How do we know the vaccine works?

Written on 2021-12-17

In the past few months, and especially in the last weeks, I have been doing some pretty intensive research on the safety and efficacy of the Covid vaccines. I was getting a lot of questions on it from some of my friends, and I wanted to be able to give them my perspective on this as a biologist looking at the scientific literature. I've been working on a longer document looking at all sorts of issues that people bring up, but for starters I‘d like to give a quick overview of some of the studies that look at the vaccines’ efficacy. In other words: how do we know these vaccines actually work?


  1. Polack et al. (2020). Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine, 383, 2603-2615. → This is the original phase 3 clinical trial of the Pfizer/BioNTech vaccine. It included a total of 44,000 participants and showed an efficacy of 95%, i.e. there were 20x more Covid infections among the unvaccinated control group than among the vaccinated group.

  2. Dagan et al. (2021). BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. New England Journal of Medicine, 384(15), 1412–1423. → This is an even larger study, conducted in January in Israel. Based on the data of 1.2 million members of Israel's largest health insurance provider, it showed that vaccinated people were 10x less likely to contract Covid, be hospitalised with it, require intensive treatment, or die (i.e. a 90% efficacy).

  3. Sheikh et al. (2021). SARS-CoV-2 Delta VOC in Scotland: Demographics, risk of hospital admission, and vaccine effectiveness. The Lancet, 397(10293), 2461–2462. → This is a study of 20,000 infections in Scotland, looking at the Pfizer/BioNTech and the AstraZeneca vaccine and contrasting their effectiveness against the Alpha variant and the (currently-dominant) Delta variant. For Pfizer, they found 90% and 80% efficacy against Alpha and Delta, respectively; for AstraZeneca the numbers were 70% and 60%.

  4. Henry et al. (2021). Effectiveness of COVID‐19 vaccines: Findings from real world studies. Medical Journal of Australia, 215(4), 149. → This is a review study that combined and compared the results of five different previous studies. It showed that the efficacy varies with various factors such as the vaccine used or the time since vaccination, but seems to consistently lie within a range of 60-90% for fully vaccinated persons.

  5. Hsu et al. (2021). COVID-19 Breakthrough Infections and Transmission Risk: Real-World Data Analyses from Germany’s Largest Public Health Department (Cologne). Vaccines, 9(11), 1267. → This is a study by the municipal health department of the city of Cologne, who are responsible for contact tracing and quarantining of infected persons and their close contacts. Here, they show that unvaccinated contact persons of infected vaccinated persons had a 15% chance of becoming infected, as compared to unvaccinated contact persons of infected unvaccinated persons, who had a 65% rate of infection. This shows that even in the case of break-through infections (i.e. when vaccinated persons do become infected), they are much less likely to pass that infection on to others.

  6. de Gier et al. (2021). Vaccine effectiveness against SARS-CoV-2 transmission to household contacts during dominance of Delta variant (B.1.617.2), the Netherlands, August to September 2021. Eurosurveillance, 26(44). → This study agglomerates contact tracing data from municipal health departments across the Netherlands during a period of Delta dominance. It shows that although 71% of the population were vaccinated, only 35% of reported infected cases were. It also showed that while unvaccinated household contacts of unvaccinated infected persons had a 22% chance of infection, that was halved to 10-13% if either the originally infected person or the household contact were vaccinated.

  7. Martínez-Baz et al. (2021). Product-specific COVID-19 vaccine effectiveness against secondary infection in close contacts, Navarre, Spain, April to August 2021. Eurosurveillance, 26(39). → This is a similar study to the two above (based on contact-tracing), this time from Spain. Here, too, the authors found a 50-80% reduction in infections among vaccinated persons, depending on the vaccine given (though quite strongly reduced for elderly persons).

  8. Bar-On, Y. M., Goldberg, Y., Mandel, M., Bodenheimer, O., Freedman, L., Kalkstein, N., Mizrahi, B., Alroy-Preis, S., Ash, N., Milo, R., & Huppert, A. (2021). Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel. New England Journal of Medicine, 385(15), 1393–1400. → Another study from Israel, this time looking at how long the protection from the second vaccination lasts and how effective a third “booster” vaccine is. They find that 5-6 months after the first two shots, the vaccine's efficacy has been strongly reduced, but can be restored with a third shot. (Side note: there are vaccines, like that against Hepatitis B, that require three shots to reach their full effect. There are reasons to believe that the Covid vaccines might be like that too, i.e. that we will not require regular boosters but be sufficiently immune for the long term after three shots. We don't yet have enough data to say for sure, but we will find out in the next few months.)

  9. Maier et al. (2021). Germany’s current COVID-19 crisis is mainly driven by the unvaccinated. ArXiv:2111.12806. → This study is not yet officially published and has yet to undergo peer review, so should be treated cautiously until it is. (All scientific studies are thoroughly reviewed by independent experts, and the authors have to address any queries or critiques the reviewers have before publication.) However, if the results hold up under review, they indicate that only 10-15% of infections in Germany are happening between two vaccinated persons, while 40-50% of infections are taking place between two unvaccinated persons.

  10. Bavarian State Ministry of Health (see image below) → This recent graph from the data of our state's MoH shows that the relative infection rate (i.e. infections per 100,000 citizens) in November (when I downloaded the graph) was much lower among vaccinated persons than among unvaccinated persons - 110 vs 1500! The rate of hospitalisation was also significantly lower - 3 vs 14 per 100,000. (Note: this is not at all a formal scientific study, but a neat illustration of the very real effects vaccination is having in preventing infections and illness of individuals at a time of generally very high infection levels in Germany.)

Vaccine protection in Bavaria

Closing comments

I have had long discussions with a number of friends here who are sceptical about the vaccines, and have read numerous websites that they passed along to me. None of them stood up to closer scrutiny. In many cases, they simply offered unsubstantiated speculations about possible long-term effects of the vaccines (which, for a whole range of biological reasons, are highly implausible). In many more cases, they grossly misinterpreted and/or misrepresented scientific data and studies (and yes, I did read the original studies to check).

Yes, epidemiology is really complicated. Who gets infected and/or seriously ill is influenced by any number of factors, including things like current infection levels in society, age, sex, vaccination status, medical risk factors, personal contacts, weather, public hygiene measures, and others. Likewise, vaccine efficacy and safety are also affected by numerous factors, which makes data analysis tricky and requires some very careful scientific work. But this work has been done.

Nothing in this life is ever one-hundred-percent effective, or one-hundred-percent safe. Neither are the vaccines. But after hundreds of millions of vaccinated persons around the world and with the accumulated knowledge of dozens of large, careful scientific studies, we know enough to say: vaccines work, and it's a lot (!) safer to be vaccinated than to risk contracting Covid.

Tagged as society, science, social media, covid-19

Unless otherwise credited all material Creative Commons License by Daniel Vedder.
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