COVID Vaccination Global: Advisory, Concern, and Reflection
By: Ajinkya Jadhav
Tags: Coronavirus, Vaccination, Covid 19

VAXXERS = IC²-d

The vaccine news remains astoundingly positive. Reacting to the upbeat mood, a reporter asks us if there’s anything that keeps us up at night. Aside from the cataclysmic current state of COVID (likely to get worse, we fear), there are a few:

First, the question of who gets the vaccine first is tricky. (Breaking news: CDC panel just weighed in: https://www.nytimes.com/2020/12/01/health/covid-vaccine-distribution-cdc.html, and we agree.) One can make a case for many groups to be first in line: healthcare workers; people >65 in nursing homes; essential workers like food handlers, police, firefighters, & teachers; and people at high risk for bad outcomes (people over 65 and those with preexisting conditions). One can make an argument for all of them to get vaccinated as soon as possible. Alas, we quickly run into a math problem…Namely, there won’t be enough vaccine for all these groups until spring.

Thanks to Ariadne Labs, which did the legwork of removing duplicates (people who fit in multiple categories) to estimate the number of people in each of the possible Phase 1 groups. They add up to 144M.

And here’s our estimate of how many people in U.S. can be vaccinated at various times in 2021. It’s based on statements made by Pfizer, Moderna & Op Warp Speed, and assumes we have enough vaccine to vaccinate 20M by January 2021, 150M by June, & the entire country by December.

As the graph shows, we estimate it’ll be ~May before we get to all 144M of the high-priority folks. This timeline could shorten if additional vaccines are approved, and lengthen if there are rollout glitches. If demand is low, we assume we’ll just broaden the eligible groups.

We’ll see how people react to the draft CDC priority list. We are concerned that these decisions will be contentious and — this being COVID — politicized, since it will raise matters of race, homelessness, incarceration, elders, healthcare workers…in other words, myriad hot buttons.

Herd immunity, which we should reach at ~70% vaccination, isn’t a magic on-off switch: as we close in on it, there will be fewer cases & fewer severe cases, since there will be fewer people vulnerable to virus & fewer who will get very sick if they do get COVID. So, even though we might not reach 70% protected until September, the impact of widespread vaccination will be felt before that. Also, there are tens of millions who are already immune via prior infection (and millions more each week, sadly), which will shorten the path to herd immunity a bit.

Second issue that keeps us awake is the vaccine shot itself. We know that a fair number of folks will have symptoms — arm pain, fever, the blahs — that will last for 1–2 days. Seems a small price to pay for immunity to a terrible infection. But will this day of discomfort dissuade people from getting their shots? Probably some, particularly in lower-risk groups — & we will need many to take shots to get to herd immunity. Analogous to the challenge of getting low-risk folks to wear masks & buy health insurance — many are too selfish to accept pain for others.

There will also be post-vaccination issues: when somebody has a post-vaccine fever, do we assume it’s the vaccine? Test for Covid if it lasts for >2 days? Should healthcare or essential workers come to work if they feel sick after their shot? We’ll need super-clear guidance.

Third concern: Misinformation. Below: if we vaccinate 10M Americans, how many will develop a serious illness in 2 months after they got their shots. Answer: many thousands (& I’ve only included 4 illnesses, plus death).



And the vaccines will have zero to do with any of them.

Whether it’s anti-vaxxers or Russian bots, if somebody wants to turn every post-vaccine illness into a “See, I warned you” canard, there will be ample fodder. We’ll need a strong campaign to combat it, i.e. this https://www.latimes.com/opinion/story/2020-10-25/roll-out-vaccine-distribution Nothing we’ve seen in 2020 reassures us here.

We also worry about the next 6 months — will folks let their guards down because vaccines are coming? That would be a terrible mistake — while vaccines will protect the recipients, they’ll do little to protect others in the community until we reach herd immunity levels next summer.

If we vaccinate 10 million people today, statistically 300 of them will die the very next day. Regardless if they actually got vaccinated or not. Over the next months, it’s important to watch for misinformation that blames adverse events on the vaccine.

Below is an example of the misinformation that can spread.

The annual incidence of Bell’s palsy is ~25 per 100k. There were 4 cases out of 40k participants. The FDA concluded it’s “consistent with the expected background rate in the general population.”

In statistics, this is a simple application of something called Bayes Rule.

In essence, we must consider the likelihood of an event happening independently. For example: a 90-year-old has a 1 in 6 chance of dying within a year. So this happening after a vaccine would not be unusual.

Furthermore, if you monitor for thousands of illnesses, of course you will find some that have a higher-than-usual incidence. The same issue occurs when looking for statistical significance in academia: if you look at 1000s of variables, you can always find significant ones.

Other worries: reviewing Biden’s appointees, from COVID task force to chief of staff Ron Klain, we have great confidence in their ability to pull off the logistics effectively, safely, & with minimum drama. But the first month of distribution will be done by Trump’s administration and, while they’ve managed Operation Warp Speed well, the Trumpers seem poised to throw monkey-wrenches into the handoffs. We doubt this will screw the whole thing up, but even a few weeks’ delay will lead to millions of preventable cases & thousands of preventable deaths.

We worry about the impact of approved vaccines on ongoing trials. If we can get EUA’s for Pfizer, Moderna & Astra Zeneca, that’s probably a deep enough bench to vaccinate everybody in the U.S. But more would be better, particularly as we think about the vast worldwide needs.

It’s going to get tougher to do placebo-controlled vaccine trials.(Is it ethical to randomize to placebo once 95% effective vaccines are available?). We may be forced to evaluate new vaccine candidates based on their similarities to ones we know work, which is a bit dicey.

We worry about kids, since we haven’t even begun to test vaccines in them. But if we can reach herd immunity by vaccinating everybody else (incl. teachers), we may not need to obsess about reaching kids, particularly the youngest ones (who are at low risk for illness/spread).

As we’ve said, while we do worry about uptake, we don’t worry too much. Unlike childhood vaccines, many people know friends & family who were sickened or died from COVID, & everybody wants their lives back. We bet that uptake is going to be quite high, especially in Hi-Risk groups.

We do worry about keeping track of who got which vaccine. Who will remind a phase to come in for a 2nd dose, and be sure that the 2nd dose is the same brand as the first? If we had a National Medical Record (like the VA or the NHS), that would be easy. But in the U.S., it’s not.

We worry a bit about how long immunity lasts, but also not too much. We’re now pretty confident that immunity lasts for >1 yr. If it turns out that we need a booster in 2–3 years, that’ll be a small price to pay to save tens of thousands of lives and a return to normal life.

So, yes, we do have worries. But let’s not lose sight of the fact that, on November 1st, we didn’t know for sure that we would have ANY effective vaccines. Today we have at least 2–3 highly effective ones, an impressive safety track record, and millions of doses ready to go.

So yes we have worries, but the light at the end of the tunnel is increasingly bright. We just need to get there.

How confident we are? First, We will get our shots the day we are eligible. And we just booked a Tomorrowland trip in September. Perhaps living dangerously, we didn’t ask about refunds.