My Take on the Vaccine News and Finishing the Drill
Dear All,
My next blog was going to address questions I’m getting related to Thanksgiving among other topics, but I’ll hold off on those to address what is perhaps the most significant development to date in the battle against COVID-19.
As I mentioned in my last post, I have been underwhelmed with ‘breaking news’ on vaccine data, treatments, and major developments to date. That changed yesterday morning when Pfizer announced its preliminary data analysis showing greater than 90% efficacy in their vaccine with no major safety events.
This is major news and suggests that in the near future we’ll have at least one vaccine that is both highly effective and safe. It was also fortuitous that Dr. Tony Fauci had a virtual lecture scheduled yesterday at NYU which I was able to attend and hear some of his thoughts on the vaccine which I’ll note below.
Let’s break this down into common questions.
How does this vaccine work?
The Pfizer vaccine is a messenger RNA (mRNA) vaccine and will be the first mRNA vaccine to ever come to market. This JAMA article from September is a great review and worth a read if you’re interested in diving deep into mRNA vaccines.
For those who want the cliff notes, most vaccines are protein-based where we inject an antigen (protein from a disrupted virus) into the body and hope the immune system generates protective antibodies to this antigen. Most vaccines such as the flu, HPV, and hepatitis vaccines are protein-based vaccines that work in this way.
The mRNA vaccine is a gene-based approach that carries the genetic code of the COVID-19 spike protein which is taken up by cells in your body and your cells generate the COVID-19 spike protein antigen directly as opposed to having the antigen protein injected into you via the vaccine. The advantages to having your body produce the antigen directly as opposed to injecting the antigen are threefold:
1) mRNA vaccines can theoretically stimulate a broader immune response than a protein-based approach including activating killer T-cells.
2) mRNA vaccines can theoretically lead to a more robust neutralizing antibody response because you reduce the risk of the immune system clearing the inactivated virus before neutralizing antibodies are formed.
3) Manufacturing mRNA vaccines is cheaper, more malleable, and more scalable using new platform technology than manufacturing protein-based vaccines.
In non-scientific terms, mRNA vaccines are in theory:
1) More effective
2) More efficient
3) More scalable
Some of the outstanding questions that still need to be answered are:
1) What does the full data look like including long-term safety data? So far, we have only seen the initial press release from Pfizer.
2) How long does immunity last after receiving the vaccine?
3) Does it work effectively across all sub-populations (elderly vs young)?
4) Does it prevent both mild and severe disease?
While there are still questions to be answered and all of the above is subject to change with new information, I am reasonably confident (as was Dr. Fauci) that this will prove to be a game-breaking vaccine.
What does it mean that it is greater than 90% efficacious?
This is a phase III randomized trial meaning that those who entered the study were randomly assigned to receive 2 doses of the vaccine 3 weeks apart or receive 2 doses of a placebo shot 3 weeks apart. All patients were pre-screened to confirm they did not have existing antibodies to COVID-19 before enrollment. Both the patients and investigators were blinded to who received the vaccine versus placebo and both groups were subsequently observed for whether they caught COVID-19.
To date, about 44,000 people have enrolled in the trial. The pre-specified end point was to wait until 164 people in the trial contracted COVID-19 and then ask an independent review board to analyze the efficacy. In conjunction with the FDA, Pfizer was planning to do an interim analysis and that data was reviewed by the independent external board on Sunday when there were 94 positive cases across trial participants. The independent advisory board reviewed this data and declared the vaccine to be at least 90% effective. Dr. Fauci suggested the full data will show the efficacy to be greater than 90% when it is released.
While we do not have the final data to review yet, the 90% efficacy far surpassed most scientists and public health officials’ expectations. Dr. Fauci said yesterday that he would have been satisfied with a vaccine that showed ~70% efficacy or better. The fact that the initial results far surpass this, along with no major safety events, is a massive development and makes it very likely that we will have 1 or multiple vaccines in the near future.
What do you mean by the near future?
Pfizer is continuing to collect safety data for the next 2 weeks and will subsequently submit an Emergency Use Authorization (EUA) which could be approved in early December. It appears that ~15-20 million doses of the Pfizer vaccine could be ready by that point which means that it is possible that some people are receiving the vaccine in mid-to-late December. The prioritization and distribution of the vaccine is outside of scope for today’s post but suffice to say the supply chain and distribution plans for disseminating a vaccine have been well underway for some time.
There are additional tailwinds with this news because Moderna’s vaccine is also an mRNA vaccine that *should* produce similar results given the similarities between their vaccine and Pfizer’s. If Moderna’s vaccine proves to be similarly effective and safe that would significantly accelerate the supply of doses ready in early 2021.
This sounds too good to be true. What am I missing?
From a vaccine perspective, yesterday was about as good of news as there could have been. I think we’ve reached a pivotal moment where we feel really good that a safe and effective vaccine is now imminent. There is light at the end of the tunnel.
The bad news is that case counts and hospitalizations are rising exponentially and this vaccine will not help us today, tomorrow, next week, or next month. My biggest fear is that we will let our guard down based on the positive vaccine news. The vaccine will help us sometime in 2021 but will not meaningfully change the trajectory of the virus over the next few months.
The chart below from Dr. Eric Topol shows how long it has taken the U.S. increase total number of cases by each million:
You don’t need a PhD to see how quickly we’re now adding a million cases in this country. Whereas it was previously taking months to add a million cases, we’re now adding millions of cases in a little over a week’s time. This is incredibly concerning and will likely worsen with the upcoming holidays and dropping temperatures as Winter approaches.
Hospitalizations are close to 60,000 which is near the max peak we saw in the first wave in the spring and the second wave in the summer as illustrated on the chart below:
And, hospital systems such as Ballad Health in the Southeast are starting to suspend elective surgeries. As many of you know, elective surgeries are the financial lifeline of a hospital so when a hospital system voluntarily starts suspending its most lucrative revenue stream, you know things are serious.
Thus, we’re at an inflection point with really positive news on the vaccine front while also witnessing exponential growth with the potential for devastating consequences if community spread continues to go unchecked. The current trends on case counts and hospitalizations are as worrisome as they’ve ever been.
Yesterday’s news was an important step towards our shared goal of returning to normal life. But, it shouldn’t be seen as a reason to let our guard down. In fact, it should strengthen our resolve to continue wearing masks and taking reasonable precautions as Winter approaches now that we have a viable exit strategy.
It is time to be optimistic about the future while recognizing the significant challenge that lies ahead over the next several months. The end is in sight. Whether and how we choose to finish the drill is up to us.
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