SARS-CoV-2 for Memory B-Cell formations?

    1. Ben says:

      Yes I believe you are correct and I am also frustrated by the attempt in the popular media to equate antibody count with immunity as if memory B cells and T cells don’t matter.

      1. x says:

        I’ve also been frustrated by this. I did a little searching the other day to see if there was anything special about COVID-19 and memory B-cell response or if there were conspicuous confirmed reinfections or if there had been any kind of challenge testing in recovered patients with low antibody titers and didn’t see anything.

        Somehow, that doesn’t stop people with no knowledge of immunology from CONFIDENTLY declaring that there is no permanent/long term immunity to this bug, no amount of cases will ever produce herd immunity, etc., and that anyone who doesn’t agree is a fool! I’m sure there’s some overlap with the “this is a biological weapon” folks, but I don’t frequent parts of the internet (or the country) where such sentiments are common and accepted…

        1. confused says:

          Yeah, there’s a huge difference between “we shouldn’t make policy assuming natural herd immunity will be achieved soon” and “natural herd immunity is impossible”. The first is a responsible thing to say, the second definitely isn’t.

          I think it’s largely a response to claims that e.g. NYC is at herd immunity and Sweden is near it. Which isn’t *impossible* – NYC is ~20% seroprevalence, and if T cells mean not everyone who is protected is seropositive, and superspreader effects/network inhomogeneity lower the herd immunity threshold… – but certainly isn’t known or a safe assumption.

          It may also be a difference in the use of the term “herd immunity”. I think a natural development of immunity (say if this pandemic had happened 100 years ago, when viruses weren’t understood) would not eradicate the virus, but it would decline from pandemic levels — it would become endemic, not epidemic or pandemic. (As pandemic flu strains have done: H1N1 isn’t gone, but it’s not at pandemic levels.)

          COVID isn’t flu, but there are probably a lot of viruses that have followed a similar pattern… just long enough ago that we don’t have records of the pandemic phase. Measles is supposed to be 1000 years old or less. The “common cold” coronaviruses must have jumped to humanity at *some* point.

          1. Barry says:

            Surely–if there were no wild reservoir, and no Typhoid Marys–herd immunity could eventually drive ‘R’ < 1? And if 'R' stays below 1 long enough, we'd see eradication?
            Alas, we already know for this coronavirus as for influenza, there is a wild reservoir

          2. confused says:

            Well measles usually gives lifelong immunity, but it didn’t go extinct…

            I think because new (unexposed) people keep getting born, so the susceptible population starts to increase again, and so R goes up. Infectious disease isn’t my field, though.

            Now, there are probably plenty of infections through human history that jumped from humans to animals and then died out entirely “on their own” (ie – before modern medicine) but we wouldn’t know about most of them…

          3. WST says:

            The “herd immunity” is bit misunderstood IMHO. The models predict that as an end result of an epidemic, the virus will get extinct, typical at immunity levels of 55-70%.
            BUT there is a hidden assumption, an artefact of the initial model’s simplified reality assumptions, the Susceptible and Recovered must be randomly spread out. This randomisation is the mechanism that extinguishes the virus (in the model !).
            In observable reality, these two populations are not perfectly intermixed.

            All serological studies show that Recovered/Susceptible are stratified by age and geography.

            Vaccinations do provide this randomisation and most important, protect the vulnerable strata, the place where the infections wildfire starts, so “herd immunity” can be a reality in this case.

          4. Webej says:

            West has made good points. The herd immunity threshold is actually a vaccination concept, where 1-1/R₀ is assumed to be the threshold for eradicating a pathogen from a community. In the real world, cross-immunity, innate lack of susceptibility, differences in transmission potential and communicability can all serve to mitigate the theoretical threshold at which a pathogen burns out and stops spreading, often at far lower levels.
            Although simplistic SEIR models assume 100% homogeneous susceptibility and transmission, it is very difficult to get a handle on other factors of variability, most especially with a new virus.

          5. Kaleberg says:

            New York City may be opening up, but everyone there who can cut back and cower responsibly is still doing so. Those who can are working from home. Most restaurants are closed, delivery/take out only or serving outdoors. The schools are out for summer and playgrounds are closed. There may be herd immunity, but social engineering, masks and improved sanitation are still in play.

            Herd immunity is a function of both population exposure and potential transmission rate. With contacts and transmission relatively low thanks to social engineering, a 20% immunity rate might be adequate to prevent runaway infection, but using that as an excuse for going back to business as usual is like arguing that seat belts save lives so that one doesn’t need to wear them.

        2. J. Steven Coyle says:

          I’ve never understood the logic of the “no immunity ever” crowd. Taken to its logical end, this virus gets unlimited shots at you until you’re dead….and game over. Furthermore, there’s no point in trying to develop a vax since it will also be useless in allowing the body to develop immunity. How does that make sense?

        3. Carla Rogers says:

          Whenever anyone implies or declares that disagreement with their debatable opinion is a sign of mental deficiency, they are lying. Exceptions are rare.

          In a way, this thread encourages me, because I see thriving, informed, brilliant minds on task making progress.

          However, your brilliant minds must also know the problem we face with covid technicalities is almost trivial, compared with the problem of the media and massively-funded liars/criminals/lunatics who inhibit action based on the science. The banner of science has been stolen and the media, funded by pharma more than any other industry, carpet bombs the world with lies under color of science.

          So, my brainy friends, what is the solution to that problem? Here is my idea: we need to educate President Trump. He has attached himself to Bill Gates! That means the President has bought Bill’s shtick!

    2. immune says:

      Good luck finding antigen specific memory B cells themselves–by definition fairly low abundance and difficult to distinguish from standard B cells using assays robust enough to handle large numbers of samples. I guess you would expect enhanced antibody responses on rechallenge after the initial circulating antibody levels have died down, perhaps possible to test in primate experiments

    3. Webej says:

      Good point, your body economizes on levels of immunoglobulins circulating in your serum. Personally have no idea what the relationship is between a healthy immune system and maintaining low levels of antibodies and serum testing.

  7. Bryon says:

    I’m curious-I’ve heard a lot about cross-immunity with different kinds of SARS viruses. Is it possible to make some kind of vaccine that provides broad protection against future strains? Maybe not immunity, but some kind of improved response.

    1. ezra abrams says:

      In theory, I think this is possible
      however, we would need to have some idea of what those strains look like at the molecular level, eg we need to know the amino acid sequence
      now we could look at known coronas and say there is some highly conserved protein, and we could make a vaccine against that – that is part of Derek’s post, that there seems to be some conservation among known and possibly unknown coronidae

      however, this would be $$$ and time consuming; given that Corona Viruses don’t cause pandemics that often, not sure you could convince people to spend a lot on this project

      1. EJ says:

        Yes, but theres a lot of money sloshing around now. I can picture someone company selling eager investors on a speculative vaccine (or at least some more preparation) for high risk future strains. Investors jump on riskier bets all the time.

        On a related note, there was a fascinating attempt at pandemic insurance in 2019, which is a similar kind of low-probability bet:

        https://www.wired.com/story/nathan-wolfe-global-economic-fallout-pandemic-insurance/

      2. x says:

        Well, if a COVID-19 prophylactic were also literally the cure for the common cold, it might be worth looking into, perhaps…

        1. aairfccha says:

          Even a vaccine against every single strain of coronavirus would only a partial protection against the common cold as that is most often caused by a rhinovirus.

          1. TabeaK says:

            There are hundreds of viruses that can cause common cold symptons. Endemic coronaviruses, enteroviruses, rhinoviruses, coxsackie viruses, parainfluenza – probably a bunch that are unknown at this point. The chance for a common vaccine is probably close to 0 – our immune system is (usually) pretty good at dealing with them – an amazing feat of evolution…

          2. Brett Bellmore says:

            “There are hundreds of viruses that can cause common cold symptons. Endemic coronaviruses, enteroviruses, rhinoviruses, coxsackie viruses, parainfluenza – probably a bunch that are unknown at this point. The chance for a common vaccine is probably close to 0 – our immune system is (usually) pretty good at dealing with them – an amazing feat of evolution…”

            Evolution on the part of the viruses, actually. The “common cold” is kind of an evolutionary sweet spot for viruses: Just bad enough to spread effectively, but not so bad that the host isolates or dies. That’s why there are so many of them: Viruses that can tend to evolve into one.

      3. Charles H. says:

        It’s worse than that. Highly conserved sections of the virus are also often highly protected. Look at the effort that’s been put into the universal influenza vaccine. The parts that are stable enough to dependably target are also usually hidden, and only revealed briefly when the virus activates.

        Actually, that seems to me as if it would be the expected evolved behavior. Viruses that didn’t evolve that behavior would fail to spread. So you could well end up with a vaccine that universally targeted the disease but was only active at such a specific part of the virus’ life cycle that it almost always failed to attack it.
        (Well, I’m a programmer, not a chemist or medic, but that’s the way I model it.)

    2. gcc says:

      A company called VBI Vaccines is working on a “pan-coronavirus” vaccine using virus-like particles (VLPs) containing SARS-CoV-2, SARS-CoV, and MERS-CoV proteins. It seems to be in early-stage development at this point. It would obviously be great if it worked and provided protection against those three viruses, but theoretically it could also provide some protection against other coronaviruses that might spill over from bats or other animals to humans in the future. That’s a long shot I’m sure, but it’s an interesting approach. More info at the link below:

      https://www.vbivaccines.com/coronavirus/

    3. anonymous says:

      There is a cooperative effort among several pharmaceutical companies and academic labs to develop a pan-coronavirus MPro inhibitor, since this protease appears to be well-conserved among coronaviruses.

      https://cen.acs.org/biological-chemistry/infectious-disease/How-big-pharma-firms-quietly-collaborating-on-new-coronavirus-antivirals/98/i18

      If such an effort had been initiated in 2003 after the original SARS outbreak, and sustained (very important), then it is possible that we would have had a truly efficacious anti-coronavirus drug sitting on the shelf at the outset of the current pandemic. Let’s hope this current anti-MPro effort is actually sustained and that such an inhibitor is developed, so that “COVID-28” or “COVID-35” doesn’t have to gum up the human world as much as COVID-19 has.

  8. MTK says:

    Not my area and I can’t keep all the various vaccine efforts straight, but given that antibody levels seem to dissipate and that T-cell based immunity is seemingly long lasting does this mean that vaccines based on S protein recognition may be barking up the wrong tree (or at least not as good a tree) as a vaccine that may also include N protein response? If so, which of the current vaccines under study include more than just S protein recognition? I guess it may not matter since the Moderna vaccine seemed to elicit T cell response similar to that of convalescent plasma, so that means that T-cells are elicited to the S protein of SARS-CoV-2. Are all T-cells as long lasting?

    Like I said, not my area, so excuse my ignorance.

    1. Riah says:

      Please see my comment dated today at the very end of the comments ( as at now) re relative importance of T cells v AB in CoVID

  9. Marko says:

    For Swedes , an important Public Service Announcement :

    https://twitter.com/UlrikaCampbell/status/1283476710005133312

    1. loupgarous says:

      Advice to young scientists: get published and married early. That way you’re safe from being cockblocked for doing good science. Anyone who pencil-whips a peer review out of fear some Swedish woman’s going to him to a list of incels ought to really consider another line of work.

      To the hearty souls who persevere… let “warmth in the winter, shade in the summer” be your watchword.

  10. TallDave says:

    wow >17 years of immune response seems helpful

    “Surprisingly, we also frequently detected SARS-CoV-2 specific T cells in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=37).” wonder if this frequency perhaps resembles the observed asymptomatic or low-symptom ratios

    a bit o/t and tbqh have no idea where this is going but it still makes me laugh every time I read about it https://www.the-scientist.com/the-nutshell/plastic-antibodies-43239

  11. Marko says:

    “…..when antibody surveys come back saying that (say) 95% of a given population does not appear to have been exposed to the current virus, does that mean that all 95% of them are vulnerable – or not?”

    That’s a bit of a trick question , since antibody surveys might be garbage if they used a lousy antibody test , of which there have been plenty. However , assuming the 5% seroprevalence figure is correct , I think the balance of the evidence – from cluster outbreaks , particularly – suggests that the other 95% are indeed susceptible to infection , i.e. , potentially becoming PCR + ( not necessarily getting sick ). For example , the Skagit choir and the ICE detention camp outbreak in Virginia are two cases where relatively few involved escaped infection. You can hand-wave away Skagit , perhaps , by noting that this was an elderly group and thus not representative. Harder to do for the ICE camp.

    This is not to say that I think the background coronavirus immunity is an insignificant factor. If it contributes to less severe outcomes for those who become infected with COV2 , it’s obviously a good thing.

    1. Marko says:

      This paper might help explain the whole coronavirus pre-existing immunity thing :

      https://academic.oup.com/jid/article/doi/10.1093/infdis/jiaa392/5868459

      Background
      While the mechanisms of adaptive immunity to pandemic coronavirus SARS-CoV-2 are still unknown, the immune response to the widespread endemic coronaviruses HKU1, 229E, NL63 and OC43 provide a useful reference for understanding repeat infection risk.

      Methods
      Here we used data from proactive sampling carried out in New York City from fall 2016 to spring 2018. We combined weekly nasal swab collection with self-reports of respiratory symptoms from 191 participants to investigate the profile of recurring infections with endemic coronaviruses.

      Results
      During the study, 12 individuals tested positive multiple times for the same coronavirus. We found no significant difference between the probability of testing positive at least once and the probability of a recurrence for the beta-coronaviruses HKU1 and OC43 at 34 weeks after enrollment/first infection. We also found no significant association between repeat infections and symptom severity but strong association between symptom severity and belonging to the same family.

      Conclusion
      This study provides evidence that re-infections with the same endemic coronavirus are not atypical in a time window shorter than 1 year and that the genetic basis of innate immune response may be a greater determinant of infection severity than immune memory acquired after a previous infection.

      1. Laura says:

        Marko, my understanding of swab tests is that the technology used is to identify RNA fragments of the virus–not live virus or intact virus cells–and that reported ‘reinfections’ are the result of swabs picking up the body’s shedding of the fragments. My understanding is, this technology is causing the confusion over whether there are ‘reinfections’ or not.

        1. Marko says:

          In the paper cited , the median time between reinfection events was 37 weeks. A positive PCR after so long is not likely to be a result of residual dead virus. Additionally , sequential serology studies have shown repeat infections by the same common cold coronavirus strains after similar time periods.

          I’d definitely be suspicious of reports of COV2 reinfections occurring within a period of a few weeks of becoming PCR-negative from the first infection because of the possibility of residual viral material , but after 6 months or more , after which time we know antibody titers wane in many cases , I’d tend to believe any reported reinfection is real.

    2. Webej says:

      Even on the Diamond Princess (old population) only 17% were positive, so your comment seems wrong at face value.

      1. Marko says:

        On the Diamond Princess , there was a strong mitigation response ( quarantined in cabins) upon the realization that an outbreak was upon them. The outbreak was slow enough developing to allow such mitigation to have an impact.The people on the DP were not all in one room singing at the top of their lungs like the Skagit choir , nor packed like sardines in their living quarters 24 hrs. a day , even as the outbreak raged , like those at the ICE detention facility.

        It’s very hard to find a natural experiment where COVID-19 would burn thru the entirety of a large , identifiable group of people , because in a non-backwards , civilized society , health officials would step in and do their job , limiting the potential final extent of the outbreak. Of course , in the US, with agencies like ICE , it looks like we’ll be witnessing firsthand what a near-100% attack rate within a group of hundreds of people looks like.

        You label my comment wrong at face value without confronting the examples I cited , then use a 19% attack rate on a locked-down cruise ship as your counter-example. Try again.

        1. Robert Carnegie says:

          Apparently, farmed mink in Europe are quite susceptible, and here yesterday (Friday) is a report from Spain where “tests showed that 87% were infected” of over 90,000 critters in one “farm”. And eight of the staff, but who caught it from whom isn’t entirely clear. These mink are being disposed of. Sorry, mink.

          https://www.bbc.co.uk/news/world-europe-53439263

          I’ve been wondering if in terms of droplets, you can only infect creatures whose air intake is as close to the ground as yours or closer. Since droplets fall. So there was an idea that schoolchildren don’t infect adults… unless the adult is sitting down?

          So many experiments that you can’t do without willing victims.

          1. Robert Carnegie says:

            Preprint study thinks that -more- tall people are diagnosed with SARS-COV-2 / COVID-19 (I am not sure which). Huh.

            https://www.snopes.com/fact-check/taller-people-covid-risk/

            (Yes, this isn’t actually the study.)

            Mainly of interest for contradicting what I just proposed. But a reason for husbands to refuse their turn at supermarket shopping. A reason for either sex to not wear high heels.

    3. confused says:

      Skagit was a case where everyone got infected from one person. Herd immunity is not really relevant here; that works by removing nodes from a network of chains of infection. If everyone gets infected from one source, there’s no “chain” to break.

      So the proportion of people infected has no relationship to any herd immunity threshold. It does show that these people weren’t completely immune (or they wouldn’t have become PCR-positive) but it doesn’t exclude some level of immunity.

  12. Barry says:

    It is vastly cheaper and faster to measure IgG titers in plasma than to look for IgA on mucosa or for T-cells. But people are working on it.We’re not doomed to only measure circulating IgG if it turns out to be an invalid surrogate metric

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161152/

    1. Marko says:

      Has anyone looked for anti-COV2 IgA and IgG in saliva of infected/diseased patients ? It seems like the current plasma-based assays could be easily adapted for such studies and that the information gleaned would be very revealing.

      1. Postdoc Panda says:

        The lab I’m a part of is attempting to do exactly that right now! While I’m excited about the progress we’ve made, I will say the following: Antibody abundance in general is much lower in saliva than serum. Anti-secretory IgA antibodies have proven much less robust in our hands than the anti-IgG or anti-serum IgA secondaries we’ve investigated. We’ve seen some pretty significant matrix effects with saliva, which due to ab abundance, we are running at lower dilutions than we can get away with in serum. Not to mention the striking inter-patient differences we’re seeing, when serum from the same patients looks similar. Our serum ELISAs run like clockwork, but the transition to saliva ELISAs from serum ELISAs is…..not straightforward. There are a lot of great groups working on this problem, so we’ll get it sorted out, but it turned out to be more significant than most of us though when we jumped into it a month or two ago.

        1. Marko says:

          Good to know , thanks !

          Not as straightforward as I thought , obviously. Saliva , sputum , nasal secretions , BAL , etc. – all would be interesting to study , but I can see how the matrix might complicate things.

          I’m particularly curious about how much IgG diffuses into the mucosa during the course of disease , and how that correlates with disease progression or resolution.

        2. Anonymous says:

          Dental/oral health research has been testing saliva and other mucosal fluids for nearly 40 years by ELISA for specific sIgA. There are some tricks to making it work, but it is definitely doable. You want to look in the dental/oral health literature back in the late 1970s/early 1980s, pre-1982, for their procedures. Look for Jeffrey Ebersole, Daniel Smith and Martin Taubman. They and William King have also looked at a sIgA response for caries via vaccine, which seems pretty relevant; that work was published probably in the 2000s in the dental/oral health literature. Dental journals don’t always show up in standard searches unless you know what you’re looking for.

          Many others have looked at mucosal immune responses. You might also look at the IADR yearly meeting abstracts to see what they are doing now. HTH!

  13. Lint says:

    Nice post, but please remove the “low homology” part, there is no such thing, call it identity or similarly.

    1. DL is quoting the Authors, so while I agree with you formally, it’s appropriate.

      Best
      GOP

  14. TallDave says:

    will be interesting to see how the COVAXX peptide candidate tests, they claim to have an advantage here… timeline a bit behind the leaders but if their claims hold up and/or the others have issues…
    ——
    COVAXX’s vaccine is comprised of amino acid sequences of the SARS-CoV-2 Receptor Binding Domain (RBD) further formulated with designer Th and CTL epitope peptides derived from the S2 subunit, membrane and nucleoprotein regions of SARS-CoV-2 structural proteins for induction of memory recall, T-cell activation and effector functions against SARS-CoV-2. Data from COVAXX’s preclinical studies demonstrated exceptionally high immunogenicity and neutralizing titers against live virus as compared to published data from other vaccine candidates to date.

  15. Barry says:

    I’m no immunlogist; maybe someone here can educate me. Do we expect a 60yr-old’s response to a vaccine to be like a 6yr-old’s? Should vaccine makers be running separate tests by age cohort? Will the ratio of humoral to cell-mediated response evoked vary w/ age?
    Thanks!

    1. TabeaK says:

      It will definitely change with age, as with all vaccines – while there is no fixed cut-off in age, the older you are the more likely vaccines are to be less effective. Nevertheless, there are vaccine failures in the young cohorts too – usually fewer though.

      Ultimately, it come down to enough younger folks being vaccinated to protect to higher incidence of older vaccine failures – herd immunity at its finest.

  16. Andrew Walsh says:

    If this stuff about T cell immunity is true maybe if we could find a less virulent virus that activates it we could just expose people to it and they just get a cold?

    1. Barry says:

      Yes, that’s essentially what a “live attenuated” vaccine would be. Still infectious, but not virulent. It would lack (at least) the ability to block our interferon response. The oral polio vaccine was in this class. Still infectious enough to infect/immunized household members when you inoculated one child, but not virulent enough to do harm to anyone w/ an intact immune system.
      But viruses mutate, and any such attenuated virus might mutate to acquire virulence once it’s out in the community.

  17. Victory Pilsner says:

    If I am understanding correctly, then are there any studies out there that suggest that pet owners, if positive for SARS-CoV-2 infection, have a higher likelihood of being asymptomatic? Seems like that would be easy enough to determine.

  18. Zee Bendelstein says:

    Incredible. So could flow cytometry based tests take the place of serology for long-term immunity testing?

    1. TabeaK says:

      Only if you know specifically what T cell(s) you are looking for. Flow cytometry for antigen specific (SARS2 specific in this case) is not straightforward or high throughput. Those cells are by nature low abundant and one needs specialized (and expensive!) reagents to make them “visible” for quantification.

  19. Kannan Hariharan says:

    Are there any large scale studies on childhood incidence of measles and/or MMR vaccines and the impact of Covid-19? I was reading somewhere that there is a 30 percent homology with respect to the proteins of the Covid 19 virus and the measles virus. Can the measles vaccine be used as a stopgap measure?

  20. Matt Gruner says:

    We desperately need a safer, more rapid T cell activation assay. Currently you must isolate live leukocytes from blood (requires access to biohazard safety level 3 [BSL3]) and grow the cells (at a minimum 24 hours but classically 4-5 days) in the presence of synthetic activation inducers such as anti-CD28 and anti-CD3 antibodies. As you can imagine how to make this high-throughput is not obvious.

  21. James Cross says:

    Okay, this may be a dumb question.

    It would seem older people would more likely have been exposed to more coronaviruses over the years yet they seem to show the least immunity. Yet young children likely with less exposure seem better able to deal with it.

    Do the complications all relate back to some epithelial dysfunction in gut or lung that accompanies aging and also may be linked to other compromising medical conditions?

    1. TabeaK says:

      More likely immune senescence – like with many organ systems, the function of the immune cells decline with age.

    2. Barry says:

      The relative resistance of children to infection suggests a large/dominant role for innate immunity. The larger repertoires of Abs older individuals bring don’t determine who gets infected.

      1. Riah says:

        Yes…and interesting that vitamin D is critical in the innate immune response. VDR’s ( vitamin D receptors,) are numerous in immune cells and act as epigenetic transcription factors to upregulate production of antivirals like cathelecidin and defensins. See
        10.31232/osf.io/73whx
        https://doi.org/10.31232/osf.io/73whx
        which suggests that the innate immune response may be more important against a Covid-19 infection

  22. Klaus says:

    Interesting post and discussion.
    Immunologists – could a partial, pre-existing T-cell immunity reduce an individual’s probability to get infected when exposed to a virus?
    By “infected” I mean, spread the virus themselves and develop serum Ab’s, whether or not they become symptomatic.
    I’m trying to understand if there could be a selection effect where people least resistant to infection preferentially catch it early. So the more resistant ones would accumulate in the uninfected, seronegative part of the population over time.
    (Pure speculation, I’m not an expert.)

    1. TabeaK says:

      I don’t see how it would prevent infection per se – but pre-existing T cell immunity certainly could clear the infection quickly enough, so that viral titers (and presumably symptoms) may never get to a level where infectiousness is a large concern.

      In cases of pre-existing (Partial?) T cell immunity you may also never get to the seroconversion step – large amounts of antibodies may just not be needed in the periphery.

      1. Klaus says:

        Thanks. With SARS-2, the large majority of infected seem to seroconvert, even the asymptomatics (from the few studies I’ve seen). But that relies on RT-PCR to identify the infected. Maybe a part-immune fraction of the population clears the infection so quickly that it is missed in RT-PCR tests? Not sure how likely this is… PCR is very sensitive.

    2. Webej says:

      preferentially catch it early

      Probably would explain why the growth rates for C19 were never exponential, but showed decelerating growth rate right from the start.

  23. Larry says:

    Very interesting, perhaps the very low infection rate in Vietnam, Cambodia, Laos, native Singapore, Myanmar, and Thailand are due to previous zoological exposure. They all have different governments and cultures but similar outcomes.

    1. cynical1 says:

      Aren’t those countries where most of the pangolins are from?

      1. loupgarous says:

        Historically, yes. Now, Taiwan’s got the highest population density of pangolins on Earth owing to aggressive conservation efforts, but bush pangolin meat and scales mainly come from those other countries and Africa.

  24. Geff says:

    Fascinating to finally see science do what it does best. Replicates earlier findings and adds to the zoonotic story.

    The question in my mind has always been
    why were the death rates on the cruise ships low? I think that was the best information we had at the time.

    From next week, not now, masks are compulsory in shops – but not the pub. A move advocated in part by the royal society.

    What a mess.

    1. Riah says:

      Hi Geff. You asked about that also in the 7th July blog. I posted an reply too late so perhaps you haven’t seen it? I have also copied and pasted my reply at the very in response to the last comment here but for some reason there is a delay in it being displayed. I can’t see it yet.

  25. Marko says:

    Do these numbers suggest that there is a significant rate of “background” herd immunity ? :

    “…The U.S. Immigration and Customs Enforcement (ICE) told 8News on July 14 in a statement that ICA Farmville offered COVID-19 testing to all detainees from July 1 to 3. According to ICE, 359 people were tested of which 268 ( 75% , now up to 80% , see below ) have tested positive, 20 (6% ) have tested negative, 71 have pending results, and one declined to be tested.”

    “On July 16, 8News received a new letter from Warner and Kaine to Homeland Security Secretary and ICE that stated that the detention center has 287 confirmed cases of COVID-19 amongst detainees, which is approximately 80 percent of the population housed at Farmville, and 26 confirmed cases amongst staff members. ”

    https://www.wric.com/news/taking-action/covid-19-cases-spike-at-farmville-ice-detention-center-after-transfers-from-florida-arizona/

    https://www.ice.gov/coronavirus

    1. Marko says:

      Update , per link above : ” According to the ICE COVID-19 data, there are 315 total confirmed cases of COVID-19 at the Farmville Detention Center. The total number of people detained at Farmville is 360. That means nearly 90 percent of the population has COVID-19. ”

      Considering the likelihood of false-negative tests , it’s not hard to imagine that essentially every detainee at this facility will be found to have been infected. If this is verified ( CDC is supposedly investigating ) , it blows the idea of some meaningful level of pre-existing herd immunity out of the water. Everyone who has not already been infected can be infected , and will then be infectious themselves. Background immunity may help protect against severe disease , but it won’t facilitate the achievement of a “herd effect”.

      1. confused says:

        I agree that this and some other similar instances mean that the T-cell data probably doesn’t imply that ~half of people are truly immune.

        But is everyone PCR-positive necessarily infectious? Given that the spread seems highly driven by ‘super-spreader’ events, couldn’t there also be people who are PCR-positive but neither meaningfully symptomatic nor meaningfully contagious?

        I’m not saying there ARE such people, but “basically everyone can become infected, in the sense of PCR-positive” doesn’t necessarily imply that basically everyone can become either sick or contagious.

        1. Marko says:

          “….but “basically everyone can become infected, in the sense of PCR-positive” doesn’t necessarily imply that basically everyone can become either sick or contagious.”

          We already know that you can be PCR+ and asymptomatic , so the “sick” part is not at issue. We also know that you can spread disease while asymptomatic. This outbreak would be relatively easy to control if only people who were obviously sick were spreaders.

          Yes , there is a continuum of infectiousness among individuals , from “superspreaders” ( some of whom have been asymptomatic at the time ) to those who don’t seem to spread so efficiently , such as young children. However , from a public health perspective , it only makes sense to treat everyone who is PCR+ as potentially infectious. I’m willing to bet it will never be proven that some who recently became PCR+ are NOT an infectious threat to others. Certainly, the burden of proof rests on those who would make such a claim to show their work.

          1. Webej says:

            The Farmville example is a facility where the spread is bound to be high. If some people are “less susceptible” it still dampens the transmission of the virus through though the population. The Diamond Princess (17% positive) offers a counter example, with people locked in the same cabin sometimes testing different than their bunkmate.

          2. Marko says:

            Aha. Now the weasel-wording emerges. “Less susceptible” rather than “immune”. Tell me , are those “less susceptible” people , once infected and PCR+ , also “less infectious”?

          3. confused says:

            >>We already know that you can be PCR+ and asymptomatic , so the “sick” part is not at issue. We also know that you can spread disease while asymptomatic.

            Of course asymptomatic/pre-symptomatic spread exists. But that does not mean that all asymptomatic positives are effective spreaders. Even some symptomatic positives might not be.

            >>from a public health perspective , it only makes sense to treat everyone who is PCR+ as potentially infectious.

            Oh, that is absolutely true! Even if partial immunity does prevent spread (or makes the risk much lower) in many people, you wouldn’t know who that applied to.

            So from a public health/policy perspective — absolutely any positive should be /treated as/ infectious. But from a science-of-the-disease perspective… if there are in fact a significant number of non-infectious positives, it could make a significant difference to how the disease acts in a population.

            And it seems like the T-cell responses should mean something biologically.

          4. confused says:

            I don’t think it’s weasel-wording. There *are* degrees of immunity in between totally susceptible and totally 100% immune. The flu vaccine doesn’t necessarily prevent infection (though it lowers the risk significantly), but it tends to significantly reduce the severity of infections that do occur in vaccinated people. And some degree of cross-immunity from different but related flu strains has been used to explain why some flu pandemics don’t seem to hit the elderly as hard as expected relative to younger people, eg 2009 H1N1.

  26. Brett says:

    The million dollar question is as follows: Are patients expressing cross-reactive antibodies better off for it, or are they worse? It’s only been 100,000 years since we left the caves for the savannah. Caves that were filled with bat coronaviruses.

    We lived with those bats for hundreds of thousands of years, as did out pre-human ancestors. If coronavirus antibody counts drop they do so for a reason. We should figure out what that reason is to be sure that lasting specificity does not have hidden pitfalls.

  27. Hib says:

    When I developed Hib vaccines a long time ago I learned from the immunologists that it is normal that after the infection or vaccination the antibody count drops in a couple of weeks/months and that repeated dosing is needed to go from IgM to IgG to B and T cell memory: the latter response being the most important to give long lasting protection. To this end the Hib carbohydrate(!) antigen had to be conjugated to a bacterial protein (e.g diphtheria toxin). For bacteria with a carbohydrate coating, the immune response creates B cells independent of T cell stimulation. By conjugating the bacterial carbohydrate to a protein carrier such as diphtheria toxin, a T cell response can be induced. In the case of a conjugate vaccine, the carrier peptide linked to the polysaccharide target antigen is able to be presented on the MHC molecule and the T cell can be activated to promote a more rapid and long-lasting immunologic memory. These well-established Hib conjugate vaccines are very safe and numerous very young children get the Hib vaccination (2-4 doses). So if we are so eager to develop protecting T-cell responses why are no SARS-COV2 vaccines based on conjugation/connecting of e.g. Spike protein with diphtheria or tetanus toxin, the latter known to boost the desired T-cell response.

  28. Barry says:

    Although the Spike protein is heavily glycosylated, the RBD by which it docks to ACE2 is bare. Mutations of the RBD seem to be mostly non-infectious, so that’s the antigen we trust viral mutants will still display.
    Carbohydrates are I think the antigens of last resort; lipophilic protein-protein interactions have bigger (negative) free energies of binding. But among the 120 vaccine efforts ongoing, we shouldn’t close our eyes to any approach that has already worked.

    1. Hib says:

      The point of conjugation/linking/fusion with a diphtheria or tetanus toxin is not to immunize against carbohydrates (these viral carbohydrates are not much different from man anyway), but the fact that diphtheria or tetanus toxins help to induce a proper T-cell response with memory effect despite the fact that the antigen to be neutralized is not capable of doing that.

      1. Barry says:

        More recently, a Stanford group has shown (in rodents) that with a sufficient adjuvant (TLR9 ligand) one can elicit an effective killer-T response to an otherwise incompetent antigen. No covalent conjugate required.

  29. Angelo says:

    Very interesting indeed! That would argue that there has been past zoonotic coronavirus transmission in humans, unknown viruses that apparently did not lead to serious disease, which have provided some people with a level of T-cell based protection to the current pandemic.

    Didn’t this smells like the Varíola vaccine, the first one?

  30. Marko says:

    OT , but this article does a good job of summing-up the situation in the US , which ain’t good :

    ““We Need Them to F–king Do Something”: Former Pandemic Officials Call Trump’s COVID-19 Response a National Disaster”

    https://www.vanityfair.com/news/2020/07/trump-administration-coronavirus-response#intcid=recommendations_vanity-fair-right-rail_b6c3d071-3c0e-4009-b24c-77564b31ceec_popular4-1

  31. Erik Dienemann says:

    I know this entry was mostly on T-cells, but Krammer’s group from Mt. Sinai, today, published a preprint of a paper where they’ve analyzed antibodies in nearly 20,000 patients and had this wonderfully pithy one sentence summary of the work. This is great news.

    One Sentence Summary: Antibody responses induced by natural mild-to-moderate SARS27 CoV-2 infection are robust, neutralizing and are stable for at least 3 months.

    https://www.medrxiv.org/content/10.1101/2020.07.14.20151126v1.full.pdf

  32. Matthew Knight says:

    According to the UK ONS not a single vet or veterinary nurse has died of coronavirus in the UK.
    That seems relevant in the context of this paper.

    1. cats says:

      If so, it maybe cats are carriers of the original less virulent virus.
      What else eats raw bats anyway? Small cats or weasels (mink, pine martins, ferrets). My neighbor’s cat has been haunting my yard the past few weeks. I moved a tarp and a small bat darted out right past my face. Certainly an AAAAHAAAAh!!! moment for both me and the bat.

      Really is time to clean my yard…

  33. Rahul says:

    Wajnberg’s team at Mt Sinai in New York has found that the neutralizing antibodies to spike proteins *do not* decline. It is the other less neutralizing antibodies to N proteins or non-neutralizing antibodies that the body allows to decline. So perhaps much of the concern around declining antibodies goes away. Surprisingly I do not see the media highlighting this story as yet. Paper:

    https://www.medrxiv.org/content/10.1101/2020.07.14.20151126v1

    1. TabeaK says:

      Not surprising in the least, I fear. This entire pandemic, the media has generated revenue on fear inducing clickbait headlines. All of them, no difference. Add to that their inability to communicate complex scientific content to lays-people….

      1. Riah says:

        Wondering if anyone has seen this newer paper which indicates 81% of people may be protected at least partially by T cells and that a T cell response looks more important than an AB response in clearing COVID. I am copying and posting here my previous comment in response to Geff (apologies for the wrong spelling Geff!) on 9July to the early July blog which I probably posted too late for anyone to notice: “Geoff, this might go some way to answering your point. Fits in with the infection pattern aboard the ship:
        https://www.researchsquare.com/article/rs-35331/v1
        Cross-reactive SARS-2 T cell epitopes revealed pre-existing T cell responses in, wait for it, 81% of unexposed individuals! The other really interesting thing is that the more severe cases of COVID-19 they looked at showed a higher level of AB response, whereas diversity and intensity of T-cell responses was associated with milder symptoms of COVID-19 ( and little or no AB response). Does this mean the T cell responses is way more important than the AB response in CoVID??? This is only a pre print but the implications are enormous – do you agree? Makes some sense given that AB’s are useless against pathogens inside cells. Only T-cells can detect those – via the MHC’s.
        A British/Scottish coy is actually trying to use a TCell approach here : https://UK.reuters.com/article/uk-health-coronavirus-britain-tcell/scottish-firm-to-trial-t-cells-as-possible-covid-19-treatment-idUKKBN24135C
        Interesting one to watch…”

    2. Riah says:

      Nor the following from a 16 June pre-print :SARS-CoV-2 T-cell epitopes define heterologous and COVID-19-induced T-cell recognition: https://dx.doi.org/10.21203/rs.3.rs-35331/v1
      “Cross-reactive SARS-CoV-2 T-cell epitopes revealed preexisting T-cell responses in 81% of unexposed individuals, and validation of similarity to common cold human coronaviruses provided a functional basis for postulated heterologous immunity[9] in SARS-CoV-2 infection
      Our observation that intensity of T-cell responses and recognition rate of T-cell epitopes was significantly higher in convalescents compared to unexposed individuals suggests that not only expansion, but also a spread of SARS-CoV-2 T-cell response diversity occurs upon active infection…..our data indicate an important role of SARS-CoV-2 CD4+ T-cell responses in the natural course of infection….Our finding that also in mainly non-hospitalized patients with a mild disease course high level antibody responses are associated with more severe symptoms of COVID-19 is in line with recent data on the correlation of antibody titers with disease severity in hospitalized patients…In contrast to the intensity of the T-cell response, recognition rates of SARS-CoV-2 T-cell epitopes by individual donors were lower in individuals with more severe COVID-19 symptoms”
      81% is very high!! Also the mild cases showed more diversity and higher levels of T cells but few or no antibodies. The severe cases showed plenty of antibodies but a poor variety and number of T cells. Does this mean T cells are far more important against COVID-19?

    3. Barry says:

      Although circulating IgG in plasma is far the easiest thing to measure, it is not what would protect one from a respiratory-tract infection. That’s the purview of IgA. It’s not established that measuring IgG is a meaningful surrogate metric.

  34. Michael Cleary says:

    The vaccine route is all well and good but harnessing the natural organic Metadichol is the best therapeutic route. It expresses the IRS1 which regulates the ACE2. Addition VDR binding to SRC leads to regulation of FURIN Finally VDR controls expression of PPARG whuch controls AR another nuclear receptor that leads to TMPRSS2 and thus all the elements needed to inhibit SARS-CoV-2 are gathered !
    Metadichol expresses FS gene that targets ACE2 Also IRS1 andIRS2 are over-expressed
    As sais IRS1 directly controls ACE2.
    Metadichol expresses 102 genes that can target ACE2. There is a wealth of potential in the armoury
    Metadichol is lipid nano emulsion of aliphatic long chain alcohols. It is simple to produce as the resource is sugar cane wax and other waste food substances, plus Vitamin E.

    Vitamin C is produced endogenously which is a vital factor when it comes to convalesence

    The Kasturba Hospital, Mumbai reported 13th June that 29 out 30 patients were tested negative ater 7 days therapeutic treatment. M is ideal as a prophlactic route to avoid viral development

    1. PK says:

      Palayakotai R. Raghavan, is that you?

      Would that be the Metadichol® that is meant to treat diabetes?

      Fkn shill, please refrain from posting nonsense spam here.

  35. Marko says:

    Nebulised interferon beta sounds promising. Small RCT but big treatment effect – not published yet :

    https://www.bbc.com/news/health-53467022

  36. daksya says:

    Based on antibody kinetics measured in a group of convalescent patients,

    “the median times for IgM, IgA and IgG to become seronegative are 4.59 (IQR 4.12-5.03), 7.78 (IQR 6.71-9.16) and 42.72 (IQR 33.75-47.96) months post disease onset.”

    Neutralizing and binding antibody kinetics of COVID-19 patients during hospital and convalescent phases
    https://www.medrxiv.org/content/10.1101/2020.07.18.20156810v1

  37. Anise Leinen says:

    Did anyone else notice this paragraph at the very end of the Mt. Sinai study??

    Conflict of interest statement
    Mount Sinai has licensed serological assays to commercial entities and has filed for patent
    protection for serological assays.

    I’m just a lowly MSW, but I’ve also worked on a lot of political campaigns… and I know what a conflict of interest is. Shouldn’t this be addressed?

  38. Dan Allen says:

    I found a study that says, “Cross-reactive SARS-CoV-2 T-cell epitopes revealed preexisting T-cell responses in 81% of unexposed individuals, and validation of similarity to common cold human coronaviruses provided a functional basis for postulated heterologous immunity in SARS-CoV-2 infection.”

    Does that mean that 81% of the population had immunity to sars-cov2 before it emerged?

    1. Barry says:

      It means that the test they used can’t discriminate among coronaviruses. They’ve found T-cells that remember other coronaviruses but which do not confer immunity to this novel one.

  39. Dan Allen says:

    The term heterologous immunity refers to the immunity that can develop to one pathogen after a host has had exposure to non-identical pathogens.

    I thought that means that previous exposure to other Corona viruses has generated Tcells that can fight covid

    1. Barry says:

      Heterologous immunity is the difference between e.g. influenza running around Europe in 1492 and the same influenza running through a naive New World population in 1493. While in Europe, a relatively few geriatrics certainly died, in the New World, ‘flu (and smallpox) killed millions.
      But this novel coronavirus acts like it’s running through a naive population. That immune memory is to other coronaviruses close enough to fool the current assay, but not close enough to confer meaningful immunity to this novel coronavirus.

  40. Dan Allen says:

    Here is what the study says. “To determine if these T-cells indeed mediate heterologous immunity and whether this explains the relatively small proportion of severely ill or, even in general, infected patients during this pandemic32,33, a dedicated study using e.g. a matched case control, or retrospective cohort design applying our cross-reactive SARS-CoV-2 T-cell epitopes would be required. Our observation that intensity of T-cell responses and recognition rate of T-cell epitopes was significantly higher in convalescents compared to unexposed individuals suggests that not only expansion, but also a spread of SARS-CoV-2 T-cell response diversity occurs upon active infection.”

    I think that means the degree of immunity that is the result of exposure to other corona viruses is not currently known. It says a specific study is required to before that information will be known. It says there are grounds for suspecting results to be favorable, which would mean there was significant immunity to sars-cov2 before it emerged.

    Am I misreading?

    1. Riah says:

      No you are not misreading. I agree with your conclusion which is why I also brought up this same study – please see 12/13 comments up from here.

      Re:”It means that the test they used can’t discriminate among coronaviruses. They’ve found T-cells that remember other coronaviruses but which do not confer immunity to this novel one.” I don’t think this can be a correct interpretation as they have clearly found that 81% of unexposed people have T-cells that cross react specifically with SARS-CoV-2 (not any old other coronavirus) epitopes (antigens). What is uncertain is how they originated (ie. through prior encounter with which Coronaviruses?) and also exactly what level of immunity these will offer in practice against SARS-CoV-2. I would imagine there is a good chance that these would offer at least some degree of protection, but that the extent would vary depending on the individual, the viral dose(as well as exactly how it gets into the body) and variety and type of different pre-existing T-cells. There are many other factors involved of course eg. MHC types, effectiveness of innate immune system, first line defences ,vitamin D status etc. I may be wrong but that is my take on it for what its worth.

      What I find even more interesting in this study is that they found that of people that had been confirmed as COVID-postive, the people that had mild symptoms or were asymptomatic had greater number and variety of T-cells but either fewer antibodies or even no antibodies. In contrast, the people that had been severely ill had more antibodies but fewer numbers and less variety of T-cells. The implications of this are interesting to say the least. It could suggest that if someone cannot mount a concerted T-cell defence they are more likely to succumb to a severe case which results in a big antibody response to try and clear it. How would the existence of pre-existing T cells or pre-existing antibodies (through immunisation or otherwise) effect this dynamic? T-cells can “see” inside cells and destroy any that have been hijacked by the virus (and which are therefore busy producing viral proteins, samples of which are presented to T-cells via MHC on the cell surface) whereas antibodies are limited to attacking antigens outside cells.
      Any other views on this?

      1. Marko says:

        Possibly the first example of herd immunity achievement worldwide could have happened recently in Iquitos , Peru. What level of infection was detected there ? 71% , as determined by serosurvey. Just about what you’d expect if there were no significant effects on susceptibility to infection conferred by pre-existing immunity :

        https://lifeinperu.com/2020/07/24/iquitos-peru-possibly-the-first-region-with-demonstrated-herd-immunity-covid-19/

        The idea , promoted by Levitt and other “reopen” shills , that the HIT is only ~20% is lunacy , IMO. In addition to the above , it is also contradicted by reams of other data showing high attack rates , from the 57% serosurvey results of Bergamo , Italy to PCR+ rates of 60-80% in settings like prisons , detention centers , choirs and the like. This simply couldn’t happen if 80% of the population was immune to infection because of prior coronavirus exposure .

        1. Riah says:

          I’m not sure that 70 % /80%(assuming they used an accurate test) seroprevalence neccesarily contradicts the study findings. Having pre-existing T-cells doesn’t neccessarily mean total immunity, just some degree of it – and nothing to preclude some of those people from also producing some antibodies. In additions, different pockets of populations will presumably have varying degrees of pre-existing T-cells. Populations will differ depending on degree of mixing with other populations.
          I personally know only 7 people I can think of who had COVID-19. In every case only one member in the family (5 male, 2 female) got it very severely while the rest of the family were unaffected/virtually unaffected.
          If you look at the UK there are virtually no deaths now now although there are plenty of cases. The daily deaths are far more relevant than daily cases which are largely a factor of how much testing gets done.

          1. Marko says:

            The antibody tests are evaluated for specificity , and that means testing for reactivity against other coronavirus strains. There’s always the possibility that someone , somewhere used a crappy serological assay , but you can’t ignore all the other evidence of high attack rates , including those determined by PCR.

            It may be that background immunity helps protect you against severe disease , though that hasn’t been proven conclusively. The high attack rates we’ve seen DO prove that there is NOT a large segment of society that is immune to infection because of background immunity. There may be a small fraction that is naturally immune. That seems to be the case with many infectious diseases. That’s not what the Reopen Cult is claiming , however. They’re claiming that such a large fraction is already immune that we only need to reach 15-20% naturally-infected to hit the herd immunity threshold.

            The Reopen Cult is pulling out all the stops. Now they’ve even got a witch doctor on their team:

            https://www.nbcnews.com/tech/social-media/dark-money-pac-s-coordinated-reopen-push-are-behind-doctors-n1235100

  41. Riah says:

    Also this is interesting re two recovered COVID individuals with agammaglobulinemia who are not able to produce antibodies – although they did receive immunglobulin treatment;
    https://doi.org/10.1111/pai.13263

    1. Barry says:

      The language may be misleading. The patients reported
      https://onlinelibrary.wiley.com/doi/full/10.1111/pai.13263
      have not merely ” X‐linked agammaglobulinemia (XLA)”, but “complete absence of B cells from peripheral blood” i.e. they’re lacking all classes of immunoglobulin. Even as the authors warn that ” B‐cell response might be important, but is not strictly required to overcome the disease”, their very language invites us to mistake IgG for the whole humoral response.

    2. Riah says:

      reply to Marco 28 July 5.36 pm comment (no “reply button under the comment so replying under my own message). 4 broad observations:

      1. At least it looks like we almost agree on this: “It may be that background immunity helps protect you against severe disease , though that hasn’t been proven conclusively.” This was precisely what I was trying to say but in slightly stronger terms. So I would replace “It may be” by ” It is likely that”.

      2. This study found pre-existing antibodies (antibodis, NOT T-cells) from 1985 that cross react with SARS-CoV-2 antigens:
      https://www.medrxiv.org/content/10.1101/2020.05.11.20086439v2.full.pdf+html See top of page 8. I don’t think anyone has picked up on this as its hidden away in the depth of this study. Pre-existing antibodies can muddy the picture too.

      3. I don’t think the epidiemologists, ( including Oxford University Proff Gupta in the recent 16 July paper) that are quoting figures like 20% required to reach herd immunity are saying this based on 80% being completely immune. Rather, they are saying 80 % will have “some resistance” which means they will not get a severe case and potentially also they get over it quickly enough to be low risk for spreading. Many of these people will still produce antibodies so it is not surprising that 70-80% seroconversion can occur. The two things are not mutually exclusive and this does not seem unreasonabe.

      4. My own experience as explained in my previous comment supports this – children and spouses of 7 COVID-19 severe cases around here did not have symptoms despite living in the same house.

      5. Cases but virtually no deaths here in the UK

      Given all the above, it doesn’t seem at all unreasonable to me that cross reacting T-cells, (and also possibly cross reacting antibodies from paper at 2 above, but to a lessor degree) might well offer a high proportion of people enough protection to prevent a serious case or death. This is a real possibility which deserves serious consideration. As does the premise that the variety and number of T-cells is paramount in successfully fighting a COVID-19 infection.

      1. Marko says:

        Cults are funny things.

  42. Albert says:

    Does anyone knows if any of SARS-1, MERS or the other “common cold” coronaviruses has ‘spikes’ or it’s only SARS-V2 with this feature

    1. Marko says:

      All the coronaviruses have them. That’s what gave them the name : “corona” = crown-like appearance on electron micrograph.

  43. Rob says:

    If some people have a fairly large degree of immunity because of a benign infection of a related virus, it’s too bad we haven’t identified the prior virus. Then we could have parties organized around that instead of the reported covid-19 parties. Like cowpox and smallpox.

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