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Homegrown coronavirus variants are on the rise in the U.S. How worried should Americans be?

Andrew Romano
·West Coast Correspondent
·10 min read
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In recent weeks, Americans have been waiting with bated breath for the arrival of worrisome overseas variants of SARS-CoV-2 — the coronavirus that causes COVID-19.

We’ve all heard of B.1.1.7 (the so-called U.K. variant), B.1.351 (the so-called South Africa variant) and P.1 (the so-called Brazil variant). We’re dimly aware of how they work, with various spike-protein mutations that confer certain advantages, making them more transmissible (like B.1.1.7) or more likely to evade our immune defenses (like B.1.351 or P.1). We know that some cases have already been detected in the U.S., and that many more have likely gone undetected. And we worry that the more they spread here, the harder it will be to end the pandemic.

Jordan Lewis, right
A patient receives a COVID-19 vaccine in Borehamwood, England. (Karwai Tang/Getty Images)

But we haven’t paid a lot of attention to the fact that homegrown variants are already spreading in the U.S.

In a study posted Sunday, a team of researchers spotted seven new variants in states across the country — all of which originated here, and all of which have independently acquired a particular mutation that could make them more contagious.

Likewise, researchers at the Cedars-Sinai Center for Bioinformatics and Functional Genomics in Los Angeles last month identified a new variant, named CAL.20C, that had become detectable over the summer but now accounts for nearly half of all cases in Southern California — and may benefit from a spike-protein mutation (L452R) that hasbeen shown to resist some neutralizing antibodies. A new study shows that CAL.20C has spread to 19 U.S. states plus Washington, D.C., and six foreign countries.

To put these homegrown variants in perspective, Yahoo News spoke to Dr. Jasmine Plummer, one of the Cedars-Sinai molecular geneticists who discovered CAL.20C. She explained why the U.S. is largely flying blind when it comes to variant surveillance; how CAL.20C likely contributed to California’s deadly holiday surge; and how, as vaccination speeds up and cases continue to fall nationwide, Americans are in a good position to put an end to the pandemic — if we heed the warning of these emerging variants and just stay put for “maybe two more months.”

“CAL.20C shows that we are the carriers,” Plummer said. “We are the way by which SARS-CoV-2 is moving. It’s a reflection of our behavior. If we don’t give it the opportunity to move, then we can curb it right now.”

Yahoo News: Tell me why you’re so interested in the CAL.20.C variant — and why readers should be interested too.

Dr. Jasmine Plummer: We weren’t necessarily interested in this variant. We’re in L.A., so obviously we were part of the holiday surge. Being in health care, we were trying to ensure that our frontline workers, as they were overwhelmed at the end of December — really at the peak of where we’ve been in terms of capacity and exhaustion — weren’t dealing with something new. In that process, we sequenced almost 200 patients, purposely collecting them to make sure we didn’t have the U.K. variant here. And when we did that, we found our own thing: CAL.20C.

What happened next?

We identified these five mutations that define CAL.20C. There are three in the spike protein and two in other regions. Then we looked at CAL.20C throughout time. There are about 500,000 [genetically sequenced] cases now, globally, that are deposited [for researchers to study]. So we look in California, and lo and behold, CAL.20C shows up in one out of 1,247 cases in July. Not even a percentage, not even noticeable.

But that’s when things get concerning. In October, you get a slight gain. I think there were four cases, so just a sprinkling. By January, however, CAL.20C had skyrocketed to literally 44 percent of cases in Southern California, and about 35 percent statewide. It could be coincidental, but the reality is you’re going from CAL.20C not even registering as a percentage to CAL.20C starting to take over — even as cases are going down. And then from when we first looked, at the beginning of January, to late January, it has moved across state lines and into other countries.

Elderly vaccination tent
A vaccination tent in Los Angeles. (Jason Armond/Los Angeles Times via Getty Images)

The implication being that CAL.20C’s specific mutations are conferring some sort of advantage and making it easier for it to spread.

I would say let the numbers speak for themselves. It is likely that CAL.20C is more infectious just by looking at the numbers we have at hand.

Assuming that CAL.20C is more transmissible, how would that actually work? For example, how does it compare to B.1.1.7 and B.1.351, the two other variants that we’ve heard the most about? Based on CAL.20C’s specific mutations, is it possible that it could behave in ways that are similar to those variants?

We’re actively looking into that. I believe CAL.20C is a little bit more like the U.K. variant, not in terms of the genetic sequence but in terms of behavior — which again, would mean it’s more infectious. There is some modeling that says CAL.20C could maybe bind better to the ACE2 receptor — that’s the place where the virus attaches to human cells, so the site of infection. There is a mutation in our strain that may make it better at binding.

You’re talking about the mutation to L452R spike protein?

Yeah. And that’s likely why CAL.20C is more infectious.

Do we think CAL.20C was driving the holiday surge in California?

It may not have been the reason for this surge, but it probably contributed to the magnitude. If a variant is more infectious and you don’t wear masks and take all the necessary precautions, then you give it the opportunity to spread. It’s Thanksgiving, we’re having all these meals together and there’s a variant that’s more infectious? It’s going to infect more people. In other words, there would have been a surge either way, but CAL.20C likely contributed to how many people got infected.

Tell me about that next step of the research. What are the questions about CAL.20C that still need to be answered, and how are researchers going about answering them?

We're doing all the important functional studies. So does that L452R mutation do anything, for instance? You can take each of these mutations and toss them on cells, on patient samples that contain the strain, and then look to see whether or not human cells are altered. Meaning, do they grow more? Do they die off? And really finding the functional consequences of that.

We’re in a hospital scenario, so we can actually look through people’s blood — vaccinated and unvaccinated — and see whether or not the vaccine will bind or not bind appropriately. We don’t have to wait for those longer cell culture experiments. If you had CAL.20C, did you end up in the hospital more? How was your outcome in the hospital?

What have you found so far? For instance, could CAL.20C be more likely to lead to severe illness?

With the very small numbers we have right now, the outcomes don’t seem to be more severe.

Health care workers
Health care workers treating a patient in the COVID-19 intensive care unit at Providence Holy Cross Medical Center in Mission Hills, Calif. (Ariana Drehsler/Bloomberg via Getty Images)

That’s good news. Still, you have to wonder if we’re paying enough attention to variants like CAL.20C. We tend to hear a lot more about the U.K. variant and the South Africa variant than we hear about homegrown variants.

That lack of attention is really a reflection of the processes. In the U.K., they sequence about 10 percent of their cases. When you look at the global public dataset we use, it’s over 500,000 cases. More than 200,000 have come from the U.K. Part of their public health surveillance has been sequencing from the beginning.

In contrast, we are just a small group running sequencers and looking for these things. We were the first study — and I think still the only study — in L.A. to deposit these samples and look for this. We’re doing the best we can, but if we had a collective federal effort, then we would probably be able to see more variants and have a better U.S. vision of what's going on.

So what you’re saying is that we could be flying blind, and that the virus may already be evolving here in advantageous ways — regardless of how many B.1.1.7 or B.1.351 cases we’ve detected.

Correct.

What does that suggest for the months ahead? We just went through this horrific surge in California. Cases are plummeting. Could the worst of it be behind us?

No. We can’t feel comfortable. I know everybody’s been saying this, but now is really the time that we could end this. This is the time. Our numbers are coming down. CAL.20C shows that we are the carriers. We are the way by which SARS-CoV-2 is moving. It’s a reflection of our behavior. If we don’t give it the opportunity to move, then we can curb it right now. I know we’re all tired, but we just have to hunker down and we might get over the apex.

Conversely, are you worried that variants will outrun our miraculous vaccines and undo all the progress we’ve made?

We’ve all learned biology, even in first grade — it’s survival of the fittest. So it’s just up to us to raise our fitness game. It’s not sexy anymore to hear the same four things over and over again. Now we finally have the fifth. It’s still wash hands, wear a mask, socially distance and stay home. The fifth is, if you’re able to get vaccinated, please do. It gets tiring to hear that mantra every day since March. But I assure you, we know how to do this.

It seems those five things are especially important now that we know these variants can capitalize on our fatigue in a way that maybe the virus couldn’t before.

Exactly. We have one, maybe two more months of really buckling down. If we could just for two more months go back to what we were like in March and April — if we could have that same stringency in our lives that we had in the early days — we really could stop this.

For the first time this year — and I’m getting emotional saying this — I can see the end of the pandemic. And I didn’t see it in November. I honestly didn’t. I felt defeated. I felt like, How are we going to get this under control? But now I truly can see the light at the end of the tunnel.

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