BY DEREK LOWE
Time for another look at the Omicron variant situation! I wrote an introductory post earlier this month on this, and now we have much more information bearing on its open questions. So let's catch up:
Why Is Omicron Spreading So Quickly?
There seems to be no doubt that that this variant spreads more quickly in populations than any we've seen so far. The South African data certainly indicated that, and the recent rises in the UK, Denmark, Norway, and other countries are following a similar sudden-take-off course. There is every reason to expect the same thing here in the US (more on that below). But the reasons for this behavior have been less clear.
Two broad possibilities could be working at the same time: this variant could be easier to transmit (and you can come up with several ways that could be happening), and/or it could be doing a better job evading our immune protections, with several possibilities there, too. Just in the last couple of days we have evidence on the first of these. A team in Hong Kong has announced that in their cell assays the Omicron variant seems to reproduce up to 70 times faster in the upper respiratory tract, while at the same time being much slower to reproduce in lung tissue. Here's a writeup on this at Stat. These are very interesting observations indeed, and they would fit rather neatly into what we're seeing so far. Increased viral load in the upper airway could very well lead to aerosols (produced by breathing, talking, coughing, etc.) that carry more viral particles. These in turn will first hit those same tissues in other people, where they can immediately start the same fast replication there. But see below - the other reason that more people are coming down with the variant seems to be that we have less protection against it, so both of those factors mentioned above seem to be operating.
Does Omicron Lead to Less Severe Disease?
This has been controversial, but there's more evidence that the answer may be "yes" - but that doesn't mean that things are going to be fine, either. South Africa is the furthest along in the Omicron world, from what we can see, and although their cases have rocketed up, their rates for hospitalization and death have only been a fraction of what was seen in the earlier waves. If that holds up in the rest of the world, we can be very glad about that, because the alternative could be catastrophic. Even with this, the problem is that this Omicron wave is hitting countries (including the US) that already have a lot of strain on their health care systems. Staffing is not where it should be, and the staff that are in the hospitals are exhausted from month after month of dealing with the pandemic. Even if hospitializations are smaller as a percentage of cases, the number of cases could well make up for that - recall the classic discount store advertising line: "How do we do it? Volume, volume, volume!"
This would be an extremely good time to stay out of the hospital, in other words. No elective surgeries (many health care systems are already pushing these off again), and I would recommend extra care on the roads, in the workplace, in the kitchen, and in other situations that are more likely than usual to send a person to the emergency room. The standard of care, from all evidence, is going to be under a lot more strain in the coming weeks and it was under considerable strain already.
That Hong Kong work mentioned above could fit into this part of the story as well. A lot of severe coronavirus cases come from infection deep in the lungs (thus intubation and such measure to increase oxygen levels). But if Omicron is more of an upper-respiratory-tract infection in many people, that could be less of a problem. Don't get me wrong - people are going into the hospital with Omicron, and people are dying from it. But nearly two years of repeated waves of this stuff are putting things into perspective (or alternatively, making us more callous), and if we're not actually looking at something like a faster-moving Delta (or worse), then I'll just try to be glad that we may have avoided an even bigger disaster. Cold comfort.
What About Immune Evasion? How Much Protection Do Vaccines Provide?
This part of the story isn't completely worked out yet, either, but we have a lot more information than we had two weeks ago. Most of that is antibody-based data, and right up front comes the reminded that while this is important, it is not the last word on real-world immune protection. T-cell mechanisms are also crucial, and T-cell data are much harder to come by. Since you don't see the number of papers in that area as you do for antibody profiling, it easy to think that they don't matter as much, but that's not true.
So with that in mind, here's what we're seeing on the antibody front. It looks like two doses of the mRNA vaccines, especially if these were given months ago, leaves patients with very poor antibody neutralization against the Omicron variant. There have been several recent preprints all pointing in the same direction on this, but they're also (fortunately) all reproducing another effect as well: a third booster shot seems to have a very strong positive effect on antibody neutralization. Preliminary data suggest that this warning seems to apply even more to people who had the single-dose J&J adenovirus vaccine, and there is also a report that two doses of the Sinovac vaccine do not provide enough antibody protection, nor does Coronavac. This fits in with numerous reports that almost all the of existing monoclonal antibody therapies do not perform well against Omicron, either. Sotrovimab, from Vir/GSK, seems to be an exception. And no, the immunity conferred by actual infection with the coronavirus is also evaded by Omicron, as is the case with other variants, so that's no guarantee, either. I realize that there's a vocal community saying that natural infection with the virus provides much more protection than vaccines do, but that is not the case.
We don't know, of course, just how long that booster-shot effect lasts, because the only way to find that out is to wait and check. But the implications seems clear: get a booster dose if you can, because the odds are very, very good that it will provide much stronger antibody protection against Omicron. And otherwise you likely don't have very much antibody protection at all, which would fit with the number of cases in South Africa and other areas that have been seen in previously vaccinated people who had not had a third shot. This recommendation has particular force as we head into the Christmas and New Year holidays in many parts of the world, and as China gets ready for the Winter Olympics. Again, none of this work addresses T-cell immunity, and that is surely a component. Being vaccinated in any way at all would be expected to provide more protection than being immunologically naive, so getting doses of all kinds into people around the world has to be a priority. It's still an open question, for example, how much of the blunted hospitalization and death numbers we're seeing from Omicron so far are the result of the vaccinations we've administered so far, and how much is due to the intrinsic properties of the variant.
Meanwhile, the Pfizer protease inhibitor (as mentioned here the other day) does appear to be just as effective against Omicron, but its supply will not be enough to make any real difference at all in the coming weeks. I hope that this drug (and other protease inhibitors that are still in trials) can make a difference eventually, but we're looking at trouble right now.
What Happens Now?
What happens now, almost certainly, is that we here in the US will experience a very strong and fast upsurge in Omicron cases. We're already seeing that in New York City and some other places. Given the state of testing in the US, we would have to assume that the true case numbers are much higher than we're picking up. The Christmas and New Year holiday season will both spread the virus more thoroughly and disrupt the monitoring of cases, just as we saw last year. As mentioned above, several other countries are already being hit hard with this variant and I will be amazed if that doesn't continue into the ones that aren't seeing it yet. It looks now as if we're going to get well and truly Omicroned - the question is the course of this part of the pandemic. South Africa appears to be coming back down already, and it will be very interesting, in a dispassionate space-alien sort of way, to see if this is a similarly fast-moving wave in other parts of the world. Medicinal chemists will be reminded of cMax-driven drugs versus AUC-driven ones; perhaps this wave will look more like the blood level data you get from an i.v. dose rather than some sort of slow-release depot formulation. We just don't know yet.
In the long run, there are of course a lot of possibilities. A bad one is that something more contagious than Omicron but more virulent develops, and this cannot be ruled out. A better one is that Omicron blasts through the world causing less destruction than we might fear, and displaces the Delta variant and others along the way due to its far-faster spread. That might lead us into a world where there is a coronavirus disease out there, less deadly than before, to which you can have immune protection through vaccines and for which there is an effective acute medication (a protease inhibitor) if you do become sick with it. At this point, I'll take it.
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