COVID Transmissions for 3-9-2022
Delta-Omicron recombinant virus
Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 814 days since the first documented human case of COVID-19. In 814, Emperor Charlemagne died. Depending on how you look at it, Charlemagne was either the first Emperor of a new Empire, or a brief resurgence of Empire in the Western Roman style. Either of these is an extreme view. Instead, I think of Charlemagne as someone who took Roman imperial ideas and merged them with his own native Frankish ideas to create something new. Still, it didn’t really last—at least, not with the level of cohesion and power that it had during his life.
Speaking of blending different things, today we are going to talk about a SARS-CoV-2 variant that combines sequence features of both Delta and Omicron variants.
Before we dive in, I want to share the results of my request about a change in schedule—I received a number of comments and emails about the change. Most people—an overwhelming majority—were OK with moving to a 2x/weekly schedule, so that is what we will do, at least until more more serious COVID-19 news motivates greater frequency.
Therefore, starting next week, COVID Transmissions will be released on Tuesdays and Thursdays, until further notice. The subscriber-only “Other Viruses” section will appear on Thursdays.1 This week will still have a Friday issue.
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Now, let’s talk COVID.
Verified Omicron-Delta recombination
There is news of a recombination event between an Omicron (BA.1) virus and a Delta variant virus. The last time we talked about this, it was in the context of reports about a “Deltacron” recombinant virus that turned out to be a sequencing error.
This new virus is not a sequencing error, but as I understand it currently, this is not entirely as scary as it sounds, as we’ll explore. Still, something to keep aware of.
Here is the information available from the GISAID2 website:
First solid evidence for a Delta-Omicron recombinant virus has been shared by Institut Pasteur via GISAID (EPI_ISL_10819657 incl. raw reads). The analysis provides definite confirmation of the structure of a recombinant virus derived from the GK/AY.4 and GRA/BA.1 lineages.
This recombinant virus identified in several regions of France by the EMERGEN consortium has been circulating since early January 2022 and genomes with a similar profile have been also identified in Denmark and The Netherlands. Further investigations are needed to determine if these recombinants derive from a single common ancestor or could result from multiple similar recombination events.
GISAID does have access restrictions on its data, because much of what is entered into it is not yet published, and users do not want to give away their first publication rights to an online database.
On the other hand, some information has been shared by virologists “in the know,” and I want to walk through it a little.
For background, one of the interesting features of coronaviruses is that they can engage in relatively frequent RNA recombination. “Recombination” is a fancy term that gets used and misused in popular literature, but I find is rarely explained. Nucleic acids like RNA and DNA are said to recombine when they swap portions of their sequence between two different molecules, creating a new genome that is distinct from either contributing “parent.”
This can lead to fairly expansive and random exchanges of genetic meaning. In order to explain that a little better, let’s use an example where we are talking about linguistic meaning. Imagine that we have two sentences—genomes—of the following forms:
The quick brown fox jumps over the lazy dog.
Four score and seven years ago our fathers brought forth on this continent, a new nation, conceived in Liberty, and dedicated to the proposition that all men are created equal.
Here are several possible recombinations of these two sentences, with asterisks denoting where sequences have been swapped in:
Four score and seven years ago *the quick brown fox jumps over the lazy dog.*
Four score and seven years ago our fathers brought forth on this continent, a *quick brown fox*, conceived in Liberty, and dedicated to the proposition that all men are created equal.
*dedicated to the proposition that all men* jumps over the lazy dog
As you can see here, some recombinations make markedly less sense than others. The same is true for genomic recombination in organisms. Instead of sentences, the information being exchanged is chemical, with long strings of nucleotide sequences being swapped. This can change not only genome sequence, but genome structure. It’s not hard to get something nonsensical or useless.
Sometimes, though, you get recombination of sequences that work well together.
There have been a few suspected Delta-Omicron recombination events, and not all of them have been terribly interesting or meaningful. This is the first one where there has been an exchange of interesting sequences. Don’t take my word for this—instead, here’s a tweet from Dr. Tom Peacock, a virologist with a sharp interest in SARS-CoV-2 evolution:
A swap where the backbone—ie, the rest of the genome—is from Delta, but the Spike protein is the Omicron BA.1 subvariant spike protein? Now, that does sound interesting.
Before panicking, though, please remember that we have vaccines that are effective protection against viruses bearing the Omicron BA.1 variant’s spike protein, and that a very large number of vaccinated people were recently infected with viruses that have that spike protein, and they fared pretty well.
Considering that many (but not all!) of the key differences between Omicron and Delta variant viruses are in their spike proteins, I think we can expect that the spike protein would have been the key difference here…but many people around the world have now had an immune challenge against that specific virus, and come out on the other end of it. So, I am not deeply fearful of what this could bring.
And it would seem that reality is lining up with my gut on this—if we look back at the text quoted from GISAID, there is one pretty interesting detail that may not have jumped out on the first read:
has been circulating since early January 2022
That is quite a while ago, in the time scales that SARS-CoV-2 waves happen on. Here we are about two months out and this new variant has not caused another wave or ground society to a halt. I don’t expect that it will.
But, it does tell us some interesting things about the biology of SARS-CoV-2. Right off the information I have, I’m able to assess that the Omicron variant Spike will still function if the rest of the virus is a Delta variant sequence. This was not a given! It was always possible that changes were needed elsewhere in the Omicron variant genome to accommodate the many changes present in its Spike gene. And yet, this virus works.3
I am hoping that the interesting nature of this observation will remain appealing only to virus geeks like myself, and that for most people, this will be nothing more than a story about how strange viruses can be. I think that is how it will remain, but you can count on me to keep an eye on this in case any practical implications develop.
Part of science is identifying and correcting errors. If you find a mistake, please tell me about it.
Though I can’t correct the emailed version after it has been sent, I do update the online post of the newsletter every time a mistake is brought to my attention.
No corrections since last issue.
What am I doing to cope with the pandemic? This:
Finally back to running 5 miles
One of the ongoing problems I’ve had since recovering from COVID-19 has been a serious dip in endurance. Before I got sick, I was running 15-18 miles per week. Lately I have been only able to accomplish 9-12 miles. I recognize this could be substantially worse, but even my mild case and mild impact represents something like a 50% performance drop on something that I was doing fairly routinely.
The nice thing is, I have been able to start training my way back up, and I believe that the impact will resolve—not everyone who gets COVID-19 with long term impacts is so fortunate.
Today, I had a quality run of 5 miles without feeling like my time was far off my pre-COVID performance, which is a milestone it has taken me three months to get to. It is alarming that it took this long, but also, I count myself very lucky that whatever impacts I experienced were reversible just with personal dedication. That will not be true for everyone with long-term impacts, either, and I hope that advancing medical science can offer assistance and relief to those who need it.
Carl Fink shared the following report on rapid antigen test false positive rates:
Nature: https://www.nature.com/articles/d41586-022-00589-3
I find it odd that this study of rapid antigen tests was only interested in false positives, and apparently made no effort to measure false *negative* results. The false positive rate was really low, though.
Here is my reply, contextualizing the work here:
There were some past issues with high false positive rates in certain studies, so I think the objective here was just to put that to bed. It's good to know. False negatives are a little more complicated to adjudicate, since the comparator would be PCR and it could detect trace RNA a person might still have from 3 months ago--and is that really a positive?
I still would have liked to see it, but I can understand a researcher deciding to keep their scope focused and limited.
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, or if you are unable to comment due to a paywall.
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Please know that I deeply appreciate having you as readers, and I’m very glad we’re on this journey together.
Always,
JS
I may be setting myself up to fail here. I never could get the hang of Thursdays.
Originally, GISAID was named as the Global Initiative on Sharing Avian Influenza Data, but it has become a much more expansive sequence repository for global virus sequence surveillance. Original funding for GISAID came from a private individual named Peter Bogner—it is in a way depressing that governments did not already see the value in having something like this.
Like how Galileo noted “and yet it moves” to refer to the Earth moving around the sun, the observation of a functional virus that has these sequence features is all the science we need to know such a virus can function—what we see in nature, is reality, no matter what we might have thought previously.