The holy grail of Covid-19 has been, for most of the year a vaccine

8 min readNov 26, 2020

The holy grail of Covid-19 has been, for most of the year, a vaccine. We’ve all been using “when we’ve got a vaccine” as a synonym for “back to normal,” because the only return to normalcy that we can really envision is based on everyone being immunized against infection. In all the conversations about how the pandemic might end, the one thing that is always featured is a vaccine that prevents the disease in the people who get it.

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Which is why the recent Pfizer news feels momentous. The preliminary results from one of the first Phase 3 trials for a vaccine against Covid-19 have been reported, with Pfizer and BioNTech announcing that their vaccine is 90% effective at preventing Covid-19 at 28 days after the vaccine was given. All of a sudden, the hazy dreams of tomorrow where we are all safe from Covid-19 have become much more realistic in the near future.

But before we declare the pandemic officially over, it’s worth noting that this is just one more step in the long haul. Yes, these results are promising — and, I personally think, incredibly exciting — but there is a long way to go before we are totally over Covid-19, if that’s possible at all.

So let’s have a look at what has been announced, and what it really means

The study itself is looking at BNT162b2, an mRNA vaccine candidate developed by Pfizer and BioNTech. It is what’s known as a Phase 3 clinical trial, which means that the companies are testing whether the vaccine actually works to prevent disease in a very large group of people — over 40,000 — using a randomized, controlled study design. This sort of study is the gold standard for finding out whether a vaccine works, and what if any side effects we need to be worried about.

The study design is pretty simple, at heart: One group gets the vaccine, another a placebo, with a second dose at the 21-day mark, and people are followed up at 28 days to see if they have been infected with Covid-19 or not. They are then followed up for two years in total, to see if they have any side effects from receiving the vaccine. The two groups are then compared to see if 1) the vaccine group has fewer infections; and 2) there are any serious side effects to worry about due to the vaccine. The full protocol is linked above, and is very long and detailed if you’re interested in reading.

I would recommend it, but study protocols make for, uh, dense reading unless you’re an expert.

Now, the study hasn’t finished, having recruited less than the full cohort of 40,000 people, but after a certain number of “events” — in this case, lab-confirmed cases of Covid-19 — an independent auditor has a look at the results to see what they are. This is in case there is either a huge benefit or a huge safety issue; in those cases we may want to pause the study and reassess. All of these measures are specified in advance by the FDA, to ensure that the process is as transparent as possible. In particular, the number of events was predecided to be 62, but by the time the analysis was done it had actually increased to 94, which means that there had been a total of 94 lab-confirmed infections with Covid-19 across both groups of the study.

So when you read the announcement that the vaccine is 90% effective, this is what it actually means: In the study that Pfizer is conducting, they found that, at an interim analysis, 90% fewer people had confirmed cases of Covid-19 in the vaccine group compared to the placebo. We are still waiting on the final results, which may take a few more months to come in, but even so it’s a pretty major finding.

Now, that sounds amazing, but let’s unpack it a bit, because there are still some huge caveats.

The first big, important thing to consider is pretty simple when you think about it: Preventing infections is potentially meaningless in and of itself. Now, cases of Covid-19 are incredibly important, because we know that cases cause hospitalizations and deaths, but the thing is that in this type of research we have to be incredibly careful about our end points. If a vaccine were to prevent infections, but not severe disease or death, it might actually be pretty ineffective as an intervention.

Similarly, it’s important to know whether the vaccine prevents symptomatic infection or laboratory-confirmed cases with everyone being tested. The protocol says laboratory-confirmed, but the press releases put out so far have not really told us much about the specifics of the findings, just the headline figures. We really need to dig down into the numbers to know whether this is cause for celebration or just another big sigh of disappointment in the year of 2020.

This is because some vaccines prevent disease symptoms but don’t necessarily stop infection entirely, which has big implications. If the vaccine stops people from having symptoms, but they can still catch and pass on the disease, then it won’t be able to get us to herd immunity — conversely, if being vaccinated completely prevents infection, then herd immunity becomes a very realistic goal.

There are more unanswered questions from these results as well. How long will protection last? The study is only powered to find a benefit up to 28 days, but it’s entirely possible that the vaccine will only protect us for a short period of time even if it does pan out. This again has many implications, not least whether we will need to get a new dose of the vaccine every year.

Also, what about the subgroup analyses? The study was very carefully designed so that we could see if the vaccine works as well for children, elderly people, minority groups, etc. This interim analysis doesn’t give us any information on whether the immunization provides protection to those over 65, who are also the group most at risk from Covid-19 and the people we really want to protect.

We also can’t forget about safety. This analysis shows a reduction in Covid-19 infections, and the press release says that there have been no serious adverse events reported yet, but it’s still early days. It’s entirely possible that there will be serious side effects from the vaccine that emerge during the study that we simply don’t know about yet.

All in all, despite the fantastic good news of the press release, we are left with almost as many questions as answers.

So that’s the study itself — the results are promising, but we still just don’t have enough information to be sure of the vaccine’s effectiveness in the real world. But that’s not the whole story, because even if the vaccine was 100% effective and we were certain about it’s safety, the pandemic wouldn’t be over tomorrow. People have been treating the idea of having a vaccine as a goal in and of itself, but the reality is that the true end goal is having people immune to the disease, and that’s about more than just creating a vaccine in a lab.

You have to actually get most people vaccinated. And that, unfortunately, is a really hard thing to do.

Let’s say that the vaccine is indeed 90% effective, across all age groups and for both mild and severe disease. It’s exactly what we were looking for in a vaccine candidate, and lasts a lifetime. How many people do we need to vaccinate to get to a reasonable herd immunity threshold?

Well, let’s say that the herd immunity threshold is around 70%, in line with traditional estimates based on the R0 of Covid-19. With a 90% effective vaccine, you’d need to vaccinate about 80% of the population to reach that 70% immune figure. So, in the United States, that would be 264 million people, but since the vaccine requires two doses 21 days apart it would be 528 million doses altogether.

Which is, I think we can agree, quite a lot.

Now, it’s certainly not an impossible figure — we’ve organized vaccine drives that capture large proportions of the population before — but it’s not a small ask either. It would take a huge portion of the medical workforce working tirelessly for months to get everyone vaccinated, and that’s assuming that there aren’t large swathes of people who decide that they don’t want to be protected from Covid-19.

This is before we even start to think about what it might mean if the vaccine protection wanes. What happens if we have to give 528 million vaccine doses in the U.S. alone once a year? It’s also just for the U.S. which is in the fortunate position of being wealthy and having a very good vaccine program — what about the rest of the world? What about countries like Pakistan and the Democratic Republic of the Congo, which have quite a bit of trouble already with giving out vaccine doses? If we want Covid-19 to be over, it can’t just be over for the wealthy among us, we need to get everyone protected everywhere or it’s just a matter of time until the disease comes back. (Also, of course, it would be morally repugnant for those of us in wealthier countries to only think of ourselves in a time of global crisis.)

The reality is that we are in this for the long haul, whether this vaccine pans out or not. Even if we are incredibly lucky and these results hold, and the vaccine is safe, and it lasts for a lifetime, it may still be months or even years before we get back to anything approaching normal.

Yes, the results are promising. You should be encouraged — I certainly am! Just don’t forget that we still have a ways to go before we can declare the pandemic officially over.

The holy grail of Covid-19 has been, for most of the year a vaccine

Written by Vhou