The epidemic continues to rage all around us. The US currently has 90,000+ people hospitalized with Covid; during the last wave, we peaked at ~60,000. The upper limit of hospitalizations will likely be dictated by running out of beds. Many states are starting to approach their capacity, and this wave is far from over. The death rate for Covid and all other severe medical conditions will spike as there aren't enough medical staff or resources to care for people.

Nine states [South Dakota, New York, New Jersey, Massachusetts, Connecticut, Louisiana, Rhode Island, Mississippi, and North Dakota] have now lost 1 in 1,000 to Covid. Some of those states are on track to lose 1 in 500 by year-end. Thanksgiving celebrations will likely cause another spike in case count, further straining a medical system near the breaking point.

The big news this week was the readout of the first data from the AstraZeneca Phase III trials. Unlike the Moderna and Pfizer announcement, the AstraZeneca [AZ] results were unclear, and the release was confusing. I'll dig into what we know, but AZ will likely have to rerun their Phase III trial in the US, which pushes the timeline for them to have a EUA out a few months. This places J&J and Novavax as the most likely to be the third authorized vaccine.

In their initial press release, AZ stated the vaccine was 70% effective compared to the 90% and 95% initial results for Pfizer and Moderna. However, the FDA has previously stated that any vaccine per 50% would be considered a success. Also, the AZ vaccine doesn't have cold chain limitations, so logistics would be significantly easier.

People started to dig into the limited data that AZ provided and came away with many critical questions. First and foremost, the 70% efficacy number came from blending the results of several different trials they had underway, which had vastly different results.

In one cohort, the efficacy was 90%, as good as Pfizer, but they had given the wrong dose to people in this trial. Instead of two equal doses of the AZ vaccine, this group got a half dose first and then a full dose.

Why would a smaller dose make the vaccine more effective? That's a question we have a possible answer to. The AZ vaccine is an adenovirus vaccine. They find a virus that humans don't have exposure to, and they replace the payload with one they create. The virus is injected, infects some of your cells, they make the desired spike protein, and your immune system responds. A month later, they do it again.

However, if in the first shot your body learns to identify and attack the virus used to deliver the payload, it can mean most of the virus in the second shot is killed before it can deliver the payload and make the protein. This effectively means you don't get the booster shot that you need. If the first dose is a half dose, it might be enough to trigger some immune response to the spike protein but not the virus vector itself.

That's the science of why it might be possible that the half / full dose regime is much more effective. There are still questions; in the 90% cohort, they were limited to people under 55 years old.

There are other questions about how they put data together to get their results. Data from trials in the UK and Brazil were used, but not all the patients in each country. In each country, the control group was treated differently. Also, their study may have artificially low efficacy due to how they were diagnosing people.

All in all, it's a mess. The FDA generally doesn't take foreign data, and AZ has a Phase III trial underway in the US. They may try to change it to the half / full dose, but that would push out approval. I suspect the FDA will heavily scrutinize any results that AZ submits. This doesn't mean that the AZ vaccine isn't useful; it just means we need to wait to get more data to know.

Switching gears to Moderna and Pfizer. Things continue to look great for both of these shots. Operation Warp Speed announced they believe they can get 40 million doses out this year. The ACIP advisory panel meets on Tuesday to detail their initial recommendations on prioritizing who gets the vaccine first. One side note is that the CDC will distribute the shots to the states, but the final decision about who gets shots is up to each governor.

Logistics for the rollout are already underway. Over the last few weeks, Pfizer has been doing dry runs with four states to refine their procedures. United Airlines announced that it is already transporting the Pfizer vaccine to pre-place them. As soon as the EUA is done, shots can begin. I would expect the first shots to go out within two weeks.

A senior scientist at Moderna stated that they think they can have a vaccine for kids ready by the summer.

The next couple of weeks are critical. Mask up, stay home, take all the precautions you can. Your actions help to save lives.

Stay strong out there.

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