COVID Transmissions for 12-22-2020

More information on the UK variant

Dec 22, 2020

Good morning! It has been 400 days since the first documented human case of COVID-19. Noah only had to stay in isolation for 40 days and 40 nights on the Ark. We’ve been in this thing for 10 times that, now.

The one headline today is really an in-depth piece. A lot of COVID-19 news is focused on the UK variant, so I really want to walk you all through it in detail, to the extent possible. Keep in mind that information is flying fast on this topic, so by the time you see this, my thoughts may already be somewhat out of date. Let me know if you find anything that contradicts what I’ve said.

As usual, bolded terms are linked to the running newsletter glossary.

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Now, let’s talk COVID.

UK Variant

Yesterday, I introduced a story about a new variant of SARS-CoV-2 that has raised some alarm in Europe and the UK. As of today, quite a few countries have closed their borders to travel from the UK, which might be the right move.

I’ve been reading up further on the UK variant today, to understand why the public health officials there are so concerned about it. In reading their statements, I find myself far from convinced that there is anything special about this variant, but I do think that caution is always warranted.

Before this variant appeared, I thought that the UK was doing a poor job of controlling COVID-19, and I also thought that there were nearby countries that were doing better jobs. I think that under those circumstances, international travel restrictions make sense. So, even before this was a news story, I probably would have been OK with trying to contain the situation in the UK using travel restrictions.

The new variant doesn’t have anything to make me alarmed, but since I already thought the UK was in bad shape, it’s good to use an abundance of caution here.

I am still concerned that UK authorities have created too much panic over this variant, though. There is no evidence that it is more transmissible. Apparently the justification for this is based on several observations and I would like to provide plausible alternative explanations. Generally speaking, “evidence” requires a set of facts that point to one explanation primarily. These observations do not.

Increased apparent spread of this lineage: epidemiological analysis suggests that this variant is spreading faster than other variants present elsewhere. However, there are a lot of variants of SARS-CoV-2. This one may have been the lucky version that infected someone who went to a party this past weekend in London and didn’t wear a mask. If that’s the case, it may appear to be spreading faster just because of risky behavior. Currently, the epidemiology is well explained by something similar to a “founder effect.” The founder effect is an ecological concept that genetic diversity is lower when new populations are founded on places like islands. In the virology context, you can see something like a founder effect in an outbreak cluster resulting from a social network of people who are engaging in risky behavior. This kind of thing has been seen in HIV and in many other viruses. In that type of situation, you can trace the outbreak by genetics, but that doesn’t mean the particular genetics were responsible for the outbreak.
Lowered “Ct” values in PCR tests. This is a little complicated, but basically, a Ct value is a count of how many times you need to double the virus genomes that are present in a sample before you can detect them in a PCR test. If a Ct value is lower, it means more virus RNA is present in the sample. UK analysts have found that patients infected with this variant typically have a Ct that is about 2 cycles lower than other patients. They use this to suggest that this variant grows to higher numbers, and possibly faster. I don’t agree with that. This is a relatively new variant, and they are actively looking for it right now. This means that patients might be getting tested a little bit sooner after showing symptoms with this variant than patients in other clusters—just by virtue of contact tracing activities. In that case, the lower Ct value might just be because patients are getting tested closer to the peak of their infections. Worse, even if there is a slightly higher amount of RNA genomes, we can’t guarantee that this means there’s actually more virus! Maybe there is a bunch of junk genomes growing in these patients, that don’t actually produce infectious virus. That kind of thing happens in plenty of viruses, and SARS-CoV-2 wouldn’t be the first. We’ll return to that idea in the next point.
Increased unique genomes in patients with the variant. This is an interesting idea. Essentially, they are capitalizing on the idea that mutations are very frequent in viruses. So if you sequence all the genomes you can inside a given patient, they presume that each mutant genome they detect represents another virus particle that is present. Cool idea, very bad logic. There are many viruses that mutate frequently and create totally broken genomes, that they then load into completely useless virus particles. These are called “defective interfering” particles and generally make it harder for the virus to effectively cause disease or infect hosts. Perhaps this variant has mutations that make it more unstable in its genome, and it produces lots of these defective interfering particles. That would be more expected, since that kind of mutation happens in a lot of other RNA viruses.
Predicted changes in transmissibility due to genomic analysis. Basically, this means that they used a computer to assess how the mutations present in this variant could affect the functions of virus proteins. This kind of assessment is only as good as our best computer. As you may have noticed, computers are not a perfect tool. This type of analysis is good for making hypotheses, not for making conclusions. It needs to be confirmed experimentally.

There are a few good alternative explanations for what has been seen with this variant. It’s possible that it’s actually less functional than other variants of the virus, and thus is easier to detect because it causes earlier disease, but without as much severity. It’s possible that the mutations in this variant do nothing, and are just the lucky beneficiaries of especially risky behavior in a certain community of partiers in southern England. Both explanations explain the data rather well.

There is, of course, the possibility that English public health authorities are correct, and this variant really is more transmissible. That doesn’t mean they are “right,” though. They are making a poorly-supported guess on weak evidence. If they are right, it is by chance.

There are experiments that can be done to show an effect on transmission, but they need to be done together and in context. I do think the epidemiological information suggest a correlation between this variant and increased spread. What we do not have is a good explanation for what caused that correlation. It is, as I see it, more likely to be the random chance scenario I described than it is to be some new feature of this variant. But that doesn’t mean it’s impossible for there to be some biomolecular explanation for this pattern either.

What I want to see are two specific types of experiment:

Tissue culture experiments showing counts of actual infectious virus particles. There has been a claim that more virus is made in patients with this variant. We can assess this experimentally, either by growing the virus in cell culture and comparing the variant to other variants, or by taking samples from infected patients with different variants and growing those samples in tissue culture—these are both standard ways to assess whether a particular virus grows faster or to greater numbers than related viruses.
Animal experimentation on transmission and growth. At this point in the pandemic, we have some animal models for transmission and also animal models where we can assess the growth of a particular variant in an individual animal. We need to be conducting these animal experiments also in order to understand if there is anything special about this variant.

At this time, I think travel restrictions on the UK are justified out of an abundance of caution, but I still don’t think that there is anything to indicate this variant is particularly special. However, I do want the experiments to be done to show whether it really is special or not. That’s the scientific way of doing things. Right now my expectation is that we’ll find nothing very different about this variant compared to others. I think we have a lot of evidence about how this virus works, and it takes a lot more evidence to suggest a new variant works any differently.

However, I am a scientist. If experiments could show there really is a difference that matters in this variant, then I want those experiments to be performed so that we can know for sure—one way or another.

Don’t panic. Do investigate.

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

Going “out” for lunch

Today, my wife got some good news and I thought it would be nice to do something different for lunch as a way to mark that. However, I’m really not into the idea of eating outside in the cold, and also am trying to stay away from restaurants.

So instead, we went “out” for food by buying something prepared from a local supermarket and bringing it home. I know this seems kind of simple, but it broke our routine of having salad for lunch every day for the last week, and gave us a chance to go for a little walk together outside.

I think this can be a good way to break up the monotony of pandemic life. Picking up food from a local restaurant works too—and is a safe way to support businesses that you like. Try it out.

You might have some questions or comments! Send them in. As several folks have figured out, you can also email me if you have a comment that you don’t want to share with the whole group.

I’ve been contemplating changing the schedule of this newsletter a little bit; perhaps reducing it from daily to 3 times a week. I’m interested in your thoughts; feel free to comment publicly or send them my way privately.

Thank you to those who answered me about this already; I’m taking all of the feedback under consideration.

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