COVID Transmissions for 11-29-2021
Omicron
Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 743 days since the first documented human case of COVID-19. In 743, Umayyad Caliph Hisham ibn Abd al-Malik died. His reign was characterized by a cessation of Umayyad expansion, particularly in Europe.
Today we will talk about the Omicron variant and what we know about at this time—which isn’t much. I have a feeling we’re going to be talking a lot more about this variant in the next few months, but I also think that the picture in the media is generating more alarm than is warranted. We need to learn more. For now, make sure your vaccination is all up to date per your provider’s recommendations. That will help no matter what happens.
Bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
Omicron variant
If the breathless headlines are to be believed, we are about to see the world taken over by the emergence of the Omicron variant1 of SARS-CoV-2.
First detected in South Africa, it is likely that the Omicron variant has been circulating for quite some time in other countries. The fact that it was detected in South Africa is probably not a product of it first appearing there, but rather speaks to the effective surveillance network that that country has set up.
In fact, within the past few days, it has become clear that this variant has made it to many countries outside of the African continent altogether. So it is probably rather widespread at this time.
There is very little definitive that I can say about this variant at this time. Despite that, I have seen claims that it is more, or less, virulent. That it substantially escapes vaccines. That it is much more transmissible than prior variants.
All of these things are speculation. Some may be true. Others, not so much. What I know so far is that we should be taking the Omicron variant seriously, but we should not be panicking about it.
What we do know at this time is that there is a new variant of SARS-CoV-2 which has quite a few notable mutations in the gene that codes for its spike protein, as well as other accumulated mutations in the sequence coding for other proteins. The spike protein mutations have attracted the most attention, partly because that protein is what the vaccines target, but also partly because it has a number of well-characterized mutations there that we already have some knowledge about. What follows, now, is my evidence-driven speculation (aka hypothesis) about what happens next. None of this is yet confirmed. We will learn more as events unfold.
Several of the mutations present in the Omicron variant have been characterized as assisting in antibody escape. Others have been identified as apparently related to transmission, or at least fitness for transmission.
The first issue that I want to address is the question of immune escape. Some time back, Paul Bienasz and Theodora Hatziioannou of Rockefeller University did some work where they created a spike protein variant that collected every potential spike protein amino acid change (aka “mutation” in some circles) into a single protein construct. They then tested the ability of immune human serum to neutralize particles bearing this “polymutant” spike protein. They found that this construct can, in certain patients, evade neutralizing antibodies. They also found that patients who had been both infected and vaccinated still had meaningful neutralizing capability against this spike protein construct. You can read that work here: https://www.nature.com/articles/s41586-021-04005-0
This polymutant had 20 antibody-evasion mutations. Omicron has fewer than that—about 8, from what I have seen so far.
What we know from Dr. Bienasz and Dr. Hatziioannou’s work is that it takes a lot of mutations to evade vaccine- or infection-induced immunity, and even that number of mutations won’t evade immunity that has been trained by both vaccination and infection. This is particularly interesting in the long run; we are not going to be eradicating SARS-CoV-2, so eventually everyone is either going to have been infected with the virus while unvaccinated, or infected with it after vaccination. That second group, in addition to meaningful vaccine-induced protection, may also see themselves at an advantage against future immune-escape variants.
I expect that Omicron will not slide right past preexisting immunity, based on this preexisting work. Instead, I think people will have more limited protection against this new variant. Vaccinated people might get sick from Omicron variant virus infections, but I expect the vast majority to have mild illness from which they recover. When they recover, they will have immune training that keeps them protected against whatever emerges next.
In some cases, infections with the Omicron variant may not be so mild in vaccinated people. Thankfully, we have drugs coming to market that this variant is likely susceptible to. This point was made by Dr. Ben tenOever2:
I believe Ben is right here; the Omicron variant is probably still susceptible to antivirals like molnupiravir. If this variant becomes globally dominant, it will be more important than ever to quickly test for COVID-19, even if you are vaccinated, and get treatment as early in the disease course as possible.
Other treatment options, like monoclonal antibodies, may not fare so well, since this variant may escape them. We will learn more about that in coming days. But we are not without defenses against this variant virus.
One defense that I don’t think will be helpful is the US government decision to impose a travel ban from specific African countries. The Omicron variant is not confined to Africa, and it is not likely that a limited travel ban will prevent it from entering the US. A complete travel ban to and from all foreign countries might do the trick, but is rather extreme. A requirement that all entering US travelers get tested at the port and isolated if positive, however, would be a lot more useful. We should have implemented such a measure a while ago—other countries have.
However, I think it is possible that the Omicron variant is already in the US just as it is in many other countries. As I mentioned, I do not think we know enough to speculate about the properties of this virus, but I have heard the following hypotheses:
It may be more transmissible than other variants, perhaps even including Delta. There is no clear information showing this at this time.
It appears more likely to cause disease in unvaccinated people than vaccinated people, based on small sample sizes from South Africa.
It may escape some preexisting antibodies to prior variants.
Each of these things are possible, but if all are true, it’s not the end of the world. In fact, the second point is good news even—it appears the vaccines still work against Omicron!
If it is more transmissible, we will offset that with masks and booster vaccinations. The second item there will also help deal with antibody escape. The various vaccine companies are already hard at work to see if, firstly, their vaccines as they currently exist produce meaningful immunity to this variant, and secondly, if they can produce a booster vaccination that specifically targets the Omicron sequence. We will find out answers about both in the coming days.
For right now, I think it is likely that vaccinated people are still well-protected. People who have received an additional booster dose are probably even better protected. If you have not gone out and gotten a booster, I would say that now is the time—provided your healthcare professional of choice agrees.
If you live in the US or Europe, Omicron is not currently the biggest COVID-19 threat you should worry about. People in the US should be concerned about Thanksgiving, upcoming holidays, and travel, which can spread the virus around the country. People in Europe should consider that there is already a lot of Delta variant SARS-CoV-2 causing a surge in cases in your continent, and that raging fire is a much more clear and present danger to you at this time. Other regions have their own unique problems, but I do not think there is currently any place where Omicron variant infections are the biggest pandemic-related worry. Most of these problems, however, can be addressed with ready availability and uptake of vaccines and boosters, and that’s what the world should continue to focus on.
Omicron may eventually rise to dominance, and I will cover it here as the story develops. However, in the meantime, vaccination remains the best tool to deal with both current problems as well as forecasted problems related to this new variant. If you’re not vaccinated, get vaccinated—even if you’ve been infected before. If you’re vaccinated, consider getting boosted. If you’re US President Joe Biden,3 please make every effort to get vaccine doses and antiviral stockpiles to the developing countries that need them most. We need to get everyone protected. That’s going to be our only way out of this thing.
What am I doing to cope with the pandemic? This:
Celebrating: (C)ha(n)nuk(k)a(h)
I hope my uses of parentheses covers all the bases for potential spellings here.
Chanuka, as I choose to call it for keystroke efficiency, is an 8-day festival celebrating the victory of the Jewish people over Syriac Greek imperial conquerors in our ancestral homeland. There’s also a story about oil in our rededicated temple lasting miraculously for 8 days after those invaders were defeated.
We light candles and eat fried foods. It’s fun, but actually a pretty minor holiday. I’ve heard lately that reading the children’s chapter book THE GOLDEN DREIDEL by Ellen Kushner is a great way to celebrate, and am looking forward to having my copy in hand soon.
Because it has happened a few times now, and the comments have been promptly deleted, I want to provide the following note on comments policy: If I think your comment is meant to spread antivaccine disinformation, I may delete it with or without warning, and I may ban you from commenting. While I am happy to answer questions asked with sincerity, I will not tolerate disingenuous attempts to spread false information.
When it seems ambiguous—in other words, someone may be asking a question about something they heard, but that is false—I will reply and explain exactly why false information is false. Good-faith questions and comments are, as ever, welcome here.
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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See you all next time. And don’t forget to share the newsletter if you liked it.
Always,
JS
So named by WHO days after it began to make headlines. Previously it was being referred to by its PANGO designation of B.1.1.529 or as the “Nu” variant based on a presumption that this would be next Greek letter name invoked. WHO elected not to use “Nu” here, or “Xi,” and instead went to Omicron.
On faculty in the department where I obtained my PhD; was one of my qualifying examiners.
I don’t think he reads the newsletter, but it’s worth a shot.
Thank you. I was looking forward to your newsletter this morning for rational and easy to understand scientific forecast on Omicron. Chag Sameach. I'll have to look for that book for my grandkids.
My biggest question is: what exactly is the regulatory pathway for an updated vaccine, should one be required? Will the FDA want a full phase III trial again? Or just safety and immunogenicity data, as with the 5-11 trial? How large will the sample need to be?
Relatedly, what does this mean for kids' vaccines? Adolescents had to wait half a year after the first EUA, younger kids almost an entire year. Children under 5 still have nothing. It seems like it would be ill-advised from a public health perspective, as well as more than a little cruel, to make children and parents wait that long again.