This post will attempt to answer the following questions:
- What is the data that has recently come out of Israel on the effectiveness of the Pfizer vaccine?
- How effective is the vaccine in real life?
- How effective is it at preventing asymptomatic spread?
- What does this mean for COVID restrictions?
It has been a snowy, dreary several weeks here in Baltimore. The days are short, gray, and cold. It has been dark when I go to work and dark when I come home, but it has been even darker in between. The long COVID winter has left a dusky haze over every thought and feeling. This was where my head was when on February 24th, without warning, the sun shone overhead and the temperatures suddenly rose. The bright sunshine reflected on the melting snow and ice. It was as if the world suddenly woke up out of a coma.
The sun warmed me on the outside, but it was the New England Journal of Medicine that warmed me on the inside.
I checked my email and opened the weekly update from the most prestigious medical journal in the world when I saw the study entitled “BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting”. For you, this title may sound bland and technical, even boring. For me, it caused my heart rate to speed up and butterflies to flutter in my stomach. I would have titled it “The COVID vaccine study you may have been waiting for since this miserable pandemic began.”
I’ll break down the title for you and then explain the study and why on the same day that the sun shone on my corner of the globe it also shone on the whole world.
BNT162b2 mRNA Covid-19 Vaccine – This is the Pfizer mRNA vaccine.
In a Nationwide – yes, this was data from an entire country
Mass Vaccination Setting – where the majority of the country was vaccinated.
The problem with perfection
The reason why this is exciting stems from inherent flaws in the initial vaccine trials. This is not a critique of the methodology – double-blind, placebo-controlled, randomized controlled trials are considered the gold standard in biomedical research because of the way that they eliminate biases and exclude confounding. They are not perfect, however. Nothing is. First, they tend to be small. The Pfizer trial was the largest vaccine trial in history, giving 20,000 people the vaccine. While this is a large number compared to other trials, it is not when put in the context of the billions that will need to get vaccinated. This limits its statistical power in answering some very specific questions. Part of the beauty of these trials is that they have very rigid control and oversight which gives confidence in the findings, the problem is that such control does mimic what happens in real life. This creates a situation where the numbers may look good in the ideal setting of the clinical trial but not in the messy setting of the real world.
Benefits of large population studies
In opposition to randomized controlled trials, observational population studies are done by observing what happens in real life. Since it is just observing and not controlling, these studies have problems with confounding variables. There could many unmeasured factors that bias the outcomes without anyone realizing it. Much of these can be overcome by having very large numbers of test subjects. This will “dilute” many of the unmeasured and unintended differences, but not all of them.
The main advantage of these studies is that they represent real life. There are no major exclusions and all the messy things that get in the way of a good randomized controlled trial are included in the analysis.
What they studied
Now, to the research in question. This study comes from the tiny nation of Israel which has been far ahead of the rest of the world in vaccinating its population. Israel has integrated healthcare delivery organizations that allow for efficient delivery and tracking of healthcare. The study was designed to investigate real-world effectiveness in diverse populations with different underlying medical conditions. It also takes into account the challenges of imperfect compliance with vaccination schedules, the need for cold storage, and complex logistics.
They essentially created a study that mimicked the original randomized controlled trial of the vaccine (for an explanation of that trial, read here). They collected data on all of their vaccinated individuals and then matched each one with an unvaccinated person who had a similar risk level for infection, risk level of developing serious illness, and overall health. They used advanced artificial intelligence algorithms to very precisely match the two groups. For example, an Orthodox Jewish man from a certain neighborhood with a certain number of influenza immunizations in the past five years and two other medical conditions would be matched with an Orthodox Jewish man of roughly the same age, the same neighborhood, and with the same number of previous vaccinations and medical conditions. It was that precise. They then followed each group to see who tested positive, who developed symptoms, who was hospitalized, and who died.
What made this study so exciting was the subgroup that was not included in the original Pfizer study, asymptomatic individuals. In Israel, anyone can get a COVID test within a few hours without a prescription at no cost (that’s my kind of public health!). The researchers knew if the people who tested positive had been vaccinated and could include that in the data analysis. The problem with the Pfizer trial was that they did not test asymptomatic people, so they did not know if the vaccine blocked asymptomatic transmission. This raised the possibility that people who were vaccinated could still get infected and spread the virus without having symptoms. Without stopping or slowing these silent infections, it’s difficult to stop the coronavirus from spreading. The Israeli study was able to get information on these individuals
The researchers were able to get data on nearly 1,200,000 individuals equally divided between the groups. They found that the vaccine was pretty much as effective in real life as it was in the initial randomized trials. Starting seven days after the second dose the vaccine was 94% effective at preventing symptomatic infection, 87% at preventing hospitalization, and 92% at preventing death. The results were similar across all age groups and regardless of underlying comorbidities.
The result that prompted me to get out of my seat and do a little dance was that the vaccine was 90% effective at preventing asymptomatic spread seven days after the second dose.
And, for a cherry on top, there was a spike in the UK strain (B.1.1.7). About 80% of SARS-CoV-2 cases in Israel during the time period of the study were caused by this strain. Israel’s vaccination drive began just before the so-called B.1.1.7 variant emerged and they did not see a change in the results as the number of cases from this variant increased. They did not measure the genetic sequences of the cases in their study, so they cannot say for sure that the vaccine was effective, but this is encouraging circumstantial evidence.
The data on asymptomatic spread is imperfect. For easy-to-understand reasons, vaccinated people are less likely to get tested as they assume they are protected. The vaccine is not 100% effective so there will still be people who are vaccinated and contract the virus. If these individuals don’t get tested they will not show up in the data. This means the numbers in the vaccine group would be higher than reported and the effectiveness would not be quite as good. With that said, it is extremely unlikely that this would drop the effectiveness
This study also did not have any data on the South African (B.1.351) or Brazilian (P.1) strains as they were not prevalent in Israel in sufficient numbers to get any data.
The big question
The question that everyone has and has had since this nightmare began a year ago is, “When can we go back to normal?” I am not qualified to answer that question. My goal here is only to try to explain the issues as simply as possible. I’m also quite glad I don’t have to make these recommendations as they carry great weight. If the recommendations are too lenient, thousands could die, if they are too strict, the economic and psychological hardship could be devastating. It’s easy to be a critic, especially using hindsight. Making the actual recommendations is another thing entirely.
With that said, evidence that the vaccines prevent transmission is steadily mounting. This is not just for the Pfizer vaccine:
- More data from a different study in Israel showed the vaccine reduced the amount of virus in those who got infected as the vaccination program was rapidly deploying.
- Yet another Israeli study showed that starting 12 days after vaccination, the people who got COVID-19 despite getting the first Pfizer dose had four times less virus in their bodies. Lower viral loads have been shown to cause less severe disease and less transmission.
- Oxford/AstraZeneca unveiled a preliminary analysis from a small subset of patients that hinted that one dose of their vaccine could cut transmission of the virus by up to 67%.
- Moderna tested individuals when they got their second vaccine dose and found fewer asymptomatic infections after one dose compared to placebo. One expert calculated that this would suggest that Moderna’s vaccine blocks about 91% of transmission.
- A preliminary study published in The Lancet found Pfizer’s vaccine to be at least 85% effective at preventing any type of infection – symptomatic or asymptomatic – in more than 23,000 healthcare workers across hospitals in the UK.
This is all very strong evidence that the vaccines prevent transmission. The largest gap in knowledge is for the new variants which may temper the enthusiasm. At the very least, this data should allow the vaccinated to relax in psychology if not in behavior. There is a complicated interplay of public health, public policy, social psychology, and marketing that needs to be balanced. At some point we are going to have to accept that this virus is now a part of our life and we have to live with it the way we live with influenza and varicella, and other viruses that have become a part of our lives but that we control with vaccination. When that is is not for me to say. What I know for sure is that the light is not only brighter outside my window right now it’s brighter at the end of the tunnel as well.