Enlarge /. Vials of the AstraZeneca COVID-19 vaccine are seen at the opening of a vaccination center in Cyprus on March 22, 2021.
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AstraZeneca's two-fold COVID-19 vaccine exceeded expectations and appeared to be highly effective against symptomatic and serious illnesses in a new late-stage study, partly conducted in the United States. The company is currently applying to the Food and Drug Administration for emergency approval. However, the vaccine can still be haunted by doubts.
The Phase III study, conducted in the United States, Peru, and Chile, found the vaccine was 79 percent effective in preventing symptomatic diseases, the company reported early Monday. Previous test results suggest that the effectiveness could be only 62 percent.
In the new study of 32,449 people, two-thirds of the participants were given the vaccine, while the remaining third received a placebo. There were five cases of serious illness in the study, all in the placebo group. None of the vaccinated participants had to be hospitalized.
In particular, the company also found no increased risk of blood clotting events or cases of a rare, life-threatening blood clotting event called CVST in the vaccinated.
A small number of serious blood clotting events in recently vaccinated individuals has caused widespread concern in Europe and other countries where the vaccine is already approved for use. In the past week, more than a dozen countries – including Germany, France, Italy and Spain – temporarily suspended the introduction of the AstraZeneca vaccine, which was developed in partnership with Oxford University.
Among the more than 20 million people who have received the vaccine in the European Union and the UK, at least 18 cases of CVST (cerebral venous sinus thrombosis), where a clot prevents blood from draining from the brain, have been reported leads to a stroke. There have also been at least seven other cases of people who developed blood clots in multiple blood vessels, a condition called disseminated intravascular coagulation, or DIC. Nine of the CVST and DIC cases resulted in death.
Last week, the World Health Organization and the European Medicines Agency carried out an independent, in-depth review of all the data and finally urged countries to quickly resume use of the vaccine. Both agencies concluded that the risks of serious illness and death from COVID-19 significantly outweighed the extremely rare risk of blood clotting events.
The WHO and EMA found that among the millions of people vaccinated, reports of blood clotting events – which are generally common – were lower than would have been expected in the general population. They also couldn't tell if the vaccine was causing the CVST or DIC cases. But they couldn't rule out the possibility either, especially since most cases occurred in people under the age of 55.
In the EMA review, the organizations found:
Based on the pre-COVID figures, it was calculated that by March 16, fewer than one reported case of DIC in people under the age of 50 could be expected within 14 days of receiving the vaccine, while 5 cases had been reported. Similarly, an average of 1.35 cases of CVST could have been expected in this age group, compared with 12 on the same reference date. A similar imbalance was not seen in the elderly population given the vaccine.
The new test results did not find any cases of CVST, but – if there is really a link – this is not surprising given the extremely low frequency of these events. The study data included safety data for just under 21,500 vaccinated people, while the small number of cases outside the study occurred in over 20 million vaccinated people.
While the real possibility is that the cases are just a statistical accident, some researchers suggest that the vaccine can – rarely – trigger an autoimmune reaction that explains the diseases, and they have suggested possible treatments along these lines. Other researchers have also found that a link between the vaccine and blood clotting events is not implausible. COVID-19 itself has been linked to blood clotting disorders, and research suggests that the SARS-CoV-2 spike protein can activate immune responses that can lead to clotting.
However, a lot more data will be needed to make the connection (if any) and how the vaccine causes such a reaction and who might be affected. Like the other approved COVID-19 vaccines, the AstraZeneca vaccine only provides the cells with the genetic code for the SARS-CoV-2 spike protein, which can be used to train immune responses to target the virus. The vaccine uses a non-replicating adenovirus as packaging, similar to the Johnson & Johnson vaccine, the latest FDA approved vaccine.
For now, the FDA is being watched as it reviews the data and decides whether to grant an EEA. The agency is likely to positively evaluate the efficacy and safety data of the new study and see the vaccine as another useful tool in the fight against SARS-CoV-2. Still, public support can be a major hurdle to the future vaccine. Blood clotting concerns aside, the vaccine has seen stumble after stumble in its clumsy development – from publicly known pauses in trials due to unexplained diseases and puzzling dosage errors in some participants to recent data suggesting it is against mild to moderate could be useless COVID-19 caused by variant B.1.351.