A doctor gives a dose of AstraZeneca vaccine against COVID-19 on March 15 in Dippoldiswalde, Germany, the day the German government said it would temporarily stop using the vaccine for safety reasons.
Jens Schlueter / Getty Images
By Gretchen Vogel, Kai Kupferschmidt
ScienceThe COVID-19 reporting is supported by the Heising-Simons Foundation.
The decision of more than 20 European countries to suspend the use of AstraZeneca’s COVID-19 vaccine this week has opened a rift between vaccine safety experts, who say the cases of severe clotting and bleeding caused by the break are worrying and unusual, and public health officials. concerned that the vaccination on a continent in the grip of the third wave of the pandemic could take a heavy toll.
“The damage caused by depriving people of access to a vaccine is likely to outweigh even the worst case if a link to the coagulation disorders is finally found,” Stephen Griffin, a virologist at the University of Leeds, told Science Media Center in the UK said. The European Medicines Agency (EMA) and the World Health Organization have recommended that countries continue vaccinations while examining the reports.
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Scientists do not know if the vaccine causes the syndrome, and if so, what the mechanism is. But vaccine safety officials say they did not take the decision lightly, and that the symptoms seen in at least 13 patients, between 20 and 50 and previously healthy, in at least five countries, occur more frequently than by chance. would be expected. The patients, of whom at least seven died, suffer from widespread blood clots, low blood platelets and internal bleeding – not typical stroke or blood clots. “This is a very special image” of the symptoms, says Steinar Madsen, medical director of the Norwegian Medicines Agency. “Our leading hematologist said he had never seen anything like it.”
A somewhat similar blood disorder, called immune thrombocytopenia (ITP), has been seen in at least 36 people in the United States who have received the Pfizer and Modern vaccines against COVID-19. The New York Times recently reported. The U.S. Food and Drug Administration said it was investigating these cases, but also said the syndrome did not appear to be more common in vaccines, and that vaccinations continued in the United States. But Madsen says the cases seen in Europe in recent weeks are different from ITP, which does not have the widespread blood clots in European patients.
The UK, which has administered the AstraZeneca vaccine to more than 10 million people, has so far not reported similar clusters of unusual clotting or bleeding disorders.
In Europe, a 49-year-old intensive care nurse in Austria was one of the first cases. She died last week of officials calling it ‘coagulation disorders’, which resulted in internal bleeding. (A colleague at the same hospital who received the vaccine had pulmonary embolism, but was expected to recover.) A similar constellation of symptoms was identified in four patients in Norway, two of whom died, Madsen said.
German officials said on Monday they had received seven reports of cerebral venous thrombosis (CVT), three of which were fatal, in patients recently vaccinated with the AstraZeneca vaccine. In this rare type of stroke, the vein that drains blood from the brain is blocked, which can lead to massive, deadly bleeding in the brain. All patients also have low levels of platelets, which help to clot, a possible sign of a wider clot. One affected patient had blood clots “from head to toe”, says Clemens Wendtner, a specialist in hematology and infectious diseases at the Munich Clinic, Schwabing. The symptoms remind Wendtner of a syndrome called disseminated intravascular coagulation (DIC), in which blood clots form in the body, which decreases the platelet supply. When the blood clots cause blood vessels to rupture, the body can stop the internal bleeding less, which can damage the brain or other organs.
Arnold Ganser, a hematologist at Hanover Medical School, says he is treating another patient who developed CVT within days of vaccination. He says the patient appears to be suffering from another condition called atypical hemolytic uremic syndrome (HUS). (The patient, a woman over 60, is not yet counted in the seven cases announced in Germany on Monday.) Although it may look similar to DIC, HUS is developing due to damage to the vessel walls. It is usually caused by a bacterial toxin, but can also be due to unknown factors. The condition can be treated with an antibody directed at the complement system, and according to Ganser, it responds as if the patient is responding to the treatment.
Germany suspended vaccinations on Monday on the recommendation of the Paul Ehrlich Institute (PEI), the country’s agency responsible for vaccine safety. Klaus Cichutek, head of PEI, says all seven cases of CVT occurred between 4 and 16 days after vaccination, and that according to an analysis, only a single case would be expected among the 1.6 million people who receive the vaccine in that time window. received. A group of experts who met on Monday “unanimously agreed that there appears to be a pattern here and that a link to the vaccine is not unlikely and that it should be investigated,” Cichutek said.
Other factors played a role in the recommendation, including the fact that the syndrome is so severe and difficult to treat, and that it affects relatively young people who are at risk of dying from COVID-19. It was also an opportunity to encourage people to seek immediate medical attention if they experience persistent headaches or unusual bruising in the week after vaccination, Cichutek says.
But the decision brings PEI into conflict with the EMA, which says vaccinations should continue for now. “When millions of people are vaccinated, it is inevitable that you have rare or serious diseases that occur after vaccination,” EMA chief Emer Cooke told a news conference on Monday. EMA will convene a panel on Thursday to find out if there was a causal link between the vaccinations and the extremely unusual syndrome. At the moment, the agency is ‘firmly convinced’ that the benefits of the vaccine outweigh any risks, Cooke said.
If possible, we need to make a European decision this week based on what we know.
Madsen believes the unusual symptoms may be the result of a very strong immune response. Wendtner says that acute infections can cause blood clotting and bleeding, which sometimes results in DIC. But abnormal coagulation is also a feature of COVID-19. Wendtner says it is possible that the unusual cases had a COVID-19 infection before being vaccinated; many were health workers and teachers exposed to the work. In addition to the infection, the vaccine can somehow cause an overreaction by the immune system, causing the clotting syndrome. Ganser believes patients suffering from CVT may be the tip of the iceberg and that more people may suffer similar, but milder, symptoms.
Some have speculated that specific groups of the vaccine caused the problem, for example because it was infected or contained a higher dose. This is unlikely, Cooke said yesterday, because across Europe, patients have received doses from many different groups. However, AstraZeneca supplies Europe with vaccines from several plants, and the EMA could not say whether all the groups involved came from the same plant.
AstraZeneca says in a statement that a careful review of all available safety data of more than 17 million people vaccinated with COVID-19 vaccine in the European Union and the United Kingdom, AstraZeneca showed no evidence of an increased risk of pulmonary embolism, deep vein thrombosis or thrombocytopenia, in any defined age group, gender, group or in any particular country. … The company is closely monitoring this issue, but available evidence does not confirm that the vaccine is the cause. ”
The break is rapidly evolving into a full-blown crisis for Europe, where vaccination has been sluggish compared to the United States and the United Kingdom, while business has been booming, thanks in part to more transferable variants. One hundred thousand people a day received the AstraZeneca vaccine across Europe until last weekend. This puts enormous pressure on regulatory agencies to solve the problem quickly.
The rate of vaccinations in the next four weeks is crucial for how many people eventually fall ill and die in the third wave in Germany, says Dirk Brockmann, a disease modeler at the Robert Koch Institute. “We really need to speed up vaccinations – a lot,” he says.
Paul Hunter, an infectious disease expert at the University of East Anglia, said in a statement that even if the risk of CVT is increased by the vaccine to five or more cases per million people vaccinated, the mortality rate from COVID-19 infection for men in their mid-40s is 0.1%, or 1,000 deaths per million infected.
Given the rarity of the syndrome and the enormous benefits of the vaccine, it may be worthwhile to start again, even if the complications are related to the vaccine, but with precautions, says Cichutek, such as informing people about what they should do if certain symptoms occur or exclude some. groups of people from the vaccinations. “If possible, we need to make a European decision this week based on what we know,” Cichutek said.
Karl Lauterbach, a German politician and epidemiologist, says he would have allowed the vaccinations to continue while investigating security issues. But Wendtner says officials had little choice given the severity of the reactions. In communicating about vaccination or drug safety, he says, “there is nothing worse than trying to sweep things under the rug.” If the investigation shows that there was no connection with the vaccine, he says, “then we can be even more sure that the vaccine is safe.”