Millions of people in dozens of countries have received the AstraZeneca Covid vaccine with few reports of harmful effects, and their previous tests on tens of thousands of people considered it safe.
But recently, blood clots and abnormal bleeding in a small number of vaccinees in European countries have cast doubt on its safety, although no causal link has been found between the conditions of the patients and the vaccine. The reports have led more than a dozen countries to partially or completely suspend the use of the vaccine while the cases are investigated. Most nations said they did it as a precaution until major health agencies could review the cases.
The AstraZeneca vaccine has not yet been authorized for use in the United States, although a review of its trial in the United States is expected soon.
What kinds of problems have led countries to take precautionary measures?
The cascade of decisions to stop using the AstraZeneca vaccine, mainly by European countries, came after reports of four serious cases in Norway, which were described among health workers under 50 who received the vaccine. Most developed clots or bleeding abnormalities and had low platelet counts, local health officials said. Two of them died of cerebral hemorrhage and the other two are hospitalized. The death of a 60-year-old woman in Denmark and a 57-year-old man in Italy has also fueled swift decisions, although none of the deaths have been fully investigated to determine whether there is any connection to the shots they received.
What is a blood clot and what causes it in general?
A blood clot is a thick, gelatinous blister of blood that can block circulation. Clots form in response to injuries and can also be caused by many diseases, including cancer and genetic disorders, certain medications and prolonged or bed rest. Clots that form in the legs sometimes come off and reach the lungs or brain, where they can be deadly.
Can the vaccine cause blood clots?
Vaccines have not been shown to cause blood clots, said Daniel Salmon, director of the Vaccine Safety Institute at Johns Hopkins University.
Blood clots are common in the general population, and health officials suspect that cases reported in vaccinees are more likely to be coincidental and unrelated to vaccination.
“There are many causes for blood clotting, many predisposing factors and many people who are most at risk – and these are often the people who are being vaccinated now,” said Mark Slifka, a vaccine researcher at Oregon Health and Science University.
From 300,000 to 600,000 people a year in the United States develop blood clots in the lungs or veins in the legs or other parts of the body, according to the Centers for Disease Control and Prevention.
Based on these data, about 1,000 to 2,000 blood clots occur in the U.S. population every day, according to Dr. Stephan Moll, a hematologist and professor of medicine at the University of North Carolina.
“The United States has 253 million adults,” said Dr. Moll. “So if 2.3 million people in the United States are vaccinated with Covid every day, it means that about 1 percent of the adult population is vaccinated every day.”
Calculating more, he said, about 1 percent of the 1,000 to 2,000 daily blood clots – 10 to 20 a day – would occur in vaccinated patients only as part of normal background rates, unrelated to the vaccine.
“Only if epidemiological data shows that this rate is higher, could we begin to ask ourselves about a causal relationship,” said Dr. Moll.
What can the existing data on the AstraZeneca vaccine tell us?
Dr. David Wohl, director of the vaccine clinic at the University of North Carolina, said he saw no evidence that any of the Covid vaccines caused blood clots, also called thrombosis, in the large clinical trials that led to his authorization. .
But Dr. Wohl also noted, “There are differences between trials and real life.”
The most extensive safety results of the real-world launch of the AstraZeneca vaccine come from Britain, where 9.7 million doses of the vaccine were distributed last month. Britain’s data found that at least some clotting conditions, while extremely rare, were equally prevalent in people vaccinated with the AstraZeneca vaccine compared to those who received the product from Pfizer. But abnormally low platelet levels were more common among people who received the AstraZeneca vaccine.
External tests, vaccines are administered to a wider range of people. So if safety issues arise as soon as a vaccine comes into more general use, the issues should be investigated, said Dr. Wohl.
“We don’t want to ignore a signal that could indicate a bigger problem,” he said. “But at this point, it is premature to think that AstraZeneca causes thrombosis.”
Do vaccines cause other bleeding disorders?
Other vaccines, particularly those given to children against measles, mumps and rubella, have been associated with temporarily reduced levels of platelets, a blood component essential for clotting.
Decreased platelet levels have been reported in a small number of patients who received the Moderna, Pfizer-BioNTech and AstraZeneca vaccines. One recipient, a Florida doctor, died of cerebral hemorrhage when his platelet levels could not be restored, and others were hospitalized. US health officials said the cases are being investigated, but have not reported the results of these analyzes and have not yet indicated that there is any connection to the vaccines.
How will researchers determine if a link exists?
The European Medicines Agency said on Monday that it was working with AstraZeneca and health officials to examine “all available data and clinical circumstances around specific cases”.
The authorities did not elaborate on what the assessment will look like. But when evaluating a possible connection between a vaccine and a serious side effect, researchers generally focus on estimating how often these medical problems would be expected to happen by chance in the group of people in question.
This may mean looking at people in the same group before they are vaccinated. It can also mean looking at a similar group of people. If the rate of these problems is higher in the vaccinated group than would be expected in a comparable population, this is a sign that the safety problem may be real, or at least it is worth more scrutiny.
These investigations usually do not depend on finding out definitively whether the vaccine was the cause of death or a serious medical problem, because in most cases it cannot be conclusively determined. But the researchers take into account the medical history, as if a person was treated for similar medical problems before being vaccinated.
Researchers also remember factors that can increase the likelihood that a group of people will fall ill. Elderly people, who have been prioritized in vaccination campaigns around the world, are at greater risk of developing blood clots than younger people.
What you need to know about the vaccine launch
Individual health ministries are also conducting investigations, and health authorities in those countries are awaiting the results of the autopsies. In addition, in Italy, authorities seized doses of the vaccine in the Piedmont region as part of an investigation into the teacher’s death over the weekend.
Can we expect updates on the investigation?
A World Health Organization advisory committee plans to meet on Tuesday to discuss the vaccine. The safety committee of the European Medicines Agency will meet on Thursday.
Jennifer Nuzzo, an epidemiologist at the Johns Hopkins University Health Safety Center, said she hoped authorities would provide regular updates on the status of the AstraZeneca vaccine safety investigation – something that often doesn’t happen when safety concerns are probed.
“I would really like there to be more continuous communication about what types of analyzes they are doing, what they are looking at, even if they are provisional – just to make the process transparent and to improve confidence in it,” said Dr Nuzzo.
What did the company say about the security scare?
AstraZeneca first publicly addressed safety concerns a week ago, after Austria suspended vaccination of a batch of AstraZeneca vaccine. A company spokesman said at the time that no serious side effects from the vaccine had been confirmed.
On Thursday, after Denmark decided to suspend all vaccinations with the AstraZeneca product, the company issued a statement defending the safety of its vaccine more forcefully. The safety data from AstraZeneca, a collection of more than 10 million records, showed no evidence of an increased risk of blood clot problems in any demographic group or country, the company said.
On Sunday, after several other countries announced plans to halt their vaccination campaigns, AstraZeneca released a press release with more details on the number of reported side effects and people vaccinated in clinical trials and immunization campaigns in Europe.
On Monday, an AstraZeneca spokesman said the company was “working with national health authorities and European authorities and we look forward to their assessment later this week”. (The company declined to name a spokesperson.)
Is there a precedent for a vaccine safety scare?
Previous concerns about vaccine safety have generally not been borne out by the evidence, although there are exceptions. In 1999, the first vaccine against rotavirus infection, which causes diarrhea in babies, was withdrawn from the market because it was found to increase the risk of intestinal obstruction.
But even unproven concerns about security have diminished public confidence.
After the Food and Drug Administration approved a highly effective Lyme disease vaccine in 1998, media reports and a class action fueled complaints from people who said they developed arthritis after being vaccinated. In 2001, the FDA convened a panel of experts to review the vaccine’s safety data – clinical trials revealed no difference in the frequency of long-term joint symptoms between the vaccine and placebo groups – and concluded that the vaccine should stay on the market.
But by then, the public’s perception of the vaccine was too far gone: a sharp drop in sales spurred the vaccine manufacturer, GlaxoSmithKline, to withdraw it from the market in 2002.
What is the status of the vaccine in the United States?
Although more than 70 countries have authorized the vaccine, the United States has not. AstraZeneca has not yet requested authorization from the Food and Drug Administration and is awaiting the results of its study in the USA, which involved more than 32,000 participants.
An announcement by AstraZeneca about these results could come soon: data from this trial are being analyzed by an independent panel of experts, Dr. Francis Collins, director of the National Institutes of Health, told Reuters on Monday.
The strong safety and efficacy results of this trial can go a long way in reassuring people about the AstraZeneca vaccine, said Geoffrey Porges, an analyst at investment bank SVB Leerink.
“But the longer this goes on, without a comprehensive review and without the results of Phase 3 in the US, the more people will be concerned,” said Porges.