What’s the future of vaccines linked to rare clotting disorders? <cite>Science</cite> breaks down the latest
|sciencemag.org 04 May 2021 at 12:20|
Vaccine regulators have delivered a clear verdict: In most settings, the benefits of the COVID-19 vaccines made by AstraZeneca and Johnson & Johnson (J&J) far outweigh the small risk they will cause an unusual and sometimes deadly clotting disorder. But many questions remain about who is most at risk, how the risk-benefit calculus changes when cases fall, and what the side effects mean for the future of these vaccines, which use adenoviruses to ferry the gene for SARS-CoV-2s spike protein into human cells.
A major concern is how the rest of the world will respond to some European countries moves to limit the use of the AstraZeneca and J&J vaccines, and the brief suspension of the J&J shot in the United States. The AstraZeneca vaccinenamed Vaxzevria, or Covishield when its produced by the companys Indian partner, the Serum Institute of Indiais the cornerstone of the COVID-19 Vaccines Global Access (COVAX) Facility, a scheme aimed at vaccinating billions in the developing world. J&J is expected to provide hundreds of millions of doses of its one-shot vaccine to COVAX this year.
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Once there are clear policies from the West regarding in what age groups to use these vaccines, its going be very hard to recommend anything different here, says John Amuasi, an epidemiologist at the Kwame Nkrumah University of Science and Technology in Ghana, one of the first countries in the world to receive the AstraZeneca vaccine through COVAX. But if no other vaccines are available, limiting use of these could ultimately cause many more COVID-19 casesand deaths.
Signs the AstraZeneca vaccine could lead to an unusual reaction that causes clots throughout the body, accompanied by low levels of platelets, . Many of the first cases of what scientists now call vaccine-induced immune thrombotic thrombocytopenia or thrombosis with thrombocytopenia syndrome (TTS), were in women under the age of 60 . But that may just be because many European countries used the shots in health care workers and educators, most of whom are women and under age 65. Indeed, the gender imbalance has started to even out as more cases came to light. Among 209 people affected in the United Kingdom, 87 were men and 120 women; 139 cases were in people younger than 60. Overall, one in roughly 120,000 AstraZeneca shots has triggered the side effect in the country.
In Sri Lanka, the health minister told Parliament last month that at least six people had developed the clotting disorder among nearly 925,000 who received the vaccine, or one in 150,000 recipients. Germany has reported cerebral venous thrombosis (CVT), an unusual type of stroke that is characteristic of TTS, in roughly one in 76,000 recipients of the vaccine.
The rate was higher in Norway and Denmark, where roughly one in every 40,000 AstraZeneca vaccine recipients developed CVT, with the frequency of other clotting events possibly even higher. Whereas most European countries have recommended using the vaccine in older recipients, Norway and Denmark have recommended against using the vaccine at all for now. Denmark announced today it will not use J&Js vaccine either.
The symptoms of TTS , a rare autoimmune reaction that is triggered by the blood thinner heparin. Despite decades of research, doctors cant predict whos at risk of HIT; it seems to affect men and women, old and young alike.
Across countries, roughly one in five patients with the clotting disorder hasdied. Health authorities hope publicizing the early signs of TTS and how to treat it can help prevent fatalities. But the severe clotting is difficult to treat outside of a well-equipped hospital, so many recipients in rural areas or regions with limited health infrastructure will have little recourse.
Early data from the United States suggestJ&Js vaccine does. So far, U.S. regulatory agencies have reported 15 cases of TTS in about 7 million vaccinees.Thats a lower frequency than the one seen in Europe with the AstraZeneca vaccine, says Klaus Cichutek, president of Germanys regulatory agency, the Paul Ehrlich Institute. But J&Js rollout is just beginning in Europe, he cautions: With vaccinations starting here, we will see whether these numbers hold true.
For an older person in an area with lots of infections, the benefits vastly outweigh the risks. For a young person in a place where the pandemic is ebbing, they may not.
Guidance issued by the European Medicines Agencyon 23 April showed vaccinating 100,000 people ages 80 and older in an area with high infection rates886 infections per 100,000 people per month, the level seen in Europe in Januarywould prevent 1239 hospitalizations and 733 deaths over a period of just 4 weeks(see tables, below). At the low infection rate seen in September 202055 per 100,000 per month151 hospitalizations and 90 deaths would be prevented. In both scenarios, only 0.4 cases of TTS would be expected in those 100,000 people.
By contrast, vaccinating 100,000 people age 20 to 29 would lead, on average, to 1.9 cases of the blood clotting disorder. But it would not prevent any deaths from COVID-19, although it would prevent 64 hospitalizations in an area with high infection rates.
There are other things to consider, however, says Jeremy Farrar, an infectious disease expert who heads the Wellcome Trust. Dont underestimate the impact of Long COVID, he says. These vaccines do appear to protect against that as well. And vaccinating younger people not only protects them, but also helps keep them from spreading the virus to more vulnerable people in a community.
The benefits of the AstraZeneca COVID-19 vaccinein hospitalizations and deaths preventedfar outweigh the risks of a rare clotting disorder for most age groups, both when infections in a region are high (top) or low (bottom). All data are per 100,000 people vaccinated.