Covid-19 vaccine-related blood clots linked to amino acids in new study



  • Canadian researchers zero in on molecular details of antibody clusters following AstraZeneca shots

Canadian researchers say they have pinpointed a handful of amino acids targeted by key antibodies in the blood of some people who received AstraZeneca PLC’s Covid-19 vaccine, offering fresh clues to what causes rare blood clots associated with the shot.

The peer-reviewed findings, by a team of researchers from McMaster University in Ontario, were published online Wednesday by the science journal Nature. They could help doctors rapidly test for and treat the unusual clotting, arising from an immune-driven mix of coagulation and loss of platelets that stop bleeding.

The Canadian study analyzed blood samples from AstraZeneca vaccine recipients and builds on recent research done in Europe and elsewhere into the infrequent blood clots linked to the vaccine. Health officials are monitoring the rare side effects balanced with the vaccines’ proven value in fighting Covid-19. The blood clotting, which some scientists have named vaccine-induced immune thrombotic thrombocytopenia, or VITT, has also been linked to Johnson & Johnson’s Covid-19 shot, though incidents have occurred less frequently with that shot than with AstraZeneca.

Though rare, the condition has proven deadly in more than 170 adults post-vaccination in the U.K., Europe and U.S., according to government tallies. Many were younger adults who appeared healthy before vaccination, researchers and drug regulators say.

The companies have said they are undertaking further research to understand the issues and believe the vaccines’ benefits outweigh the risks. Health and government officials have said that the benefits of both vaccines generally outweigh their risks but recommend warnings about the potential risks.

Mortimer Poncz, pediatric-hematology division chief at the Children’s Hospital of Philadelphia, who wasn’t involved in the study, said the findings could help doctors rapidly identify VITT and get researchers closer to understanding what causes it. Another VITT researcher, Andreas Greinacher, professor of transfusion medicine at Germany’s Greifswald University Clinic, called the findings “highly interesting" as a new clue to vaccine-induced clotting that could improve treatment.

Scientists say research about Covid-19 vaccines could influence the safety of shots and treatments for other uses. Mass inoculations have provided a rare chance to study side effects that might go unnoticed in smaller vaccination drives.

Rare reports of blood clots first surfaced in early March among people in Europe who had received the vaccine developed by AstraZeneca and the University of Oxford. Since then, the U.K., Canada, Australia and countries in Europe and globally have limited use of the vaccine to older adults, with some countries declining to use the shot at all. Sometimes-deadly blood clotting has also surfaced among people in the U.S. and Europe who have received the J&J shot.

AstraZeneca, with more than 600 million doses distributed globally, remains an important vaccine, particularly for countries lacking access to more-expensive shots, but isn’t authorized for use in the U.S.

Researchers are racing to understand the rare combination of low blood platelets and clots and their connection to the vaccine in the hopes of rapid diagnosis and treatment and ultimately clot prevention—possibly by altering the shots’ makeup.

VITT has occurred in 1 to 2 people per 100,000 first doses of the AstraZeneca shot in the U.K., with cases more common in people under 50. The total number of cases after first or second doses in the U.K. was 395 through June 23, of roughly 45.2 million doses administered. Of the 395, 70 people have died.

European officials said this month that they have seen 479 potential cases of VITT out of 51.4 million AstraZeneca vaccinations, or just under 1 per 100,000 vaccinations. Far fewer potential cases—21 out of 7 million vaccinations, or about 0.30 per 100,000 people—followed J&J vaccinations in Europe. Of those cases, 100 deaths occurred after AstraZeneca vaccination and four after Johnson & Johnson, European regulators said.

U.S. health officials said in late June that they have identified 38 confirmed cases of the blood-clotting syndrome out of more than 12.3 million people who received the J&J vaccine, correlating to a frequency of about 0.31 in 100,000. The Centers for Disease Control and Prevention said in May that three cases had been fatal and evidence “suggests a plausible causal association" between the combination of low platelets and clotting and the vaccine. The CDC didn’t respond to requests for comment.

Both shots are so-called viral-vector vaccines, which use altered cold viruses to ferry genetic material into human cells instructing them to create Covid-19 spike proteins. That action spurs the immune system to create antibodies and defensive white blood cells that prime the body for a protective response against Covid-19.

But in rare cases, vaccinated people have experienced an autoimmune reaction in which antibodies bind with unusual strength to a blood component called platelet factor 4, or PF4, forming distinct clusters resembling a bunch of grapes. This so-called immune complex, a molecular formation in the blood, activates more platelets, “like putting a match to gasoline," said John Kelton, an author of the Nature paper and researcher at McMaster University. He is involved in testing blood from people across Canada who develop blood clots after Covid-19 vaccination.

The process accelerates, he and other researchers say, triggering simultaneous bleeding and clotting, sometimes in the brain, stomach and other areas that can in rare cases be deadly. “We think these antibodies are incredible amplifiers, in a bad way, of the normal coagulation system," says Dr. Kelton, who has been studying clotting effects of the blood-thinning drug heparin since the 1980s.

For the Nature article, he and fellow researchers analyzed blood from five people aged 35 to 72 who developed VITT after a single dose of the AstraZeneca vaccine. They compared the platelet and clotting responses to observations from 10 people who had suffered heparin-induced thrombocytopenia, or HIT, and 10 healthy people.

Using methods developed in part to study HIT, they mapped out where the VITT antibodies clung to the PF4. The antibodies reliably targeted eight surface amino acids, a fraction of PF4’s total.

“That’s where the forest fire starts," said Ishac Nazy, another McMaster University researcher and an author of the Nature study. “These amino acids are super important to VITT but not to HIT."

This story has been published from a wire agency feed without modifications to the text

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