Is the clotting issue with the Oxford vaccine being blown out of proportion?

[bhobba]

I am confused about the 'hoopla' around Oxford's vaccines clotting issue. It is an issue with all the vaccines:
https://www.prnewswire.com/news-rel...n-physicians-and-surgeons-aaps-301262360.html

Am I missing something?

As it stands now, I am fine with the reported clotting. It occurs in about 4 in a million cases. If caught is entirely treatable, so now we are aware of it, the chances of a fatal outcome will be even less. Just out of curiosity, I picked a random vaccine, smallpox (I know it is not used any more - it was just a random pick), and it had a 1 in a million fatality. No worries with getting smallpox vaccines, yet everyone in Aus is going wild about this. Now 55% do not want the Oxford vaccine. As it stands now, I have no issue. The biggest problem in Aus is getting a booking - I will be discussing it with my doctor Monday when I get the Flu jab.

Thanks
Bill

 

[jedishrfu]

It's the fear factor. People are watching for any reason to avoid the newly tested vaccine.

Blood clotting is a worry but as has been reported statistically it's at the same level of occurrence as the general population.

However, it could be significant at some point (depending on your level of Chicken Littleness) and so people are fearful.

What gets me is the number of people who decide against the vaccine. We know there are special people who can't get the vaccine because of some special health reasons. (eg people allergic to eggs).

They depend on herd immunity to survive. However, when a significant percentage of the herd decides against the vaccine then those special people are denied protection.

It reminds me of how some selfish people take handicap spots. The spots are there for people who really need them. When you take it even for a few minutes then you're denying a handicapped person who needs it the most.

 

[Ygggdrasil]

No worries with getting smallpox vaccines, yet everyone in Aus is going wild about this.

The small pox vaccine is a bad example to choose here, because it is associated with serious side effects. According to the CDC, for every 1,000 people vaccinated, 1 person experiences a serious but not life-threatening reactions, and 14-52 out of every million people vaccinated suffer life-threatening reactions. After 9/11 in America, there was some push to revive the smallpox vaccination program in the US to pre-emptively protect against bioterrorism (currently, the smallpox vaccine is not in widespread use as the smallpox virus does not circulate in the wild anymore), but it was concluded that such a program would likely kill more people than it would save.

I am confused about the 'hoopla' around Oxford's vaccines clotting issue. It is an issue with all the vaccines:
https://www.prnewswire.com/news-rel...n-physicians-and-surgeons-aaps-301262360.html

Am I missing something?

As it stands now, I am fine with the reported clotting. It occurs in about 4 in a million cases. If caught is entirely treatable, so now we are aware of it, the chances of a fatal outcome will be even less.

The specific type of blood clotting seen in the people receiving the AstraZeneca vaccine is very unusual and has certain characteristics (e.g. low platelet levels) that make it look much different than the typical type of blood clots observed in the general population. As far as I know, these unusual type of blood clots have not been reported for those taking the other types of COVID-19 vaccines.

The argument that the rate of blood clotting is similar between the general population and people taking other COVID-19 vaccines is somewhat misleading as the total rate of blood clotting is much higher than the incidence of the rare Oxford-AstraZeneca-vaccine induced type of clotting. The most common type of blood clotting occurs at a rate of 1-2 per 1,000 people each year; adding an additional ~4 per million to that rate will not make an appreciable impact on the overall incidence of blood clotting.

The European Medicines Agency recently concluded that the unusual blood clots are indeed a side effect of the Oxford-AstraZeneca vaccine, but note that the condition is rare and in most cases the benefits of the vaccine outweigh the risks.

EMA press release: https://www.ema.europa.eu/en/news/a...very-rare-cases-unusual-blood-clots-low-blood

Popular press coverage: https://www.statnews.com/2021/04/07/astrazeneca-covid-19-vaccine-linked-to-blood-clots/

 

[bhobba]

The small pox vaccine is a bad example to choose here, because it is associated with serious side effects. According to the CDC, for every 1,000 people vaccinated, 1 person experiences a serious but not life-threatening reactions, and 14-52 out of every million people vaccinated suffer life-threatening reactions. After 9/11 in America, there was some push to revive the smallpox vaccination program in the US to pre-emptively protect against bioterrorism (currently, the smallpox vaccine is not in widespread use as the smallpox virus does not circulate in the wild anymore), but it was concluded that such a program would likely kill more people than it would save.
\ other types of COVID-19 vaccines.

Wow - that's news to me. Here in Aus, although I do not think it was mandatory, everyone seemed to get it. It left a scar, and we as kids used to compare the scars we had from vaccines. The same with TB. It left a whopping scar and was actually given to all kids at school.

Thanks
Bill

 

[Filip Larsen]

It's the fear factor. People are watching for any reason to avoid the newly tested vaccine.

With the data and recommendations presented so far by both national health authorities and EMA in Europe, it is not surprising that "young, otherwise healthy" persons will not accept the tiny risk of fatal or serious side effects compared to the slightly higher (my estimate) risk of "mild flue with some long term effects" of Covid-19.

If I was 30 and had a history of auto-immune reactions I doubt I would accept the risk. This position seems to be backed up by the decision from at least some national authorities to only offer AstraZeneca to people above a certain age. I assume such decisions has been taken both based on medical data, but also in order to reduce reasons for vaccine fear in the general population, which is strongly tied to how much said population trust the authorities to cater for their personal safety.

 

[Filip Larsen]

Just as a follow up, Danish health authorities, which paused use of AstraZeneca around a month ago, has today decided to stop using AstraZeneca in the continued vaccination program. AstraZeneca is still approved for use in Denmark, but in light of all data and the availability of other vaccines, the actual use for mass-vaccination has been stopped.

Additionally, it seems that a Danish/Norwegian register-study has estimated that around 1 in 40 thousand will be in risk developing the newly named VITT syndrome. Furthermore, authorities say it is currently not known how to avoid long-term effects of VITT (or a fatal outcome). All combined, it means it makes no sense (for Denmark) to continue use of AstraZeneca.

 

[bhobba]

Additionally, it seems that a Danish/Norwegian register-study has estimated that around 1 in 40 thousand will be in risk developing the newly named VITT syndrome.

I notice you said 'in risk'. I didn't know research into it had progressed to determine risk factors, aside from age and sex. The latest here in Aus is about a 1 in 250000 chance of getting it. It is treatable and, from what I can gather, has about a 75% success rate, but unfortunately, 25% die. That gives about a 1 in a million death rate. When analysing low probability events to keep them in perspective, I like to compare it to the chance of death while crossing the road. One road crossing has about 3.3 deaths per billion. So this compares to 330 road crossings. I do not think anybody would worry about doing that. Of course, each person should decide in conjunction with their doctor. Personally, I will be getting mine in May sometime. I was worried because my GP practice was booked out until the end of August in a week and are not taking any more bookings right now. However, my GP told me he already booked me when I saw him on Monday to get the Flu jab.

Added Later:
The following breaks down the statistics further and if the risk of getting a severe reaction is higher than the risk of contracting Covid and dying (which, of course, depends on how bad the pandemic is where you are):


Interestingly, if you had both a blood clot and a low platelet count, that is what the worry is. They found from preliminary data that it also happened with the Pfizer Vaccine but at about half the rate - although further data is needed. So going to another vaccine may not be the answer.

Doing the risk vs benefit analysis here in Aus, where there is zero community transmission, shows no vaccination has the best profile. Of course, maintaining no community transmission without a vaccine program is the problem.

Added even later:
This just gets weirder and weirder. See my post, 26. The difference between Pfizer and AZ was not about half - it is nearly the same - but did not include a low platelet count. And I made a goof, it was not 1/2, it was 1/20 including the low platelet count. More research is definitely needed.

Thanks
Bill

 

[Filip Larsen]

I notice you said 'in risk'. I didn't know research into it had progressed to determine risk factors, aside from age and sex.

So far I only got the numbers verbally from the press conference that has the general population as audience. The written press release can be found here, but that exclude the interesting and surprising numbers like 1 in around 40,000. The director mentioned, during the presentation, that the study would be published and presented internationally in the near future, but I don't recall any explicit date or publisher was mentioned.

It was mentioned (again verbally) that the authorities at this point was not aware of any study that had found statistically significant correlation or non-correlation with age or gender of the identified VITT syndrome cases, which is also part of the reason why the choose to stop using AstraZeneca and not use the ones already stock (at this point in time). Also mentioned repeatedly was that this decision makes sense in the context of the situation in Denmark at this point (in short, Denmark is currently relatively well off in controling the epidemic), and for other countries in a different situation a different decision could be just as justified.

 

[Filip Larsen]

I found the offical note regarding continued vaccination without Vaxzevria (in danish).

My translation of a section that seems to explain the numbers (note, I am not a doctor):
Preliminary yet unpublished result from the danish experts work with national and Danish-Norwegian data indicate a frequency of cerebral veneral thrombosis amongst persons under age 65 (health workers and similar) vaccinated with Vaxzevira is 2.5 cases per 100,000 vaccinated in the first 2 to 4 weeks after vaccination, which is considered a significant frequence increase compared to expected background level of cases.

And later (again my translation):
The fatality rate [of VITT] cannot be specified with certainty from the available data, but based on case reports on hand so far it looks to possibly be in the range 20% to 40%, which corresponds to a risk of 1 death per 100,000 to 160,000 vaccinated.

 

[PeroK]

It's probably just a coincidence, but there seems to be an anti-correlation between susceptibility to COVID and susceptibility to blood clotting. The risk of blood clots appears to be higher in younger people, which is the opposite of the risk from COVID. Also, the blood clotting has been identified in countries with low COVID fatality rates (Norway and Denmark). In general, countries like the UK that has been ravaged by COVID have identified far fewer blood clots.

I believe that 20 million doses of the AZ vaccine have been given in the UK and 79 cases of clotting, with 19 fatalities, have been identified. The UK estimates the risk of death at about one in a million. The plans are to limit the use of AZ to people over 30. We are now well-advanced on the second round of vaccinations and there seems to be little reluctance to get a second shot of the AZ.

 

[bhobba]

I believe that 20 million doses of the AZ vaccine have been given in the UK and 79 cases of clotting, with 19 fatalities, have been identified. The UK estimates the risk of death at about one in a million. The plans are to limit the use of AZ to people over 30. We are now well-advanced on the second round of vaccinations and there seems to be little reluctance to get a second shot of the AZ.

If you look at the video, you get the exact figures, and death is something like 1 in 1,300,000 or roughly about the same as 300 street crossings. The interesting calculation is at what age does the risk become greater than the reward. For the UK, that turned out to be 30. But it is dependant on how well controlled the pandemic is. Figures are given for different levels. Here in Aus, they recommend, not compel mind you, recommend, you get Pfizer if under 50. It happens, according to preliminary data, about half as much. The obvious question is why we have not heard of it in the US. They use Pfizer a lot. It is just not widely reported - that's all:
https://www.the-sun.com/news/2305200/doctor-dies-36-others-develop-rare-blood-disorder-vaccines/

The J&J vaccine has shown the same problem, but like the Pfizer, it seems to be less, and they could be hot on the trail of the cause:
https://www.nbcnews.com/health/heal...ne-could-explain-risk-extremely-rare-n1263939

As I said, Aus has basically eradicated Covid, the risk vs reward is not to get it. Of course, we must prevent future outbreaks from quarantine escape etc. So Aus must vaccinate. But there is no need to rush.

Some interesting country dependant decisions are now required to manage risk. Call in the Actuaries :) :).

Personally, I do not worry about risks this low and am getting the Oxford jab sometime in May.

Thanks
Bill

 

[Ygggdrasil]

If you look at the video, you get the exact figures, and death is something like 1 in 1,300,000 or roughly about the same as 300 street crossings. The interesting calculation is at what age does the risk become greater than the reward. For the UK, that turned out to be 30. But it is dependant on how well controlled the pandemic is. Figures are given for different levels. Here in Aus, they recommend, not compel mind you, recommend, you get Pfizer if under 50. It happens, according to preliminary data, about half as much. The obvious question is why we have not heard of it in the US. They use Pfizer a lot. It is just not widely reported - that's all:
https://www.the-sun.com/news/2305200/doctor-dies-36-others-develop-rare-blood-disorder-vaccines/

The J&J vaccine has shown the same problem, but like the Pfizer, it seems to be less, and they could be hot on the trail of the cause:
https://www.nbcnews.com/health/heal...ne-could-explain-risk-extremely-rare-n1263939

As I said, Aus has basically eradicated Covid, the risk vs reward is not to get it. Of course, we must prevent future outbreaks from quarantine escape etc. So Aus must vaccinate. But there is no need to rush.

Some interesting country dependant decisions are now required to manage risk. Call in the Actuaries :) :).

Personally, I do not worry about risks this low and am getting the Oxford jab sometime in May.

Thanks
Bill

According to a meeting of the US CDC's Advisory Council on Immunization Practices yesterday, here are the current statistics on the prevalence of cerebal venous sinous thrombosis (CVST) among individuals vaccinated with the various types of vaccines in the US:

(see slide #14 from https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-04/03-COVID-Shimabukuro-508.pdf)

According to the presentation, the incidence of CVST in the general population is estimated at 0.22–1.57 per 100,000 (~0.5-1% of all strokes).

The article from The Sun (a British Tabloid) that you cite describes a immune thrombocytopenia, which is different from the CVST events that are at issue (though the CVST events are accompanied by thrombocytopenia). If a large number of other immune thrombocytopenia events are observed, that would be cause for concern, though if it is just one case in the almost 100 million doses of the Pfizer vaccine administered, it is more likely an unfortunate coincidence that the individual had immune thrombocytopenia after vaccination than a causal relationship.

It is certainly worth checking more carefully to see if there are unreported cases of CVST after vaccination with the mRNA vaccines, but the current data suggests that these vaccines do not induce the VITT associated with the Oxford-AstraZeneca vaccine (and potentially the Johnson & Johnson vaccine). This makes sense given that the Pfizer and Moderna vaccines are mRNA vaccines that are based on a completely different technology than the adenoviral vector technology used for the Oxford-AstraZeneca and J&J vaccines.

 

[bhobba]

The article from The Sun (a British Tabloid) that you cite describes a immune thrombocytopenia, which is different from the CVST events that are at issue (though the CVST events are accompanied by thrombocytopenia).

Drats - I didn't notice it was the US Sun. While not the notorious UK Sun, it does not bode well. It does, however, give a link to the much more reliable New York Times:
https://www.nytimes.com/2021/02/08/health/immune-thrombocytopenia-covid-vaccine-blood.html

And yes - you are correct about the other issues.

Please, those reading this, do not get too excited. We have some irrational fear appearing. For example, I am watching a program right now where some young front line workers in aged care facilities, who already have had the first dose without issue, do not want to get the second dose of Oxford because of fear. There have been no reports of problems with second doses to the best of my knowledge.

Thanks
Bill

 

[lavinia]

Drats - I didn't notice it was the US Sun. While not the notorious UK Sun, it does not bode well. It does, however, give a link to the much more reliable New York Times:
https://www.nytimes.com/2021/02/08/health/immune-thrombocytopenia-covid-vaccine-blood.html

And yes - you are correct about the other issues.

Please, those reading this, do not get too excited. We have some irrational fear appearing. For example, I am watching a program right now where some young front line workers in aged care facilities, who already have had the first dose without issue, do not want to get the second dose of Oxford because of fear. There have been no reports of problems with second doses to the best of my knowledge.

Thanks
Bill

Fear yes. Irrational yes since few know the science of vaccines. But I still wonder whether an incompletely tested vaccine that was rushed under an official emergency (EUA, Emergency Use Authorization) should not be questioned to some extent at least.

This leads to a technical question: The current statistics on adverse effects of the vaccine are based on short term experience. While they are consistent with other widely accepted vaccines they are not vetted over a long time frame. So how valid is the sample distribution at this point in time? Otherwise asked: how reliable is a short term sample as an indicator of the long term distribution for vaccine side effects?

Also, I have looked around on the web for an explanation of the biology of these Johnson and Johnson and Astra-Zeneca vaccine side effects and didn't find anything. So the next question is, what is known about the biology here? Correct me if this is wrong but I thought that the adenovirus system has been used in other vaccines and seems to be acceptably safe. So if it is not the adenovirus itself does it boil down to the spike protein and if so wouldn't that be true of all of the vaccines?

 

[jedishrfu]

Ars Technica has an article that may shed some light here:

https://arstechnica.com/science/202...edient-at-the-center-of-jj-astrazeneca-drama/

 

[Ygggdrasil]

Fear yes. Irrational yes since few know the science of vaccines. But I still wonder whether an incompletely tested vaccine that was rushed under an official emergency (EUA, Emergency Use Authorization) should not be questioned to some extent at least.

Although all the vaccines currently in use in the US are authorized for distribution under an EUA, the FDA had much more strict requirements for the COVID vaccines than it typically requires for an EUA.

Drugmakers seeking an emergency authorization for a Covid-19 vaccine will have to meet a higher standard of efficacy than normally would be required for such a clearance, the head of the U.S. Food and Drug Administration’s office that handles vaccines said.

Typically, an emergency use authorization, or EUA, would require a company to show their product may be effective. Peter Marks, director of the FDA’s biologics office, said Thursday that the agency will require more robust data about how well a Coronavirus vaccine works before granting an emergency waiver -- something he called “EUA plus.”

[...]
Marks said the data requirement will more closely mimic the standards that apply for an application for a regular approval. The emergency pathway will be used mostly to help shed some paperwork and technical requirements to get the vaccine to Americans more quickly, he said.

https://www.bloomberg.com/news/arti...-bar-for-emergency-covid-19-vaccine-clearance

Indeed, all of the vaccines given an EUA from the FDA have undergone large phase III clinical trials in tens of thousands of people to show efficacy, and the trials were required to show at least two months of data post vaccination for monitoring of any adverse events.

This leads to a technical question: The current statistics on adverse effects of the vaccine are based on short term experience. While they are consistent with other widely accepted vaccines they are not vetted over a long time frame. So how valid is the sample distribution at this point in time? Otherwise asked: how reliable is a short term sample as an indicator of the long term distribution for vaccine side effects?

As you correctly note, we don't have much data on any long term effects of the vaccines. Based on our experience with other vaccine trials, we would expect most adverse events to occur in the short term (weeks after vaccination). However, there are extensive systems in place to monitor for adverse events that are longer term or sufficiently rare that the would not be apparent in the clinical trials (which is how potential issues with the Johnson and Johnson vaccine were identified).

Also, I have looked around on the web for an explanation of the biology of these Johnson and Johnson and Astra-Zeneca vaccine side effects and didn't find anything. So the next question is, what is known about the biology here? Correct me if this is wrong but I thought that the adenovirus system has been used in other vaccines and seems to be acceptably safe. So if it is not the adenovirus itself does it boil down to the spike protein and if so wouldn't that be true of all of the vaccines?

No. While scientists have been studying adenoviral vectors for various clinical applications for decades, the COVID-19 vaccines are the first example of adenoviral vectors being used for vaccines in humans. See the article posted by @jedishrfu above or this article from C&EN News for more information.

 

[Laroxe]

I think the majority of scientists studying these clotting disorders, see CVT and Splanchnic Vein Thrombosis as only one manifestation of specific immune mediated thrombophylic disorders, there are others that can be just as dangerous. They are not a new disorder and they have been associated with other infections and with other vaccinations, there are also some inherited conditions which show a very similar pathological process. A variety of thrombophilic disorders have been seen with all the Covid vaccines.

Currently its not clear what pathophysiology explains the condition but there are some ideas around that suggest that the vaccine stimulate some cross reactive antiodies that attack platlets and various other clotting factors which leads to a situation in which abnormal clotting and increased risk of bleeding co-exist. Its very likely that the vaccination interacts with a variety of other risk factors these may include inherited traits, being a premenopausal woman, pregnancy, being on the pill, a history of clotting disorders etc. I'm surprised that its been suggested that there is no association with age or sex, most studies identify these as extremely important.

Adenoviruses have been used in other vaccines and the viruses used in the AZ and J&J are different, we have no information about the Sputnick vaccine which also uses adenoviruses.
Because these events are rare and require particular diagnostic approaches its still not clear if this association is real and if it is whether its only associated with the adenovirus vector vaccines. The differences in rates will be explained by the way in which the vaccine was rolled out, generally it would be the elderly who would get the vaccine first exept in Europe where this low risk group didn't get the vaccine.
Comparisons with population norms are of limited use as there are some well known risk factors that have a massive effect on the relative risk. These would all interact with the immune responses.
https://pubmed.ncbi.nlm.nih.gov/30005273/

This gives some info on pathology and on comparisons between the vaccines.
https://www.bmj.com/content/373/bmj.n883/rr-1

Because these clotting disorders can be difficult to diagnose they are often managed in the same way as other clotting disorders, this might in fact be the major determinant of outcome, starting treatment with heparin worsens prognosis. Effective early treatment greatly reduces mortality.

 

[bhobba]

Fear yes. Irrational yes since few know the science of vaccines. But I still wonder whether an incompletely tested vaccine that was rushed under an official emergency (EUA, Emergency Use Authorization) should not be questioned to some extent at least.

This is a difficult one. My solution is to educate the public. Out here in Australia, they kept on saying it is safe; stage 3 trials have been done, you can see the results if you are into that sort of stuff. Get vaccinated ASAP. Basically, it is true. BUT a better, deeper answer is it has passed stage 3 trials, but that does not give data on very rare or long term complications. We already have had experience with that - the 1976 Flu vaccine:
https://www.smithsonianmag.com/smart-news/long-shadow-1976-swine-flu-vaccine-fiasco-180961994/

Some people will not worry about such low probability complications, while others will. The government should make all the issues known to everyone via an extensive campaign, e.g. experts appearing on talk shows etc. Like I think most countries are doing, the vaccine should be implemented in a phased way, with the most vulnerable getting it first. Also, anybody who does not want the vaccine should be required to discuss it with their doctor. After they can still decline it, but it will be an informed decision. Many will take up the offer - some will not. But we will get large population data that will either convince those worried, or a new vaccine will need to be used. New ones are being developed all the time, e.g. the Novavax Vaccine will likely be available and approved soon. It is a more traditional vaccine, so it may not have the same complications. That is basically what is going on anyway - but it will be an informed choice.

Regarding the infrequent complications, scientists must do further research. Only in that way can the public be reassured. It may turn out to be not a rare complication, occurring with the same frequency as those not vaccinated. Or not. But research is the only thing that can answer that. And the public must be kept in the loop.

The big issue I see is how bad the pandemic is. My proposal would work fine in Australia, where Covid is basically eliminated. However, it was running wild in the UK before they started mass vaccination. It now is a lot better. On a risk vs reward basis, they can lower the age where you get the vaccine choice to 30. Other countries like Brazil need to vaccinate everyone quickly until it gets under control, like the UK. So no choice there - you get whatever vaccine is available. The risk vs reward is regardless of vaccine; you are better off getting it. For Australia, they could choose any age really but chose 50 because that is the age where if you get Covid the chances of death start to be of concern. Some infectious disease experts think those healthy and under 50 do not even need to be vaccinated - I do not agree - but it is what they think.

After penning the above, I now think people really need to understand risk vs reward better. That is a big problem. Even highly educated people here in Aus, but not trained in math and risk, are acting irrationally. A well-known commenter here in Aus, very well educated as a lawyer and head of staff to a previous Prime Minister, just turned 50 and will only be offered the Oxford vaccine. She will now not get vaccinated. Amazing, isn't it.

Thanks
Bill

 

[lavinia]

This is a difficult one. My solution is to educate the public. Out here in Australia, they kept on saying it is safe; stage 3 trials have been done, you can see the results if you are into that sort of stuff. Get vaccinated ASAP. Basically, it is true. BUT a better, deeper answer is it has passed stage 3 trials, but that does not give data on very rare or long term complications. We already have had experience with that - the 1976 Flu vaccine:
https://www.smithsonianmag.com/smart-news/long-shadow-1976-swine-flu-vaccine-fiasco-180961994/

Some people will not worry about such low probability complications, while others will. The government should make all the issues known to everyone via an extensive campaign, e.g. experts appearing on talk shows etc. Like I think most countries are doing, the vaccine should be implemented in a phased way, with the most vulnerable getting it first. Also, anybody who does not want the vaccine should be required to discuss it with their doctor. After they can still decline it, but it will be an informed decision. Many will take up the offer - some will not. But we will get large population data that will either convince those worried, or a new vaccine will need to be used. New ones are being developed all the time, e.g. the Novavax Vaccine will likely be available and approved soon. It is a more traditional vaccine, so it may not have the same complications. That is basically what is going on anyway - but it will be an informed choice.

Regarding the infrequent complications, scientists must do further research. Only in that way can the public be reassured. It may turn out to be not a rare complication, occurring with the same frequency as those not vaccinated. Or not. But research is the only thing that can answer that. And the public must be kept in the loop.

The big issue I see is how bad the pandemic is. My proposal would work fine in Australia, where Covid is basically eliminated. However, it was running wild in the UK before they started mass vaccination. It now is a lot better. On a risk vs reward basis, they can lower the age where you get the vaccine choice to 30. Other countries like Brazil need to vaccinate everyone quickly until it gets under control, like the UK. So no choice there - you get whatever vaccine is available. The risk vs reward is regardless of vaccine; you are better off getting it. For Australia, they could choose any age really but chose 50 because that is the age where if you get Covid the chances of death start to be of concern. Some infectious disease experts think those healthy and under 50 do not even need to be vaccinated - I do not agree - but it is what they think.

After penning the above, I now think people really need to understand risk vs reward better. That is a big problem. Even highly educated people here in Aus, but not trained in math and risk, are acting irrationally. A well-known commenter here in Aus, very well educated as a lawyer and head of staff to a previous Prime Minister, just turned 50 and will only be offered the Oxford vaccine. She will now not get vaccinated. Amazing, isn't it.

Thanks
Bill

I did not mean to question whether it was prudent to vaccinate as many people as possible. I just got the second Moderna shot two days ago and opted for Moderna over Johnson and Johnson because it is a new technology. (Although I missed out on the complimentary bottle of Johnson and Johnson Baby Shampoo. Sigh. I was hoping for No More Tears.)

I suppose is it not the place on Physics Forums to speculate on the causes of these clotting episodes since one cannot document that which is not understood. By the same token, asserting that the risk of the vaccine is low is a conclusion without proof. IMO one can only say that past experience with vaccines indicates that these new vaccines are of low long term risk.

I suppose an appropriate question for Physics Forums would be: Is it understood why COVID-19 can incite violent responses from the immune system and specifically does this have to do with the spike protein itself? And have clotting events been previously seen in cases of severe insult to the immune system?

 

[Ygggdrasil]

I suppose is it not the place on Physics Forums to speculate on the causes of these clotting episodes since one cannot document that which is not understood. By the same token, asserting that the risk of the vaccine is low is a conclusion without proof. IMO one can only say that past experience with vaccines indicates that these new vaccines are of low long term risk.

Physics Forums is focused on discussing established scientific knowledge published in the scientific literature. There have been case studies describing the cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) following vaccination with the Oxford-AstraZeneca vaccine (see this article in the New England Journal of Medicine for a review). These articles have noted a similarity between the VITT and previously observed cases of heparin-induced thrombocytopenia (HIT), including the observation of antibodies that react with platelet factor 4 (PF4) very similar to those found in cases of HIT. Here's a summary from a news article from Science Magazine on the topic:

"The symptoms resemble a rare reaction to the drug heparin, called heparin-induced thrombocytopenia (HIT), in which the immune system makes antibodies to a complex of heparin and a protein called platelet factor 4 (PF4), triggering platelets to form dangerous clots throughout the body. Sickened vaccine recipients also had antibodies to PF4, the researchers found."​

https://www.sciencemag.org/news/202...ca-vaccine-and-rare-clotting-disorder-becomes

What exactly causes these antibodies to come about is not yet fully understood. Research into this issue could potentially clarify the risk factors for VITT, specify which vaccines would pose the greatest risk for VITT, and provide a means of developing safer vaccines in the future.

I suppose an appropriate question for Physics Forums would be: Is it understood why COVID-19 can incite violent responses from the immune system and specifically does this have to do with the spike protein itself? And have clotting events been previously seen in cases of severe insult to the immune system?

So far the evidence does not point to the VITT being related to the spike protein of COVID-19. Here's a relevant excerpt from the news article from Science:

"Early suggestions that the rare reactions may be the result of a COVID-19 infection before vaccination have not been substantiated. None of the five patients in Norway had been infected, for instance. Others have suggested that antibodies against the virus’ spike protein—which many vaccines seek to elicit—somehow cross-react with PF4. That could spell trouble for nearly all COVID-19 vaccines. But so far, there is no evidence that the messenger RNA–based vaccines made by the Pfizer-BioNtech collaboration and Moderna, which tens of millions of people have received, are causing similar clotting disorders.​

Initial studies by Greinacher’s team, posted as a preprint, don’t support that theory either. Among more than 200 patients who had recovered from COVID-19, they found only a few with antibodies that reacted to PF4, and those reacted relatively weakly. More importantly, Greinacher says, the platelet-activating antibodies isolated from VITT patients did not react to the Coronavirus spike protein."​

https://www.sciencemag.org/news/202...ca-vaccine-and-rare-clotting-disorder-becomes

 

[bhobba]

Indeed we discuss peer-reviewed science here, not personal theories unless, of course, they have been peer-reviewed. We also discuss reports from reputable sources, which is why it was my bad in citing the US Sun as a 'reputable source' and gave the link to the New York Times, which is reputable. Interestingly, however, Dr Campbell has discovered a peer-reviewed article from 2006 about adenoviruses. He also discusses injection techniques other countries have adopted:


I found it very interesting, and when I get my vaccination will ask my doctor, as other countries require, to inject with asperation if he does not do so already. It certainly can't hurt.

Thanks
Bill

 

[AndreasC]

It's the fear factor. People are watching for any reason to avoid the newly tested vaccine.

Blood clotting is a worry but as has been reported statistically it's at the same level of occurrence as the general population.

However, it could be significant at some point (depending on your level of Chicken Littleness) and so people are fearful.

What gets me is the number of people who decide against the vaccine. We know there are special people who can't get the vaccine because of some special health reasons. (eg people allergic to eggs).

They depend on herd immunity to survive. However, when a significant percentage of the herd decides against the vaccine then those special people are denied protection.

It reminds me of how some selfish people take handicap spots. The spots are there for people who really need them. When you take it even for a few minutes then you're denying a handicapped person who needs it the most.

I agree with the overall point however it is not accurate to say that it is at the same level of occurrence as the general population, or at least it is misleading. It is not the same to say "this happens to 1 in 100 people in their life" and "this happens to 1 in 100 people within a few days of being vaccinated". Apparently around 12% of adults have diagnosed heart disease. Imagine if around 10% of people who took a certain drug developed some kind of heart disease a few days after getting the drug, would you call it safe?

Beyond that, the benefits certainly outweigh the risks. My father got it recently and I am very happy and relieved.

 

[lavinia]

I think the majority of scientists studying these clotting disorders, see CVT and Splanchnic Vein Thrombosis as only one manifestation of specific immune mediated thrombophylic disorders, there are others that can be just as dangerous. They are not a new disorder and they have been associated with other infections and with other vaccinations, there are also some inherited conditions which show a very similar pathological process. A variety of thrombophilic disorders have been seen with all the Covid vaccines.

Would DIC be among these disorders?

https://www.nhlbi.nih.gov/health-topics/disseminated-intravascular-coagulation

 

[Laroxe]

Well it occurs in Covid19 infection so I suppose its a possibility, but to be honest I haven't seen in discussed in relation to the vaccine. If I see something I'll let you know.

 

[Mary Conrads Sanburn]

NEWS 09 APRIL 2021
How could a COVID vaccine cause blood clots? Scientists race to investigate
Researchers are searching for possible links between unusual clotting and the Oxford–AstraZeneca Coronavirus vaccine.

Heidi Ledford

The very rare occurrence of a mysterious blood-clotting disorder among some recipients of the Oxford–AstraZeneca COVID-19 vaccine has got researchers scrambling to uncover whether, and if so, how the inoculation could trigger such an unusual reaction.
After weeks of investigation, the European Medicines Agency (EMA) announced on 7 April that it is possible there is a link between the clots and the vaccine. Even so, the clotting disorder — described today in two reports in The New England Journal of Medicine1,2 — is so uncommon that the benefits of the vaccine still outweigh its risks, EMA executive director Emer Cooke told reporters. “These are very rare side effects,” she said. “The risk of mortality from COVID is much greater than the risk of mortality from these side effects.”
But the finding leaves researchers wrestling with a medical mystery: why would a vaccine trigger such an unusual condition? “Of course, there are hypotheses: maybe it’s something with the vector, maybe it’s an additive in the vaccine, maybe it’s something in the production process … I don’t know,” says Sabine Eichinger, a haematologist at the Medical University of Vienna. “It could be any of these things.”
Unusual locations
Eichinger was among the first to notice the clotting disorder, a strange combination of blood clots — which can be dangerous, and potentially fatal, if they block blood flow to the brain or lungs — and a counter-intuitive deficiency of cell fragments called platelets that promote clotting. The clots also appeared in unusual parts of the body, such as the brain and abdomen, rather than in the legs, where most deep-vein blood clots form.
This rang alarm bells for Eichinger, who had previously encountered a similar phenomenon in a few people who had been treated with the blood-thinning drug heparin. Heparin is normally used to prevent clotting, but in very rare cases can trigger a syndrome called heparin-induced thrombocytopenia (HIT), which causes blood clots and low platelet levels.
By 22 March, the EMA had assembled 86 reports of people who had experienced blood clots in the brain or abdomen within two weeks of receiving a dose of the Oxford–AstraZeneca vaccine, developed in Britain by AstraZeneca in Cambridge and the University of Oxford. Some of these cases have been confirmed to bear the hallmarks of HIT, even though these people had not received heparin.
Risk factors
The EMA is asking AstraZeneca to conduct a number of investigations, including laboratory studies to determine the effect of the vaccine on blood clotting, and evaluations of data from clinical trials, to try to glean any further information about risk factors. Although there are reports that the syndrome is seen more often in women than in men, particularly in women aged under 60, the EMA was unable to conclude that women are at higher risk. Many countries prioritized health-care workers to receive the inoculations, and women comprise a larger segment of this workforce.
The EMA is also supporting studies by two academic consortia centred in the Netherlands, one led by Erasmus University Medical Center in Rotterdam and the other by investigators at Utrecht University and the University Medical Center Utrecht.
Their project list is ambitious. One of the consortia, co-chaired by virologist Eric C. M. van Gorp at Erasmus, consists of 22 hospitals that have been working together to study the effects of Coronavirus on blood coagulation. The team will look for potential cases of HIT among people who developed blood clots following vaccination with the Oxford–AstraZeneca vaccine or other COVID-19 vaccines. It will also conduct lab studies to look for signs that the already-small risk could be cut further by reducing the amount of vaccine administered in each dose.
The EMA expects to obtain some results from the projects within the next two months, said Peter Arlett, head of the agency’s Data Analytics and Methods task force. The team will also try to tease apart whether this problem is restricted to certain populations. “What we find in Western Europe will not automatically be true in South America or other populations,” says van Gorp. “This is a worldwide problem; everyone is concerned.”
And, crucially, van Gorp and his colleagues will try to further evaluate whether the “probable” association between the vaccine and the syndrome is real. It is notoriously difficult to confirm whether a suspected rare effect of a vaccine is truly linked to the vaccine — particularly when it is one that has been used in tens of millions of people. “Somebody who gets the vaccine could have a stroke or a heart attack a week later because they were already going to have a stroke or a heart attack,” says cardiologist Behnood Bikdeli at Brigham and Women’s Hospital in Boston, Massachusetts. “It’s good to be vigilant about these things as we move forward and collect the data, but the absolute number of events and the event rate are so remarkably low.”
Underlying causes
Bikdeli would also like to see researchers collect — and share — more data about the incidence of this clotting condition in unvaccinated populations. Heightened awareness of the possible link between vaccination and the syndrome could lead to increased reporting rates among those who have been vaccinated compared with those who have not, which could falsely inflate the perceived rate at which the syndrome occurs, he says. And such concerns could spread to other Coronavirus vaccines.
Other researchers are keen to pick apart what triggers the syndrome. HIT is thought to be the result of an immune reaction to complexes formed when negatively charged heparin molecules bind to a positively charged protein called platelet factor 4, which is important for clotting. This activates platelets, kicking off a chain reaction. “Once you get the platelets activated, it’s like putting a match to tinder,” says John Kelton, a haematologist at McMaster University in Hamilton, Canada, who has been studying HIT for 40 years. “They recruit more and more platelets, and when they are activated, they explode and produce coagulant material. HIT is like a forest fire; it just self-perpetuates.”
Although exceedingly rare, cases of ‘spontaneous’ HIT in the absence of heparin treatment have been reported before, with suspected triggers including infection, knee surgery and treatment with drugs that — like heparin — are negatively charged. Kelton recalls a case he worked on years ago of a woman in her forties experiencing catastrophic strokes who had not been treated with heparin. “We tested her blood and found reactions exactly the same as reported for the AstraZeneca reactions,” he says.
Kelton’s lab is now working full time to try to determine what might be causing HIT-like symptoms in vaccine recipients, and he’s confident that other labs will be doing the same. It is a tricky phenomenon to study: its rarity makes patient samples difficult to come by, and there are no good animal models, Kelton says.
One result of all of this activity will be increased attention to the relationship between the immune system and blood coagulation, says van Gorp, and the results could inform further vaccine development. “We are going to get new Coronavirus variants and are going to develop new vaccines,” he says. “We need answers for the future.”
Nature 592, 334-335 (2021)
https://www.nature.com/articles/d41586-021-00940-0

 

[bhobba]

I agree with the overall point however it is not accurate to say that it is at the same level of occurrence as the general population, or at least it is misleading.

Correct.

But here is something interesting - the following includes both CVT and PVT on both the AZ and mRNA vaccines like Pfizer - see from about 8.30:


A couple of comments:

1. The chance of getting blood clots is significantly higher than the vaccine if you get Covid. So if Covid is really raging where you are - get vaccinated, and you have actually reduced your risk of clots.

2. The incidence of CVT is about, in the general population, .41 in a million in a two week period. Oxford is 5 in a million; mRNA vaccines are 4.1 in a million. While treatable, it has about a 20% fatality rate. So yes, mRNA vaccines are better in this study - but only slightly so. The question then is, why is the mRNA vaccine recommend due to CVT? Others may know more about this - my suspicion is we have vaccinated mostly older age groups at the moment, and for younger people, the odds change - just a guess.

3. We also have PVT, which also has a horrid death rate of 18.8%. The comparison between the vaccines is 44 per million for Pfizer and just 1.6 per million for Az. That is markedly in favour of AZ.

The government reactions and the above data are not clearly linked IMHO. I will not comment on it, except more research is obviously urgently required, e.g. the data depending on age. If offered either, I would take the AZ based on the above. But I have to say you should always discuss it with your doctor first. And also, if Covid is raging where you are, like PNG or India, forget about the clots from the vaccine - it is much less than if you got Covid. Where that leaves me in Aus is interesting. It is eliminated but can come back at any time. Personally, I would keep doing what we are doing, where for some reason, we are slowly vaccinating but still producing 1 million doses a week - much more than is being used. CSL must store the rest - you need to store some for the second dose, but the difference between those made and used is much greater than that. A few weeks ago, I heard 2.8 million doses were in storage - probably more now. If it comes back, mass vaccinate like crazy using vaccination hubs, chemists, physiotherapists etc., with the vaccine in storage.

The following gives an interesting comparison on risks:
https://www.bbc.com/news/world-56763490

Notice it gives a rate of serious harm from the vaccine as 11 in a million for the young than 4 in a million over 55. I would like to see that compared to mRNA vaccines. But when PVT is taken into account, that 44 in a million chance still seems to favour the AZ .

Thanks
Bill

 

[Laroxe]

Yes this is an incredibly important issue, the vector based vaccines which are most associated with these abnormal clots are an important part of the current global vaccine drive. Part of the problem in the investigation is the rarity of the condition, its only very recently that there has been sufficient data to suggest there is an increased risk.

It may be that heparin-induced thrombocytopenia (HIT) may be the best model for understanding this unusual set of symptoms in which bleeding and hyper coagulation co-exist. This condition occurs rarely in people treated with heparin, an anticoagulant and tends to be transient. It appears that heparin can trigger the production of antibodies that bind to receptors on the surface of platelets destroying them. This destruction causes the release of other clotting factors, the loss of the platelets reduces the ability of the blood to clot, the clotting factors increase clotting, this would explain the rather contradictory symptoms. This idea has been supported by antibody studies in people affected post vaccination and currently guides treatment guidelines.
There is a particular problem in investigating very rare adverse events, particularly ones that are likely to have complex causes, particularly when as Mary's post points out there are still questions about whether the association is real. Its certainly important to try and identify what parts of the vaccine might be responsible but we already know that immune thrombocytopenia can occur with all the Covid vaccines and several others, but this doesn't explain the differences seen in the occurrence of abnormal clotting between the mRNA and vector based vaccines.
We also know that in studies of CVT prior to Covid, several other risk factors have been suggested that may also influence the vaccine response, these might include Obesity, pregnancy, other clotting or autoimmune disorders, the contraceptive pill, age and gender. Putting some sort of picture together when we have so little data may be a long job.

Despite these issues the fact remains that these vaccines are important until more become widely available, they are effective and these adverse effects are extremely rare. Unfortunately, people pay particular attention to possible risks but fail to consider this risk in the context of the pandemic. While most scientific advisory groups suggest the vaccination program should continue to use these vaccines, Covid 19 continues to kill thousands across the world, Governments have restricted their use. Often these restrictions are based on findings from early studies which rapidly become obsolete.
Not only do people pay attention to indicators of risk, they also remember them, it seems unlikely that new evidence will restore faith in this group of vaccines. As there is a large number of potential new vaccines that use a variety of delivery platforms we may have to wait before adequate control of the pandemic is achieved.
This is an explainer from Nature which might add to the valuable information in Mary's post

https://www.nature.com/articles/d41586-021-00998-w

 

[Ygggdrasil]

2. The incidence of CVT is about, in the general population, .41 in a million in a two week period. Oxford is 5 in a million; mRNA vaccines are 4.1 in a million. While treatable, it has about a 20% fatality rate. So yes, mRNA vaccines are better in this study - but only slightly so. The question then is, why is the mRNA vaccine recommend due to CVT? Others may know more about this - my suspicion is we have vaccinated mostly older age groups at the moment, and for younger people, the odds change - just a guess.

These figures are inconsistent with data from the CDC that I posted earlier:

(source: April 14 meeting of the CDC Advisory Committee on Immunization Practices: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-04/03-COVID-Shimabukuro-508.pdf)

 

[bhobba]

These figures are inconsistent with data from the CDC that I posted earlier:

Yes, they are. I will try and get the preprint it came from so an appraisal can be made of data very much at odds. Hang on a minute.

Added Later:
Ok - here is the news article about it from Oxford:
https://www.ox.ac.uk/news/2021-04-15-risk-rare-blood-clotting-higher-covid-19-vaccines

At the bottom is the link to the paper:
https://osf.io/a9jdq/

Hopefully, we can get to the bottom of it because, to be blunt such a divergence is - well - bizarre.

Tentatively my take is what was said at the end of the paper:
'The rarity of CVT in all populations means that larger sample sizes are required to confirm the results, and complementary study designs are needed to aid interpretation. Nevertheless, the current data highlight the risk of serious thrombotic events in COVID-19, and can help contextualize and inform debate about the risk-benefit ratio for current COVID-19 vaccines.'

Also very surprising was for mRNA vaccines the high incidence of PVT compared to AZ. The difference was large.

Thanks
Bill

 

[Ygggdrasil]

Yes, they are. I will try and get the preprint it came from so an appraisal can be made of data very much at odds. Hang on a minute.

Added Later:
Ok - here is the news article about it from Oxford:
https://www.ox.ac.uk/news/2021-04-15-risk-rare-blood-clotting-higher-covid-19-vaccines

At the bottom is the link to the paper:
https://osf.io/a9jdq/

Hopefully, we can get to the bottom of it because, to be blunt such a divergence is - well - bizarre.

Tentatively my take is what was said at the end of the paper:
'The rarity of CVT in all populations means that larger sample sizes are required to confirm the results, and complementary study designs are needed to aid interpretation. Nevertheless, the current data highlight the risk of serious thrombotic events in COVID-19, and can help contextualize and inform debate about the risk-benefit ratio for current COVID-19 vaccines.'

Also very surprising was for mRNA vaccines the high incidence of PVT compared to AZ. The difference was large.

Thanks
Bill

My criticism of the estimate in the paper is that the denominator for the estimate of the incidence of CVT after COVID-19 vaccination is likely wrong.

The paper looked at anonymized electronic health records from 59 healthcare organizations primarily in the USA. These organizations cover 81 million patients according to the authors. Their data looks at the population of people who received at least one dose of a COVID-19 vaccination before March 25, 2021. According to the CDC, 95 million people had received at least one dose of a COVID-19 vaccination by March 25. This amounts to about 29% of the US population. However, their dataset only has N = 489,871 patients who received a COVID-19 vaccination (0.6% of the 81 million patients). They observed 2 cases of CVT in this cohort, which is the source of the 4.1 per million statistic. However, only 490 thousand vaccinated individuals in this cohort is an implausibly low number; the expected number of vaccinated individuals should be ~23 million, which would lower the incidence of CVT to ~0.09 per million in the two weeks after vaccination.

This discrepancy in the observed number vaccinated versus the expected number vaccinated likely comes about because vaccinations in the US are being distributed through a number of means, not necessarily through one's primary healthcare provider (e.g. thorough pharmacies or mass vaccination sites run by the government). Therefore, patients who got vaccinated through these means would not have a record of vaccination in these electronic health records. This information would only be entered if the patient had to go to their healthcare provider for another reason. Thus, the method has a selection bias for vaccinated people who experienced adverse events. This error could have come about because the authors are from Oxford University in the UK, so they may not be familiar with how the US healthcare and vaccine distribution system has been operating.

Assuming that ~29% of the patient population was vaccinated (as opposed to the 0.6% they observe), the risk of CVT in the sample would drop significantly (by a factor of ~50, which would bring the incidence of CVT in the vaccinated cohort below the expected incidence of CVT).

I will write to the authors of the study to notify them of this major flaw in their data.

 

[Laroxe]

My criticism of the estimate in the paper is that the denominator for the estimate of the incidence of CVT after COVID-19 vaccination is likely wrong.

The paper looked at anonymized electronic health records from 59 healthcare organizations primarily in the USA. These organizations cover 81 million patients according to the authors. Their data looks at the population of people who received at least one dose of a COVID-19 vaccination before March 25, 2021. According to the CDC, 95 million people had received at least one dose of a COVID-19 vaccination by March 25. This amounts to about 29% of the US population. However, their dataset only has N = 489,871 patients who received a COVID-19 vaccination (0.6% of the 81 million patients). They observed 2 cases of CVT in this cohort, which is the source of the 4.1 per million statistic. However, only 490 thousand vaccinated individuals in this cohort is an implausibly low number; the expected number of vaccinated individuals should be ~23 million, which would lower the incidence of CVT to ~0.09 per million in the two weeks after vaccination.

This discrepancy in the observed number vaccinated versus the expected number vaccinated likely comes about because vaccinations in the US are being distributed through a number of means, not necessarily through one's primary healthcare provider (e.g. thorough pharmacies or mass vaccination sites run by the government). Therefore, patients who got vaccinated through these means would not have a record of vaccination in these electronic health records. This information would only be entered if the patient had to go to their healthcare provider for another reason. Thus, the method has a selection bias for vaccinated people who experienced adverse events. This error could have come about because the authors are from Oxford University in the UK, so they may not be familiar with how the US healthcare and vaccine distribution system has been operating.

Assuming that ~29% of the patient population was vaccinated (as opposed to the 0.6% they observe), the risk of CVT in the sample would drop significantly (by a factor of ~50, which would bring the incidence of CVT in the vaccinated cohort below the expected incidence of CVT).

I will write to the authors of the study to notify them of this major flaw in their data.

I think your first sentence summarizes the real problem, people are trying to make sense of very low frequency events and currently each new data set seems to muddy the water rather than clarify things. Hopefully given time the picture will become more accurate. Remember we still have the very basic argument about whether this is even a real effect, the data we have is so contaminated by other effects. There seems to be some basic differences in many of the groups studied these might include age, gender, risk of exposure, dose of exposure, ethnicity etc, so we end up with some big differences in findings.

 

[bhobba]

I will write to the authors of the study to notify them of this major flaw in their data.

I think you are correct. In fact, taking into account your analysis, I am not sure it would pass peer review. That is the problem with this pandemic - things move so fast papers before peer-review are discussed. They then get discussed in the media. A talk show discussed this paper last night where the host observed just who do you believe with so much conflicting information around. I well remember the egg I had on my face when I argued with Chemisttre about the value of face masks. We had experts, a number with Nobel's in Epidemomology like Peter Doherty, who said face masks are useless. I was wrong - Chemisttre was right:
https://www.nature.com/articles/d41586-020-02801-8

Despite the evidence of their value, there are still people that say they are useless. It's a problem - maybe even one of the biggest issues with this pandemic.

As an aside, I did not know that about the way things are done in the US either. You live and learn. Here in Aus we have a centralised database of everyone's Covid vaccine - what little has been done .

Thanks
Bill

 

[Ygggdrasil]

Useful slide from the April 23 ACIP meeting that puts the relative risk of thrombotic thrombocytopenia from the Johnson & Johnson vaccine into context with other vaccine-related adverse events:

(source)