Why Doesn’t the Vaccine Safety Debate Seem Settled?

(Bloomberg Opinion) -- The European Union’s Covid-19 vaccination effort has been rocky, with inoculations lagging behind the U.S. and U.K. even as an increase in cases in the region has prompted fresh lockdowns. Most recently, concerns about blood-clot risks related to the AstraZeneca Plc-Oxford University vaccine — one of four given emergency use authority in the EU — led several countries to suspend the shot pending a fresh regulatory review from the European Medicines Agency. So it was good news, then, when officials from the EMA on Thursday backed the shot as safe and effective, saying the benefits of protecting against Covid-19 outweigh any risks.

The pronouncement wasn’t entirely clear cut, though. While officials said they did not think there was a link between the Astra vaccine and some rare blood-clotting events, they could not categorically rule out a connection. There were 18 cases of cerebral venous sinus thrombosis, or blood clotting that impacts the draining blood vessels of the brain, and seven cases of disseminated intravascular coagulation, a widespread clotting issue. This is out of 20 million doses of AstraZeneca’s vaccine, according to the EMA. It is technically difficult to prove a link in such rare instances and it will take more research and time. In the meantime, the EMA recommended a warning label be applied to the shot so people are aware of the potential risk. We asked Sam Fazeli, a Bloomberg Opinion contributor who covers the pharmaceutical industry for Bloomberg Intelligence, whether all doubts about the shot had been put to rest.

Is there more the EMA could do to help ease concerns and increase understanding on vaccine risks?

I appreciate the EMA’s honesty in saying it couldn’t definitively rule out any link between Astra’s vaccine and those blood-clotting issues. But given the uncertainties some may still have, I think the agency could have gone further in providing details about the whole vaccination program and its analysis of the safety worries around the AstraZeneca vaccine. I am not a public relations expert, but as a scientist I feel the agency lost an opportunity to reassure parts of the public that still may be skeptical — not just of the AstraZeneca vaccine, but of all Covid-19 vaccines.

There is so much vaccine skepticism. Couldn’t this have been a good chance to educate people with real-world specifics showing why the benefit outweighs the risks of disease?

Many people may not know this, but Covid-19 is actually associated with an increased risk of blood clots, as well as a whole host of other symptoms. In fact, one of the therapies being used in hospitalized patients is anti-coagulation therapy. The EMA could have made a few slides to show how many Covid-19 hospitalizations would be avoided by vaccinating x% of the population compared with the percentage of cases of these rare events that would be expected, if indeed there is a link. This would have helped people understand the “benefits outweigh the risks” comment that it has made several times. Show, don’t tell!

While the EMA was talking vaccine safety, it could have broadened its discussion to include other vaccines. It didn’t explicitly say, for instance, that none of the rare events have been seen after the use of the Pfizer Inc.-BioNTech SE or other vaccines. Isn’t that important, too?

The EMA had an excellent opportunity to spell this out and tell people that they haven’t had reports of those two rare blood-clotting events after doses of the Pfizer-BioNTech vaccine. One could argue that this can be inferred from what was said, but an explicit comment would have gone a long way. The EMA did say that there were cases of more general types of blood clots in people that have received the Astra, Pfizer or Moderna Inc. shot — but they said these were not seen at a rate above what is expected in the general population. The EMA did note that there are 100,000 blood-clotting cases per month across the EU unrelated to vaccinations. Here’s some science: All vaccines induce an immune reaction, which can, in rare cases, interfere with the blood-clotting system. Given that the majority of vaccines for Covid-19 target the “spike protein” of the Sars-Cov-2 virus, the immune response should be similar between them. But AstraZeneca’s vaccine — as well as ones developed by Johnson and Johnson, Russia (Sputnik V) and Cansino Biologics Inc. — uses a virus as a “Trojan horse” to bring the gene for the spike protein into the body, compared with the synthetic “messenger RNA” vaccines of Pfizer-BioNTech and Moderna. These use fat globules (technically called lipid nano particles) to take in the genetic code for the spike protein. As such, the Astra vaccine is taking with it other viral proteins. The EMA did not even attempt to discuss the possibility that this could be a driver of a possible link to the rare cases of clotting.

One difference between the EU and U.K. – where the Astra vaccine has been given to more than 11 million people with only  five cases of this blood-clotting incidence so far – is that the EU didn’t use the AstraZeneca vaccine in its older population. Could this have been a driver of the side effects seen with the vaccine in the EU and not the UK?

This is another key element that the EMA should have discussed. In response to a question about why the U.K. hasn’t seen many cases of these rare events, the EMA said it’s likely because of the older age group which the U.K. has been vaccinating. If that is truly the case, it should have shown the age distribution of people who have been vaccinated in the EU by each type of vaccine rather than leave this question hanging in the air.

Why do younger women seem more at risk?

Twelve of the 13 cases of cerebral venous sinus thrombosis that have been seen in Germany are in women under 50. Where was the EMA’s slide that showed that this population is already at a higher risk of blood-clotting disorders? And that some of this may be due to the higher use of oral contraceptives, augmented by smoking. Why not discuss this? This is important.

Any last thoughts?

All in all, I am happy that the Astra vaccine is back on track for being used in the EU, which certainly needs it given the recent rise in cases across many countries. As I have said before, I would happily take the Astra vaccine and probably will next week in London. The effectiveness of vaccines in the real world is proving their huge benefit when measured against the small risks of rare side effects. The latest data from England show that a single dose of either the Pfizer shot or Astra’s vaccine reduces the risk of being hospitalized after a Covid-19 infection by 35% to 45%, which combined with the 60% reduction in the risk of catching an infection suggests an 80% overall reduction in the risk of getting severe enough Covid to require hospital treatment, according to Public Health England’s latest data. I just wish the EMA had done a better job of discussing the whole issue. I wish the EMA — and British regulators too — were more like the U.S. Food and Drug Administration and Centers for Disease Control and Prevention in holding public meetings with independent experts. The public deserves this.

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

Sam Fazeli is senior pharmaceuticals analyst for Bloomberg Intelligence and director of research for EMEA.

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