COVID Transmissions for 1-7-2022

How many "boosters" are we going to need?

Jan 07, 2022

Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.

It has been 752 days since the first documented human case of COVID-19. In 752 there was a strange episode with the Roman Papacy, where one pope died and was succeeded by another Pope (Stephen), who died before he could be fully consecrated to the role—four days after his election. The very next pope also chose the name Stephen, becoming Stephen II.1

Speaking of meeting the new boss, today’s issue is, in a way, themed around succession. Omicron and Delta are the successors to older variants of SARS-CoV-2 that initially emerged. We are using boosters against those older variants to fight their successors, and today I’m asking the question: is that the right approach? We’ll walk through it.

Also, I actually discuss the TV show Succession.

It’s a real through line.

Have a great weekend!

Also, we’ll talk about a concerning surge in pediatric cases in the US.

Bolded terms are linked to the running newsletter glossary.

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Now, let’s talk COVID.

Dose Number Four?

By now many folks have heard that Israel, often a leader in vaccine news, is considering fourth vaccine doses to bolster people’s immunity. Some preliminary work has been conducted and it is now apparent that this fourth dose does boost antibodies, at least according to Israeli PM Naftali Bennett: https://www.reuters.com/world/middle-east/israeli-study-finds-fourth-dose-covid-19-vaccine-boosts-antibodies-five-fold-pm-2022-01-04/

However, I really do not think it is enough to just look at antibodies and say “they went up” without considering the nature of these antibodies. I’d like to give you some understanding as to why.

Antibodies are sticky. I don’t mean this metaphorically. I mean they are literally sticky. They stick to virus proteins for the same reason that gum sticks to your shoe: electrostatic interactions, at a molecular level, that make it take more energy to separate two objects from each other. When we say something is “sticky” that’s literally what we’re talking about. Antibodies work on that same sticky principle, though they have a targeted stickiness that makes them stick better to specific things than to others. That sort of highly selective stickiness is how they recognize very specific parts of very specific molecules.

The antibodies that the vaccinated have—and the recovered, from variants other than omicron—are sticky to an older variant of SARS-CoV-2. The sequence they target was published back in January of 2020.

Omicron, in the meantime, has evolved some traits that make it less sticky to particular antibodies. Here I’m not being literal, but it is almost as though it has made its surface smoother such that it is harder to stick to. If before, the specific antibodies stuck very well—almost like they were a piece of gum on carpet—now they are on a finished hardwood floor. But the antibodies are still sticky.

If you throw enough of something sticky at a smooth surface, some of it is going to stick. Everyone has heard the cliche of throwing spaghetti at a wall to see what sticks. It is, quite literally, the entire mechanism of a booster dose in the prevention of symptomatic disease with the Omicron variant. Omicron is different from its ancestors, and that difference is enough to make antibodies against those ancestors stick less well. But, they might still stick a little. Their affinity is lowered, but not all gone. If you keep the antibody level high all the time, then there is a better chance that something will stick to incoming virus and completely prevent disease. It’s incredible that this brute force approach works, but it does! This is, for the time being, a pretty good reason to get a booster dose.

The problem is, the level of antibodies falls eventually. Data that I have already shared here suggests that symptomatic disease protection falls away by about 10 weeks after a boost. 10 weeks of protection is a good thing to have during a surge, don’t get me wrong. But it’s not the ideal. Still, we’re protected against some pretty bad outcomes with 2 or 3 doses of a vaccine, and we’re in the middle of a huge surge right now. The 10 weeks of protection that the booster dose offers you is worth it, and I think it’s a good idea.

When it comes to hospitalization and death, vaccination provides protection at least partly because the introduction of the virus and the onset of infection ramps up antibody production again. It isn’t always in time to prevent infection or symptoms, but it can limit the course of disease, make it less severe, and make it shorter. The vaccinated immune response here may also be limiting the number of contagious days. Amounts of virus in the body peak when the immune system is able to control the virus. The faster that control comes, the sooner the peak is reached. Also, ideally, the peak is lower. This is why you want to have the vaccine before you get infected. It gives your body control over the virus, allowing your experience to be one that doesn’t go off the rails and land you in the hospital.

That’s good, but we still do ideally want to keep control over infection and even the mildest symptoms if we can. So, we return to using boosters to keep antibody levels high and rely on this principle of stickiness. I again want to note that I am not kidding about these being sticky. When I worked with antibodies in the lab—they are used to do a lot of molecular detection work to make things we can’t normally see become visible at scales for the human eye—we had to do a lot of work to make up for their sticky nature. We would dilute them by factors of between 1 in 1000 and 1 in 10,000. We would use substances that created a lot of nonspecific “noise” to drown out off-target binding by these antibodies; anything with a lot of junk protein would do. One common option is Carnation nonfat instant milk. No, I’m not kidding.

Milk has a lot of protein in it, and antibodies that are very sticky and nonspecific will bind to that protein. Wash away the antibodies, wash away the nonspecific junk.

Now look, my experience with nonspecific antibodies in the lab is genuinely very different from human antibodies in a live body. The antibodies that a vaccinated person makes against that two year-old variant of SARS-CoV-2 are not going to bind in huge quantities to milk you’re drinking. However, they are going to bind with less effectiveness to things that look similar to, but maybe not entirely like, the original thing they targeted.

In low amounts, this sort of binding may not be enough to totally cover a virus particle and neutralize it. But if you’re carrying a lot of antibodies against the virus? Well, then you might have a chance of neutralizing even something like Omicron that has the ability to escape antibodies with a high affinity for older variants.

That’s, effectively, what I believe the boosters are giving us against Omicron. It’s a little bit like trying to fight a tank with bullets. You’re going to need a whole lot of bullets.

Overall, I’d really like to see a booster that targets the Omicron variant specifically, or perhaps whatever variant is the ultimate successor to Omicron. That sort of thing would create a diverse pool of antibodies that would keep things up to date with what is currently circulating. I understand there are at least some companies working on this.

Repeated boosting has potential pitfalls. The New York Times ran an article about this recently, exploring how these pitfalls may apply to the SARS-CoV-2 situation in particular: https://www.nytimes.com/2022/01/06/health/covid-vaccines-boosters.html

They highlight a potential situation called anergy, where continued boosting leads to a gradual weakening of response. As the article points out, that is not likely to happen here, based on available evidence.

The other situation that could be problematic is called “original antigenic sin.” This is a well-known concept in viral immunology, where the immune response becomes so biased towards the first version of a pathogen that it saw that it has a weaker response to later variants of that pathogen. By continuing to boost against an early variant, we might be biasing our immune responses to be less effective against future versions of SARS-CoV-2.

I don’t think that another dose or two is going to necessarily lead to this situation, but an endless parade of boosters against the same exact virus might do that.

The reality is, the virus is evolving. We are all used to situations like this, because we’ve lived in a world with seasonal influenza viruses. Those evolve over time and we have to repeat the vaccinations that we get to maintain protection. No one treats this as strange, because we’ve accepted that viral evolution occurs.

In my opinion, we need to accept this with SARS-CoV-2 also. It took two years for escape mutants to start to really emerge, and people are beginning to develop immunity to those escape mutants now. I have a sort of hybrid immunity myself—to the vaccine strain as well as to Omicron following my mild infection. I would like others to be able to obtain this immunity without having to be infected.

If every couple of years or so, we have to get a new booster against a new version of SARS-CoV-2, we can live with this virus. It can offer protection against disease, hospitalization, death, and I believe even the post-acute sequelae commonly called Long COVID.

This requires a bit of a mental repositioning for us, since I think many of us pinned hopes on vaccination just putting an end to this altogether. However, we know this isn’t going away. Instead of being a momentary flood that we have to deal with, SARS-CoV-2 is now a body of water that we have to build a dam against. Future, specific vaccination against emergent strains is how I think we’re going to do that.

For the time being, my message is the same, however: we’re in the middle of a major surge, and you will benefit right now from as much protection as you can get. Get your booster. It’s important, and it’s the best tool we currently have available. Eventually, we have more specific tools. It won’t be “boosters” forever. It will be new vaccines against new strains of this virus, to keep us all safe.

What am I doing to cope with the pandemic? This:

Watching: Succession

Yeah, everyone else is already watching this, I get it. We’re late to the party, but we just started watching it.

And wow, it’s some party. This is an incredible show. It’s like if Macbeth was a very solemn satire.

Reader EH had the following question about COVID-19 and children (and also throat swabs):

I'd like to understand more about the pediatric situation. Putting it bluntly: do parents need to worry or not? Should we not be sending our kids to school, especially unvaccinated ones? It is extremely frustrating that the CDC is seemingly ignoring young children and their parents, so I have trouble knowing what actions to take and decisions to make.
Separately, are throat swabs necessary now? Here's one of a few sources reporting this.
https://www.nbcchicago.com/news/local/omicron-symptoms-with-sore-throats-common-should-you-also-swab-your-throat-to-test/2720958/
I've heard reliable anecdotes that Israel was swabbing nostrils and throat at the airport a few months ago already.

Here’s my response:

Jan 5
AUTHOR
As a parent of a young child who cannot be vaccinated, I very much relate to your situation. The vacuum of guidance--and to a lesser extent of evidence to serve as a foundation for that guidance--is very concerning to me. I try to comment on pediatric developments as often as I can, but frequently I find that there is not much I can say.
Right now, the average parent of a young unvaccinated child probably doesn't need to worry, but the problem with the word "average" is that I've never met an average person. Much to my own frustration, I've opted for keeping our child relatively isolated, and she sees people outside our household only on the rare occasion that family or friends visit. With her being 3 months old the decision to do that is easier for me than for parents of older children, but I still don't love it. I worry about what choices we will need to make when she gets older.
My clearest position on children who cannot be vaccinated right now is that I would only expose them to others if the child(ren) is/are either old enough to use a high-filtration mask, or you are confident in the vaccination and COVID-19 infection status of whoever they are being exposed to. High-filtration masks for children are easier to find than most people may realize; I would use Project N95 to identify child-appropriate high filtration masks. They have a dedicated section: https://shop.projectn95.org/masks/child-masks
It's notable that none of those masks are intended for use by children younger than 4 years, but probably children ages 2 and up should be masked. If you cannot find a high-filter mask for a child 2-4, or they simply won't wear it (I'm trying hard not too live too much in a fantasy land about what kids are willing to do), then a surgical mask is an inferior, but still somewhat protective, alternative.
This isn't something I have personally had to navigate because at this point my own child is not sufficiently developed for a face covering to be safe for her, and I don't look forward to having to deal with it when she gets there.
I'm sorry that I don't have much to say beyond this. The dearth of information from public health authorities affects me as much here as it does you.
Speaking of a dearth of information, I'm afraid I don't have a specific comment on the throat swab procedure. I have heard only anecdotal information about it, and while I cannot specifically see why it would be a bad idea, it's also not an instruction in the label of any of the at-home tests. I'm reluctant to advocate for something outside the label of a diagnostic without clear data supporting it.
I hope this is at least somewhat helpful.

I’ve been informed since writing this that the child masks on that website are currently out of stock, but the point is that these products exist and can be made. I hope they become a priority because kids need to navigate this pandemic world, too.

Next up, reader Astrid Bear had a question about rapid test accuracy:

Question about at home testing kits: are they all reliable at detecting Omicron? I've read that sme of them are not, especially those that detect a single protein. Asking specifically about the iHealth test, which says it detects the N proteins.

My response:

Good question. In principle the N protein should be still detectable as it has few changes in Omicron. However, I can't really speak for individual tests. I do know that Abbott Labs has put out a statement that BinaxNOW is not affected by Omicron and can still detect it; BinaxNOW is an N protein test as well.
I would check with the company that manufactures your test, at least until FDA provides overriding clarification.

You might have some questions or comments! Join the conversation, and what you say will impact what I talk about in the next issue. You can also email me if you have a comment that you don’t want to share with the whole group.

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