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How the variants evolve

I thought this STAT News piece from last August was informative for this moment. It’s about how viruses mutate, something that is of acute interest in light of the Omicron variant:

It’s impossible to say how the coronavirus will continue to evolve. Those changes, after all, are a result of random mutations.

But there are some fundamental principles that explain why the virus has morphed as it has, principles that could guide our understanding of its ongoing evolution — and what that means for our future with the pathogen.

The great fear is that nature could spit out some new variant that completely saps the power of vaccines and upends the progress we’ve made against the pandemic. But to virologists and immunologists, such a possibility seems very unlikely.

That’s not to say variants won’t impair immune protection. Already, it appears Delta is causing breakthrough infections and symptomatic cases at higher rates than other variants. But vaccines have shown they don’t lose much oomph at protecting people from hospitalization and death, no matter the variant they’re up against. The way the vaccines work leaves experts optimistic that mutations won’t suddenly leave everyone vulnerable again.

“I don’t think that we’ll end up with variants that completely escape antibodies or vaccine-induced immunity,” said vaccinologist Florian Krammer of Mount Sinai’s Icahn School of Medicine. Already, Krammer said, we’ve seen the immune system’s ability to neutralize viral variants drop — to the greatest degree with the Beta variant — but it still persists. Because of that, vaccines haven’t lost major steps at protecting people from the worst outcomes of Covid-19.

Something unexpected could happen, scientists caution — another twist in a pandemic full of them. Already, they’ve had to reassess their thinking about the coronavirus’ evolution. This family of viruses proofreads itself as it replicates, which means it picks up mutations more slowly than viruses like influenza. For the first several months of the pandemic, the virus didn’t seem to be changing in dramatic ways. But now, variants are dominating the conversation.

“This virus has been surprising us,” said Ramón Lorenzo-Redondo, a molecular virologist at Northwestern University’s Feinberg School of Medicine.

Below, STAT outlines some of the key questions about the virus’ evolution — and what it means going forward.

Why does the virus keep getting more transmissible? 

When the coronavirus started circulating among people in late 2019, it was already quite the spreader. Cases overwhelmed Wuhan and led China to impose what were then jaw-dropping lockdowns.

But to the virus, people were a new host. A change in its RNA genome had enabled it to infect our cells, replicate inside them, and jump to other people, but the pathogen hadn’t had much of a chance to figure us out yet. It had a lot of room to get better at using us to proliferate.

That meant there were a lot of low-hanging fruit mutations that the virus could pick up and that would give it a competitive advantage over other iterations of the virus. It’s not that the virus was knowingly figuring out which mutations would make it a better spreader. But as the virus made copies of itself, sometimes it made errors. And by chance, some of those errors gave it a boost over its siblings, helping it outcompete them.Related:‘It’s soul-draining’: Health workers deployed to Covid hot zones are overwhelmed by deaths among the unvaccinated

It’s happened throughout the pandemic. An early change dubbed D614G led to a strain that was better at spreading than the very first version, enabling that variant to sweep around the world. For a while, that strain was dominant, but then Alpha appeared, and now Delta. Each subsequent iteration was a more effective spreader than the strains before it, so it outran the others. (One note about Alpha: scientists believe it emerged from a person who was immunocompromised and had a rare chronic Covid-19 infection, which allowed the virus to pick up a lot of mutations in a relatively quick period in one host, and then spread from there.)

One way to think about a virus’ transmissibility is on a curve, one that rises fast and tapers off toward some peak ability. It’s going to get better at spreading comparatively quickly, particularly when there’s been uncontrolled transmission for a year and a half. Over time, it could evolve more slowly, with fewer new combinations of mutations that might increase its transmissibility. Some scientists have questioned whether Delta is so transmissible that the virus might be nearing the flatter part of the curve. But to virologist Adam Lauring of the University of Michigan, “We just don’t know where we are in terms of that leveling off.” It’s possible then, that the virus could still stumble upon mutations that help it spread even more efficiently.

The virus could change in other ways too. If there’s one silver lining about Delta, it’s that it’s so transmissible that it’s crowded out other variants that are more worrying from an immune perspective, namely Beta, as well as Gamma. But scientists caution that there’s no fundamental reason why a variant couldn’t emerge that combines Delta’s spreading prowess with Beta’s ability to partially sneak around immune responses.

Such a variant might look different than we would imagine. Sometimes combining mutations that would seem to maximize transmissibility and immune-dodging abilities actually leads to a virus that fizzles out. Variants that can escape the immune response might be inept at hacking into cells to cause infections. But more worrisome variants are possible, and the best way to prevent them, experts say, is cutting transmission.

We don’t know how “worrisome” the omicron varient is going to turn out to be. The CEO of Moderna sounded an alarm about it this morning that had the markets falling out of bed again. So, who knows? But it’s probably not a good idea to make any assumptions until the scientists weigh in.

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