What’s new with delta, other COVID variants?
Can ivermectin protect you from COVID? What’s up with delta, lambda and the rest of the variants? Why do viruses have regular seasons — the flu season, the COVID season?
To answer those questions and more, we turned to Ben Neuman, who’s researched coronaviruses since 1996 and is now chief virologist at Texas A&M’s Global Health Research Complex. He also excels at explaining science to regular human beings.
A Chronicle reader writes that he recently heard a podcast in which two doctors said that according to some studies, ivermectin may be almost as effective as the vaccines in preventing COVID-19. He asks, “What is your view on the credibility of this evidence and whether it’s sufficient to recommend ivermectin to people who refuse or can’t take the vaccine?”
My one word response would be “dim.” My view is dim.
Let’s unpack ivermectin. Ivermectin is a veterinary anti-worm medication. It’s very good for that purpose.
So I might give ivermectin to my dog for heartworms?
And it’ll cure your dog. That’s fantastic for you and your dog.
So how is ivermectin connected to COVID-19?
Maybe a year-and-a-half ago, when scientists were just trying things — anything to defeat this monster! — we started hearing about things like azithromycin, hydroxychloroquine and zinc pills. (Laughs.) It was like, “licking metal can make everything better!”
The benefit of all these is that they’re cheap medications that are available widely. They were good things to try.
A bunch of studies show no effect or no clear difference in outcome. There was one with around 500 people in Argentina, one with 400-ish people in Colombia, and several others. Two studies – both with fewer than 100 people – each showed mild positive results, but with some problems of size and how the study was done.
The proponents always say that ivermectin blocks virus growth, but that is one thing the studies make it clear that’s not right. A few say it might get people feeling better soon, but those are always rather squishy measures compared to the hard, cold virus numbers.
The early papers, where they showed that there was a little bit of an effect, were working in cell cultures: You take cancer cells,
you artificially put a virus on top of them, and then you treat them with a drug. Then there are several ways that the drug can make the virus appear to go down. One of those is by poisoning the cells or just interfering with them in some kind of nonspecific way. So we get a lot of potential drugs that come out looking real good in tests like that.
But when they do the next stage — testing in animals and then eventually in people — the effects just disappear because they weren’t direct effects on the virus or direct effects on something that is key to the virus and somehow not important to the cell.
So yeah, I don’t see any reason why ivermectin should be considered a viable treatment in light of the information we have.
I know some people definitely do consider that it’s the best thing since aspirin. But one of those groups, the one that testified before Congress, actually say on their website that they don’t believe ivermectin should be tested or can be tested. They say it would actually be immoral to hold a test because you’d have to give somebody the placebo. They’re convinced before actually testing the thing that the thing actually works.
That is exactly the spirit you want going into the big game. But that’s simply not how science works. [Laughs.] I admire their enthusiasm and very little else.
Why do you study how coronaviruses evolve? Besides that the science is cool — is there some use?
This is “Know thy enemy.”
The idea is, knowing the evolution of a virus is a powerful tool that you can use against the virus. If you are good enough at tracking evolution, and if you have enough data, the path that the virus takes will show you what is important and what is not important.
Looking at different coronaviruses is like looking at a car and a motorcycle. What do they have in common? Some kind of tires or wheels; some kind of engine. Those are the fundamental things that make it a vehicle.
We’re looking for the fundamental parts of a coronavirus. The virus can and will change any of the non-fundamental parts, so things like the spike evolve really fast. The spike’s job is just to get the rest of the virus inside of a cell so the virus can start running off copies of itself. How it gets in doesn’t matter. As long as the virus doesn’t get shut down, that’s good enough. Evolution does not care. So it’s not surprising that we see more changes in the spike.
That brings us to the variants of the coronavirus that causes COVID. We’ve been hearing a ton about the delta variant and a little bit about lambda. What’s new about those variants? Are the differences in the spike protein?
There are differences up and down the genome. We focus on differences in the spike because we have some way to understand what those differences mean. A few of the other changes are actually common to all of the variants. We can go into those if you want.
Let’s! How significant are those other changes? Are they in important parts of the viruses? If we’re comparing a car and a motorcycle, would those differences be in engine? or in the rear-view mirrors?
Maybe in the go-faster stripes on the side? (Laughs.) Viruses are pretty changeable.
At the coronavirus conference about a month ago, there were some really interesting new ideas. One of these is that we can think of the virus’s evolution as a pendulum. It’s as if the virus is swinging back and forth. On one side, there’s having a spike that’s more stable, and on the other side, there’s having a spike that is easier to unravel and use to punch through a cell. It swing-swing-swing-swing-swings back and forth.
The idea comes from some new work from Tom Gallagher about the first really popular change in the spike, a thing called D614G. It’s a minor change, and it’s not in a place that makes any sense. It’s not in the part that grabs the cell. It’s not in the part that unravels or the part that punches through. It’s just kind of beside all those parts. But it turns out that this one change dramatically boosts the stability of the spike.
With the original version of this virus, if you added the changes to the spike protein that we see in delta and alpha and all that, everything just falls apart because it’s not very stable. It had to make that first swing towards stability.
That D614G change by itself made only a tiny, tiny incremental increase in how infectious this thing becomes. But now that it’s more stable, it has more options to start playing with. It can destabilize a bit, experiment with being able to spring a little harder, get into the cell, poke it a little faster. So now it’s kind of swinging back the other way
Deltas have stabilized with a sort of hyper-fusion versions of the spike, but they’re also less stable. So there’s a penalty to that, in addition to the benefit.
Right now, with the world as vaccinated and unvaccinated as it is, delta is the variant that’s doing the best out there. But as the playing field changes, Delta will get pushed out by something else — maybe something that’s good at defeating low-level immunity, or really old immunity from, say, vaccine two years ago. We’ll have to wait and see.
But the idea is neat. It explains what’s going on.
So is that why we weren’t seeing many variants of concern at the beginning of the pandemic? The spike hadn’t become stable enough to evolve?
Yeah. I guess there weren’t any major differences that the virus could make until it had made that one change, but after that, there were several that it could make.
We don’t know which mutations that it can make from that point going forward. That’s a thing you can theoretically figure out in the lab, but those experiments are kind of fiddly and expensive. It’s one of the things we’re going to be trying to do here, and I think some other groups are trying to do it as well. It’ll be neat to see and see if we can peek around the corner and see what’s coming.
Scientists were expecting transmission to die down during the summer — and not just because lots of people have been vaccinated. Why do viruses have seasons?
(Sighs.) That’s like when a kid asks you, “What happens after you die?” You can ask a bunch of people, you can get a lot of answers, and those people will defend their answers very, very vigorously. But it’s still an open question.
I lean toward the idea that the change in human behavior leads to greater opportunity somehow for virus.
There are also people who very much believe it’s the change in temperature, but that is really hard to replicate with actual experiments. You can take cells and do a thing called “cold-shocking” them. When you get cells suddenly too hot or suddenly too cold, they will make different sort of proteins, expressing different genes. It’s like putting on a coat or saying, “Turn up the A/C.” When a cell is in one of these altered states, there will be differences in how easily a virus can get in and how well various other cell parts work, including some antiviral defenses.
The thing is, with seasons, we’re not talking about a sudden change. We’re talking about a change in temperature that takes place over months. It’s going to be much less than the sudden change you get every time you walk out of the air conditioning and into that good old Texas heat. So it doesn’t completely make sense from a temperature standpoint.
There are different seasons for different viruses. And it’s kind of weird: The old human coronaviruses, the ones that don’t really do as much, tend to peak in the spring — even though they are infecting pretty much the same cells in the lung as the flu virus is infecting in the winter.
So it may be that when the flu is in there, you build up enough of a generalized antiviral response to keep out those coronaviruses. A lot of the defenses you would use against one virus will actually work to some extent against all viruses. So it may just be because there’s a flu season, there is a coronavirus season. Or vice versa.
Maybe all these things take their turns. It could be that’s it’s an equilibrium, like a standing wave set up inside a tube. Maybe the virus seasons aren’t tied to the climate as much as they’re tied to succession, one thing after the other.