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
"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
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
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
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
"Covid-19 is much, much, much more dangerous than this extremely
rare condition," Prof. Greinacher said.
Write to Bojan Pancevski at firstname.lastname@example.org
(END) Dow Jones Newswires
May 13, 2021 05:44 ET (09:44 GMT)
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