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Blood Clots and the AZ Vaccine, Revisited

Once again, what’s going on with vascular events and the AZ/Oxford vaccine? I last wrote about this situation a couple of weeks ago, and it’s taken some real turns since then. At that point several EU countries had suspended dosing, but over the next week several began administering the vaccine again after the European Medicines Agency recommended it, in some cases with advisories about which age groups should be targeted.

But there’s more to the story, it seems. Here’s an excellent writeup at Science (open access) by Kai Kupferschmidt and Gretchen Vogel.   A possible concern is what’s being called vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) by Andreas Greinacher at Univ. Griefswald. This is a blood clotting syndrome that’s similar to what’s observed with the (already known) syndrome of heparin-induced thrombocytopenia. That problem, first over 40 years ago, is a paradoxical effect that occurs in a few people of administering heparin for blood clotting problems and actually making the situation worse. The mechanism for HIT is apparently the generation of antibodies to the complex of heparin bound to platelet factor 4 (PF4) protein. That binding sets off further inappropriate platelet activation, and that’s why the free platelet count drops (the “thrombocytopenia” part) as new clots form and existing blood clots become larger and more dangerous. You’d be used to someone presenting with thrombocytopenia to be at risk for bleeding disorders, not suffering from too many blood clots, but HIT is coming around from the other direction.

Greinacher’s team showed that patients who developed clotting disorders after vaccination showed the anti-heparin/PF4 antibodies, as in HIT, but it looks like these also bind to PF4 even when it’s not complexed to heparin. It’s possible that this happens (at least partially) via the adenovirus vector binding to platelets, but the details aren’t clear. There apparently is a subset of “classic” HIT cases who have shown this atypical PF4-alone antibody binding, so it’s a phenomenon that can happen without vaccination. The question, though, is whether vaccination is making it more likely, and whether there are particular populations who are more at risk.

Kupferschmidt passed on more information from Germany’s Paul-Ehrlich Institute just this morning. 2.7 million people have received the AZ/Oxford vaccine there, and 31 patients have been identified with cerebral venous thrombosis. Not all of those are HIT or VIPIT, though, because only 19 of the 31 had thrombocytopenia. There have been nine deaths, and as always, key questions are how many cases one would expect in the population that’s been dosed so far. Earlier this month, the figures were 1.7 million vaccinated and 7  cases of CVT, and the institute said that they would have expected about one case as normal background. The EMA, when they came out recommending the vaccine earlier this month, noted that figuring these background rates is not easy. But they found that if there is indeed an imbalance, it’s most noticeable in the younger age cohort and not in the older. The PEI mentioned today that of the 31 cases they have analyzed, 29 of them have been women, which certainly seems significant as well.

The UK experience with this vaccine has apparently shown no overall increase in thrombotic events – if anything, the vaccinated cohort has been slightly lower in that regard than the general population. But if there is an increased risk in people under 50, especially women, that’s actionable, as they say, even if the risk is very small (as it certainly appears to be). Other vaccines need to be available so that the doses can be aimed better. It’s also worth remembering that HIT (and presumably VIPIT, if it does turn out to be a real subset) can be treated with non-heparin anti-clotting drugs and/or by immunoglobin infusions, so the attempts by the EMA and others to raise awareness among physicians of this side effect are well worth it.

This is all happening against a background of increased infection in many European countries, of course. A worry is that some people will decide not to get vaccinated at all after hearing about these side effects, and regions where most of the available vaccine is the AZ/Oxford one may well see people deciding to wait for a different one, if that’s a possibility. If such things noticeably affect the number of people getting vaccinated, they could easily end up killing off more people in general than any of the vascular side effects will. But it’ll be in different groups – if the information we have now holds up, then younger women would be at small-but-greater-than-others risk of side effects, but the pandemic fatalities would probably be more in older men. A grim thing to be totaling up – more on this as we get more information.

248 comments on “Blood Clots and the AZ Vaccine, Revisited”

  1. Andy K says:

    is there any way of trying to work out if this is AZN-specific, or common to all adenovirus vaccines (i.e. J&J etc might be impacted), or to do with the antigen itself (i.e. we’ll see it with mRNA vaccines too when they get used down the age range)?

    1. Rob McMillin says:

      Not sure, but it’s been speculated that, since the AZ vaccine does not use the prefusion spike protein (J&J, Moderna, and Pfizer/BioNTech all do), it may have some difference otherwise as well.

    2. da says:

      Andy K,
      In the USA, over 55 million doses of Pfizer/BioNTech + Moderna + J&J/Janssen vaccine have been administered to people age 49 and younger. The vast majority* of these doses are Pf/BNT & M.
      So, we’ve done the experiment, at least with these other two (three) vaccines.

      And as Derek notes — essentially no signal of VIPIT/HIT above background. VAERS reports a total of 46 cases of “immune thrombocytopenia” associated [NOT caused by] with Covid-19 vaccination. That’s for all ages; ~148 million vaccine doses. Another 26 cases (some may be duplicates) have the word “coagulation” in the adverse event description. Restricting to age 49 and younger: 12 and 6 reports, respectively.

      *Total doses administered [all ages], per CDC, as of March 30:
      Pf/BNT = 75,386,890; M = 68,858,013; J&J/J = 3,215,657

      1. ^^^ “da” is me; name cut off for some reason

      2. Chris Phillips says:

        We have done the experiment with AstraZeneca in the UK too …

        1. Adrian says:

          And in the UK the Oxford vaccine also came out worse on that.

          Until a few weeks ago the majority of doses administered administered in the UK were of the Pfizer vaccine, and this is the one mainly used for younger people (under 50) so far.

          Despite that, the Oxford vaccine had more than twice the number of Immune thrombocytopenia cases than the Pfizer vaccine (28:13).

          1. Roland says:

            That’s too simplistic. Distribution differences mean the Pfizer is available in limited locations in the UK. A lot of Pfizer was given early on to young healthcare workers yes, and to non-house (/nursing-home) bound older people. Later on young nursing home staff along with very old residents, and young clinically vulnerable people received the Oxford one in large numbers. Quite long enough ago that they would have shown complications by now on the same timescale as the German cases.

            I don’t think we have any idea how the background rates of non-vaccine induced immune thrombocytopenia compare between the two populations, considering the massively complicating factor that Covid itself is a known cause (even otherwise-asymptomatic Covid), the two populations will have different risk profiles for that, and will also have different rates of Yellow Card reporting.

            The many-fold difference of characteristic widespread/cerebral thrombosis in one specific sub-population seems much more significant and the UK has dosed enough young women by now that should show up if the rate was similar to Germany. Either UK authorities are being extremely underhanded (not impossible), the cases aren’t being spotted for what they are (quite possible – but then we do need to question other vaccines for the same reason), or else this looks like some kind of batch problem, a drug interaction specific to certain countries, or maybe even an interaction with a certain Covid variant in some countries? Or it could still just be a statistical anomaly, but I think that’s beginning to look unlikely.

          2. Chris Phillips says:

            “Until a few weeks ago the majority of doses administered administered in the UK were of the Pfizer vaccine, and this is the one mainly used for younger people (under 50) so far.”

            I don’t think those figures have actually been released.

            The best indication I have seen of the time-course of AZ versus Pfizer in the UK was this plot of supplies expected for Scotland (which was hastily withdrawn at the government’s request, but not before it had been copied):
            https://news.sky.com/story/covid-19-every-uk-adult-could-be-vaccinated-by-mid-july-if-these-figures-are-anything-to-go-by-12188909

            On that basis, while it may be true that AZ didn’t overtake Pfizer until early March, AZ has accounted for more than 40% of the vaccinations given in the UK since late January.

            As for Pfizer having “mainly” been used for young people, I am sceptical unless you have definite information to back it up. I have already posted figures on the numbers of younger people vaccinated in the UK, and I’ve pointed out that a quarter of the health workers in the Siren study received AZ. (And of course, health workers would be only a minority of the 7 million under-60s vaccinated by early March.)

            But in any case, regardless of whether what you describe as the “majority” and “mainly” are in reality 40%, 50% or 60%, what’s obvious is that many more people in the under-60 age group will have been vaccinated with AZ in the UK than in Germany. So the suggestion that problems won’t have been picked up in the UK because the numbers are too small is a non-starter.

          3. bewd says:

            as of 14th March 13.7 million AZ 10.9 Pfizer 1st doses in the UK
            https://www.channel4.com/news/factcheck/factcheck-does-the-uk-have-enough-covid-vaccine

    3. TorOnto says:

      The risk of CVST in users of Oral Contraceptives is 750% higher than that of the general population. What we are learning perhaps is our lack of awareness of the risks that we are already taking.

      https://www.frontiersin.org/articles/10.3389/fneur.2015.00007/full?utm_source=twitterfeed&utm_medium=twitter

      1. Jay Lu says:

        U maybe on to something. I’m not sure, but I sure hope it’s just that simple

      2. Maureen Cronin says:

        What about anemia (iron deficient anemia) as a risk factor? (DOI: 10.7759/cureus.8917)
        Many women take oral contraceptives to reduce their heavy menstrual bleeding. Did anyone look at the vaccine cases for OC use or anemia?

        Thanks,
        Maureen

    4. oreoeater says:

      Early on there was a case of fatal thrombocytopenia in that doctor in Florida. Post vaccination and only mRNA vaccines were available in the USA then. Strange to think that this event was unrelated?

  2. Eric says:

    What’s the likelihood that this is just a classic effect of sub-group analysis? It’s particularly odd that here in the UK, where more people have had the vaccine, no signal has been seen.

    1. Marko says:

      I wonder about why it’s not seen in the UK also. Is the delayed second dose in the UK playing a role? Are most of the European VIPIT events seen in fully-vaccinated women, and does it show up soon after the second dose? Are seropositive vaccine recipients at greater, equal, or lesser risk? Is injecting the vaccine into a blood vessel a risk factor? I asked the tech who vaccinated me yesterday if they had received any guidance on aspiration before injection, and she looked at me like I was crazy, then buried the plunger. Oh well.

      1. johnnyboy says:

        Keep in mind that vaccination in the UK has been pretty tightly controlled by age group (excluding the vulnerable groups), and we’re currently at the 50 and over. So the younger cohorts have by and large not received vaccines. If there is indeed a link with adenovirus vaccines, we’ll see it in the coming weeks/months in the UK.
        Nothing mentioned about side effects of the Gamaleya vaccine, but even if they saw such events we’d never hear about it. J&J is too early to tell, but this might temper enthusiasm for it as well.

        1. Marko says:

          “As of 21st March, 2,539,057 people aged 50 to 54 and 5,410,856 people aged under 50 have been vaccinated with at least one dose. ”

          https://www.england.nhs.uk/statistics/wp-content/uploads/sites/2/2021/03/COVID-19-weekly-announced-vaccinations-25-March-2021.pdf

          Not huge numbers yet, but I’d think enough to generate a few cases, anyway. If the second dose is the culprit, it’ll take more time.

          1. bewd says:

            from all the cases reported , how come nobody knows if these events are happening after first or second dose of vaccine??

          2. Marko says:

            I suspect it is known, just not by myself.

          3. bewd says:

            reading the preprint reporting on 9 cases it suggests the adverse events are occurring after first dose of vaccine

          4. RichW says:

            BBC is commenting:
            “In the UK, five cases of CSVT – one of them fatal – have been recorded among 11 million people who received the vaccine.”

            ( https://www.bbc.co.uk/news/world-europe-56580728 )

            I cant find any breakdown of age or gender on the MHRA site though to compare or quote anything except BBC at this time.

            One thing to note is the UK AZ vaccine has gone disproportionately to the older.

            The younger people vaccinated so far are mainly health workers and the extremely vulnerable.
            The former were in the first priority group and as a result due to this, most of them had Pfizer (Pfizer was 4 weeks before AZ in rollout and also is only given in some mass centres and hospitals – where health workers work or can get to).
            So currently we haven’t given AZ to that many younger cohorts so its possible if there IS any sort of signal there we might not have seen it yet.

            You would guess if it is an issue to start to see it from May onwards when the under 50s get called forward in bulk as the vast majority of those will now receive AZ.

          5. Chris Phillips says:

            As discussed on the other thread, it’s not the case that only small numbers of younger people have been vaccinated with AstraZeneca in the UK.

            At the time vaccination was opened to under-60s three and a half weeks ago, 6.99m people under 60 in non-age-related categories had already been vaccinated (that was 37% of all vaccinations).

            The most recent figure is 10.89m under 60 (46% of all vaccinations). Half of those were under 50.

            As far as I know the UK statistics for different vaccines aren’t publicly available, but overall there have been more AstraZeneca than Pfizer/BioNTech. It’s probably true that the proportion of Pfizer among health workers is higher, but still in the recent SIREN preprint about a quarter of the participants had received AstraZeneca rather than Pfizer.

          6. HerrIvan says:

            From the tweet in German that’s in the thread from Kai Kupferschmidt, and which is a communication of the Paul Ehrlich Insitute: I Germany (as of yesterday) 2.7M first doses against 767 second doses of AZ have been administered. And yes, the 4 orders of magnitude difference is not a typo. So it can only be a problem with the first doses.

        2. stewart says:

          The UK now has a greater proportion of the population fully vaccinated than most EU countries (exceptions are Denmark, Lithuania, Spain, and any that I’ve overlooked). Vaccination of healthcare and care home workers will mean that this will include a number of younger people. But it is conceivable that these people mostly got the earlier approved Pfizer vaccine.

          1. Adrian says:

            The opposite usage happened in Germany.

            Until the beginning of this month, the Oxford vaccine was not to be used for elderly people.
            In Germany elderly people only got the Pfitzer and Moderna vaccines.
            The Oxford vaccine was used for working-age people, mainly care personnel and also groups like elementary school and kindergarten teachers. In Germany a large part of the Oxford vaccine doses went to young women.

      2. Christian Weisgerber says:

        At least in Germany, all VIPIT events should be after the first dose only. The AZ vaccine was approved on January 29 with second doses to be given after 9 to 12 weeks. (This has since been pushed up to 12 weeks.) Not enough time has passed for second doses to be given.

        Today’s STIKO press release mentions that AZ vaccinations started in early February and second doses are due in early May. Further guidance on how to proceed with the under-60s that already received a first dose of AZ will be issued by late April.

        1. Tong Wara says:

          The risk of the second dose causing VIPIt should be more or less after the first dose according to the current findings, pls?

      3. Shirley says:

        Marko, my family enjoys reading your comments just as much as Derek’s! We appreciate the well thought out remarks especially the comedy!

        1. Marko says:

          Thanks. If some of my comments have elicited the occasional laugh or smile, then my efforts here have been worthwhile.

    2. Getting carried away here says:

      If I understand right, this signal is only seen when the data is manipulated in exactly the right way, and all data is rejected except for young women in a few chosen countries. If this was a clinical trial for efficacy, and a pharma company did its analysis post-hoc to select the population that responded best to its treatment, then tried to cook up a plausible rationalization, wouldn’t the regulators be right to point out that they’d massaged their results into the most favorable shape?

      Caution is all very well but I can’t help thinking that everyone who’s assuming that this is being caused by the vaccine is being premature. It might be, but it seems too early to say.

  3. Jonas says:

    I mentioned this before:
    There was a case if transverse sinus thrombosis (so clots in that specific venous sinus in the brain) among the 30K people vaccinated with the Johnson&Johnson Ad26 vectored Covid vaccine as part of the clinical trial! (Just look up the FDA briefing for the Jansen vaccine )

    That was in a 25 y/o with no medical history.

    So maybe it is the Adenovirus. Or maybe it’s the plants where the vaccines are made.

    The UK is using mostly UK made AZ vaccines whereas tEU countries is using the ones made in Belgium mostly.

    In the UK the 5 cases of CVST recorded up to 14 March among 14 million AZ vaccinees were all in men! Go figure..

    1. Maureen Treadwell says:

      Marko, CVST is not that uncommon but in combination with low platelets and one or two other markers, it is normally vanishingly rare. So yes, male cases were seen but were they cases with these unusual features? If not, it does look like the younger female population – ie those below 50 or 55.

  4. dearieme says:

    Some British figures quoted a week or two ago implied that the Pfizer jab was equally prone to the problem. But the small numbers involved left me doubting whether the comparison was meaningful.

    The mendacity, stupidity, and hysteria of EU politicians concerning AZ: does that affect their scientists? Should I look at Canadian figures instead?

    1. Jurgen De Jonghe says:

      Canada just recommended to reserve AstraZeneca to over-55 only.
      The mendacity, stupidity, and hysteria of Canadian politicians concerning AZ ?

    2. WST says:

      AZ Canadian figures :
      “As of 3/20, No one in Canada has received the AstraZeneca or Janssen COVID-19 vaccines yet.”
      Canadians refers to EMA figures for motivation of their decision:
      https://www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/rapid-response-recommended-use-astrazeneca-covid-19-vaccine-younger-adults.html

      1. FM says:

        “As of 3/20, No one in Canada has received the AstraZeneca or Janssen COVID-19 vaccines yet.”
        This is a false statement, my mother (82yr old) received her first dose of AZ (Covishield) on Mar 15, near Montreal…
        Half a million AZ-Covishield doses were allocated to provinces prior to Mar 14. While I can’t quickly find the stats on how many AZ were distributed in arms by Mar 20, it is likely in the tens of thousands if not hundreds of thousands.

        1. bewd says:

          Health Canada said Monday that 300,000 doses of AstraZeneca vaccine have been administered and no cases of the rare blood clotting adverse events have been reported in Canada, but that it was aware of additional cases that have recently been reported in Europe.

        2. WST says:

          Oh, I’m sorry, they information came from Canadian health authority site, obviously updated with latest information.

          https://health-infobase.canada.ca/covid-19/vaccination-coverage/

          1. FM says:

            Thanks, I somehow hadn’t seen navigated to thoses stats looking at that exact site earlier.

            The text says “no one” but the graph just below illustrates the 309k doses administered (from the CSV).

            Either a case of the website admin not knowing that Covishield=AZ, or simply an error in updating the text from previous weeks.

            There are also sometimes issues with importing/normalizing provincial data, especially Quebec’s which often shows as N/A.

        3. Kelly says:

          Yes…confusing. my husband had his AZ vaccine March 16th in Canada. I was at the tail end of the distribution in our province of that limited supply, and received mine March 21st.

    3. Ono says:

      Shame to see standard anti-European tropes appear here. Brits should be asking why the MHRA was so slow reporting known cases; why it didn’t report fatalities (until pressed by the media); and why it still hasn’t reported age/sex distribution of cases or fatalities? Something ‘political’ perhaps? (Some) EU countries have been much more open with their population in the face of a clear suspicion of a catastrophic illness linked to a vaccine which is still effectively in trial.

      1. Chris Phillips says:

        I was inclined to agree until you went into an “anti-vaccine trope”!

        Whether it is well under 1 in a million as the UK figures indicate, or 4 in a million as the EU figures are said to indicate, this is an extremely rare side-effect.

        Less than three months ago COVID-19 was killing 8,700 people a week in the UK. Now the death rate is just 3% of that, and it is currently dropping at a weekly rate of 43%. That is a much more rapid rate of decrease than we have ever seen for infections, and there is no doubt it is mainly due to vaccination. If the EU had not been so hesitant about AstraZeneca many European lives would have been saved.

        1. Ono says:

          No, not anti-vax! What you and sgcox say from PH perspective is right. BUT – taking on board this (from Derek’s commentary above – in relation to UK): “If there is an increased risk in people under 50, especially women, that’s actionable, as they say, even if the risk is very small”, there are other vaccines, apparently without the same reports (in the UK), which could be targetted, plus we need to understand if AZ needs more engineering moving forward. So it depends what is meant by ‘actionable’ (and some European countries have taken a radical view). My main point was about MHRA and lack of clarity.

        2. Doug H MD says:

          No doubt? Good science mandates doubt.There are some good counterexamples. South Africa comes to mind if you want doubt.

      2. sgcox says:

        Yeah, “catastrophic illness linked to a vaccine which is still effectively in trial.”
        About 20,000,000 vaccinated in UK alone with Covid deaths dropping from ~1,000 per day to ~30. So, whatever. Do you need 2,000,000,000 inoculations to finish “trial” ?

  5. Eugene says:

    The high level of surveilance on these vaccines is pushing these very small subset effects to the forefront. I womder how many obscure side affects arise from other commonly used vaccines (flu, MMR, etc.) are out there but not amplified like this. With the variability of the immune system being what it is, I am sure this happens at a similiar rate (<100 per several million doses).

    1. JF says:

      We had two cases, among which one fatality, in the rural Euskirchen county (< 200k inhabitants) alone, which was the first county to suspend AZ vaccinations this week. I do not know how many AZ doses they gave there, but doubt it is more than a few thousand. So this is clearly not a "very small subset effect".

      1. Chris Phillips says:

        Pfizer has announced the results of a trial of their vaccine in 12-15 year-olds, showing “100% efficacy”. Maybe I’m missing something, but I can’t see any explanation of what they have looked at. Symptomatic disease?

        Anyhow, it is 18 cases in the placebo arm and none in the vaccine arm. I reckon they would do better to quote a confidence interval, which I think should be about 79-100% on those figures.

        https://www.pfizer.com/news/press-release/press-release-detail/pfizer-biontech-announce-positive-topline-results-pivotal

  6. bacillus says:

    Canada is now recommending that the AZ vaccine only be administered to those aged 55 or older. This should lead to these cohorts getting immunized even faster than originally expected.

  7. Alberto J. Villena says:

    It seems that thrombosis is not only an adverse reaction of the AstraZeneca vaccine. A syndrome similar to immune thrombocytopenia has been observed for the mRNA vaccines:
    – Lee, E.‐J., et al., (2021), Thrombocytopenia following Pfizer and Moderna SARS‐CoV‐2 vaccination. Am J Hematol. https://doi.org/10.1002/ajh.26132.
    Thus, it is possible that the problem is not the adenovirus, but the antigen (some epitopes) itself.

    1. sPh says:

      Could these effects be related to “COVID toes” and similar lower extremity side effects reported some days/weeks after severe COVID19 illness?

  8. Chris Phillips says:

    Now Germany has decided AstraZeneca should be used only in the over 60s:
    https://www.bloomberg.com/news/articles/2021-03-30/germany-to-recommend-astra-vaccine-use-only-for-people-over-60

    “You put your left leg in
    Your left leg out
    In, out, in, out
    You shake it all about
    You do the hokey cokey
    And you turn around
    That’s what it’s all about”

    1. Rob Sutherland says:

      30 March, 2021 at 9:56 am
      Chris,
      I left this in reply to you at the bottom of the previous scary AZ article:

      Things just continue to get more and more ridiculous up here in Canada/Ontario.
      I posted some of this in an earlier thread on Mar 19, but now we have the NACI getting involved again. As a reminder:
      “Up here in Ontariario, vaccination is a mess!
      Only a week or so ago Health Canada finally OK’d the AZ vaccine for everyone over 18, but another Fed agency (NACI – National Advisory Council for Immunization) came out with recommendation to limit AZ to those under 65. This was based on lack of data showing ‘efficacy in over 65s’, despite the huge Scottish and English studies coming out some time before they made this announcement.
      I’d never heard of the NACI prior to this, so maybe they do indeed live under a rock!
      If that was not sufficiently confusing, the NACI also OK’d a booster delay of up to 4 months, for which there is no data AFAIK. A week later, they may have relented in the face of loads of evidence for AZ vaccine’s effectiveness in over 65s, but it is hard to keep up…..
      On top, you have the Provincial Governments doing their own thing as well. Only Quebec has followed the UK approach almost from the beginning, but now most (I think) are now following the 4 month delayed booster approach.”

      Last night I witnessed a highly unimpressive interview on CBC with the head of NACI.
      She tried to justify the earlier flip flop on the AZ vaccine noted above by claiming again that when their original decision was made NACI was following the early trial data in which insufficient data was available re efficacy in over 65s.
      Jesus H Christ! What does she think happens to the immune system after 64 years and 364 days?? It is old folks that bore the brunt of earlier waves of the Pandemic and those most requiring vaccination ASAP.
      She cited ‘new data’ as the reason for dropping the over 65’s restriction. New data (UK Scottish and English data presumably) that came out well before the original decision to deny the vaccine to the over 65s.
      She then had the chutzpah last night to essentially blame AZ for all the problems this vaccine has had!! She reckons Health Canada needs to do a risk-benefit analysis in the younger folks to ensure that we do not see any HIT-like issues on Canada, before they will no doubt do another about-face! She also (mistakenly) claimed that no other vaccine (let alone a covid vaccine) has been associated with this HIT-like syndrome.
      Meanwhile the B.1.1.7 variant is beginning to cause all sorts of bad things up here with ICU-occupancy running very high, lock-downs on the upswing again and as we all know on this blog, the UK variant is now getting into younger groups and causing increased lethality therein.
      Holy crap!
      She totally failed to see the irony of her organization performing the modern day equivalent of the Hokey Pokey wrt the AZ vaccine and how such has had a terrible effect on folks desperately trying to get vaccinated up here.
      “You bring the vaccine in,
      You keep the vaccine out,
      In, out, in, out,
      You screw it all about…”
      Such effects will not just affect acceptance of the AZ vaccine when they perform their next flip-flop. It will instead cause a drop in acceptance of all covid vaccines.
      Due to these and other uncertainties generated by the blood clotting issues, most lay folks are desperately trying to avoid the AZ vaccine.
      I would take it in a heartbeat at 70y/o!!
      I tried to register to get access to the AZ vaccine for me and the wifey during the short period in which it was OK to get this in a pharmacy as an over-65 year old. We heard absolutely nothing back from the two pharmacies we registered with. Meanwhile Toronto has insufficient folks turning up to get the vaccine (we live outside the Greater Toronto area) and are pleading with folks to ‘come on down’ and get it.
      So finally, I got registered in my local area to get (on G dod Friday) what will likely turn out to be the Pfizer vaccine (based on the Q’s I was asked re allergies to PEG).
      “Its Good Friday; its Good Any day” 😉

      1. Jonas says:

        Not only the English and Scottish study showed great efficacy in older people (better than Pfizer on a first dose basis), but the headline figures for the US AZ trial has better efficacy in older people! Fine, some will say we need the peer reviewed paper or the FDA analysis of that, but the truth of the matter is that this vaccine has been shown to be efficacious for a long time, even if pinpointing a headline figure has been confused.

        Some commentators and even authorities heave such binary thinking. The UK authorities on the other hand ought to be praised for their common sense approach to vaccination. No pussyfooting- just clear, pragmatic decisions taking into account both pre-clinical and clinical trial data, and impact in the real world.

        1. Richard says:

          Nice summary of the loopiness here in Canada, Mr. Sutherland. As a semi-retired physician I’ve been able to invest the time to understand the basis of the decisions made, but for the intelligent lay person this could be a real challenge. I got the AZ vaccine 3 weeks ago in a mad scrum at a local pharmacy — so much for a well-organized rollout! I certainly hope that someone is collating detailed case histories of all the individuals with VIPIT across national boundaries. If this is done, I trust that epidemiologists, hematologists, and infectious disease specialists will sort out this clinical puzzle pretty quickly.

          1. Rob Sutherland says:

            Congrats Richard on getting the vaccine.
            Our GP, a wonderful old Irish guy of 87 only recently managed to get a vaccine. He’d had to stop going to his office prior to that for obvious reasons.
            I had been defending the public officials up here who were being pilloried for the lack of vaccine despite ordering more per capita than anyone else, but the recent scale of sheer incompetence among the myriad Fed and Provincial Governments has me spitting feathers, as they say.
            As a biomedical researcher for about 45 years before I got ‘volunteered’ for retirement at UHN, this is all so disappointing.
            It almost seems like an International conspiracy to demean the Oxford-AZ vaccine but by the time the NACI get around to allowing it’s unfettered deployment again, no-one will trust it.

      2. Katie says:

        EXACTLY!!!
        There is actually evidence published in the BMJ beginning March – which demonstrates antibodies in those over 70 are vastly reduced after 3 weeks after the first dose, and even more so in those over 80 (less than 35%). B.C. also has an ongoing study about the risk of delaying the second dose in the elderly. I’ve tried asking everyone based on what evidence NACI is recommending the schedule delay carte blanche, and enrolling all Canadians without their consent in a clinical trial to evaluate schedule delay to no avail – same boiler plate response from all municipal and provincial health/political respondents (although the HCPs have talked to individually do not support the decision). Not trusting anything coming from NACI at this point when they’re not willing to address evidence out there.

  9. Philip says:

    At this point in time the clotting problem looks real and rare. The AZ vaccine is different from the three with EUAs in the US in two ways. First, it does not use a prefusion stabilized version of the spike protein. Second, it uses a chimp adenovirus for its vector.

    If adenovirus vectors are the problem, you would expect the same problems for the J&J and Russian Sputnik V vaccines. If the problem is with the spike protein, you would expect the Sputnik V vaccine to have the same issue, but not the J&J vaccine. If the problem is caused by the chimp adenovirus vector, then only the AZ vaccine would have the problem.

    I hope we find out soon.

    1. sgcox says:

      Extra complication here is that the problem looks to be limited to doses made in Belgium plant for EU. No problems in UK with either locally made or by Serum Institute in India. India also reported no problem despite inoculated many many millions.
      We had this discussion here before and batch problem looks like the most reasonable explanation. May be some polyanions contaminations? The paper specifically points on the similarity with heparin linked thrombotic events. Could be absolutely wrong of course.

      1. Some idiot says:

        I know I have raised the (remote but not unreasonable) possibility of site-to-site variation in production, but to me the differences in age ranges in Uk vs EU starts to feel to me to be the more likely “real” cause… I personally haven’t ruled production site out, but it is (thankfully!) starting to be overtaken by age ranges… Will be interesting to see which way it falls in the end…!

    2. RvH says:

      Note that there are also substantial differences in the antigens. Although they all express spike, there are differences in de stabilization, cleavage, signal sequence etc.

      1. sgcox says:

        Possible but I think unlikely.
        All reports are limited to events before 14 days as I understand. That is before antigen (Speke) get recognised by immune system and it starts to build up the response. Feels like the reaction to the jab itself, not the load. Also does not explain the Europe specific AEs. If not batch variation than what, Brexit allergy ? OK, just kidding.

      2. Philip says:

        RvH, IIRC, the mRNA vaccines use the same modifications. The J&J uses the same stabilizing modifications as the mRNA vaccines and deletes the furin cleavage site.

        See: https://mbio.asm.org/content/12/2/e02648-20
        for more information.

        1. Rvh says:

          Yes, mRNA vaccines and J&J use a more or less similar antigen. But AZ is different since it uses a wild type spike with an tPA leader sequence. Due to the wild type sequence, the S1 subunit is also secreted from expressing cells in contrast to the modified version from JNJ, Pfizer and moderna, so the antigen from AZ could harbor unique features with still unknown impact.

          1. Jonas says:

            But keep an eye on J&J events. Not sure how many have been administered..but see my early comment. A transverse cerebral venous sinus thrombosis case Ina 25 yo male among the 30K vaccinated participants in their trial (and an overall imbalance of thromboembolic events 6 in vaccine, 2 in placebo).

        2. Wilhelm Cody says:

          For Jonas, the CDC website says that abut 3.2 million J&J vaccinations have taken place in the USA so far with about 6.3 doses total being delivered and an additional 4.9 million doses available next week. This should supply lots of data on any issues.
          see https://covid.cdc.gov/covid-data-tracker/#vaccinations and https://data.cdc.gov/Vaccinations/COVID-19-Vaccine-Distribution-Allocations-by-Juris/w9zu-fywh

          1. Jonas says:

            Thank you!
            Let’s hope that the US has good pharmacovigilance in place so that any possible adverse events can actually be picked up.

    3. KikiO says:

      Thank you – this is helpful!

  10. Blaine White, M.D. says:

    Venous thrombosis in the brain in relatively young females is vanishingly rare in day-to-day medical practice. There is evidence both Spike itself (Zhang S et al. SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19. J Hematology & Oncology 2020; 13:120. https://doi.org/10.1186/s13045-020-00954-7) and IgG immune complexes from C19 patients (Zlamal J et al. cAMP prevents antibody-mediated thrombus formation in COVID-19. MedRxiv 2020; https://doi.org/10.1101/2020.12.15.20247775) can bind and activate platelets. For Spike itself this appears to be mediated by the ACE2 receptor on platelets, and for the C19 immune complexes it is mediated by the Fc-gamma-2-receptor on platelets for IgG immune complexes. I don’t know what antigen was on the patient’s immune complexes, but since S and N are immunodominant for IgG production, it could certainly be Spike. A modest suggestion is to put vaccinees on lo-dose aspirin (irreversible acetylation of serine-530 on cycloxygenase-1, thus inhibiting platelet production of thromboxane A2) for a month. Indeed, lo-dose aspirin has been shown to reduce morbidity and mortality from C19 infection (Chow J et al. Anesthesia Analgesia 2020; doi: 10.1213/ANE.0000000000005292.) and (Osborne T et al. MedRxiv 2020; https://doi.org/10.1101/2020.12.13.20248147). It is certainly tempting to hang the tragic death of fairly young women on AZ’s vector choice, but there is reason for a nagging worry that it is actually a result of the chosen antigen. And that will require a careful sorting out.

    1. Mandark says:

      Why do I hear many doctors advising against using aspirin to reduce the risk of this type of clotting with vaccine? Is there any reason why it could lead to adverse outcomes (beyond its known safety issues independent of vaccine use)?

  11. ScientistSailor says:

    VIPIT,
    VIPIT good,
    When a problem comes along
    you must VIPIT…

    1. Devo Fan says:

      Ah yes, somebody had to say it. So thank you. I really needed that laugh.

      1. ScientistSailor says:

        I’m glad I’m not the only one from the ’80s on this board…

        1. Miles says:

          Nope – lots of us old gits here, and even some that have read Pynchon! (For the younger readers, Gravity’s Rainbow inspired the Devo song).

          1. Some idiot says:

            Ah… Also for the older readers! I didn’t know that this was their inspiration…! Happily you just reassured me that one is still never too old to learn! 🙂

        2. Vader says:

          Dare to be stupid.

          https://youtu.be/SMhwddNQSWQ

          Weird Al is a genius.

  12. bewd says:

    just to make everything clear in the EU
    In Spain, the AstraZeneca will be restricted to adults up to 65 years of age, with one new exception: essential workers above that age will also be eligible for the shots.
    So Spain under 65 only , Germany over 65 only , Italy and rest of EU?

    1. Adrian says:

      Germany is over 60 only, not over 65 only.
      Here in Finland it is over 65 only.

      It was a bad decision that the EMA failed to impose a EU wide age limit.

      In all EU countries the vaccine distribution is roughly half AZ and Pfizer and no EU country has finished even first doses for everyone over the age of 65, so restricting one vaccine to elderly does not even affect the overall vaccinations speed.

      The worst part is that one of the effects to the display of gross incompetence by the University of Oxford and AstraZeneca during the trials of their vaccine was that data on elderly was very scarce during initial approval causing several countries to recommend not using if for elderly until recently, which resulted in many countries like Germany now having an opposite age restriction than a month ago.

      1. Jonas says:

        Your accusation of “gross incompetence” on Oxford not to have enough over 55s is plainly unfounded. You can accuse them of being too cautions as it was an “ethics” argument of when over 55s would join the trial. They did , as did over 70s- but hardly any got infected as at that point the lockdowns had meant minimal transmission and even less in an age group that were more careful.

        So throwing dirty water like that is not right. You are not the only one, though. “Renowned” commentators with vested interests have done worse.

        1. Adrian says:

          The worst part of gross incompetence was the University of Oxford dosing only half the intended dose to many volunteers in a trial.

          And many other aspects of how the trials were run and the results presented.

          As a matter of fact Pfizer and Moderna managed to run their trials in a way that sufficient data was available on elderly people at the point of emergency approval.

          1. Corsica says:

            What are are you spouting about dose testing? The worst thing about the American tests is they only took place in the USA where only the Wuhan-variant existed.

            The real debacle was caused by Brussels with politicians in Finland, France and Germany all creating confusion has made this just a complete cluster****

  13. Geoff Harrison says:

    Interesting that a recent video from Dr John Campbell quotes very recent Danish advice that the clots might be caused by the occasional intravenous injection as modern practice does not advise the person administering the vaccine to aspirate first to check they’re not in a blood vessel. The UK health advice indeed says there is no need to aspirate but this has been regarded in the past as an important precaution to ensure the needle is only in muscle.
    Could the cause of the clots be as simple as poor injection technique?

    1. A Nonny Mouse says:

      I would have to say that they took quite a bit of time to get the correct position and depth for the injection when I was being done (AZ) though I would have to say that they probably touched a nerve as I could feel the coldness all the way down to my finger which lasted a few minutes.

      1. Mariner says:

        I don’t think there was much attempt at placement with my AZ jab (in the UK). Just stuck it in and sent me on my way. I was in the room for perhaps 1 minute in total, but was advised to sit in my car for 15 minutes before driving away.

        1. Marko says:

          “… I was in the room for perhaps 1 minute in total, but was advised to sit in my car for 15 minutes before driving away.”

          That’s a smart policy. That way, if you go into anaphylactic shock and die, it will be in your car rather than in the clinic, where it would make the others uncomfortable and, perhaps, vaccine-averse.

          1. Some idiot says:

            🙂

            Here in Denmark there are dedicated COVID-19 vaccination centres, and at the end of the “flow” in them is a waiting area (with seats at least 2 m apart, and staff there disinfecting each seat after use) where you have to wait 15 minutes before you leave. The area is patrolled by nurses, keeping an eye out for anyone who might get an allergic reaction etc.

            Incidentally, this morning I heard that the SSI here in Denmark has just passed the 100 000 mark for numbers of COVID-19 viruses sequenced from positive PCR tests…!

          2. Mariner says:

            To be fair, it did take me another couple of minutes to put my coat back on and walk out of the building. They’d probably have spotted any anaphylaxis as I hit the deck on the way out… 😉

          3. A Nonny Mouse says:

            Strange as they insisted that anyone driving had to wait 15 minutes before they could go.

            Also, today’s news is that the UK have found more cases of this type of blood clot. 30 now out of 16m doses of AZ. None in the P-B vaccine. No breakdown of age/sex of the new cases.

          4. Chris Phillips says:

            Here is the relevant part of the report from the MHRA:
            The risk of having this specific type of blood clot is very small. Up to and including 24 March, we had received 22 reports of cerebral venous sinus thrombosis (CVST) and 8 reports of other thrombosis events with low platelets, out of a total of 18.1 million doses of COVID-19 Vaccine AstraZeneca given by that date. There were no reports for the Pfizer/BioNTech vaccine.
            https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting

            Just over one report of CVST per million AZ vaccinations. No information about any fatalities.

            I think that is around twice the estimate of the normal rate of CVST made by the Paul Ehrlich Institute, but less than a third of the rate of cases reported in Germany.

    2. Andy says:

      I was wondering the same thing. IV adenovirus injection and thrombocytopenia seem to be well known to be associated, for example:

      https://ashpublications.org/blood/article/109/7/2832/125650/Adenovirus-induced-thrombocytopenia-the-role-of

      I have never noticed anyone aspirating when giving me an IM injection. I’ve also only rarely noticed anyone aspirating when giving me a subcutaneous allergy shot despite the frequent presence of checklists at the injection station advising nurses to do exactly that. I have no idea what the risk of death due to an incorrectly administered allergy shot is, but the risk of an unpleasant experience is probably orders of magnitude higher than the risk from an AZ vaccine.

      1. Not-an-epidemiologist says:

        In the absence of any evidence to the contrary, this seems by far the most likely explanation, with an easy fix (i.e. aspiration) if this does indeed turn out to be the cause.

      2. bewd says:

        The MHRA said on Thursday there had been “22 reports of cerebral venous sinus thrombosis (CVST) and 8 reports of other thrombosis events with low platelets”. from 18 million AZ Oxford doses.

    3. Philip says:

      45 years ago when I was taught how to do IM injections, I was told to always aspirate. In reality, it depended on what was being injected. Innovar, that could be given IM or IV, I would short cut and skip the aspiration.

      Boy that brought back some old memories. It was a very long time ago I worked with wetware.

    4. Nathan says:

      One would wonder if that’s why results are biased towards women (at least in some countries); less shoulder muscle mass and so more chance of hitting blood vessel.

    5. Rob Sutherland says:

      Geoff.
      I tried to post a response to Marko about this issue last night. It included a link to John Campbell’s video about this ‘aspiration’ issue together with the English translations of the two Danish publications but it was disappeared……..

      1. Marko says:

        Rob,

        This comment site usually gets indigestion if you include more than one link per comment. If you have more than one, reply to your own comment to post a second link, reply again for a third, etc.

        1. Rob Sutherland says:

          Thanks Marko,
          I note that Geoff has now linked to John Campbell’s video, so the other links that were ‘disappeared’ are contained therein.
          If this ‘very rare’ issue was being caused by something so basic as this, wow!
          I doubt from the there comments here that the Brits know how to do this better than the Germans or Danes.
          There are so many explanations being bandied about re this issue but I hope one of them turns out to be accurate, and soon.
          best

      2. Geoff Harrison says:

        Here’s the link to Dr John Campbell’s YT video on the possible aspiration issue with a nice demo with an orange and the description text under the video includes links to the Danish documents.
        https://www.youtube.com/watch?v=md8pJFbMVnk
        As I say the UK guidance says you don’t need to aspirate which saves time but maybe you do, and I like the thought about women having maybe less muscle mass as a possible factor.
        Also consider just how mass this mass vaccination drive is historically and whether less experienced staff have been drafted in. Easy to fix if its the issue.

        1. Sarah king says:

          Ahh! I had AZ injection. Site bled immediately as the needle was removed. Dr commented it was ‘unusual’, gave me a cotton wool ball to press against it. It stopped bleeding after about 5 mins. Had migraine, heat rate racing (100bpm laying down when usually 55 bpm) chills, nausea start about 8 hours later and was awful for about 12 hours. Migraine persisted on and off (with help of sumatriptan and ibuprofen) for almost a week. Now wondering if the bleed was something I should have questioned?

          1. Sarah Packham says:

            Interesting, EXACTLY the same thing happened to me.

  14. bewd says:

    yes interesting theory , think the Danes have changed their policy to now aspirate

    https://www.berlingske.dk/nyheder/dansk-professor-forkert-vaccineteknik-kan-udloese-blodpropper

    1. Chris Phillips says:

      Except that the article you have linked to says “It is not known whether this blood disorder is related to the Covid vaccines.”!

      We seem to have a hell of a lot of misleading anti-vaccine propaganda here all of a sudden!

      1. Diana says:

        but that’s true of the AZ vaccine as well, what I am saying that in my opinion the focus on AZ is political, when you look at the facts, these rare cases happen with the mRNA vaccines as well and in all cases we don’t know if the vaccines are causing them

        1. Bannem says:

          Nahh, it’s just preparations being made for the next phase of the vaccine program. Once the threat of the pandemic has been blunted, and its boosters every year, flu shot style, it’s obvious that the mRNA boys want to be the only game in town . . .

        2. Chris Phillips says:

          Sorry if I misunderstood. There have been so many comments here recently that assume anything that happens after someone has been vaccinated must be caused by the vaccine.

    2. Rob Sutherland says:

      Thanks for the link Diana!!
      It reads like deja vu all over again, except this all came out well before the ‘AZ maybe causing lethal blood clots’ scares that have received so much bad press.

  15. Dr Mark says:

    A real life example of the Trolley Problem https://en.wikipedia.org/wiki/Trolley_problem
    Even more complicated by the decision makers likely more represented in one of the groups that will be struck by the Trolley.

  16. Donna says:

    The problem with statistical analysis is that there are ways to arrange the numbers to give wildly differing outcomes. Examination of individual cases is needed to show causation or lack thereof. Please take a look at the following statements from Ann Taylor (AstraZeneca chief medical officer) and Sara Viksmoen Watle (Chief physician at the Norway Institute of Public Health).

    “On 14 March, AZ responded to the reported link, saying 15 events of deep vein thrombosis and 22 events of pulmonary embolism had been reported across the UK and EU, out of a total of 17 million people who had taken the vaccine – a similar rate to those observed in other approved Covid-19 vaccines. The number of cases of blood clots reported in this group is lower than the hundreds of cases that would be expected among the general population,” said AZ chief medical officer Ann Taylor. “(1)

    “Norway, which has administered the AstraZeneca vaccine to 130,000 people under age 65, has reported five patients who had low platelets, hemorrhage, and widespread thromboses, three of whom died. That’s about one case in 25,000 vaccinees, “a high number with a very critical outcome in previously healthy, young individuals,” Watle says. ” (2)

    Links in “reply”

  17. Marko says:

    Vaccine manufacturing screw-up ruins 15 million doses. Not AZ :

    https://www.nytimes.com/2021/03/31/world/johnson-and-johnson-vaccine-mixup.html

    1. Marko says:

      Emergent Biosolutions has come up with a new name and business focus:

      “Emergency Biosolutions: When SPEED Is Your ONLY Concern”

    2. A Nonny Mouse says:

      Yes, but it was an AZ ingredient that they put in there, so it will affect both.

      1. Marko says:

        So, they put an AZ vaccine component into a J&J batch? Wow. It just shows that contract manufacturers have to be closely monitored by the drug companies , even in the US. I guess the concept of Six Sigma QC protocols never caught on among these guys.

  18. Marko says:

    “There is no evidence to support restricting the use of the Oxford-AstraZeneca vaccine in any population, according to the European Medicines Agency’s executive director.

    Emer Cooke defended the vaccine after several European countries suspended the jab’s rollout due to fears of blood clotting.

    The agency said a causal link between blood clots and the vaccine was not proven, but that it might be possible and further analysis was being done.

    At a press briefing on Wednesday, Ms Cooke reiterated to Europeans the vaccine’s safety and said its benefits far outweighed the risks.

    “Our position has not changed,” she said. “According to the current scientific knowledge, there is no evidence that would support restricting the use of this vaccine in any population.”

    https://www.independent.co.uk/news/health/astrazeneca-oxford-covid-vaccine-ema-b1825082.html

  19. Marko says:

    One widely-held argument against delayed dosing was that people wouldn’t show up for the second jab. Not a problem in the UK :

    https://www.thesun.co.uk/news/14514955/99-25-per-cent-brits-second-jab-appointments/

    1. Rob Sutherland says:

      Thanks again Marco for the great links, but I am getting a bit worried about you using ‘The Sun’ in the UK as a reliable source;-)

      1. Marko says:

        You’re right. I just did a quick search and can’t find any other source for that number, so the Sun may have just made it up. My bad.

  20. Marko says:

    FDA finally authorizes over-the-counter rapid screening tests:

    https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-continues-advance-over-counter-and-other-screening-test-development

    A good day for Michael Mina, who deserves credit for relentlessly pushing for this.

  21. Rob Sutherland says:

    This just in: “Thromboembolism and the Oxford–AstraZeneca COVID-19 vaccine: side-effect or coincidence?”
    https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00762-5/fulltext

    1. Christian Weisgerber says:

      The safety signal is specifically about cerebral venous sinus thrombosis associated with thrombocytopenia, and the article explicitly says “These outcomes are not included in the present analysis”.

      So what the article confirms is that an adverse outcome that nobody claims is associated with the AZ vaccine is indeed not associated with the AZ vaccine.

  22. Chris Phillips says:

    An update of efficacy from the Pfizer Phase III trial, now covering a period up to six months after vaccination.
    Efficacy against symptomatic disease: 91.3% [confidence interval 89.0, 93.2] from 77 versus 850 cases.
    Efficacy against severe disease either 100% [88.0,100.0] from 0 versus 32 cases (CDC definition) or 95.3% [71.0, 99.9] from 1 versus 21 (FDA definition). [I think they must have used only the FDA definition in their previous report, as that included one severe case.]
    Efficacy against symptomatic disease in South Africa: 100% [53.5, 100.0] from 0 versus 9 cases. Only 6 of the cases were B.1.351, but obviously that’s as reassuring as it could have been given the low numbers.
    https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-confirm-high-efficacy-and-no-serious

  23. Chris Phillips says:

    Independent study of serological and cellular response to Pfizer/BioNTech vaccine in 100 people aged 80-96, by the University of Birmingham:
    https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3816840

    From the abstract:
    Antibody responses were seen in every donor with high titres in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher respectively after dual vaccination. Post-vaccine sera mediated strong neutralisation of live Victoria (Wuhan-like prototype) infection and although neutralisation titres were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective.

    1. Marko says:

      Some good new info in there. It seems that a single dose is probably sufficient for seropositives, even in the elderly:

      “…we observed that 10% of the cohort had evidence of prior infection. This was associated with substantially stronger humoral and cellular immunity after vaccination. Indeed, no
      participants with a history of previous natural infection had suboptimal cellular immunity
      compared to 44% in uninfected donors. Interestingly, we also observed strong responses after only one vaccine dose in this group, with no significant increment after the second dose when administered with a 3-week interval.”

      Also, they found a 14x reduction in the live-virus neutralization assay for the P.1 variant compared to the Wuhan/Victoria strain, but the remaining titer was still significant at a median of ~180, meaning likely good protection against P.1 for most vaccinees, although durability still needs to be investigated.

      1. Marko says:

        I should have noted that the neutralization titers noted above were for the seronegative cohort. Seropositives would likely have had even higher titers.

  24. Ranga says:

    With so many doubts on the AZ vaccine like blood clots and incompatibility with pain killers like diclofenac, I am hesitant to get vaccinated.

    1. Chris Phillips says:

      I was puzzled by the reference to diclofenac, did a little Googling, and found there had been an anti-vaccine scare story circulating on social media about an Indian woman who died after being injected with diclofenac. It was a month since she had been vaccinated, and the hospital that treated her ruled out any connection with the vaccination:
      https://www.thenewsminute.com/article/fact-check-madurai-doctor-haiharinis-death-not-due-covid-19-vaccine-say-officials-145994

      1. Marko says:

        Disinformation Lobbyists & Brexit Business Bosses Finance Conservative COVID Sceptics’ PR

        https://bylinetimes.com/2021/04/01/disinformation-lobbyists-and-brexit-business-bosses-finance-conservative-covid-sceptics-pr/

  25. Marko says:

    Despite Chile’s Speedy Covid-19 Vaccination Drive, Cases Soar

    https://www.nytimes.com/2021/03/30/world/americas/chile-vaccination-cases-surge.html?smid=tw-share

    “…experts say the country’s speedy and efficient vaccination drive — only Israel, the United Arab Emirates and Seychelles have vaccinated a larger share of their populations — gave Chileans a false sense of security and contributed to a sharp spike in new infections and deaths that is overloading the health care system.

    The surge in cases, even as more than one-third of Chile’s population has received at least the first dose of a Covid-19 vaccine, serves as a cautionary tale for other nations looking to vaccination drives to quickly put an end to the era of beleaguered economies, closed borders and social distancing. The rise in cases prompted a new set of strict lockdown measures that have restricted mobility for much of the country, affecting nearly 14 million people.

    “When transmission rates are high, the vaccine does not rein in new infections right away,” said Dr. Denise Garrett, an epidemiologist at the Sabin Vaccine Institute in Washington. “And with the new variants, which are more contagious, we’re not likely to see a big impact until the vast majority of the population is vaccinated.”

    Don’t worry, though, this doesn’t apply to the US, because we’re exceptional. Or something.

    1. Chris Phillips says:

      “only Israel, the United Arab Emirates and Seychelles have vaccinated a larger share of their populations [than Chile]”

      Presumably they are mixing up percentage of the populaton vaccinated and total number of doses given per head of the population.

      The article says more than a third of the population of Chile has received at least one dose. In the UK it is now about 60% of the adult population.

      1. stewart says:

        They mean fully vaccinated. Chile is giving the 2 doses 4 weeks apart, and is at 20% fully vaccinated, behind Gibraltar, Israel, the Seychelles, and the Cayman Islands. (The site I’m looking at isn’t giving out data for the UAE.)

        https://ourworldindata.org/covid-vaccinations

        The UK is now mostly doing second doses, and is catching up on (has overtaken most of the EU) on other countries on fully vaccinated status, but because of the 12 week interval had been lagging on this metric. The British Crown Dependencies are running ahead of the UK; the IOM could even possibly overtake Chile on the fully vaccinated metric.

        1. Chris Phillips says:

          Thanks. That explains it.

        2. Marko says:

          I think Chile has been mainly using the Sinovac vaccine, so the comparison may be complicated by unknowns about relative efficacy and such. At any rate, I think the cautionary tale told by the Chile situation applies to the US much more than the UK currently. I just heard that the US reached 4 million doses in one day, so if we can keep improving on the vaccination rate we may be able to limit the damage caused by the variants over the coming weeks by reducing the exponential rate of spread. The weak spot in the US now is that about a quarter of over-65s still haven’t received a first dose, and I know from one first-hand account that it’s not for a lack of trying. Getting an appointment is like winning the lottery in my area, even for someone of that age group. It’s shameful.

          1. stewart says:

            Elsewhere I’ve seen a report of a low risk American ~20 year old being vaccinated. For all the reports of chaos in the rollout in the US the numbers do seem to be getting achieved, but they may not be well directed.

  26. Marko says:

    The Pandemic’s Wrongest Man : In a crowded field of wrongness, one person stands out: Alex Berenson.

    https://www.theatlantic.com/ideas/archive/2021/04/pandemics-wrongest-man/618475/

    Interestingly, on occasions when I’ve visited Balloux’s twitter in the past, one of the accounts that often showed up in twitter’s “You Might Like” box was Alex Berensen. Twitter’s wrongness algorithm seems to be working well, at least.

  27. Marko says:

    For those who think vaccine availability is no longer an issue, check out this website that tracks the current status in the DelMarVa region:

    https://www.dmvvaccine.com/

    All locations in Delaware, Maryland, and Virginia, save one (for the moment, anyway), are fully booked.

  28. bewd says:

    no safety data available on mixing vaccines but better than a second dose of AZ Oxford vaccine ??
    In an updated recommendation on its website, STIKO said there was no scientific evidence on the safety of a mixed series of vaccines.

    “Until the appropriate data is available, STIKO recommends for people under 60 years old that instead of the second AstraZeneca dose, a dose of an mRNA-vaccine should be given 12 weeks after the first vaccine,” STIKO said.

  29. Marko says:

    Troubling rise in PCR positivity among aver-65s in FEMA Region 10 only. Proximity to P.1 variant clusters in BC…..early immune escape signal? :

    https://twitter.com/justthefacts85/status/1377037040710115331/photo/1

    CDC hasn’t reported large numbers of P.1 anywhere yet, but they’re barely scratching the surface re: variant surveillance.

  30. RichW says:

    MHRA in the UK find 25 more cases of clotting issues (on top of the 5 it knew about).

    https://news.sky.com/story/covid-19-thirty-blood-clot-cases-reported-in-uk-after-18-million-oxford-astrazeneca-jabs-says-medicines-regulator-12263543

    “Our rigorous review into the UK reports of rare and specific types of blood clots is ongoing. Up to and including 24 March, we have received 22 reports of cerebral venous sinus thrombosis (CVST) and 8 reports of other thrombosis events with low platelets, out of a total of 18.1 million doses of COVID-19 Vaccine AstraZeneca given by that date. There were no reports for the Pfizer/BioNTech vaccine. To note, the current analysis prints include data up to and including the 21 March.”

    https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting

    Thats potentially more interesting. No breakdown of age, gender or anything i can see.

  31. Chris Phillips says:

    The BBC reports that the MHRA has told it that seven people have died. (Being the BBC, they don’t make it clear whether that is 7 out of 30 or 7 out of 22.)

    Obviously this news and the way it has been released raise several questions of an essentially political nature, but at least make the scientific position clearer. Unfortunately this does look like a genuine but extremely rare side-effect of the AZ vaccine.

    1. A Nonny Mouse says:

      A medical professional on the radio this morning suggested that, although random clusters can occur, this seems like a genuine concern due to the incidence in a few countries.

      Could still be an injection problem, though one not seen with the P-B vaccine?

      1. Chris Phillips says:

        I think the “not seen with the P-B vaccine” part is the difficulty with the idea that it’s an injection problem.

        Perhaps people just need to face up to the fact that a vaccine capable of saving up to 1 life in a hundred has an extremely rare side-effect capable of costing perhaps 1-4 lives in a million.

        1. Not-an-epidemiologist says:

          Well, it suggests it’s not injection alone, but it doesn’t exclude that it’s a combination of both injection + vaccine. Given the points noted above about the established link between intravenous injection of adenoviral vectors and thrombocytopenia, the combination on the surface makes a lot of sense (to me, at least). (Of course, if we don’t see the same rare side effect with the J&J and Sputnik vaccines, then it would be clear evidence that this theory is wrong — so I guess we’ll know soon enough.)

          I agree that regardless of cause, you wouldn’t want to stop using this vaccine given the large risks of inaction vs. such a incredibly small risk of action. But it would seem silly to not at least test changing injection technique moving forwards — there’s no point having even extremely rare side effects if you don’t have to.

    2. Anon says:

      There is an issue with under reporting of side effect issues in the NHS. It is probably down to an institutional reluctance not to be seen undermining the (extremely successful) vaccination programme, whether that is right or ethical is a different issue. Folk might want to check out the number of thrombosis cases shortly after AZ vaccination being seen at St Thomas’ Hospital (where the PM was treated) which are far too many (order of magnitude) to fit in the with the 30 cases out of 16 million narrative being issued to the media. This knowledge is causing increasing disquiet amongst UK health professionals.

      It is clear the Germans do not believe the official numbers coming out of the UK. Quote from the Sueddeutsche Zeitung https://www.sueddeutsche.de/politik/astra-zeneca-grossbritannien-corona-impfung-1.5253025 – its behind a paywall so most relevant detail via Google translate

      “Robert Klamroth, chief physician and hematologist at the Vivantes Clinic in Berlin, is critical of the British reporting system. He had only just spoken to colleagues from the UK on this subject. “They are not at all satisfied with the yellow card system because it is not standardized at all,” he says. In Germany, however, there is a standardized questionnaire for complications from the Paul Ehrlich Institute. “Wherever there is such a slight degree of standardization, colleagues report an increase in the number of cases, especially since younger people have been vaccinated.”

      1. Chris Phillips says:

        Anon

        “Folk might want to check out the number of thrombosis cases shortly after AZ vaccination being seen at St Thomas’ Hospital (where the PM was treated) which are far too many (order of magnitude) to fit in the with the 30 cases out of 16 million narrative being issued to the media.”

        Yes, I should very much like to check that out. Can you offer us any means of doing so, by providing the numbers involved?

        I must say I find it difficult to understand your suggestion of looking at the number of cases associated with a single hospital, because that number will imply an incidence an order of magnitude larger than 30 cases nationally. Presumably that means it they would extrapolate to 300 cases nationally. Given the number of hospitals in the UK is much higher than 300 (namely, about 2000) – even allowing for the fact that St Thomas’s is a large hospital – I can’t help wondering how your conclusion could make any statistical sense.

        Seeing that an order of magnitude would still imply less than one case per hospital. And on the other hand, seeign that a statistically meaningful number of cases in a single hospital would imply a much bigger factor than an order of magnitude.

        But perhaps if you can provide more information it will somehow make your claim seem less nonsensical.

        1. Anon says:

          I cant say too much for pretty obvious reasons, as you can imagine there is a lot of nervousness around all this. No one wants to cast doubt on the vaccine programme. The issue is the numbers given out by the UK dont seem to be realistic and are not believed elsewhere in Europe. Unfortunately there is far too much politics here.

          No you cant see the figures for St Thomas’ unless you work high enough up in the NHS. St Thomas’ is a large central London hospital with a well known Haematology dept. , if the 30 cases in 16 million numbers are correct you would expect to see maybe one at most two cases in all probability none. There have been many more.

          Clearly you cant simply extrapolate from one hospital to the whole country but neither should one hospital be so far out of line with the (supposed) national figures. There is a significant anecdotal evidence that the UK “yellow card” system is not working well. I understand the desire to reassure people that the vaccine is safe and serious side effects rare but not sure it helps if the perception takes hold that things are being hidden, no matter how good the intentions.

          1. Chris Phillips says:

            “No you cant see the figures for St Thomas’ unless you work high enough up in the NHS. St Thomas’ is a large central London hospital with a well known Haematology dept. , if the 30 cases in 16 million numbers are correct you would expect to see maybe one at most two cases in all probability none. There have been many more.”

            So how many do you claim there have actually been, and how many do you think should have been expected on the basis of the official figures, and what is the basis of your calculation? And if you tell us that, maybe we can judge the merits of your claim.

            You’re the one who said we might “want to check out” this information. So here we are, trying to check it out! Please give us some help in doing so. Otherwise …

          2. Anon says:

            @Chris Phillips (seem to have run out of replies)

            I phrased that badly. If you work in the field (this blog is read by medical professionals) you could contact the team at St Thomas’ (there are internationally known Haematology experts there) to ask about this. Clearly they wont be answering questions from random people or are unlikely to want to talk to the media.

            There are people here who want to look behind some of the headlines, it is worth doing so, I would guess there will be evidence around. There has been far too much political nonsense around AZ and some of the decisions made by individual countries have been nonsensical (restricting it to under 60s etc) but the caution shown by some countries with regard to the blood clot issue might be more justified than is currently being portrayed in the UK media.

          3. Chris Phillips says:

            Anon

            So can you at least clarify whether you have actually seen these figures you are talking about? And explain more clearly why you won’t tell us what they are, if you have seen them?

            It’s just very difficult to understand why you should urge us to “check out” these figures, and then when asked how we can do that, essentially tell us we can’t.

            Obviously you’re aware of the context of a lot of people posting unsubstantiated scare stories about vaccines on social media. Given that, personally I tend to treat online claims that can’t be substantiated as valueless in practical terms.

          4. bewd says:

            Anon
            are you suggesting that medics at the hospital are not reporting instances via the yellow card system? or are you saying the yellow card information is being hidden ?

          5. Corsica says:

            Anon, what is it that you “cant say too much for pretty obvious reasons”? Can you substantiate your comments that the UK has “a lot of nervousness around all this. No one wants to cast doubt on the vaccine program”. The only people who so far want to cast doubt are politicians in countries where the vaccination rate is low, but the case count high. A paraphrased quote a newspaper behind a paywall dues not justify you spreading online rumors without supporting your claims. If you have any proof or validity for your claims though, I would be happy to review and assess.

          6. Anon says:

            The current issues are not being raised by politicians but by medical professionals. For instance German politicians are very frustrated that the slow vaccine programme there is being disrupted even more by what many see as overly cautious medical decisions. The UK has been very successful (arguably the best in the world) with its vaccine programme. Politicians elsewhere are pointing to the UK to say “there are hardly any cases there so why are we worrying”. The issue with this is it depends on the reliability of the published data from the UK.

            I am not suggesting at all there is any “conspiracy” or anything similar but there is inevitably pressure to not disrupt the vaccine programme and any hint that the number of thrombosis episodes are higher than currently published would be a big issue especially when the UK is so reliant on AZ. It would not be surprising if Doctors might be somewhat reluctant to report possible side effect issues unless the linkage was very clear.

            The EMA is due to report further this week, it must be hoped that they will be able to look at as wide a set of data as possible (including, I would assume, from the UK). Lets see whether they support the Germans, Scandinavians etc with their cautious approach and whether they have any thoughts on the clear disparity in the data (eg Germany suggesting 30 cases out of 2.8 million, the UK suggesting 30 cases out of 16 million).

            Personally I have had my first shot of AZ and no issues with having my second (the benefits outweigh any risks) but I know a number of Haematologists are very concerned by all this. They are very torn between being seen as alarmist and so damaging the vaccine programme (possibly leading to more deaths) and wanting to raise what is a serious issue.

            This is an anonymous internet forum, not an academic journal. By all means say you don’t believe any of this, that’s not the point. What concerns me is that if the quality of the data is called into question then it undermines the vaccine, which seems to have been an issue with AZ from the start. It would be tragic if an effective, cheap vaccine is lost due to poor decision making.

          7. Chris Phillips says:

            Anon

            As you are continuing to post these claims I will ask again.

            (1) Are you claiming actually to have seen these figures you are talking about, or have you just heard rumours along the same lines you are posting?

            (2) If you are claiming to have seen them, what exactly is stopping you from posting them, rather than posting these vague claims?

            (3) What is the statistical basis of your claims about the figures? Is this claimed number of cases at this single hospital a statistically significant one? If so, please clarify how the figures from a single hospital can extrapolate to as little as just one order of magnitude larger than the official figure (which amounts to less than 2 in a million). How many million vaccinations are you claiming that the St Thomas’s figure represents?

  32. JJ says:

    https://www.bbc.co.uk/news/health-56620646

    “There have been two cases of CVSTs after Pfizer in the UK, out of more than 10 million vaccinated, but these did not have the low platelet levels. ”

    Thank you for this blog which I find most informative and which is on my reading list.

  33. Marko says:

    Former Biden, Trump advisers renew push to delay second Covid vaccine

    https://www.statnews.com/2021/04/02/democrats-and-republicans-alike-pressure-biden-administration-to-pursue-single-dose-vaccine-strategy/

    “You Don’t Need to Wear a Mask” Fauci is against the idea, of course.

    1. Marko says:

      I don’t consider Makary at the WSJ a go-to source, but he gets this exactly right:

      “U.K. Vaccination Puts U.S. to Shame”

      https://www.wsj.com/articles/u-k-vaccination-puts-u-s-to-shame-11617315471

  34. Marko says:

    Red States show that Covid-19 cases are reduced if you don’t look for them:

    https://www.nytimes.com/2021/04/01/us/coronavirus-testing-declines.html

    New hospital admissions will probably be the better metric to monitor new surges in these states.

    1. Marko says:

      “Certainly, it is strange that the one vaccine to be sold at cost price, and which has eschewed the typical high-pricing plans of big pharma, is the one that has been subjected to the greatest vilification.”

      Rather than “strange”, I would have used “predictable”.

      1. A Nonny Mouse says:

        Interesting that, after the cock-up of putting the wrong A-Z material in the J&J vaccine, the plant is now no longer allowed to make the A-Z vaccine, only the J&J one.

        1. WST says:

          Logical decision, J&J is an approved vaccine, long awaited one dose not needing special storage, at $10 cheapest of approved, its availability is a part of US vaccination plan.
          AZ production has been relocated elsewhere.

    2. sgcox says:

      Interesting angle in FT. Should be in open, I think.
      https://www.ft.com/content/2ce008f2-b5d2-4578-802d-d69b89d7036c

      1. Marko says:

        Nope, not for me. Behind the paywall.

        1. sgcox says:

          Hope it is not copyright violation, few paragraphs in the end:

          Inside AZ there is a belief the company’s current travails are due to geopolitical and commercial pressures unrelated to the merits of its Covid vaccine. Reflecting Soriot’s thinking, one insider said: “We are stuck in a post Brexit political tornado, where the European Commission is using us as a scapegoat.”

          Samuel Johar, who chairs Buchanan Harvey, a board advisory firm, argues most leaders would never have agreed to partner with Oxford University in the first place. “Any normal FTSE 100 company, deciding by committee, would have thought ‘we’re not going to make much money so we don’t want to get involved’.

          It’s only because of this mercurial leadership style of Pascal that he managed to roll all the obstacles away and make it happen.” If manufacturing supply to Europe improves and the vaccine continues to prove its worth through global mass immunisation campaigns, Soriot’s Rooseveltian risk and reward calculus will have been vindicated. But if the political noise around the jab limits its uptake, the CEO who has reformed AZ so completely in his own image will undoubtedly pay the price. Whether, in Roosevelt’s words, he ultimately knows “the triumph of high achievement”, or “fails while daring greatly”, it is a gamble he is clearly prepared to take.

          1. Marko says:

            Thanks. (Hope you got to read this before they locked you up.)

        2. sgcox says:

          Oh, the reference is to Theodore, not FDR. It was clear in the full article,

  35. Mark says:

    I wonder whether the first dose of the AstraZeneca vaccine may sensitize people so that they are more likely to get VIPIT after the second dose. If that is the case, we may see more VIPIT after the second dose, making this a greater risk than the current numbers suggest. Any thoughts?

  36. Diana Tracy says:

    Hello

    I would like to comment that the link between the clots, low iron and women should be looked into further. Under 50 year old women tend towards lower iron due to monthly cycle. The side effects to the vaccine can be linked to low iron. The blood clots can be caused by low iron.

    Perhaps if women were give more iron before the vaccine and after the risk would reduce.

    Thanks 😊

    1. Jane Mack says:

      A frightening thought for me as my iron levels are extremely low and my ferritin level is 3! I had my first AZ jab Feb 25th and was very unwell with a high fever, shivering and feeling faint for 24 hours then ok. I am concerned about the risk of blood clots with the 2nd dose. One thing I am wondering though, is whether the rare blood clots could be linked with women taking the contraceptive pill who have the AZ vaccination as the pill is a known risk anyway and the AZ vaccination could add to it?

      1. Chris Phillips says:

        The increase in anti-vaccine postings here seems to be almost as dramatic as the decrease in deaths and cases in the UK and Israel.

        One first-time commenter pops up to claim, without producing a shred of evidence, that “The side effects to the vaccine can be linked to low iron”. [?]Another first time commenter then jumps to back her up by saying how frightening it is and to add another bit of speculation about oral contraceptives – “the AZ vaccination could add to it”. On other threads we have people posting about deaths in their families following vaccinations. Very sad if true, but of course in scientific terms such deaths are bound to occur by sheer chance, given the number of vaccinations. And of course we have no way of separating truth from anti-vaccine fiction, of which there is a mountain online.

        Meanwhile in the real world.

        In dramatic contrast to Continental Europe, where cases are still rising despite lockdowns, in the UK the number of new cases is currently falling by 35% per week and the number of deaths by 45% per week.

        And in Israel, a study has found a rapid decrease in the number of infections among those unvaccinated as the percentage of vaccinations in the community increases:
        https://www.medrxiv.org/content/10.1101/2021.03.26.21254394v2.full.pdf

  37. Petya Gueordjeva says:

    I am not aware of any study in the US looking into type of antibodies in people with ITP related to post m RNA vaccination ,how do we know this is not the same as the VIPT?

  38. Chris Phillips says:

    Preprint on the ongoing evolution of the virus in Brazil:
    Abstract. Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the SARS-CoV-2 Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil is generating new viral lineages that might be more resistant to neutralization than parental variants of concern.
    https://virological.org/t/the-ongoing-evolution-of-variants-of-concern-and-interest-of-sars-cov-2-in-brazil-revealed-by-convergent-indels-in-the-amino-n-terminal-domain-of-the-spike-protein/659

  39. Marko says:

    Recovery from acute SARS-CoV-2 infection and development of anamnestic immune responses in T cell-depleted rhesus macaques

    https://www.biorxiv.org/content/10.1101/2021.04.02.438262v1

    “…To investigate the specific role of T cells in recovery from SARS-CoV-2 infections we studied rhesus macaques that were depleted of either CD4+, CD8+ or both T cell subsets prior to infection. Peak virus loads were similar in all groups, but the resolution of virus in the T cell-depleted animals was slightly delayed compared to controls. The T cell-depleted groups developed virus-neutralizing antibody responses and also class-switched to IgG. When re-infected six weeks later, the T cell-depleted animals showed anamnestic immune responses characterized by rapid induction of high-titer virus-neutralizing antibodies, faster control of virus loads and reduced clinical signs. These results indicate that while T cells play a role in the recovery of rhesus macaques from acute SARS-CoV-2 infections, their depletion does not induce severe disease, and T cells do not account for the natural resistance of rhesus macaques to severe COVID-19. Neither primed CD4+ or CD8+ T cells appeared critical for immunoglobulin class switching, the development of immunological memory or protection from a second infection. ”

    Surprising. I’ll be interested to see if this can be confirmed by others.

    1. Alex Beribisky says:

      This really flies smack in the face of a growing body of evidence indicating otherwise and also goes against the (so far, preliminary) findings that drugs that modulate T-cell activity have shown great success in treating severe Covid:

      https://www.timesofisrael.com/new-israeli-drug-cured-moderate-to-serious-covid-cases-within-days-hospital/

      So really not sure about this, perhaps species-specific mechanisms at play here? Incomplete T-cell abrogation?

    2. Alex Beribisky says:

      On the other hand, from from what is known, severe covid presentation (e.g. cytokine storm) is associated not with T-cell depletion, but rather hyperactivation. So it is possible that what is observed in this paper does not contradict the function that these cells play in severe disease onset.

      1. Marko says:

        I’m not sure what to make of it either. Although T-cell independent antibody production is not that uncommon, including in some respiratory viral diseases, it seems late in the game to be discovering that this is the case in Covid-19. I’d want to see the comparable studies in humans, though I’m not sure how those could be done. Perhaps by studying patients with inherited T-cell deficiency syndromes, if there are enough of them around that aren’t already living in bubbles.

        It does fly in the face of the “T-cells will save us” narrative, which is why I found it interesting. I have to think it will either be debunked or confirmed in fairly short order.

        1. Alex Beribisky says:

          I have to admit, I am indeed part of the proverbial “T-cell bandwagon”, so personal bias might creep into my posts.

          However, a quick glance at the relevant literature suggests that immunocompromised patients with low lymphocyte count (AIDS, cancer, organ recipients taking immunosuppressive medication) are clearly at a higher risk for severe Covid… This would further be indicative that in humans T-cells would be important in severe disease modulation.
          A personal hunch: It is really T-cell misregulation and not absence is what leads to cytokine storm, acute respiratory distress syndrome (ARDS) and other severe covid morbidities. But then again, I am not an immunologist.

          1. Marko says:

            That’s probably a good hunch. See this recent paper :

            https://www.cell.com/med/fulltext/S2666-6340(21)00115-X

            “…We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic programme evident in CD8+ T cells as well as elevated production of type-1 cytokines and IL-17…”

            Some patients with long covid report an improvement after vaccination, so it could be that the vaccine helps “reset” dysregulated T-cell responses to a more normal state.

          2. Rob Sutherland says:

            Hi Alex,
            I’m not an immunologist either but in X-linked hyper-IgM syndrome, there is an inability to perform Ig class switching from low affinity IgM to higher affinity IgG , IgA and IgE. This disease is not however down to a B cell defect but to a T cell defect.
            T cells express CD154 and this interacts with CD40 on B cells and this interaction promotes class switching from low affinity IgM production to higher affinity IgG production once an ‘immunogen’ has been encountered. In the absence of functional CD154, class switching fails to occur and boys with this defect show a spectrum of severity of this disease, depending on the severity of the CD154 mutation.
            In the paper cited, wiping out T cells apparently did not prevent the development of high affinity IgG antibodies. I wonder how efficiently, the T cells were ‘wiped out’ in these animals…….

  40. Chris Phillips says:

    I had missed this. The Spanish paper on Vitimin D that was so highly publicised, was retracted by the Lancet six weeks ago, “due to concerns about the description of the research in this paper”. It seems the participants weren’t randomised at all, but whole wards were allocated to one arm or the other:
    https://retractionwatch.com/2021/02/19/widely-shared-vitamin-d-covid-19-preprint-removed-from-lancet-server/

  41. Brussels bureaucrat says:

    Notice in the discussion above how one theory is been substituted for another, as novel facts come to light and in accordance with the serious scientific method.

    First, the criticism of the AZ vaccine was allegedly nothing more that lies typical for the vindictive and despicable EU still angry and frustrated with the UK for leaving the EU. How exactly the evil bureaucrats managed to influence the regulatory authorities of individual member states remains unknown, but this is of less importance since it is a fact that the member states of the EU have absolutely no self-determination and ultimately the EU (also known as “the Soviet Union 2.0”) was behind the evil plot against the AZ vaccine.

    Then, as the EMA did not change its full recommendation of the AZ vaccine the unfair criticism of AZ vaccine now had to be explained in a different way. Now the sinners were found among the national bureaucracies in continental Europe. Thus, it was admittedly perhaps no longer a politically motivated plot directly instigated by the dictatorial Brussels (always sniffing about for ways to bully the freedom-loving people of the UK), but rather simply due to common stupidity and laziness so ever typical of people on the old European continent.

    Then later, as Canada (grateful member of the Commonwealth) also decided to subject the AZ vaccine to closer investigation the theory had to be adjusted slightly and once more. Now, the unfair criticism of the AZ vaccine was obviously caused by those with a dog in the race. There are strong economic interests in COVID vaccines and no doubt some dubious and powerful individuals (unfortunately such can be present also outside the EU!) were unfairly producing misinformation to try to push the AZ vaccine out of the race in order to leave the marked open to non-UK vaccines.

    Then, suddenly, it was revealed that also in the UK there had been a low number of thrombotic events in connection with AZ vaccination, in some agreement with what was first observed in several pathetic EU slave nations. It was therefore immediately concluded that the observations were worth considering after all since the information was obtained in the incorruptible UK.
    😉

    1. Subject of the unelected monarchy says:

      Spoken like a genuine brexiteer! Pity those of us who have to share an island with people who really do think like that…

      On the other hand, if we in Brexitania were guilty of taking risks over delaying the second vaccination (which we did), so others may now be guilty of overcaution over what may just be spurious statistical blips. The way this is being presented will lead to more deaths in the end, I fear.

  42. Marko says:

    Researchers Are Hatching a Low-Cost Coronavirus Vaccine

    https://www.nytimes.com/2021/04/05/health/hexapro-mclellan-vaccine.html

    Uses the HEXAPRO upgrade on the 2P technology, and will permit royalty-free usage in low- and middle-income countries. Also will be prepared using standard flu vaccine technology, which will help alleviate the job loss fears of millions of chicken eggs.

  43. Mariner says:

    Here in the UK, Channel 4 News (that’s a national TV channel/news operation) is reporting that the MHRA may be considering changing their advice about the use of the AZ vaccine in younger people:

    https://www.channel4.com/news/uk-medicines-regulator-considers-issuing-new-advice-over-oxford-astrazeneca-jab

    Usual sort of report – senior anonymous sources supposedly providing the information.

    I’ve also seen it reported elsewhere that younger people in the UK (those in their 20s were mentioned in a report I read but can’t remember where!) will eventually be offered the one-shot J&J vaccine when we have it available. I’d imagine this is reliant on no similar risks of thrombosis being discovered in the J&J vaccine. I’d also imagine that they think younger people are less likely to turn up for two appointments.

    It wouldn’t surprise me if the MHRA took the middle road for now and recommended that younger women (i.e. those in their 40s) be offered the Pfizer vaccine with men in a similar age bracket continuing to be given the AZ. I suppose it all rather depends on the breakdown of the Yellow Card report data.

    1. Chris Phillips says:

      Obviously a problem with that is that if you are directing the more efficacious vaccine to those at lower risk from COVID-19, you may be raising the substantial overall risk from COVID-19 in order to lower a tiny risk from vaccination.

      1. Mariner says:

        I suppose depends on how likely the scare stories are to reduce vaccine uptake. If 20% of those offered it refuse the vaccine, it’s not going to make up for any potential reduction in efficacy between the two.

        I’d also note that we still don’t have good data about the efficacy of the AZ vaccine when the doses are given 12 weeks apart. It might end up to be closer in efficacy to the J&J vaccine than the 4-week dosing in the trials show. It would be helpful if it was! Also helpful to see it if did have more (or even some) efficacy against B1.351. That’s a different matter, however.

  44. Chris Phillips says:

    Valneva has announced positive results from its Phase 1/2 trial and hopes to initiate a Phase 3 trial by the end of the month (I’m not sure how or where):
    https://valneva.com/press-release/valneva-reports-positive-phase-1-2-data-for-its-inactivated-adjuvanted-covid-19-vaccine-candidate-vla2001/

    Apparently there was no one over 55 in this trial.

  45. Eve Purvis says:

    I had the Moderna vaccine on March 9th. I had a routine blood test for my annual check up at my general practitioner two days later. I have Non Hodgkin Lymphoma B Cell. I got a call the 12th from GP that my blood test showed very low platelets. They were 30k, and the lowest level should be 144k. I called my oncologist and they thought lab error but had me right in the 12th to re test. My platelets were 26k. That was a Friday. I went back Monday and the level was 29k. I have had a test every Monday since and a month later, yesterday, the level had gotten to 65k. I have my second vaccine today and both my GP and oncologist say go ahead and get it so I am. My age is 64, I’ll be 65 in September. Female.

  46. Petya Gueordjeva says:

    I still don’t understand why none of the CVT cases are not tested for prior or recent Covid 19, it is well known by now that those people have a much stronger first dose immunogenicity and we are likely dealing with the same hematological immune phenomenon as the one with Covid or any sirs . I do not believe we should keep recommending vaccination for recent Covid survivors

  47. Marko says:

    NYT update on variant prevalence in US states:

    https://www.nytimes.com/interactive/2021/04/06/us/variants-cases-spread.html?action=click&module=Spotlight&pgtype=Homepage

    Upturn in hospitalizations is concentrated among those under age 60, showing the effect of vaccination of the elderly.

  48. Anon says:

    Does anyone yet know how soon after the astra zen vaccine that people discovered they have CVT clot?

    1. Anon says:

      I mean are we talking days, weeks, months?

      There’s been a great discussion here but as a 30 year old female who had Astra with clotting in the family, my anxiety is a lot and I’m trying to stay calm. It’s been four weeks since my first shot and I’m getting increasing concerned.

  49. bewd says:

    from what I have seen reported
    Time-to-onset ranged from 0 to
    16 days.

    1. Anon says:

      Thanks

      I wouldn’t be as concerned but I was reading about as I had a headache and eye pain, still have it today but not as intense. I’m presuming since it’s been 4 weeks since my vaccine it’s more likely just a coincidence but tell that to my anxiety!

  50. Andrew Hartley says:

    If a male in the UK has had the first dose of the vaccine without any side effects would this mean that they would be most likley ok to have the second dose?

    1. Marko says:

      If it was me, I’d get the second dose, but if you become the one in a million that gets a blood clot that turns you into a vegetable, don’t blame me.

    2. Chris Phillips says:

      Yes, I can confirm that you will most likely be OK.

      On the figures we’ve seen, you would most likely be OK even if you had the vaccine every single day for a thousand years.

      1. Andrew Hartley says:

        Thanks for your reply. What I forgot to mention was that my son as also already had and recovered from Covid

  51. Marko says:

    Durability of antibody response for the Moderna vaccine:

    https://www.nejm.org/doi/full/10.1056/NEJMc2103916

  52. Marko says:

    New preprint from Sato Lab reports on potential cellular immunity escape by the California variants (L452R mutation):

    https://twitter.com/SystemsVirology/status/1379207393729384448

    California’s pandemic numbers continue to look pretty good, but this may be as much due to NPIs as to population immunity.

  53. Marko says:

    I hate to boost a company like Blackrock, but they do have a good country-based Covid tracker, covering things like like mobility, NPI stringency, vaccinations, etc. I wish I’d found it sooner:

    https://www.blackrock.com/corporate/insights/blackrock-investment-institute/interactive-charts/covid-tracker#virus-trends

    1. Marko says:

      The sharp upturn in test positivity in the US and, especially, in Canada, suggests that things may be progressing somewhat more rapidly than is reflected by case counts :

      https://ourworldindata.org/explorers/coronavirus-data-explorer?zoomToSelection=true&time=291..latest&pickerSort=desc&pickerMetric=new_cases_per_million&Metric=Share+of+positive+tests&Interval=7-day+rolling+average&Relative+to+Population=true&Align+outbreaks=false&country=USA~GBR~CAN

  54. Marko says:

    White House : “…nearly 1 in 3 Americans and over 40% of adults have received at least one shot”

    Bhutan : ” Hold my beer ”

    https://pbs.twimg.com/media/EyV1gNCWgAMl6RV?format=jpg&name=900×900

  55. Chris Phillips says:

    Latest modelling of a likely third wave in the UK in late Summer/early Autumn, following the relaxation of restrictions, given that the vaccination of under-50s is likely to be slower than previously expected:
    https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/975909/S1182_SPI-M-O_Summary_of_modelling_of_easing_roadmap_step_2_restrictions.pdf

  56. Brussels bureaucrat says:

    Finally some good news about the vaccine roll out in the EU.

    https://www.politico.eu/article/europe-vaccination-coronavirus-success-story/

    1. A Nonny Mouse says:

      Haven’t laughed so much in ages; thanks for that!

      I quote

      ….”With all the shots rolling in, it’s even no longer unthinkable that the EU will finish vaccinating its entire adult population ahead of the U.K. To use Council President Charles Michel’s imagery: While the U.K. is likely to finish its vaccination marathon crawling on all fours, the EU will be sprinting toward the tape.”

      Hilarious!

      I liked the bit about the only authority to fully license 4 vaccines. “Fully license” puts all the burden of liability on the vaccine producer which, in this time of a need for speed, is not the way to go.

      Anyway, it is no use using “US equivalent numbers” it’s actual doses that count. With the calculations there the UK would have been doing 2.5 million a day on US Eq, rather than the 5-600K achieved.

      1. Mariner says:

        A very peculiar tone in that Politico article. A bit immature to my ear.

        The EU may well be able to finish their vaccination programme more quickly than the UK due to their greater manufacturing capabilities, but at what cost due to the overly-slow initial rollout?

        The UK’s lack of manufacturing capability will obviously slow our rollout plans, especially as as the expected (perhaps hoped for?) doses ordered from SSI in India aren’t likely to materialise due to the surge in infections over there.

        We’ll also have to wait to hear what the MHRA say about the AZ vaccine later today to see how that will impact the vaccination programme in the UK. If they suggest limiting its use in younger people (and women, especially), it is going to put a big dent in plans and we would be reliant on the J&J and Novavax vaccines becoming available more quickly. Difficult to put a timescale on either of these with publicly available information and, as Valneva has only just finished their early stage trials, I can’t see that vaccine becoming available until much later in the year.

      2. Some idiot says:

        Yes, the article was quite unintentionally humorous… I really felt at one stage that the next line would be a Monty Pythonesque “I fart in your general direction!” Parts of the logic had loopholes so large you could drive a bus through them…

        And this is me as an EU resident speaking…! That said, yes, it is expected that all the adult who want to be vaccinated will be finished sometime late June. With the UK probably finishing somewhat before that.

        1. Some idiot says:

          Should have read “it is expected that all the adult population in Denmark who want to be vaccinated”…

          Sheesh… Remember to proof-read before sending.. What an Idiot! 🙂

          1. Brussels bureaucrat says:

            Assuming the info in the Politico article holds true, the next few months are going to decisive with respect to how the EU has handled the pandemic. If there is an upcoming dramatic increase in cases in the EU then cumulative deaths may increase from the current 1400 dead/million in total EU, to the levels seen in the UK (1900 dead/million & stagnating) , the US (1700 dead/million, still increasing slightly), and Italy (1800 deaths/million, increasing rapidly).

            So, the next few months are going to be crucial for the EU, but of cause some new mutant could change the game completely…

  57. ERJ says:

    I wonder whether there is a link between adenovirus-based vaccines (such as AZ) and clotting. Will the Johnson and Johnson vaccine cause similar side effects? It must be too early to tell.

  58. FrankN says:

    The MHRA has just presented updated figures on blood clot cases in the UK. From https://www.theguardian.com/politics/live/2021/apr/07/uk-covid-live-news-mhra-astrazeneca-vaccine-coronavirus-latest-updates

    “15:27 MHRA chief says there’s ‘strong possibility’ AZ vaccine causing extremely rare blood clotting side effects

    15:31 She says up to 31 March there had been 79 cases of this condition, with 19 deaths. All occurred after the first dose.

    The risk is about four people in a million, she says.

    She says three of the 19 people who died were under the age of 30.”

    Their recommendation is to stop vaccinating people under 30 with the AZ vaccine.

    Makes one wonder what took the MHRA so long to identify the problem. A few days ago, when the German PEI had already identified 17 cases among some 1.7 Mio. AZ vaccinations, the MHRA knew just about two incidences in the UK, after some 12 Mio. vaccinations.

    This makes me also wonder whether the UK figure of “four people in a million”, or the PEI figure of “one in one hundred thousand” will ultimately turn out to be closer to reality.

    1. Ono says:

      I stick to my previous, which seemed to raise some hackles when I posted it a few days ago:
      “Brits should be asking why the MHRA was so slow reporting known cases; why it didn’t report fatalities (until pressed by the media); and why it has not reported age/sex distribution of cases or fatalities? Something ‘political’ perhaps? (Some) EU countries have been much more open with their population in the face of a clear suspicion of a catastrophic illness linked to a vaccine which is still effectively in trial.”
      To follow up:
      Clear suspicion = now confirmed;
      Catastrophic illness = apparent 25% mortality (don’t know about severity of other outcomes);
      Effectively in trial = ie until vulnerabilities of specific groups can be assessed.
      Not an anti-vaxer.

      1. Brussels bureaucrat says:

        As for critical questions, my guess is that this latest development will be largely ignored in the UK. The success of the vaccination campaign is closely tied to Brexit and the British press is overwhelmingly in support of the UK Brexit government. Boris will get in front of the cameras with a pie or an ice cream and tell the EU to go stuff itself and everybody will cheer. The BBC is too scared to say anything. Perhaps The Guardian will do some follow up reporting, but they are getting weak at the knees also…

        1. Mariner says:

          It might just be a different, slightly more sanguine approach. The numbers of issues appearing obviously only showed very low risk factors for the majority of vaccinees and the view might well have been taken that a lot more good would be done by continuing the rollout as possible. The fact is that the UK is running lowish on vaccine doses during April as older people begin to get their second jab after 12 weeks. Rather than scaring the horses, it might well have been seen as a good idea to have the reporting of issues slower to ensure those more at risk took up their second dose. Few younger people (i.e. Under-40s or even Under-50s) are receiving their first dose of vaccine at present so little additional risk and no doubt that there will be a great many lives saved with older people fully vaccinated.

          The sad thing, of course, is that more lives would be saved in the EU if they had been following the UK route, given the higher levels and therefore higher risk over there at present. It’s why the EMA have taken their stance.

          Of course, it could just be organisational differences between the way some of the European and the UK authorities operate.

          1. Brussels bureaucrat says:

            I see your point – vaccine skepticism is an important issue, but I also believe it is very difficult to assess and it is presently linked with many other issues.
            For example, how many Italians have actually refused to get vaccinated for COVID? And given that the Italians had managed to grab early vaccines from the UK and Israel (Italy of cause was and still is free to buy all the vaccines it would like from anywhere in the world) would it have been able to roll out faster due to a possibly less efficient public sector? Did Italy have a choice in this matter? Also, the French were relatively skeptical of vaccination before the AZ vaccine showed side effects. So how many lives lost are we talking about due to some nations deciding to “err on the side of caution” and thus risking creating fear of vaccines? Is it better to “hide” the side effects and then risk the data coming out later in an uncontrolled manner? And isn’t the live of one 25-year-old more precious than the life of a 75-year-old? Etc.

            All these philosophical questions are thrown into the political arena. Add different cultures to the mix also…

            Clearly, the EU as a whole, as well as individual EU countries, have made mistakes, and also need to learn from how the UK and the US managed the pandemic.

  59. Marko says:

    UK gov’t statement:

    https://www.gov.uk/government/news/statement-on-astrazeneca-covid-19-vaccine-following-mhra-update

    “…“Everybody who has already had a first dose of the AstraZeneca vaccine should receive a second dose of the same brand, irrespective of age, except for the very small number of people who experienced blood clots with low platelet counts from their first vaccination.

    The government will follow today’s updated advice, which sets out that, as a precaution, it is preferable for people under the age of 30 with no underlying health conditions to be offered an alternative vaccine where possible once they are eligible….”

    1. A Nonny Mouse says:

      The 79 seems to be from 20m+ doses which is more than the UK has given so probably includes the German data.

      1. Tony M says:

        “Up to March 31, the MHRA in the UK has received 79 reports of blood clots accompanied by low blood platelet count, all in people who had their first dose of the vaccine, out of around 20 million doses given. Of these 79, a total of 19 people have died” and “The 79 cases occurred in 51 women and 28 men, aged from 18 to 79. Of the 19 who died, three were under the age of 30” and “Some 14 cases of the 19 were cerebral venous sinus thrombosis (CVST), a specific type of clot that prevents blood from draining from the brain. The other five cases were other kinds of thrombosis in major veins. The figures suggest the risk of rare blood clot is the equivalent to four people out of every million who receive the vaccine.” Table indicates that as at 6 April, 31.7M first doses of all vaccines had been given, and
        “in Europe, the EMA has carried out an in-depth review of 62 cases of CVST and 24 cases of splanchnic vein thrombosis in which 18 people died.”
        Source: https://www.standard.co.uk/news/uk/astrazeneca-pfizer-people-moderna-vaccination-b928359.html

    2. Will says:

      Hi, I am one of the people who has had my first doze of AZ vaccine. I’m a 23 year old male. What is people’s opinion on getting the second dose? I am a little concerned following all the news today.

  60. Marko says:

    Still no closer to knowing what happened in Manaus. From a Stanford Zoom seminar today:

    https://pbs.twimg.com/media/EyZXjpsWYAEs_kA?format=jpg&name=small

    1. Marko says:

      It’s hard to place the blame on Brazil here, since we’re just as clueless about reinfections in the US :

      https://www.statnews.com/2021/04/07/covid-19-reinfections-still-seem-rare/

  61. Marko says:

    Over-65s who’ve received at least one dose, by state :

    https://pbs.twimg.com/media/EyZqF9FWYAsWPsS?format=jpg&name=small

    Not surprising that Vermont leads the way. The laggards aren’t too surprising, either.

  62. Jonathan B says:

    Just to be accurate because regulators are getting mixed up in the summaries above, the MHRA in the UK has not changed its recommendation that the AZ vaccine’s risk is small in relation to the benefit and there is no change in its authorisation.

    However, the representative of the JCVI at the same meeting (Joint Committee on Vaccination and Immunisation, which has given guidelines for vaccine administration in the UK) stated that given the presence of alternative vaccines, where possible the AZ vaccine will no longer be given to under-30s. The data presented suggests that they assess the risk from Covid at its present prevalence to be more than the risk of vaccination, but the balance will reverse as Covid prevalence falls.

    Similarly in the EU, the EMA determined on the basis of risk-benefit that no change be made to the AZ vaccine authorisation, but that individual countries might choose to preferentially allocate different vaccines to different age groups depending on availability. They do however propose to adjust side-effect advice in the documentation to take account of the new observations.

  63. Kate Moir says:

    Any data on cvst/thrombo cases age/medical history/current medication?
    Also cases after 1st or 2nd dose?

  64. Marko says:

    Unlike Big Pharma and its army of shameless shills , Ireland believes in Vit. D :

    https://www.oireachtas.ie/en/press-centre/press-releases/20210407-oireachtas-health-committee-launches-report-on-addressing-vitamin-d-deficiency-in-ireland/

    “…daily Vitamin D supplementation of 20-25µg/day should be recommended to the entire adult population as a public health measure, with higher doses recommended for vulnerable groups under medical supervision…..specific measures need to be put in place for vulnerable groups, and for frontline and healthcare workers, so that Vitamin D supplementation is administered on an opt-out basis, and for the duration of this pandemic, people should be offered Vitamin D supplements when presenting at Covid-19 test centres.”

    Expect a flurry of designed-to-fail RCTs for the purpose of disabusing Ireland and others of this notion.

  65. Alex says:

    I am intrigued why the under-30s demographic in the U.K. has been singled out as ‘not recommended’ to have the AZ vaccine on balance of risk/benefit when in fact it is women aged 30-55 who have predominantly died from CVST events?

  66. Marko says:

    COVID-19 Pandemic-Related Excess Mortality and Potential Years of Life Lost in the U.S. and Peer Countries

    https://www.healthsystemtracker.org/brief/covid-19-pandemic-related-excess-mortality-and-potential-years-of-life-lost-in-the-u-s-and-peer-countries/

    In short: Having dark skin in the US is very bad for your health, especially during a pandemic.

  67. Marko says:

    Why US coronavirus tracking can’t keep up with concerning variants : The country has an enormous virus-sequencing capacity, but funding and an inability to get its shit together are holding it back.

    https://www.nature.com/articles/d41586-021-00908-0

  68. bewd says:

    https://www.reuters.com/article/us-health-coronavirus-europe-vaccines/eu-reviews-jj-covid-19-vaccine-for-blood-clots-expands-astrazeneca-probe-idUSKBN2BW1MB?il=0

    Four serious cases of rare blood clots with low platelets, one of which was fatal, have been reported after inoculation with J&J’s vaccine from its Janssen unit, the European Medicines Agency (EMA) said.

  69. JJ says:

    I posted a link to a recent video by Dr. John Campbell ‘Vaccine Safety Update’ – 8th April. Useful for those who have asked particular questions on locating source data and related matters. He also finishes by reinforcing what he has said previously about the importance of injecting properly. It has disappeared so presume this site does not like YouTube links. It is easy enought to locate his videos.

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