COVID Transmissions for 11-25-2020

Last issue before a Thanksgiving break

Nov 25, 2020

Good morning! It has been 374 days since the first documented human case of COVID-19.

Today we’ll do a couple of headlines, and I’ll say happy—distanced—Thanksgiving to you all. Please don’t travel to see family. Please keep you and yours safe so that you can meet again next year.

I’ve also got a response to a reader comment in today’s issue.

The newsletter will be going on a holiday break after today, unless there is some urgent COVID-19 news that I feel I need to report on. There will be no issues until November 30th.

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

Keep the newsletter growing by sharing it! I love talking about science and explaining important concepts in human health, but I rely on all of you to grow the audience for this:

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Now, let’s talk COVID.

US seeing worsening hospitalization and deaths, but some states’ control measures are having an effect

CIDRAP has a story summarizing an internal White House memo that contains a mixed bag of news on the COVID-19 situation in the US: https://www.cidrap.umn.edu/news-perspective/2020/11/us-sees-rise-covid-hospital-cases-deaths-community-spread

Overall, the picture isn’t good. 48 states are in a bad situation. However, the memo reportedly highlights that states which took aggressive control measures are starting to see some effects.

Stay safe out there, readers in the US.

D614G mutation

Earlier in the pandemic, there was a sensational paper published by a group at Los Alamos National Laboratory documenting a gene mutation in the spike protein of SARS-CoV-2 that gives rise to a change in the spike protein. The genetic mutation changed one amino acid, aspartic acid (D), to a different amino acid, glycine (G), at position 614 of the spike protein. For this reason, the amino acid variant is called D614G, according to convention for how we name these things. If anyone is interested, I can explain the difference between a “mutation” and an “amino acid variant” in the comments.

At the time that it was first described, I was very skeptical that this mutation was proven to do anything. Viruses mutate at high rates compared to regular living organisms, and they often accumulate mutations as outbreaks progress. Often these mutations are meaningless, sometimes even when they do give rise to amino acid variations. As a result, there’s a high bar to be passed for declaring a given mutation meaningful.

I can report, now, that I’m convinced this variant has passed a bar that leaves me convinced it probably has an impact on virus function.

A story ran yesterday in The New York Times that neatly summarizes the situation and the findings: https://www.nytimes.com/2020/11/24/world/covid-mutation.html

The gist of it is that the D614G variant has an impact on the efficiency of virus transmission, making it better able to transmit. This does not mean that it makes the virus more deadly, or that it changes the mechanism of transmission, or that there will be a problem with vaccine development posed by this variant. There is no evidence of that. However, there are two recent studies that do provide evidence for an effect on efficiency of transmission.

First, a paper in Cell looked at spread of the D614G-mutated virus in the UK: https://www.cell.com/cell/fulltext/S0092-8674(20)31537-3

This paper concluded that D614G offers some kind of selective advantage to the virus, because it came to dominate circulating populations of the virus. It goes further and establishes that outbreaks that were seeded by viruses with the amino acid change grew to larger sizes than outbreaks that were seeded by viruses without the amino acid change. However, the authors stop short of saying that there is a definitive benefit in transmission, noting several potential limitations—this is responsible on their part, because they had a very noisy real-world dataset.

However, it’s safe to say that this paper establishes that there is a real selective advantage for D614G, and that this advantage may be related to a boost in transmission. I like this paper because its design—and focus on the UK—means that we are comparing similar events in similar populations, limiting the possibility of confounding factors affecting the findings.

The other paper looked in a hamster model of disease, and was published in Science: https://science.sciencemag.org/content/early/2020/11/11/science.abe8499

This paper looks at a lot of different aspects of this variant, but the bottom line is that it demonstrates that D614G-variant viruses spread faster between hamsters than viruses with the original amino acid sequence, and it shows few other unusual properties.

These data, taken together, leave me reasonably convinced that there is an effect on transmission benefiting viruses that have the D614G change.

Importantly, these studies indicated that there was no difference in disease severity in viruses with this change.

It’s still possible that this variant does something else, or even nothing at all, but this is good evidence that it does impact transmission meaningfully.

I do want to note that one variation does not mean that this is a new “strain” of virus. Again, viruses mutate a lot. “Strain” is a word that means there is a substantial difference in the circulating viruses in two different locations, or when an observed change in the virus impacts the way the immune system, or a vaccine, affects the virus. Nothing like that has happened here.

For what it’s worth, SARS-CoV-2 is a virus strain. It is a strain of the species known as SARS-related coronavirus. SARS-CoV-1, the other strain of this species, causes the disease known as SARS. That should give some sense of how different two viruses have to be for the word “strain” to be applied. One little change isn’t enough.

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

Peking-style duck

This year we don’t have enough people for a turkey at Thanksgiving, so my wife and I are going to opt for duck instead. Since I like to go overboard, I’m planning to prepare the duck at least as close to the classic Peking Duck approach as I can.

That’s an involved experience, with the duck being inflated to separate skin from fat, flash-boiled, then air dried and sugar-glazed. Guess what I’m doing tomorrow!

After that, it gets roasted until it reaches a crispy, brown color. We’ll see if I manage that.

I’ve done it before, to…some success. I’ll send updates next week.

Reader Lisa Hertel left the following comment on yesterday’s issue, and I thought it raised some interesting ideas to respond to:

Obviously they used a chimp adenovirus on the belief that few humans would have been exposed to it. The Astra Zeneca Oxford vaccine seems to be a lot cheaper than either Moderna's or Pfizer's version. The two-dose regimen is a definite drawback; humans are notoriously bad at coming back for the second dose. Ideally, a nasal spray would make it more palatable, as there's a lot of needle phobia out there, and some wacko conspiracy theories.
When I was a kid, vaccines were mandatory and administered in school. Unfortunately, that's no longer the case. It does seem like unless we get the entire world vaccinated over a month period this will be a chronic problem. Or maybe we'll get lucky and the virus will mutate into something more benign.

Here’s my response:

Yes; the rationale for choice of the chimpanzee vector background was discussed in previous issues. The objective was to avoid host reactions for certain. In fact, this "ChAdOx" design was made before the pandemic, to provide a ready-made vaccine design in the event of a pandemic involving a then-undiscovered pathogen.
All of the vaccines currently en route to approval use two doses, so there's no competitive advantage for anyone there.
For the AZ vaccine, an inhaled version is in development, but it's not the version that was reported on here. We'll have to wait for results on that at scale.
Right now the AZ vaccine is priced lower, yes. I'm curious to see how long that arrangement actually lasts, and whether it will apply to all countries. AZ has committed not to take profits on the vaccine during the pandemic, but I don't believe that's going to be sustained in the long run. Eventually I expect all of these products will settle at similar prices to one another.
It's doubtful that SARS-CoV-2 will mutate to become more benign. What is more likely is that it will become a common infection in childhood, and that experience will shape the immune system to respond to it in the future in a way that does not lead to severe disease. This is probably what happened when the current circulating human coronaviruses entered humans from their prior animal hosts.
Eradication of SARS-CoV-2 looked more possible some months ago, when it wasn't as clear how readily it adapts to jump back and forth from human-adjacent animals like cats and minks. Seeing documented evidence of a jump from humans to minks back to humans has convinced me that there's no way we'll ever eradicate this virus, not unless the vaccine is incredibly effective at limiting transmission. We still don't know if it even does that at all.
Getting people to actually take the vaccine is going to be a tricky policy problem. Thankfully, given its high efficacy, most people who do get the vaccine won't need to worry about the people who don't get it. Unfortunately, about 5-10% of people who get it, as well as whatever percentage of people aren't healthy enough to be vaccinated, will be vulnerable to transmission by the unvaccinated. That's going to be a major issue and I hope serious effort is made to encourage extremely high vaccine uptake.

You might have some questions! Send them in.

Join the conversation, and what you say will impact what I talk about in the next issue.

Also, let me know any other thoughts you might have about the newsletter. I’d like to make sure you’re getting what you want out of this.

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