The Rare And Serious Adverse Blood Clotting Events Temporally Linked To The Johnson & Johnson COVID-19 Vaccine.

On the weekend (see post-script), we noted that blood clotting events have been noted in a small number of people after they received the Johnson & Johnson vaccine.

This has led to a call for a pause of the vaccine's use in the United States while the American Center for Disease Control's 'Advisory Committee on Immunization Practices' reviews the data (they are scheduled to meet tomorrow/Wednesday).

As Helen Branswell, who is an excellent science journalist, reports in STAT News, the events identified so far are very rare. However, they are also very serious and appear to be similar those that have occurred rarely after administration of the AstraZeneca vaccine:

Federal authorities on Tuesday recommended that states stop using Johnson & Johnson’s Covid-19 vaccine while an investigation is conducted into six serious cases of clotting problems — one of which was fatal — that were reported among women who received the vaccine.

The blood clots are similar to those reported by several European countries after use of AstraZeneca’s Covid-19 vaccine. And they are similar to an event that occurred during Johnson & Johnson’s U.S.-based clinical trial, an event that led to a temporary pause in that trial last fall. That case involved a man in his 20s, STAT reported at the time.

The clotting problem appears to be quite rare. As of Monday, more than 6.8 million doses of the Johnson & Johnson vaccine had been administered in this country...

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...The blood clots reported in the six cases are known as cerebral venous sinus thrombosis (CVST); in all cases, the clots were seen in combination with low levels of blood platelets, a condition known as thrombocytopenia. All occurred among women between the ages of 18 and 48, the statement from the CDC and FDA said, and symptoms occurred between six and 13 days after vaccination...


Clearly, this is an abundance of caution issueand the pause appears completely reasonable at this time. While the incidence rate is lower for the J&J vaccine than with the AZ vaccine at the moment, that could change with increase surveillance.

If the post-J&J vaccine events truly are the same as those post-AZ innoculation they will hopefully become increasingly diagnosable and treatable, as has been suggested by recently published findings in the New England Journal of Medicine (see Update IV at top of the post).

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So, what might be causing the problem here?

Originally, some folks speculated that the AZ vaccine issue might be occurring because the spike protein produced by that vaccine was not in the 'locked' conformation which could lead to bits of the protein being released and an initiating a rare adverse immunological response. However, the J&J vaccine produces the 'locked' form of the spike protein, as do the mRNA vaccines for which these types of clotting events have not been reported. Thus, the unlocked spike protein hypothesis has fallen from favour.

Another hypothesis is that the problem might, at least in part, be caused by the adenoviral vehicle that is used to deliver both the J&J and AZ vaccines, but not the mRNA vaccines, to our cells. If that turns out to be the case this could also be problematic for the Russian Sputnik and the CanSino vaccines as well as they, too, are in the adenoviral vaccine 'class'. Helen Branswell reports on that as well:

...The concern over Johnson & Johnson’s vaccine is raising questions about whether there is what’s known as a “class effect” — a problem one would expect to see with all vaccines made in the way the J&J and AstraZeneca vaccines are made. The Sputnik V vaccine, made by Russia’s Gamaleya Research Institute and the vaccine made by CanSino, a Chinese manufacturer, are made in the same way as the Johnson & Johnson and AstraZeneca vaccines.

The four vaccines use modified adenoviruses — viruses that cause colds — to deliver instructions to human cells to make the SARS-CoV-2 spike protein, the exterior proteins that allow SARS-2 viruses to attach to and invade cells. Those vaccine-induced spike proteins teach the immune system to look out for and defend against SARS-2 viruses.

Theories about the cause of the rare clotting issues hinge on the possibility that, in small numbers of people, the adenoviruses trigger an aberrant immune response. That, in turn, results in a rare combination of widespread clotting and low platelet counts...

{snip}

...“It’s a reasonable but unproven assumption that the J&J and AstraZeneca vaccine safety concerns are linked by being related to an immune response against an adenovirus component,” he (John Moore, an immunologist at Weill Cornell University) said. “So, FDA and scientists need time to better understand what is going on, which means a pause is the right course of action.”...


Having noted that, it is important to realize that at this point this is only an hypothesis at this time. Thus, there are no hard data yet to either support or refute it.

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Here in British Columbia there has been a delay in delivering Johnson & Johnson vaccine but we are  currently offering the AstraZeneca vaccine for folks between 55-65 where the risk/reward ratio tips more heavily towards the latter than it does in younger people. 

Again, the science on what causes these rare adverse clotting events is not clear, but protocols for diagnosing and treating them are being developed and apparently the first case identified in Canada has been successfully treated.

Finally, to reiterate, these events have not been found in people that have received the mRNA vaccines from Pfizer and Moderna.

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The mRNA vaccines use a 'lipid nanoparticle particle' ('LNP') coating as the delivery vehicle...Folks here in Vancouver were critical to the development of that technology.

Update, Wed April 14th: Drug development guy Derek Lowe has an excellent overview of all this, including from a regulatory point of view....Here.

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