Inside the Hunt for a Link Between Some Covid-19 Vaccines and Rare Blood Clots

By Bojan Pancevski 

Scientists world-wide are racing to understand why Covid-19 vaccines from AstraZeneca PLC and Johnson & Johnson are causing rare but potentially deadly blood clots.

Determining the connection would help patients, doctors and health agencies better assess any risks posed by the vaccines and safely calibrate their use. In recent weeks, the U.S., the Canadian province of Ontario and several European countries including Norway and Denmark either paused or completely halted rollouts involving these vaccines.

"Understanding the cause is of highest importance for the next-generation vaccines, because [the novel] coronavirus will stay with us and vaccination will likely become seasonal," said Eric van Gorp, a professor at Erasmus University in the Netherlands who heads a group of scientists studying the condition.

In Germany, one researcher thinks he has found what is triggering the clots. Andreas Greinacher, a blood expert, and his team at the University of Greifswald believe so-called viral vector vaccines -- which use modified harmless cold viruses, known as adenoviruses, to convey genetic material into vaccine recipients to fight the coronavirus -- could cause an autoimmune response that leads to blood clots. According to Prof. Greinacher, that reaction could be tied to stray proteins and a preservative he has found in the AstraZeneca vaccine.

Prof. Greinacher and his team has just begun examining Johnson & Johnson's vaccine but has identified more than 1,000 proteins in AstraZeneca's vaccine derived from human cells, as well as a preservative known as ethylenediaminetetraacetic acid, or EDTA. Their hypothesis is that EDTA, which is common to drugs and other products, helps those proteins stray into the bloodstream, where they bind to a blood component called platelet factor 4, or PF4, forming complexes that activate the production of antibodies.

The inflammation caused by the vaccines, combined with the PF4 complexes, could trick the immune system into believing the body had been infected by bacteria, triggering an archaic defense mechanism that then runs out of control and causes clotting and bleeding.

Prof. Greinacher has compared the activation of the dormant response -- which has been supplanted in the evolution of the human immune system, but still lurks in its foundations -- to "awakening a sleeping dragon."

Prof. John Kelton of McMaster University in Canada, whose outfit runs Canada's reference lab for testing patients with blood-clotting symptoms after vaccination, said the lab replicated some of Prof. Greinacher's research and confirmed his findings.

Yet the cause was unclear. "[Prof. Greinacher's] hypothesis could be right, but it could also be wrong," Prof. Kelton said.

Prof. Greinacher is working to confirm his theory, hoping to get cooperation from vaccine makers. His team has tested AstraZeneca vaccines and has just received doses from Johnson & Johnson. Greifswald University is now negotiating with the drugmakers about greater access to their vaccine-making processes.

"We strongly support raising awareness of the signs and symptoms of this very rare event, and we are currently exploring a potential collaboration with Dr. Greinacher," said a Johnson & Johnson spokesman.

AstraZeneca didn't respond to a request for comment.

The type of clotting observed is known as vaccine-induced immune thrombotic thrombocytopenia, or VITT. Peer-reviewed studies by Prof. Greinacher's group, as well as from teams at the University of Oslo and University College London have independently confirmed its existence.

Most of the science hubs investigating the clotting issue, first identified in March, are experts in a condition called heparin-induced thrombocytopenia or HIT, which has near-identical symptoms and outcomes to VITT. With HIT, the blood-thinning drug heparin causes clots paired with an abnormal decrease in the blood's natural clotting agents.

Some scientists think the adenoviruses themselves could play a role in triggering the condition because they have been linked to blood clotting. Others speculate that people affected could have genetic predispositions, or that their immune systems had previously developed the problematic antibody.

Another theory suggested by Prof. van Gorp is that the brief but strong flulike symptoms many recipients report after taking the shot are also causing inflammation that could trigger or exacerbate autoimmune reactions leading to blood clotting.

One reason vaccine-induced clotting might not have been reported in the past is because shots using viral vector technology haven't been administered at scale. The Russian vaccine Sputnik V and the shot by CanSino Biologics from China use the same technology as AstraZeneca and Johnson & Johnson, but haven't been linked to the condition so far.

The only similar shot widely administered before the pandemic is one against Ebola by Johnson & Johnson, which was given to at least 60,000 people as of last July.

Clotting occurs between one in 28,000 and one in 100,000, according to European data -- extremely rare amid the hundreds of millions of doses administered so far, yet higher than one in 150,000 previously assumed by some medical authorities, Prof. Greinacher said. Most of the hundreds of people who have been diagnosed recover, but between a fifth and a third have died, and others could suffer permanent consequences.

Data from U.S. and European regulators so far suggest young women are primarily affected by the condition. But several scientists, including Sabine Eichinger, a senior Austrian hematologist who treated one of the first-known patients, have said the correlation could reflect that medical workers and teachers were among the first to get the vaccines in Europe, and the majority of them are younger women.

There is no indication that taking contraception pills or having a history of similar diseases puts vaccine recipients at greater risk, Prof. Eichinger said.

Anton Pottegård, a professor of pharmacoepidemiology at the University of Southern Denmark, co-wrote a study of more than 280,000 people in Denmark and Norway who received the AstraZeneca vaccine. The study, which was published in the British Medical Journal on May 5, found the incidence of rare but severe blood clots among vaccine recipients was 2.5 in 100,000.

Prof. Pottegård added that countries such as Denmark and Norway, which this week discontinued using AstraZeneca's vaccine and donated its doses to other countries, were able to change their inoculation plans because they had alternative shots and low infection rates. Doing the same in countries where the pandemic is raging, such as India or Brazil, could result in more deaths, he warned.

"Covid-19 is much, much, much more dangerous than this extremely rare condition," Prof. Greinacher said.

Write to Bojan Pancevski at [e-mail]

(END) Dow Jones Newswires

May 13, 2021 05:44 ET (09:44 GMT)

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