public health

How Worried Should We Be About the Coronavirus Variants?

Coronavirus vaccine.
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Since the novel coronavirus first appeared in Wuhan, China, in late 2019, it has mutated thousands of times, resulting in countless variants. While this may sound alarming, it’s not that remarkable: All viruses mutate, and compared to other common viruses, the rate at which the coronavirus undergoes this natural process is pretty slow. But in the past few months, a number of notable variants have emerged, prompting researchers to raise the alarm for one reason or another: a British variant, a South African variant, a Brazilian variant, and a variant found in California.

While each of the aforementioned variants carries its own set of risks — both the British and the South African variants appear to carry significantly higher transmission rates, current research shows, whereas the Brazilian variant has caused a surge of cases where the virus previously infected huge numbers last spring — of utmost concern is whether the available COVID-19 vaccines are effective against the mutations. To better understand the variants and exactly how concerned we should be, the Cut spoke with Michael Worobey, a professor of evolutionary biology at the University of Arizona who studies the evolution of flu viruses.

This interview has been lightly condensed and edited.

The main variants we’re hearing about right now are the British variant, the South African variant, the Brazilian variant, and the variant found in California. Are there any others that should be on our radar?
Those are pretty much the big ones right now.

And what do we know about each of their transmission rates and death rates?
The British variant does seem to be considerably more transmissible — as much as 50 percent higher — and there’s evidence that it generates a higher amount of virus in the nose and throat of people who are infected, which is probably why it has the higher transmission rate. There’s also fairly compelling evidence that it causes a higher mortality rate, as well. My grad students and I posted a scientific paper [that has yet to be peer-reviewed] showing that the British variant probably got established in November in both California and Florida. So, it’s had a head start.

The South African variant also seems to be more transmissible — as much as the British variant, if not more. I’m not sure where things stand in terms of death rate, but it wouldn’t be surprising if it was similar to the British variant. As of now, we don’t really have good information on either the Brazilian variant or the Californian one yet. However, with the Brazilian variant, judging by the mutations it has, which are some of the same ones that we think are causing the increased transmissibility in the British and the South African one, I would not be surprised if it was more transmissible.

Obviously, you don’t want either of those rates to be high, but is one more worrisome than the other? 
Let’s start with the death rate. Imagine the virus infects a hundred people. How many of them are going to die? Now, just to get into the weeds a little bit, the death rate is not a fixed constant. For example, if you are in a European population where there are quite a few people on the older end of the spectrum, the death rate is going to be higher than it is in countries where there aren’t that many older folks, because the virus is much milder in younger people. The transmission rate determines how many people get the infection.

Even without a higher death rate, with a higher transmission rate, more people are going to die than would have died if that variant had not arisen. And that’s dramatic. In England, hospitals are filled with patients who wouldn’t have been there if the variant hadn’t been as transmissible, and that is in store for us here in the U.S. The variant has got its hooks into us. In three, four months from now, almost all, if not all of the cases of the virus, are going to be caused by variants.

Last week, Moderna announced that its vaccine was effective at protecting against the British and South African variants, though its efficacy rate did drop for the latter. Still, the company said that the neutralizing antibodies were generated by the vaccine. But now, both Moderna and Pfizer are developing booster shots to add to their vaccine regimens, specifically to protect against variants. How do we process this information? Are the approved COVID-19 vaccines effective against the variants, or will they slowly be rendered obsolete?
I think the companies are just being cautious and starting that work in case it’s beneficial, but at the same time, the studies that are happening simultaneously are indicating that, thankfully, that might not even be necessary. At the moment, there’s no indication that the vaccines will fail against these new variants. In fact, the vaccine seems to produce a more powerful immune response than natural infection. 

If we already know that the available vaccines are 95 percent effective, in the best scenario, there are going to be some people who get infected after vaccination. Now, I do think that if you take the vaccine that was generated with the original formulation, and you use it in an area with a variant with an escape mutation, it will be slightly less effective. But it’s hard to quantify how much less effective. [Editor’s note: This interview was conducted before Johnson & Johnson unveiled a summary of the results for its global vaccine trial, effectively corroborating Worobey’s assessment: In the U.S., the vaccine was 72 percent effective against moderate to severe cases; in South Africa, where most COVID-19 infections are caused by that country’s variant, the efficacy rate dropped to 57 percent.] 

There have been some reports about the Brazilian variant possibly causing reinfection. Could it be evading the antibodies made against the previous version of the virus?
The Brazilian variant does have a particular mutation called E484K, and we know from lab experiments that this mutation can allow the virus to escape some antibody responses. For a few people, that might make a difference and allow them to become reinfected, but the good news is that, from what we can tell, the vaccines have enough of a buffer in terms of how powerful the antibody response is that they generate. For most people, that mutation is probably not going to allow the virus to completely escape that response.

I’d also like to touch on the reports that the British variant may have originated in an immunocompromised patient. Could you elucidate this connection for me?
Yeah, that’s what most people think happened. The British variant has so many mutations, it doesn’t fit what we call the molecular clock of viruses, where we expect a mutation from this virus about every two weeks. This virus just picked up so many mutations that it looks like something that traveled back from the future.

The variant has a couple of amino acids that are deleted in the spike protein, and those same mutations — the deletion at sites 69 and 70 of the spike protein — have arisen multiple times in people who have been immunocompromised and chronically infected with the virus. The peoples’ immune systems aren’t quite working correctly; they can’t clear the infection like most people, so they end up being infected for months. And in multiple cases, these people have been treated with what’s called convalescent plasma, which is basically just antibodies from someone who’s been infected.

This should certainly inform how we treat immunocompromised people, who could be a crucible for generating the next variant of concern. We really need to be very careful about onward transmission from chronically infected patients. If they’re in hospital, that means having them in isolation and enforcing very strict procedures to limit interaction with staff or visitors.

Do you think we’ll see other variants emerge that are just as alarming?
These won’t be the last variants that we hear of. Once we vaccinate everyone, the virus is going to experience a much stronger selective force to come up with new variants that escape immunity to some degree. Where there’s a big rollout of vaccines, over the next several months, we’re going to see that mutation process accelerate. Now, how concerned should we be? Again, we should be fairly reassured that for most people, the vaccine is still going to hold. But again, the virus is going to continue to evolve as well. I do think that we will need to be updating vaccines at some point in the future, though exactly when is hard to say.

So what exactly do we do with this information? How should it inform our actions in the foreseeable future?
To me, it’s all the more reason to keep your face mask on, and to hope that those around you do as well. That just became that much more important. If we didn’t have the potential cavalry of vaccines on the horizon, we would be in a lot of trouble in this country in March and April. So let’s hope that the logistical issues and the fuck-ups that have characterized so much of our country’s response to the virus can be ironed out.

How Worried Should We Be About the Coronavirus Variants?