Should You Give the AstraZeneca Vaccine a Shot?
How the risks of the AstraZeneca COVID-19 vaccine stack up against the waiting game.
If you were offered a shot of the AstraZeneca COVID-19 vaccine, would you take it? If you’d hesitate, you’re not alone. Many Canadians would rather hold out for Pfizer or Moderna mRNA vaccines, than take AstraZeneca.
The Great COVID-19 Vaccine Dilemma is a problem we’re lucky to have, but is weighty nonetheless. To resolve my own dilemma, I dug into the latest science to estimate my risk of blood clots from the AstraZeneca vaccine, my risk of serious COVID-19 outcomes while playing the waiting game, and the real-world performance of COVID-19 vaccines.
For me, the answer was clear — get the shot, ASAP. My risk of a vaccine-related blood clot is lower than the risks I face from being exposed to COVID-19 over two months. Furthermore, it turns out that we can’t assume that Pfizer is a better bet than AstraZeneca. Science communicators have been warning us to avoid making “apples to oranges” comparisons between vaccine trials, and it’s time to start listening (see Vox and Dear Pandemic).
My risk calculus applies to my context — a healthy woman in her forties, in a region with moderate COVID-19 levels, with low to moderate exposure to COVID-19 through my three young children who are attending school. The information below can and should be adapted to your situation, so that you can make an informed choice.
So many names! The AstraZeneca vaccine is also known as the COVISHIELD vaccine (made in India), Vaxzevria, and Oxford-AstraZeneca.
Is the AstraZeneca vaccine safe? What are the risks?
The AstraZeneca COVID-19 vaccine has been linked to rare but serious adverse events — potentially fatal blood clots. They are thought to occur through a different pathway than most common blood clots, one that mimics autoimmune heparin-induced thrombocytopenia (HIT). This phenomenon is called Vaccine-Induced Prothrombotic Immune Thrombocytopenia (VIPIT) or Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT).
The risk of vaccine-related blood clots varies across populations. My fortysomething friends and I are in the highest risk group, with an estimated risk of 1 in 100,000. In older adults, the risk of blood clots is lower, in the range of 1 in 250,000 to 1 in a million. Currently, a distressingly high fraction of cases cause death (20%–40%), with some optimism that this figure will decrease with increased awareness and appropriate early treatment. Notably, due to its atypical mechanism, traditional risk factors don’t seem to apply, including personal or family history of blood clots and pregnant women.
Do other COVID-19 vaccines carry the same risk of blood clots?
The story is similar with the Johnson & Johnson vaccine, which, like the AstraZeneca vaccine, is also based on an “old school” adenovirus platform. In the United States, use of the J&J vaccine was paused due to 6 cases of vaccine-related serious blood clots, all of which occurred in women. Currently, the estimated risk of such events is about one in 140,000 in women 18 to 49 years old and one in a million for women 50 and older (see Dear Pandemic article for more information). By contrast, there have been no reports of vaccine-related blood clots with the mRNA COVID-19 vaccines from Pfizer or Moderna.
Based solely on the risk of adverse events, waiting for Pfizer or Moderna seems worth considering. Yet, there’s more to the whole story. We also need to also consider how the risks of vaccines stack up against the risk that come from being unprotected while you wait for a different vaccine.
What risks do I face while waiting for a different vaccine?
Our personal risk balance sheet depends on our chances of getting COVID-19, our chances of serious health consequences from COVID-19, and how well the vaccine would protect us against these events. The personal benefits of vaccination are greatest when we are highly exposed and highly vulnerable to severe outcomes (due to age or pre-existing health conditions), but can still be substantial in more modest situations.
To get a rough sense of my personal risk profile, I whipped out some “cocktail napkin” math (see Appendix). Using local data, I estimated that my chances of getting COVID-19 in the next two months, if I remain unvaccinated, are about 1 in 333 (300 per 100,000). This is clearly far greater than my risk of getting a blood clot from the AstraZeneca vaccine (~1 in 100,000).
However, what I really care about is my risk of severe health outcomes. Using local data and simple assumptions (see Appendix), I estimate my COVID-19 related risks over the next two months to be (very roughly): Hospitalization: 1 in 10,000 (10 per 100,000); ICU: 1 in 50,000 (2 per 100,000), Death: ~1 in 333,000 (0.3 per 100,000).
Based on these estimates, it seems that my risk of hospitalization or an ICU visit is lower from the vaccine than it is from my exposure to COVID-19 over two months (about 10x and 2x respectively). For deaths, the balance sheet is fairly even, if we assume 40% of blood clots result in death.
While these are very rough calculations, they align well with population-level analyses by public health leaders.
The Cambridge’s Winton Centre for Risk and Evidence Communication, compared the risk of ICU admission from COVID-19 over sixteen weeks to the risk of blood clots from the AstraZeneca vaccine. Notably, the risk-benefit balance depends heavily on the local COVID-19 rates. However, even in the “low” COVID-19 level model, shown here, the benefits of vaccine protection outweighed the risks of blood clots for all ages groups — except the youngest adults (20–29 years).
The European Medicines Agency produced a similar analysis of benefits versus risks for the AstraZeneca vaccine, also over a sixteen week period. Again, the benefits depend on the local COVID-19 rates. This chart shows the “medium” level, which is similar to what we face here in Vancouver. Again, vaccine protection far outweighed the risks of blood clots for adults, with an age-dependent effect. The report also contains charts for hospitalizations, which favour vaccination even more strongly, and deaths, which still favour vaccination, but less dramatically.
Assumptions and Limitations: The models assumed 80% effectiveness at preventing severe outcomes and estimated outcomes over sixteen weeks. The benefits of being vaccinated would be lower over shorter periods, or if one is not actually exposed to the local community rates of COVID-19. The benefits of being vaccinated would be higher for those with co-morbidities like asthma, obesity, or diabetes, as the models apply to “average” adults.
All of these approaches point to the same conclusion. Getting vaccinated with AstraZeneca now, rather than waiting a few months for another vaccine brings me a far lower risk of hospitalization and a moderately lower risk of a trip to the ICU. Unfortunately, I’m likely to face a small chance of death over the next few months, to the tune of 1 in 200,000–300,000 either way. I could dial this down to zero by completely isolating myself and my family, but this is not something I’m prepared to do.
How well does the AstraZeneca vaccine prevent COVID-19? Is Pfizer better?
At face value, it seems that the AstraZeneca vaccine is a worse bet than Pfizer and Moderna for protection against COVID-19. Yet, this belief is problematic for several reasons.
- The AstraZeneca COVID-19 vaccine is stellar at preventing the outcome we care most about — severe disease. Phase III trials reported 100% protection against hospitalizations and deaths.
2. We can’t directly compare results from Phase III trials of AstraZeneca and Pfizer-BioNTech. Doing this is like comparing long distance runners who ran different marathon courses against different competition. Each Phase III trial was run in a unique population, with unique outcome measures, and a unique mixture of SARS-CoV-2 variants. In many ways, Pfizer’s Phase III trial had the odds stacked more heavily in its favour.
3. We cannot extrapolate perfectly from Phase III trials to the real world. Clinical trials involved targeted populations, with strict protocols that don’t capture the range of human behaviours.
4. Vaccine efficacy is a moving target. It depends on the current mix of viral strains, which is constantly evolving. Thus, the vaccine that looks best right now may no longer be best in a few months. Furthermore, the major vaccines were all designed against the original “wild type” virus, so there is no reason to expect that one will fare better than others against the evolving strain landscape.
So… how good is AstraZenica?
In Phase III clinical trials, AstraZeneca reported 75% protection against symptomatic disease and 100% protection against severe disease, with equal or greater efficacy in older adults.
In the first real-world studies, the AstraZeneca is looking very solid, on par with Pfizer-BioNTech, at least after one dose. A Scottish surveillance study (pre-print) of five million adults reported similarly strong efficacy for both AstraZeneca and Pfizer after a single dose, to the tune of 85%-95% fewer hospitalizations. A UK study, published in April 2021, compared the AstraZeneca and Pfizer-BioNTech vaccines across 370 000 adults. Three weeks after a single dose, there were 72% fewer symptomatic infections and 57% fewer asymptomatic infections, for an overall drop of 65% in new SARS-CoV-2 infections. There were no significant differences between the AstraZeneca and Pfizer vaccines (again, after one dose). A report by Public Health England echoes these conclusions.
It seems that once the playing field is levelled, there is no clear winner. When data from second doses come in, differences may emerge, though, by that time, we may be facing a new target, and new strains.
My Bottom Line
My personal risk analysis led me to sign up for AstraZeneca, rather than wait for Pfizer-BioNTech. I got my first dose two days ago, and am feeling very comfortable with my decision, though a bit under the weather. I’m self-monitoring for any blood clot signs over the next few weeks, but am not unduly stressed given their rarity.
Vaccine-related adverse events are tragic and devastating, but they do not mean that the AstraZeneca vaccine should be discontinued. Every choice we make is a trade-off, whether we realize it or not. The toll of this pandemic will continue to extend beyond that of the virus itself.
Your analysis should reflect your personal context. My calculus reflects my age (40–49 years), my health (good), my level of exposure (low to modest, ~2 cases per 10,000 per day), and my expected wait for a different vaccine (one to two months).
If I were older, had a pre-existing health condition, lived somewhere with higher COVID-19 rates, or had to wait even longer for an alternative vaccine, the benefits of jumping on board with AZ would be even greater. If I were younger, had very little exposure to COVID-19, or had a shorter wait for a slightly safer vaccine, the benefits of taking AstraZeneca right now wouldn’t be as impressive.
If your personal calculus favours getting the vaccine, I strongly encourage you to follow the evidence, and go for it. Getting vaccinated is an opportunity to help yourself and others. By protecting yourself from COVID-19, you can prevent many more cases, hospitalizations, ICU visits, and deaths. You can also help us all move one step closer to normalcy.
It’s also fair to consider your personal risk psychology. I tend not to get very stressed out about potentially catastrophic events. I might feel differently if I expected to spend the next three weeks panicking about getting blood clots, even though I knew my odds were very low.
In fact, the Great Canadian Vaccine dilemma raises some interesting questions about risk psychology. Why aren’t Canadians heeding public health advice to get the AstraZeneca vaccine? Part of the answer likely lies in how we think about risk. Unfamiliar, highly publicized, serious blood clots often raise our alarm bells more than the now-familiar risks associated with COVID-19. We also think differently about risks that we assume in one shot (literally) than over the course of time, like the tiny daily exposures to COVID-19 that I accept when sending my kids to school.
Another part of the answer likely lies in AstraZeneca’s very public stumbles, from erroneous dosing in part of their Phase III trial, to conflicting press releases, to potential cross-contamination issues in a US manufacturing plant (Emergent). To make matters worse, it seems that expensive mRNA vaccines have become status symbols, deemed more desirable than lower cost vaccines developed for worldwide distribution.
Whatever you choose, I hope you do so with peace of mind. When you do get vaccinated, I wish you high titres and minimal side effects.
Disclaimer: This article should not be seen as personal medical advice. If you have questions about your personal vaccine risk benefit, please consult with your healthcare provider.
Risk of getting COVID-19
My hometown (Vancouver, Canada) is seeing about 20 new cases of COVID-19 per 100,000 people per day (BCCDC April 28, 2021). If this rate is unchanged (a big assumption), we expect about 600 new cases per 100,000 people in the next two months. This number is based on an “average” level of exposure to COVID-19. My personal COVID-19 exposure level is likely below average; I don’t have a job that puts me at risk, but I do have three kids attending school. To be generous, I cut my risk in half, down to 300 per 100,000 (0.3%)
Risk of severe outcomes
In British Columbia, among those 40–49, we have had 16,939 COVID-19 cases, of which 563 (3.3%) have been hospitalized, 123 (0.07%) have landed in ICU, and 18 have died (0.001%). In reality, a significant fraction of these poor outcomes have occurred in those with pre-existing health conditions. Given that I don’t have notable risk factors, I cut these numbers in half for my rough estimates. Source: BCCDC report (April 2021),
I’m a scientist and mother of three young children. I completed my PhD in genetics at Stanford and spent the first decade of my career working in cancer research, drug development, and personalized medicine.
My new career chapter is dedicated to empowering others to make well-informed healthy choices, rooted in science. I’m also passionate about helping people to fall in love with the plants on their plates.