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Covid-19

Autoantibody Problems

Here’s a preprint from a large team at Yale with a close look at a less-studied aspect of coronavirus infection. It’s been well established by now that a feature of severe cases is a misfiring immune response (the “cytokine storm”, etc.), and one reason that fatality rates have been going down for hospitalized cases is better management of this problem. But the details are still being worked out – and since we’re talking immunology, there are a lot of details.

And it looks like one of those details, potentially a very important one, is a striking correlation with autoantibodies. Those are antibodies to a person’s own proteins – the sort of friendly fire that you see in autoimmune diseases of all sorts (acute and chronic). This work features a new assay (Rapid Extracellular Antigen Profiling, REAP) against a displayed library of 2,770 extracellular (secreted) human proteins displayed via yeast cells, providing a high-throughput method to check a patient’s own serum for antibodies to these. 194 subjects (Yale patients and healthcare workers) were screened, with a wide range of disease severity, as compared to 30 uninfected controls. The new assay showed good correlation with standard ELISA assays as a reality check.

It appears that the more severe a coronavirus infection a patient has, the better the chances that they show a wide variety of autoantibodies towards their own cell-surface and secreted proteins (see the figures above). I wrote here about a study that showed that patients with antibodies towards some of their own interferons have a harder clinical course of the disease, and this new paper confirms that work and extends it. A set of patients were examined over time, and it appears that at least 50% of these reactivities were observed early enough in the course of the disease that they may well have been pre-existing. Around 10% of them were seen to increase over time, though, suggesting that the coronavirus infection was bringing on such autoimmune problems. Interestingly, about 15% of the antibody titers seemed to decrease over time, and I’m not sure what to make of that.

The paper goes on to make connections between specific autoantibodies and immune function – for example, some of the ones that target specific proteins on the surfaces of immune cells are associated in patients with decreased numbers of those cells. The team also looked for correlations between antibodies to specific targets (or those associated with specific tissues) and clinical outcomes. It’s a complex thing to untangle, though. If you think about some specific circulating cytokine protein, antibodies to it could help to clear it from the bloodstream more quickly, or to bind to it in a way that keeps it from working (either partially or completely, which seems to be the case for the interferon autoantibodies), or at the other end of the scale, to bind to it in a way that doesn’t interfere so much with its function and could even stabilize its levels in the blood.

But overall, there was no well-defined set of “COVID-19” antibodies that showed up in infected patients but not in controls, and no obvious ways to match up antibody profiles to specific outcomes. Some of that difficulty, though, may be due to the wide variety of responses seen. Instead of broadly obvious trends, what shows up are a great number of individual responses that can add up to real outcomes, but which are very hard to untangle. Immunology!

One of the things that needs to be done, then, is more extensive profiling in the population. I would assume that ideally you’d want to get a good-sized sample of healthy people, profile them for autoantibodies, and then watch over time to see what happens. This isn’t just a coronavirus story at that point. Are there people who have greater susceptibility to various diseases, or to worse outcomes, if they have particular autoimmune fingerprints? Or will it still be a big tangled ball of yarn if you try to track these things down? At the least, I would expect that if there is indeed a population who have some sort of partial failure of immune tolerance and thus show existing high levels of auto-antibodies, then they would be at greater risk of severe coronavirus infection. How many such people are there, and how many of them are currently unrecognized?

Beyond that, there’s the possibility that some of the autoimmune effects are being actually brought on by the infection. We already know about some of the larger, more obvious examples of this sort of thing (such as Guillain-Barré and others), but profiling via an assay like REAP could help to shed more light. There are already several mechanisms known for such tolerance failures, but it’s for sure that there’s a lot more to learn, and I would think that a good-sized longitudinal study might have a lot to tell us. (Of course, I’m not the person who has to go out and get funding for it, so that’s easy for me to say!)

84 comments on “Autoantibody Problems”

  1. Dave says:

    Pfizer trial guinea pigs have to wait to get the vaccine like everyone else

    They just told me that they will NOT unblind me nor give me the real thing if I had the placebo (as I suspect). Not until I would get it anyway.

    That is not what I was told when I went in to get the first dose. Now what do I do if Moderna is available but pfizer is not? I don’t know that I didn’t get the vaccine. I don’t know if the two cross-react. I think the answer is ” NEVER TAKE PART IN A PFIZER TRIAL *

    1. MeChem says:

      I watched the FDA hearing. Pfizer requested to vaccinate the placebo group but it was the FDA who disagreed and argued that long term data collection was more valuable. Unfortunately, for you, this would have happened in any clinical trial.

      1. David E. Young, MD says:

        Screw the FDA. Unless that is in the consent form, they can’t make you do that.

        It’s very simple. If the consent form stated “If you are randomized to the placebo injection, then you agree to not get the real vaccine until the time comes when we feel it is okay to get it, even if that is long after everyone else gets vaccinated” then you would not sign the consent. You would not consent to be on the trial. And, there would be no trial. They can’t change their mind later on. Especially the FDA. The FDA cannot make that provision. Peto in Britain cannot make that provison.

        So, Pfizer should be able to provide you with the vaccine no later than anyone else. In my opinion, you should be able to get it rather quickly,

        Do note. If you get the vaccine you are still on trial. You still get phone calls, app forms and visit. And…. you still get paid for those.

        Stay with it, but get your vaccine.

    2. Giannis says:

      Get an antibody test. If you are positive for anti-Spike antibodies then you either got a natural infection at some point or got vaccinated. I think what FDA did is deeeeply unethical.

      1. Jurgen says:

        Why would it be unethical to ask the Pfizer trial guinea pigs group to stand in line until its their opportunity to get the vaccine, depending on their individual profile?
        And once it’s your chance, I guess you will be informed that you already got the vaccine or not.

      2. debinski says:

        I’m in the Pfizer trial and was 99.9% sure I got the placebo but I got an antibody test recently that was negative so now I’m 100% sure. However, you can drop out of a clinical trial at any time and if you are eligible to get a vaccine outside of the trial, Pfizer is obligated to break the blind. But I was told by the study coordinator on Monday that Pfizer would vaccinate anyone who qualified according to local guidelines (and would continue to follow them in the study), and they were hoping to be able to vaccinate everyone at their 6 month visit at latest. But the FDA will have to approve that as a protocol amendment and may not. I think it stinks if they don’t. We put our health on the line and now we are being told we get no benefit from it whatsoever!

        1. David E. Young, MD says:

          Phoey on the FDA. I you were not allowed to get a vaccine after the approval, then that should have been part of the original protocol and consent. The fact that it was not conveyed means that Pfizer should not depend on the FDA to go ahead and provide the vaccine. Remember, if you were informed that you could not get the vaccine for a period of time after approval if you were on placebo, you would not have consented. I would not have consent. No one would consent.

          I asked Moderna if I could get another vaccine if the Moderna vaccine was not approved and they said “we can’t stop you….. go ahead. We understand.” So, I consented to be on the study.

          1. Ian Malone says:

            “Remember, if you were informed that you could not get the vaccine for a period of time after approval if you were on placebo, you would not have consented. I would not have consent. No one would consent.”

            Actually, I would, because a major reason for taking part in this kind of trial is to help others. So far we only have evidence this vaccination works in the short term, and short term data on any side effects. People staying in and on placebo to the end are important. This is quite a different scenario to some life-saving treatment where if you have established beyond doubt it works then it’s unethical to deny it to people on placebo. I find it really strange to see this viewpoint that they must now vaccinate everyone when a few months ago commenters here were shouting for challenge trials.

            Of course people’s circumstances are different, and if you’re in a high-risk group then I can completely understand wanting to get vaccinated as soon as possible. You can’t be forced to continue in a trial, you can withdraw consent at any time. Above all, if you do get vaccinated and are in a trial then let them know, because otherwise you will screw up the data, we don’t want Pfizer to wrongly conclude the vaccine efficacy disappears after six months because unbeknownst to them all the placebo participants got vaccinated and now they’ve got the same infection rate as the treatment group.

          2. Sc says:

            Speaking realistically, the placebo-controlled trial could only tell us if and how well it works across the short term and if there’s an acute safety signal. If those came through we were always going to roll it out, and if they didn’t it would be DoA. Maybe if there were some in between response we’d need more data? But with 95% efficacy and no serious safety issues that decision was trivial, especially now that we have days exceeding 9/11 in deaths. At this point any more useful information we get will be from the much larger sample in the general population.

            I got the real thing in the Pfizer trial based on side effects, but was definitely given the impression that I would be first in line when an approval came if I were in the placebo arm. I personally would have still signed up if they didn’t say that but it does feel like they have been at best careless in how they communicated about this. It’s a bad look to make promises (or implications of promises) you can’t keep to get people to participate in your trial, especially when they have a potentially non-medical interest in getting it set up quickly to get results before the competition in addition to the normal good reasons to want that.

        2. DrOCto says:

          ”No benefit whatsoever”?? You had a 50% chance to be first in line for a vaccine, which I’m sure you knew, and was the reason you ”put your health on the line”. I agree that you shouldn’t be punished for being in the placebo group, but neither should you be bumped forward in the queue ahead of people that are more at risk.

          1. debinski says:

            I was hoping to get the real vaccine but I also wanted to help “the cause” and do something to end the pandemic. The 2 are not mutually exclusive. And it was a difficult/scary decision to make because there were no published data, not even in animals, and not even a preprint, when I received the vaccine. My family thought I was nuts. The efficacy is so clear now, at least short term, and even safety is pretty well established outside of rare events that I don’t buy that continuing a placebo group for years is critical. And I do have risk factors, but they may not be on the official list. But I heard today that placebo subjects will get active no later than their 6 month visit, so I can live with that.

      3. Samuel says:

        As far as I have read, antibodies produced in response vaccination are not the same as those produced in response to natural infection. Antibody tests currently being used only test for the latter is I’m not mistaken, so getting tested is pointless.

        1. Antibody guy says:

          Um, no. The antibody response to spike protein-based vaccine will be focused on the spoke protein by design, but will register (barring a false negative) as a positive result in a COVID antibody diagnostic test in exactly the same way as antibodies resulting from response to infection.

          1. Pharmcurious says:

            THE spike protein, or part(s) of the spike protein?

    3. Pv=nrt says:

      If you indeed decide to take yourself out of the trial (I would), then just please be honest with them and let them know what you did. Let’s not add noise to the data.

    4. MagickChicken says:

      Weird. I asked my nurse the same question about unblinding after EUA when I interviewed (mid-October), and she said, “We don’t know if we’ll be allowed.”

      Maybe you had a crappy nurse.

    5. David E. Young, MD says:

      I heard otherwise. I would check again. I heard that Pfizer will unblind and will notify placebo participants that they can get the vaccine, and get it rather soon.

      You signed a consent that did not indicate that you would not qualify for the vaccine. They can’t change their mind. Contact the IRB if otherwise.

      I am on the Moderna trial and am 95 percent sure that I got the placebo. They have already told me that I can get the actual vaccine, and rather soon, I think.

    6. David E. Young, MD says:

      I’ll ask it again, “are you sure?”

      I believe that pfizer will honor their responsibility to tell you if you got the vaccine or a placebo and either offer you the actual vaccine, or allow you to get a different vaccine. That’s what I’ve heard.

      I received an email, with an attachment, that made it clear that Moderna would offer me the actual vaccine if I was assigned the placebo. i received that email about 2 to 3 weeks ago.

      They didn’t say when but there was no indication that it might be a long wait.

      1. Dave says:

        Yes I am sure. They said first it would be medical professionals. Then nursing homes. And eventually I would qualify. They said they will follow “local guidelines”. Not some FDA rule. Not some law. “Guidelines”. I am 64 and a diabetic, so I am concerned. And the Doctor leading the trial locally told me (and my son) if they got the EUA they would immediately unblind and I would get the read thing if I got a placebo (which I am pretty certain I did.)

        1. guneapig says:

          Supposedly this is the current plan. Note ‘discuss’ rather than ‘get’ at Visit 4…

          https://www.covidvaccinestudy.com/participants

          1. paperclip says:

            Well, I think they mean “discuss” because they can’t force you to do anything. It sounds like at 6 months the vaccine will be available to all those who were randomized to placebo. I’m not sure whether they will say “If you delay even longer, it will help the study” or “Of course, you fool, take the vaccine.” I’m in the study, suspecting I got the placebo, and my 6 month visit is in March. I’d probably agree to the vaccine, as my next visit wouldn’t be until September 2021.

        2. Michael says:

          Your local health department had to file a plan for vaccine allocations in compliance with the CDC’s vaccine allocation decisions, in order to receive doses to give.

          When you would otherwise be eligible for the vaccine, they will unblind and let you get it.

          In the meantime, there’s a 50% chance you got it before everyone else.

        3. David Eugene Young says:

          I just got an email from Moderna today informing me that the study will be unblinded and I can ask if I received the placebo. If so, I can get the actual vaccine in one to two weeks after approval (which should be tomorrow). I am happy on how Moderna is handling it. (I am pretty sure I received the Placebo).

    7. guneapig says:

      When I signed up for the Pfizer trial, they said we’d get the real vaccine if we were in the placebo arm (were the vaccine approved), but they couldn’t say when that might be. Pfizer sent a letter a month or so ago that basically said the same thing “we don’t know when we can give it to you, but still promise to do so when the regulators let us”.

      I was under no illusion that we’d get to jump the line, but one recent e-mail says they will un-blind on request when it’s your turn to get the vac, so if you are a frontline healthcare worker, you could find out real soon now. The rest of us might need to wait until 6 months post 2nd dose (so still March-May-ish for most), unless our CDC number comes up sooner.

    8. idiotraptor says:

      Go back and ready your informed consent form for details.

      1. MagickChicken says:

        My informed consent from the trial (Aug 4) makes no mention of a cross-study at all. Either “You get the vaccine” or “You get the placebo.”

    9. David Eugene Young says:

      See? I was right. You can get your vaccine early:

      https://www.yahoo.com/lifestyle/did-2020-covid-vaccine-sooner-183115747.html

  2. partial agonist says:

    I am participating in the Janssen trial, injection next Monday. They told me if I qualify for an approved vaccine, then I can request to be unblinded and they will let me know if I am in the placebo group. I hope that the FDA does not require otherwise.

  3. Toni says:

    If I understand it correctly, there is the risk of auto-antibodies against interferones – possibly as a result of phenocopies as already known from other infections. And now we see more autoantibodies against other targets.
    In this context, it may be interesting to note that some literature is pointing to the role of so-called Netosis or NETs (Neutrophile Extracellular Traps) in Covid. e.g.:
    https://stm.sciencemag.org/content/12/570/eabd3876.full
    https://www.genengnews.com/news/in-covid-19-blood-clots-may-form-via-netosis/

  4. Nathan says:

    I wonder how much might be discovered about immunology if we put a quarter of the funding the NIH puts into cancer into researching a coronavirus version of the common cold.

    Seems like there are truly fundamental responses to viral infections that are “poorly known” or genetically diverse in nature, which would benefit from a big(ger) data approach. We should thoroughly analyze the response to simple, mostly harmless diseases on a genomic/proteomics basis.

  5. Erebus says:

    >Beyond that, there’s the possibility that some of the autoimmune effects are being actually brought on by the infection.

    Anecdotally, my wife experienced a case of autoimmune alopecia areata a month after she came down with a very mild case of Covid-19. It took three months and a couple runs to the dermatologist for corticosteroid injections before that cleared up. (And we weren’t sure that it would clear up, because, for a time, it was progressing rapidly.)
    I’ve heard that there are many similar accounts, so there might be something to this.

    1. Irene says:

      I do know someone who lost a lot of hair after COVID-19, but not in patches, just all-over hair thinning. I wonder if that is the same mechanism, or a different type of reaction. She just cut her hair shorter and waited it out.

  6. Lane Simonian says:

    If a person already had the coronavirus and then got the vaccine would that be too many antibodies?

    1. Lane Simonian says:

      The dengue vaccine is a cautionary tale of what can go wrong.

      https://www.npr.org/sections/goatsandsoda/2019/05/03/719037789/botched-vaccine-launch-has-deadly-repercussions

      This is of course comparing apples to oranges, but you have to carefully consider which groups were excluded from the coronavirus vaccine trials because maybe there was a good reason for excluding them then and now.

  7. Barry says:

    Levy (Stanford) has reported that a sufficient TLR9 ligand (CpG)–given without any antigen–can elicit immune attack on a tumor the rodent had previously tolerated. I don’t know if that includes Abs. But all Hell can break loose if the immune system mounts a storm.

  8. debinski says:

    It seems like someone could take advantage of all the blood being collected in that vaccine trials for antibody testing and look at autoantibodies also.

  9. Roney says:

    Those decreasing 15% antibodies might be of IgM-autoantibodies?

  10. Brett says:

    >Beyond that, there’s the possibility that some of the autoimmune effects are being actually brought on by the infection

    Not just this (COVID-19) infection. My daughter had an HHV-6 infection (then mono) a few years ago and she subsequently developed idiopathic hypersomnia and POTS (also widely observed in COVID-19).

    Kem’s lab at University of Oklahoma has been showing for a few years now that POTS patients have autoantibodies against various GPCR’s important in blood pressure regulation (PMID 24572257, PMID 27702852, PMID 29618472).

  11. Bob says:

    One silver lining of this pandemic might be a much better understanding of immune disorders underlying all kinds of diseases. I hope the research keeps up after this dies down.

  12. CLS says:

    Where, in all of the corona investigations, is the focus on vitamin D levels ?

    It has been known for decades the active metabolite of vitamin D moderates cytokine production.

    One study reports vitamin D deficiency results in a 3.7 fold increase in Covid ICU patients.

    Nearly a full year into this pandemic and no requirement by medicine, health authorities and governments to test blood levels? And to supplement at least a billion humans who are deficient?

    Prevention not worth a nickle but trillions in treatment.

    1. Wallace Grommet says:

      Vaccines are a preventive measure, or are you suffering from vitamin D overdose?

    2. Bill says:

      It begs the question. If government distributed Vit D supplement broadly, would our hospitals have many more open beds? Would the death count be a fraction of what it is? There are certainly indications supporting that.

      1. Jane says:

        Or you could just go stand outside for 15 minutes every day.

        1. Eric Kishel says:

          Try living in Buffalo Jane! Ha

    3. Charles H. says:

      The US govt. has already required that many foods be enhanced with vitamin D. If you’re deficient, you may need to check your diet. Excess vitamin D is reliably associated with many health problems. (Perhaps my problem with bone spurs is related to a moderate excess of vitamin D. I’ve cut back a bit.)

      Vitamin D is largely a dietary issue. Eat more cheese or drink more milk. And get out in the sun at least a bit every day. Precursors can be converted to the active from by exposure to the sun. Of course this also depends on where you live. Northern sunlight in December isn’t very effective, so you need to be consuming the active form. From Wikipedia:

      In general, vitamin D3 is found in animal source foods, particularly fish, meat, offal, egg and dairy. Vitamin D2 is found in fungi and is produced by ultraviolet irradiation of ergosterol.

      1. metaphysician says:

        Also, correlation != causation. A link between low vit d and worse covid 19 outcomes does not mean vit d supplements would improve outcomes. An equally plausible hypothesis is “low vit d is associated with old age and/or poor health, both of which make one vulnerable to covid and neither of which can be fixed by vit d supplements”. An 80 year old on vit d is still an 80 year old… and even if a clinical vit d deficiency makes one more vulnerable, doesn’t mean supplements will help someone who isn’t deficient.

      2. Marko says:

        “Vitamin D is largely a dietary issue. Eat more cheese or drink more milk. And get out in the sun at least a bit every day”

        Dietary sources, including supplemented foods( in the US ) like milk, come nowhere near providing enough Vit D to prevent insufficiency in most people. ~90% of Vit D in most people results from sun exposure, and sun is an inadequate source in winter for most people in the northern latitudes ( above 35-40 degrees ) and especially so for darker-skinned people.

        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091001/

        Combine this with the fact that the blood levels considered to indicate deficiency (<20 ng/ml) or insufficiency (<30 ng/ml) are set based on bone health criteria, not immune health criteria. Studies in humans exposed to Cov-2 suggest increasing benefits from higher blood levels of Vit D up to ~50 ng/ml. If all you consumed was egg yolks and milk you'd still never achieve that level.

      3. Irene says:

        I think a lot of the hype about vitamin D for COVID-19 approaches woo. That said, as I have several risk factors for having low vitamin D anyway, I take an ordinary supplement (not a mega dose) and trust that if there is any validity to the vitamin D thing that I will have some protection, and if not, I am not taking enough to do any harm.

  13. Marko says:

    These people in trials whining about access to the vaccine brings to mind a vision of rich white guys on the Titanic, knocking over women and children in their efforts to secure a spot in a lifeboat. Understandable at a certain level, but undignified in any case.

    1. Michael (but not the other Michael in these comments) says:

      That’s really harsh, Marko, and I usually find you very reasonable.

      First of all, many in the trials *are* at high risk due to age or comorbidities. Many don’t fit the mold of the Titanic tuxedo set.

      Secondly, these volunteers entered the trial with limited safety and no efficacy information. And many of them got ill (and maybe got their families ill) thanks to not getting the real thing. With future phase III trials likely to compare new vaccines to approved vaccines, I don’t see why these participants need to be *disadvantaged* compared to all other trial participants going forward.

      1. Marko says:

        “First of all, many in the trials *are* at high risk due to age or comorbidities.”

        And based on that risk profile, they will have access to that vaccine when those in the general population ( i.e. , the “women and children” )with the same risk profile gain access.

        “Secondly, these volunteers entered the trial with limited safety and no efficacy information.”

        You can tell from the comments that have been posted here why most people entered the trials. Not to advance the science, but to be first in line for a chance at a protective vaccine. How can you tell? By the reports of people scrambling for ways to tell whether they’re in the vaccine group or the placebo group. If you’re simply interested in advancing the science, you’d be content with your role in the placebo group, and content to wait with everyone else for your number to be called for the vaccine once approved for your risk group.

        My comment sounded harsh? Good , that’s what I intended.

        1. debinski says:

          You have no idea what you are talking about. I did hope to get the real vaccine IF it was safe and effective, both of which were unknown in early August when I signed up. There was much more of a question with the mRNA vaccines. I also knew I may get placebo or may get a vaccine that was unsafe or ineffective. I entered the trial anyway not only because I was hoping for some prevention for myself, but also because I could be helpful to the discovery of a vaccine, regardless of what I got. So what about the vast majority of the US population who didn’t sign up (yourself included)? They are the true warriors? Why didn’t they selfishly sign up for a study for that 50% chance to get a vaccine? Let’s thank all the people who did NOT sign up for a trial.

        2. Sc says:

          You are out of line. This is about people feeling they were promised something and then not being given it, not demanding something above and beyond. At the very least it is a failure of communication on Pfizer’s part which is itself a legitimate ethical problem when you’re asking for people to take a risk like this. Pfizer had (in addition to others) a financial interest in getting as many people to join as quickly as possible, which is why it is very important to cross all the ts and dot the is on that being done ethically, and why if they didn’t it’s a big problem.

          Judging peoples’ imagined motives for participating is peurile, especially if you haven’t participated yourself.

          1. Marko says:

            “At the very least it is a failure of communication on Pfizer’s part….”

            I have no issue with complaints like this, if legitimate. However, I have yet to see an actual consent form posted online , to be able see if the wording was, in fact, misleading.

            This letter from Pfizer suggests that, to some extent at least, the decision about what to do about vaccine participants’ access is out of their hands, requiring regulatory approval :

            https://beta.documentcloud.org/documents/20418679-pfizer-letter-to-participants

          2. guneapig says:

            According to my Pfizer Informed Consent documents (I just checked), there is nothing at all about participants in the placebo arm getting the real vaccine if it’s approved.

            It was something I specifically asked about with the investigating Dr. beforehand because it wasn’t in those documents. At that point all they could say was that was the plan but they had no more information.

            I signed up chiefly because my Dad, a scientist to the end, said he “always wanted to be somebody else’s data-point”, but sadly the carcinoma was too far advanced by the time the trial got underway. Doesn’t mean I’m not somewhat interested to know which I got though.

    2. Micha Elyi says:

      Marko, on the Titanic’s fateful voyage a female travelling third class was more likely to survive than a man travelling first class.

      Pro tip: Movie dramas are not historical documentaries. They’re fiction.

  14. sgcox says:

    Comments in this thread are amazing and interesting sign of the troubled times we live.
    Derek posted a very nice and timely post about the clinical immunological pattern induced by SARS-CoV-2 infection. Very relevant and important topic which can clearly help us to understand and treat this terrible disease.
    Alas, all comments so far were about will the placebo participants receive vaccine shot now or later…

    1. Marko says:

      Haha, yes, Derek must be saying : ” What am I , chopped liver ?”

      It is ironic, because the paper he discussed may end up being one of the most important to come out of the research on the pandemic to date.

  15. Dave says:

    I note the comments are relevant to Derek’s post because no one knows what will happen if you get the real pfizer and then moderna becomes available in your area. (Which very well could happen). Will you *cause* a problem when your immune system sees the Moderna vaccine if you have already been vaccinated by the pfizer vaccine?
    But regardless, the Dr. running the local study told both my son and I that when the EUA came, we would be unblinded and receive the real thing (if we had been given the placebo.) We were told this on the phone when we signed up, too. I feel they did a bait and switch on me. And I thought the risk of trying out a new vaccine variety that had never been tried before was worth it, for that pay off. One member in my family did not, specifically because we needed to have someone alive to take care of another family member who needs care, in case we two died. It was not a decision without risk. I am 64 with diabetes, so I do have co-morbidities. But who made the decision to break the promise made to me so as to give the vaccine to someone else (not a health care worker working with Covid patients… I understand that).

  16. Marko says:

    ‘We want them infected,’ Trump HHS appointee said in email pushing to expose infants, kids and teens to Covid to reach ‘herd immunity’

    https://www.cnbc.com/2020/12/16/we-want-them-infected-trump-hhs-appointee-said-in-email-pushing-to-expose-infants-kids-and-teens-to-covid.html

    ” “Alexander wrote in a July 4 email to Caputo and six other HHS communications officials that the U.S. needed to establish herd immunity………”It may be that it will be best if we open up and flood the zone and let the kids and young folk get infected as we acutely lock down the elderly and at risk folks” to get to “natural immunity…natural exposure,” he wrote on July 24 to Hahn, Caputo and other HHS officials. Caputo asked Alexander to look further into the idea, further emails show. ”

    “Flood the zone” ? That sounds just like Steve Bannon and what his army of disinfo agents do every day, here and almost everywhere else.

  17. Trebitch says:

    “No matter what age, there is at least about a 10 times or larger chance of dying from something else then COVID” from: https://wmbriggs.com/post/33849/

    Soldier on with your vaccines! Nobody will ever die from anything ever again!!!! Just mask on and hate your neighbor, keeping exactly six feet away!

    The insanity of it all is a wonderful illustration of our lord’s words: “My kingdom is not of this world”

    1. Marko says:

      COVID-19 Was the Leading Cause of Death in 20 U.S. States Last Month

      https://www.newsweek.com/covid-19-was-leading-cause-death-20-us-states-last-month-1553664

      But, if you combine all the other causes of death, in a comparison that makes no sense whatsoever, you can try to minimize the impact of the article above. Some morons may even buy into it , so why not give it a try ?

      1. Trebitch says:

        Newsweek is the gold standard of unbiased, no-nonsense, no panic truth! You are so right!

    1. eub says:

      That sharp post-May(?) knee in the “not classified elsewhere” black line is unpleasant. Either that’s COVID deaths being missed, or it’s valid non-COVID classifications that occurred because of COVID (aftereffects or pressure on the medical system), or 2020 has something additional to lay on us.

      1. Marko says:

        My bet is that it’s mostly Covid deaths that are misclassified. I’d like to see how the numbers break down by states, to see if it’s mainly a problem in red states, like Florida, where reports of political pressure to massage the numbers have emerged.

        These numbers are only from Orange County, but they argue against a sharp increase in deaths from other causes inflating the excess mortality data :

        https://twitter.com/AndrewNoymer/status/1339999207881547776

        1. eub says:

          I don’t know how to deep-link into their Tableau graphs, but some comparison on the CDC’s “Excess Deaths Associated with COVID-19” (linked from name) suggest yes, when Florida has a Covid wave, its cardiovascular and dementia deaths also rise above expectation, 15% of the Covid rise.
          California shows roughly similar behavior, however.

          Compare “Excess deaths with and without COVID-19” and “Weekly Number of Deaths by Cause Group”, filtered by “Select a jurisdiction”.

          (Of course Florida has been playing various games with their data reporting, so who knows how much it should be relied on to support comparisons like this.)

  18. Marko says:

    “Fourth, many, if not most, COVID-19–related deaths could have been prevented…”

    https://jamanetwork.com/journals/jama/fullarticle/2774445

      1. Marko says:

        Sorry, that’s a duplicate link. I meant to pose the link for the SA article (from Oct.) referenced in the Topol tweet , above :

        https://www.scientificamerican.com/article/covid-19-is-now-the-third-leading-cause-of-death-in-the-u-s1/

        So , in Oct. Covid-19 was the 3rd-leading cause of death. Now it’s #1.

  19. Aaron Smith says:

    With no referenced test and the PCR test unable to detect even 1 whole transmissible virus. Using and solely relying on a test that can’t be used to create “cases”( wait… thats exactly what these fraudsters are doing)there is no ” covid19″ . And whoever says ” Its the flu bro’ may well be right with the total absence of science in the matter of “covid19”.
    The first problem with these studies is that they use a reference-less test (PCR) and claim the subject has it “covid19″ just from the test . Then in studies all particles( exosomes) they find are said to be ” sars cov2 virions” Please this covid19 hoax must be getting embarrassing for people to keep it going with a fraudulent PCR test .
    https://notpublicaddress.wordpress.com/2020/12/17/lancing-a-lancet-hoax-study/

    1. Chris Phoenix says:

      My father died of COVID. His wife called his brother-in-law to see if he’d gotten a memorial CD. The brother-in-law told her, “I don’t know what the big deal is, it’s just the flu.”

      Take a person, scoop out his brains and replace them with right-wing talk-show propaganda, and that’s what happens. It would be disgusting if it weren’t so pitiful.

      1. Micha Elyi says:

        Chris Phoenix, avoid the political hysterics please. It dims ones own intellect.

  20. TL says:

    Biden’s new science posts are a scientific disgrace. No bench experience for one. Pompous MDs more worried about elite education and leftist values. Pray that the current vaccines work, because there will not be more quickly approved under the Biden leftwing anti-science slugs of an administration.

  21. RHB says:

    Received loud and clear. Drills down to:

    https://www.youtube.com/watch?v=kANkpqtWLN4

    Only 10 minutes in so far, will work through over festive period. Boils down to… T cells and prior immunity… asymptomatic spread myth… PCR all over the place in concept and practice… hidden agendas and actors (we’ll never know), controllers and responders… political and scientifical hubris… and/or just the Alan Bennet school of history as one f****** thing after another, as per The Sleepwalkers in run up to WW1.

    Good luck with taking forward to all GerBrits and other nationalities involved. Am keeping a regular watch on the badlands and the sheep.

  22. Bertie Wooster's Diary says:

    Front page of yesterday’s London Times:

    ELDERLY TOLD NOT TO VISIT FAMILY AT CHRISTMAS

    More of the same as 9 months ago on Mothering Sunday, same source – you’ll know who I mean, HIM AGAIN, went to that posh school (none posher), did that Classics degree at that posh university (ditto), got a 2.1 but complained he should have got a first, went into career as glorified gossip columnist, blagged his way into politics, blagged away ever since, and blagged on the message from unwhittingly doctors, unvallanced SAGE scientists and associated nannies, killjoys and delusional psyche controllers…

    STAY AWAY FROM MUM ON MOTHERING SUNDAY

    I ask you – how did we get to this? 9 Months of a*se about face government and counting. For the record, and at risk of hubris (as ever), unless obvious threat of illness of any party intervenes, the 90something will be visiting the 60something and the 50something on Christmas Day, where partaking of lunchtime turkey and usual trimmings will also be the 20something and the nearly 20something. Afterwards we might all nip outside to binge a while on the fading winter light and the old Vitamin D.

    Sheep update as passed on by RHB: Sheep since escaped from badlands. More than once. Last time, Jeeves caught ’em at it through the old binoculars, but by time Jeeves got up there with the yard brush whole flock out and about up at the Hall (and mercifully taking elevenses on the Hall’s flower beds not ours…). So Jeeves instructed to summon Farmer Giles, who kindly popped out later that morning.

    Netting duly put along entire south side of the badlands to supplement strands of slack barbed wire and rickety fence posts. With sheep you never can be too cautious.

    Have to say do not get why sheep wander to this side of the badlands in the first place to graze on an old and badly neglected potato field, that’s by now mostly soil, flock having already grazed away at hearts’ content at few years’ worth of docks, nettles and thistles. Most of flock now seem to be nibbling away contentedly at soil. Soil eating sheep, how very odd? No wonder the flock’s leaders want to get out.

    Anyway, leaves Bertie and Jeeves to focus for now on that other, more concerning, flock of 67 million, among whom Bertie only knows in person of six Brits for certain that truly think for themselves about this virus business.

    Thankfully quite a few online thinkers for themselves evident on Twitter, Lockdown Sceptics and In the Pipeline, some, clearly, thinking very clearly, and a few heroes and heroines plotting the flock’s escape from eating soil.

    Meanwhile Bertie himself in person can see through the binoculars the leaders of the real-life flock of real-life sheep’s real-life leaders eyeing up the netting and plotting the next Great Escape.

    Better send Old Jeeves up there to do a bit of the old dispersuading with the old yard brush…

  23. Gb says:

    Here is an interesting anecdote– I had an uncle that was dying during the pandemic of a relatively uncommon disease for a 45 year old ( not covid ). I am a PhD and i wrote educated polite emails asking for help from 3 separate people. 2 were experts in the relevant field of his illness employed at top institutions. 1 was at the FDA but not as expert. I got no response from the high institution “experts”. The fda guy helped me, but again he didn’t have the specifics because he wasn’t am experts. Later this uncle died. I think that speaks volumes about the arrogant garbage that inhabits our ” doctor class “. I’ve experienced this many times, not just in this example.

  24. watsoneee says:

    So if someone had a severe case due to autoantibodies, will the vaccine trigger this same response? Is it safe for them to get?

  25. Karen Gatewood says:

    I’m a little confused.. can someone help? To my simple mind I can’t get around this.. our cells are getting a message to make a protein. Wouldn’t that be considered to be a self protein even though the message was introduced via vaccine? We then make antibodies to a protein we created. Isn’t that an autoantibody? Once our bodies have done this, what is preventing our bodies from going into a kind of overdrive where it starts making autoantibodies to other proteins we make? Did the vaccine research assure us we wouldn’t initiate an autoimmune disease?

    1. Derek Lowe says:

      Ah, the key is that the vaccine is forcing cells to make a new protein. All the body’s own proteins are “grandfathered in” as far as the immune system is concerned (or they should be, ideally). It’s the appearance of a new one that sets things off.

      1. covidvaccinesyndrome.com says:

        you are wrong buddy. even in covid infection, the spike proteins are produced by our own cells. this is how the virus replicates by giving instructions. the answer to the question of whether we generate antibodies against the covid vaccine is still unknown.

        1. Doug H MD says:

          umm, no that question is well answered. we know we generate Abs to the vaccine.

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