Nov 24 2020

We Have Several Vaccines for COVID – Now What?

Two weeks ago Pfizer and German company BioNTech announced preliminary analysis of their phase 3 trial of an mRNA-based vaccine for SARS-CoV-2 showing it is 90% effective (later updated to 95%). One week ago Moderna announced that they too had promising results from their phase 3 trial, also an mRNA vaccine showing 95% efficacy. This week AstraZeneca announced they have developed a COVID vaccine as well (in partnership with Oxford University).

I have not discussed the AstraZeneca vaccine before, so here are the basic facts: “It uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein.” In the study, overall there was a 70% efficacy in reducing symptomatic cases of COVID-19. However, in a subgroup analysis, those receiving a half dose followed by a full dose (instead of two full doses) had 90% efficacy, which is closer to the two mRNA vaccines. It is too early to say if this difference is real, and it does not make biological sense, so the company plans to expand the number of subjects getting this dosing regimen to see if the higher efficacy holds up. One advantage to this vaccine is that it can be stored in a regular refrigerator for up to 6 months, while the mRNA vaccines have to be frozen for transport (the Pfizer vaccine at -70 degrees C, the Moderna vaccine at -20).

All three vaccines have a good safety profile so far, but it always takes time to monitor for side effects so this is an ongoing assessment. Pfizer and Moderna say they can  produce over a billion doses by the end of 2021, and AstraZeneca says they can produce 3 billion doses. That is enough for about a third of the world’s population. Of course, there are many other vaccines being developed around the world so these won’t be the only three.

Pfizer has already applied to the FDA for emergency use authorization (EUA) with Moderna and AstraZeneca likely to do so very soon. Assuming everything checks out and they get their EUAs, what happens then? There are basically four phases to getting people vaccines. The first is developing the vaccine itself. This phase is now coming to fruition – I won’t say it is ending, since development is ongoing, but with the EUA’s they can move onto the second phase, which is manufacturing. I have no reason to doubt the stated numbers of the companies, so let’s assume that they will produce about as many doses as they claim.

The final two phases are distribution and administration. Distribution will be a challenge, but doable, at least in developed nations. It will be more challenging is less stable and developed parts of the world. But we do have an existing infrastructure for this. That infrastructure will likely have to be supplemented by an influx of resources. In the US, at least, this is all part of Operation Warp Speed. However, this is also happening in the middle of a presidential transition. This is, in fact, one of the main reasons for criticizing Trump on delaying the transition. The Biden administration will be primarily responsible for overseeing the distribution of these vaccines in the US, and the hand-off needs to be smooth. But it does seem the transition is now moving forward, so hopefully no harm was done by the delay.

This brings us to the final phase, getting vaccine doses into people’s arms. All three vaccines require two doses. This does impact compliance, as some people will fail so show for their second dose several weeks after the first. But also – how many people want the vaccine at all. It’s amazing we even have to aske this question. A recent survey of people 50-80 years old found this:

When asked how likely they would be to get a COVID-19 vaccine when available and if no cost to them, 58% of older adults indicated they would be likely to get a COVID-19 vaccine (33% very likely, 25% somewhat likely), 28% said they were unlikely (11% somewhat unlikely, 17% very unlikely), and 14% were unsure or did not know.

That is a horrible result – only 58% of older adults say they are likely to get the vaccine, even if it’s free. Breaking this down a bit – “One in five older adults (20%) indicated they want to get a COVID-19 vaccine as soon as possible. Nearly half (46%) said they want to wait to get a COVID-19 vaccine until others have received it, 20% were unsure about getting it, and 14% did not want to get it.”

This suggests that these number might improve over time, which does make some sense. I do find it interesting that many people prefer to use their fellow citizens as guinea pigs before subjecting themselves to a new treatment. That makes sense if you are in a high risk group. New treatments should be used on healthier patients with fewer comorbidities first, but that logic breaks down when dealing with vaccines. In this case we want the sickest and most vulnerable people to get the vaccine first. This means, however, trusting the trial results. And that is what it all comes down to – trust.

It is likely that the vaccines will go to front-line workers early, including health care workers, who are much more likely to take the vaccine since they are part of the health care system. Hopefully this experience will engender more trust in the general population when it comes their turn to get the vaccine. The figure that worries me the most is the 14% that straight-up do not want the vaccine. This number may be firm, which means we will hit a ceiling of 86% compliance in this age group.

The question, then, is what is the critical number of people who need to get vaccinated to achieve herd immunity? This is the number needed to stop spread of the virus through a population, essentially shutting down the pandemic. That is the ultimate goal – getting back to some semblance of normal life. Experts have been saying, and I agree, that we will not get there until a vaccine is widely distributed, which looks like mid to late 2021.

Hopefully we can turn pandemic fatigue into vaccine acceptance, and early positive results will encourage more people to line up and get both doses of whichever vaccine they are offered. As a risk-vs-benefit calculation, this is a no-brainer. But it does require a minimum amount of trust in the relevant institutions – and that has been a casualty of our current political environment.

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