COVID Transmissions for 12-10-2021
The Omicron variant will likely render some drugs useless
Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 754 days since the first documented human case of COVID-19. In 754, Caliph as-Saffah of the Abbasid Caliphate died of smallpox. I’m glad that’s not a thing that happens anymore.
Today I discuss the projected impacts of the Omicron variant on some monoclonal antibody therapies.
Have a great weekend!
Bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
Evidence is in: many monoclonal antibody cocktails will not work against the Omicron variant
I’ve just seen a preprint that is concerning for the use of several key drugs against COVID-19, suggesting that several major monoclonal antibody cocktails (including the Regeneron and Eli Lilly products) will have no or low effect against the Omicron variant. It can be found here: https://www.researchsquare.com/article/rs-1148985/v1
The authors did a lot of work in this paper; they were also interested in the behavior of individual mutations. However, what’s most important is the work they did with an antibody neutralization assay where they used “pseudotyped virus particles” with Omicron variant spike proteins on the surface. We’ve discussed this pseudotyping approach before, but here’s a refresher: you take some other virus system, one that has been designed to bud off virus particles that are not infectious, and you introduce the spike protein into that system so that it appears on the surface of those particles. It now has a fake serotype—serotype being the word for immune reaction profile—which is called a “pseudotype.” In this case, we’re interested in SARS-CoV-2 so as mentioned, these particles are pseudotyped with the spike protein. Specifically, one with the changes that appear in the Omicron variant.
Pseudotyping is not perfect. Making sure that one gets the right amount of the introduced protein on the surface, so that there is an adequate model of the virus one is interested in, can be difficult or impossible. However, this can be controlled for, and I think the authors here did adequately control for it—by comparing the effects of these antibodies on Omicron variant particles to their effects on other particle types where the antibodies’ effects are already known. That way, the experiment is internally consistent. Here is their key figure:
This is very disheartening to see. Only two antibodies here—GSK’s VIR-7831 and BeiGene’s DXP-604—had reasonable activity against the Omicron variant. The rest basically faceplanted.
This is particularly concerning for the two antibodies from AstraZeneca, labeled AZD here. These two antibodies are part of a cocktail that was recently1 given a US EUA for use to prevent COVID-19 in patients who cannot receive vaccines. You can read about it here: https://www.ndtv.com/world-news/us-authorizes-astrazeneca-evusheld-drug-for-covid-treatment-in-some-cases-2643322
It would have been nice to have an alternative to vaccination to protect people with compromised immune systems, but if Omicron is on its way to eventual global dominance, it is likely that this drug simply won’t work anymore.
Neither, apparently, will Eli Lilly’s monoclonals nor Regeneron’s cocktail, both of which are popular tools to keep people out of hospitals. It will be a shame to see these products, which required a lot of research and investment and have turned out to be quite useful, end up on the shelf again.
Of course, maybe there is something that these experiments missed, and there are effects of these drugs that aren’t dependent on neutralization. Some clinical data will be needed as well. But it looks pretty bleak to me.
Thankfully, these antibody-escape changes will not impact antivirals like Pfizer’s PAXLOVID, which should still affect Omicron variant viruses. However, I like having a deep bench of options, and this research suggests it is getting narrower.
The Omicron variant continues to be something I just don’t like.
What am I doing to cope with the pandemic? This:
Running: focusing on Heart Rate
I know, it’s been a lot of fitness lately. There is a reason for this that I hope to share with you all soon!
Something I’m cognizant of is that cardio workouts are supposed to be a road to better heart health, and trying to run as fast as you can all the time doesn’t actually get you to this goal so easily. Something that is also important is to work on endurance. To that end, I’ve fallen into a pattern of doing speed interval training once a week on a long distance run, a shorter distance run (5K) where I just aim for speed the whole time, and then finally one long distance run (well, long distance for me—a 10K) where I try to keep my heart rate low, despite the speed impacts that are required for this.
I’ve noticed a real effect here. With only a couple of minutes added to my overall time, a run where I used to average 165 bpm is now a run where I average 158. And my HR averages on the speed runs has also come down. I don’t know exactly why it works, but it’s working for me.
While we did have some nice comments on the last issue, we didn’t get to anything that was too informative on COVID-19, so I’ll leave them out this time. Go back and read them if you’re so inclined!
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.
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.
See you all next time. And don’t forget to share the newsletter if you liked it.
Always,
JS
Literally this week.