COVID Transmissions for 1-28-2022
Omicron subvariant BA.2 deserves attention, but not speculation
Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 773 days since the first documented human case of COVID-19. In 773, Caliph Al-Mansur ordered the translation of many treatises on mathematics into Arabic, including ones that introduced the concept of zero into the Arabic numeral system. The Arabic numeral system is pretty amazing. I try to use it as often as I can.
I’ll use it today, in fact, in talking about the BA.2 subvariant of Omicron.
We’ll also talk about a spillback, followed by spillover, event where hamsters got COVID-19 and gave it back to humans.
Have a great weekend!
Bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
Spillback-to-spillover event at a Hong Kong pet shop chain
A recent ProMED mail mentions the transfer of SARS-CoV-2 from an infected pet at a pet store, back into humans. SARS-CoV-2 getting into hamsters is a type of “spillback” event, where a virus that entered humans from animals later entered an animal from a human. It was followed here by a “spillover,” where the virus entered humans from an animal.
The pet(s) in question here are hamsters, and so far, several people have become infected.
Here’s the ProMED post: https://promedmail.org/promed-post/?id=20220126.8701086
Two things jump out at me here:
This demonstrates that even a place with a Zero COVID policy is subject to spill-back events from animal populations; Hong Kong has a Zero COVID policy and that didn’t stop this from happening
This also demonstrates (again) that animal-to-human transmission can readily initiate disease clusters, something that adds to the plausibility of SARS-CoV-2 emergence in the course of live animal trade
If, like me, you are interested in global disease surveillance, ProMED-mail is something that will fill your inbox with it. However, reader beware—if you are afraid of viruses it will make you realize they are everywhere, and that the exchange of pathogens between humans and animals happens pretty routinely. I read it as a matter of personal and professional interest, but it can be pretty overwhelming—both in volume and in the realization that global biosecurity is pretty tenuous.
BA.2 subvariant
A “subvariant” of Omicron called BA.2 (distinct from BA.1, which is what has appeared in most countries) is now spreading in some countries around the world.
Where this has generated the most attention is in Denmark, where it appears to have displaced the BA.1 subvariant to some extent.
BA.2 has been called a “stealth variant” because it does not display what is called “S gene target failure” (SGTF) in PCR. SGTF is a phenomenon where the spike gene doesn’t come up on PCRs; it happens with spike genes that have mutations in critical portions that make the PCR not work anymore. You still get a positive PCR, because PCR does not only look for the spike gene, but it is easy to tell that someone probably has Omicron BA.1 from a PCR alone, without sequencing the virus, because of SGTF.
For BA.2, SGTF doesn’t happen. So a patient with an Omicron-variant infection is thought to have a different variant because you still detect the spike gene. Hence, “stealth” variant. While the term sounds interesting it doesn’t really have much of a functional impact. People who have this still have COVID-19; Danish health authorities have made it clear that there is no indication of any difference in severity between these two subvariants.
I am not going to link to a news article about it because I can’t find one that limits itself to what I feel are actually evidence-based claims regarding this new subvariant.
Instead, here is a thread by Tom Peacock about BA.2:
While the thread there is a little out of date, it does clarify some important things about the subvariant. One thing I want to emphasize is that there is really no definitive evidence at this stage for two claims I have seen made about this subvariant:
The claim “it is more contagious” than Omicron BA.1
The claim that “it can reinfect” people who have recently recovered from Omicron BA.1
Both of these are based on the idea that it has out-competed BA.1 in Denmark to a degree, but you cannot conclude these things from that unless everyone—and I mean everyone—in Denmark was infected with BA.1 or exposed to both it and BA.2 at some point. It’s nowhere close to that, of course.
What we’re seeing is that in an environment where there are still plenty of susceptible hosts to both subvariants, BA.2 is outcompeting BA.1. There are many possible explanations for that phenomenon, and while the above two options are among them, I don’t think they’re the first explanations I would leap to.
However I do not have any data to provide a definitive explanation, so I’m simply not going to speculate.
I do want to mention what evidence I’d need to agree with the above. For (1), I’d want to see some evidence that the secondary attack rate (the percent of contacts of a case who themselves get infected) for BA.2 is higher than BA.1. For (2), I’d need to see a study specifically of infection risk among the recently-recovered, and I’d also want to see some experiments where we see if antibodies from people recently-recovered from Omicron BA.1 can neutralize BA.2 virus.
Without that, these claims are unsupported speculation. I will be keeping an eye on this BA.2 subvariant, though.
What am I doing to cope with the pandemic? This:
Cowboy Bebop
Widely considered a landmark anime, Cowboy Bebop is a science fiction Western that has a great many fans. Netflix adapted it into a live-action series recently (which I didn’t watch, I heard it wasn’t very good and it was canceled before I got the chance to confirm that). I think because Netflix did that, Hulu decided to get the rights to stream the original animated version—and that I did want to go back and watch again. I’d only seen a little of it before, and years before I could really “get it.”
Anyway, it has held up pretty well—and it’s on Hulu for 6 more days, a piece of information that I think some readers here might be interested in.
Carl Fink pointed out that I should have explained what “focus-forming units” actually are:
Thanks, as always.
I had never encountered the initialism "FFU" (used in the graph you reproduced), so I looked it up. For anyone else's benefit, it's Focus Forming Units, the equivalent of the plaques I was taught about back in biology school during the dark ages (1980s) for viruses that don't lyse their host cells.
FFU are an alternative to plaque-forming units, as Carl mentions. In my reply I briefly explain what they are:
It's not exclusively for viruses that don't have a cytopathic effect (what you're calling lysis here). FFU are used to increase the speed of virus infection assays. Instead of waiting for cytopathic effect, you use some easily-visualized stain that detects active virus replication. Usually, a fluorescent antibody that lights up nicely under a microscope and targets a critical and abundant virus protein. This lets you see little dots of virus replication--foci--and you count the concentration of foci in different wells down a dilution series to be able to determine the FFU concentration of the original sample.
So instead of counting plaques you're counting glowy things, usually.
I think this bears a little elaboration though. Both a plaque assay and a focus formation assay are experiments to ask the question, “How much virus do I have here?”
In both assays, you take your original sample and “serially dilute” it—for example, 1:10, 1:100, 1:1000. Then you do the experiment. Both are intended to create distributed spots of infection on an even “lawn” of cells in a dish. If you have diluted enough that your dish contains spread-out islands where single infections took place, these will show up as dots of one kind of another (more on this in a minute).
You dilute until you have a concentration where the dots are nicely separated from each other and few enough that you can reasonably count them. Then you can use math to determine how much was in your original sample—if you found 100 dots in your 1:1000 dilution of a single milliliter of your original sample, then you have 100 * 1000 dot-forming units per mL in your original sample (or, in other words, 1 million “dfu” per mL.
In a plaque assay, the dots are empty spaces created by virus killing cells on the dish, and we call those “plaques.” This measures pfu/mL. Not every virus kills cells in lab culture, so you can’t do a plaque assay for every virus.
Here’s what a well from a plaque assay looks like:
In a focus formation assay, the dots are usually islands of fluorescent cells stained by an antibody against a virus protein that is designed to glow under a microscope. Those islands are called “foci” and so we call the unit “ffu/mL.”
It’s the same idea for both units, but it can be a little faster to do a focus-formation assay. And in some cases, where the virus doesn’t kill cells in a dish, the plaque assay is not viable at all and this type of measurement can only be done in FFU.1
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Always,
JS
Other methods of virus quantification exist; one common method is based on the amount of your sample it takes to infect half the cells in a dish (“tissue culture infectious dose 50, or TCID50)…but the focus-formation assay and plaque assay both offer a very nice quantification method and are extremely popular with many virologists.
For what it's worth, as someone who watched two episodes of the original Cowboy Bebop and couldn't deal with even dealing with a third, the live-action was pretty awesome the couple episodes of it I've seen, and the season should still be up.
It's still really pretty, it starts with actual action, and there's a plot that's a lot easier to follow if you don't already know what's going on.
(pandemic partner adds that mileage probably varies for someone who actually liked the original, and points out that if one stuck with the original for more than four episodes it actually does get going. since I rarely watch any media unless I'm with someone else, it may be obvious why this has yet to happen.)