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## Let’s Clear This Up: What Does 95% Covid-19 Vaccine Efficacy Actually Mean?

In popular press and social media, there’s been a misunderstanding of what is actually meant when scientists say that the Pfizer and Moderna Covid-19 vaccines have an efficacy of 94-95%. It does not mean that 95% of vaccinated people are protected from infection โ these vaccines are better than that. Dr. Piero Olliaro explains in a letter to The Lancet:

The mRNA-based Pfizer and Moderna vaccines were shown to have 94-95% efficacy in preventing symptomatic COVID-19, calculated as 100 x (1 minus the attack rate with vaccine divided by the attack rate with placebo). It means that in a population such as the one enrolled in the trials, with a cumulated COVID-19 attack rate over a period of 3 months of about 1% without a vaccine, we would expect roughly 0.05% of vaccinated people would get diseased.

Another way to put it: you’re 20 times less likely to get Covid-19 with a vaccine than without. (And again, data indicates these are safe vaccines.) Olliaro explains with some simple math:

If we vaccinated a population of 100,000 and protected 95% of them, that would leave 5000 individuals diseased over 3 months, which is almost the current overall COVID-19 case rate in the UK. Rather, a 95% vaccine efficacy means that instead of 1000 COVID-19 cases in a population of 100,000 without vaccine (from the placebo arm of the abovementioned trials, approximately 1% would be ill with COVID-19 and 99% would not) we would expect 50 cases (99.95% of the population is disease-free, at least for 3 months).

And of course if you vaccinate widely, it becomes a compounding situation because the virus just runs out of people to infect.

## The Covid-19 Vaccines Are Amazing. Let’s Quickly Get Them into People’s Arms.

You probably read something yesterday, maybe just a headline, about Moderna’s Covid-19 vaccine being “six times less effective” against the B.1.351 coronavirus variant first identified in South Africa. This is, to put it plainly, a bullshit take on what is actually excellent news. This is the important bit, via Stat:

Both the Moderna vaccine and the immunization from Pfizer-BioNTech produce such powerful levels of immune protection โ generating higher levels of antibodies on average than people who recover from a Covid-19 infection have โ that they should be able to withstand some drop in their potency without really losing their ability to guard people from getting sick.

“There is a very slight, modest diminution in the efficacy of a vaccine against it, but there’s enough cushion with the vaccines that we have that we still consider them to be effective,” Anthony Fauci, the top U.S. infectious diseases official, said Monday on the “Today” show.

Let’s hear that again: “Both the Moderna vaccine and the immunization from Pfizer-BioNTech produce such powerful levels of immune protection…” These vaccines are so good, so potent, that even this sixfold drop in one measure of the vaccines’ ability to neutralize this one SARS-CoV-2 variant isn’t even enough to significantly reduce their overall protective power.1 That’s the important news here, that’s the very good news, that’s what you should be taking away from this. We have miraculously developed a near-perfect medicine for a plague that has significantly disrupted all human life on Earth and we’re flipping out over some technical details that the experts assure us don’t mean much in terms of overall effectiveness?! No thank you. Not today.

In a Twitter thread, Zeynep Tufekci is tearing her hair out because of the media’s misunderstanding and sensationalization of the “sixfold drop”.

I know people are tired but needless anxiety isn’t helping us. Let’s focus on getting through these months โ better masks if indoors with others, more strict attention to our precautions โ and the real problem: making more of these amazing vaccines quickly & getting them out there!

I get it, we want to understand but not how it works. Stop worrying about Nab titers. That does NOT mean the vaccine is six times less effective. People whose job it is to worry about it are on it & we just got confirmation: it works against the variants.

Plea to media: this isn’t a good headline. It makes people think the vaccine is six times less effective against the new variants (FALSE!) when the news today is *excellent*: The vaccine continues to work well against the new variants. That’s the headline.

For a much more technical take on the efficacy of the vaccines against variants, see virologist Florian Krammer’s long thread. His conclusion:

mRNA vaccines induce very high neutralizing antibodies after the second shot (consistently in the upper 25-30% of what we see with convalescent sera). If that activity is reduced by 10-fold, it is still decent neutralizing activity that will very likely protect. Furthermore, we know that the mRNA vaccines are already protective after the first shot when neutralizing antibody titers are low or undetectable in most individuals.

There is a concern here and it’s that B.1.351 or B.1.1.7 might mutate into variants that are significantly resistant against the vaccines’ good effects. Krammer again:

First, we need to do what every good scientist is praying for a year now: We need to cut down on virus circulation. The more the virus replicates, the more infections there are the higher are the chances for new variants to arise. Also, we need to try and contain B.1.351 and B.1.1.248/P.1 as much as possible.

That’s why, aside from preventing hundreds of thousands of deaths in the next several months, getting these vaccines into people’s arms is so important: the less the virus spreads, the less opportunity it will have to mutate into something even more dangerous. The US vaccination effort is slowly ramping up โ we’re at an average of 1.3 million doses per day right now and the trend is heading in the right direction. We can get this done!

1. Obviously, this could change! But the situation right now w/r/t variants is very good.โฉ

## Initial Data Shows Covid-19 Vaccine Is More than 90% Effective

In a press release (and not a paper in a peer-reviewed journal) based on a preliminary outside review of data from its phase 3 trial, Pfizer says its Covid-19 vaccine was more than 90% effective in preventing the disease.

The company said that the analysis found that the vaccine was more than 90 percent effective in preventing the disease among trial volunteers who had no evidence of prior coronavirus infection. If the results hold up, that level of protection would put it on par with highly effective childhood vaccines for diseases such as measles. No serious safety concerns have been observed, the company said.

I really hope this analysis holds up when more data from the study is released:

The data released by Pfizer Monday was delivered in a news release, not a peer-reviewed medical journal. It is not conclusive evidence that the vaccine is safe and effective, and the initial finding of more than 90 percent efficacy could change as the trial goes on.

The world, and the United States, could really really use some good news like this about the pandemic.

Update: Here’s Pfizer’s press release. And a thread from Dr. Natalie Dean on how she is interpreting this news (“Celebrate, but let the process play out over time as intended.”)

Pfizer’s first analysis was planned for 32 events, which they pushed back after discussions with FDA. But by the time they analyzed the data, 94 had accrued. This shows how quickly trials can generate results when placed in hotspots (and how much transmission is ongoing!).

These vaccines are tested until a certain number of infections happen. So you have this interesting paradoxical situation where if a potential vaccine is more successful at curbing infection, the longer it takes for the study to conclude. You get a better vaccine but wait longer for it. Countering that are the rising transmission counts in the US โ more community transmission will get you to the target number of infections more quickly.

Update: From virologist Dr. Florian Krammer, a thread about what Pfizer and other companies will be looking for in terms of the efficacy of vaccines in a number of different situations. Overall, he is optimistic about these preliminary results. And here’s a FAQ about the vaccine from the NY Times.

Another open question is whether children will get protection from the vaccine. The trial run by Pfizer and BioNTech initially was open to people 18 or older, but in September they began including teenagers as young as 16. Last month, they launched a new trial on children as young as 12 and plan to work their way to younger ages.

Update: A very simplified explanation of Pfizer’s RNA-based vaccine.