Transmission electron micrograph of SARS-CoV-2 virus particles isolated from a patient. Image acquisition and color enhancement at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Image Credit: NIAID

Say you’re a new member of the SARS-CoV-2 family, with some genetic improvements that set you apart from the rest of the clan. You may have changes in your spike protein that allow you to enter cells more easily, or a random mutation that helps you evade the virus-killing effects of COVID-19 treatment.

You could be a contender. But first you need to get out of the body you are in and infect more people.

What would you need to be successful and have success? Alternatively, what would make you die on the vine, a short-lived experiment in the tough test chamber of evolution?

A modeling exercise by researchers at the Fred Hutchinson Cancer Research Center in Seattle suggests that having a genetic variant of SARS-CoV-2 to become a threatening new presence isn’t enough to be scary and highly transmissible. It also takes a number of happy breaks to establish yourself.

Most importantly, it must have access to a superspreader event if it is to have a fighting chance of planting its flag in a population. In the short time its wearer is at or near its highest viral load, the new variant has to make a trip to a place like a choir practice, a political gathering, a poorly ventilated bar room or a crowded indoor arena where people are entertain, couple up close and many do not wear masks.

It must infect at least a handful of people there. Five would be enough for the new variant to live on and compete for more victims. If you infect 20 or more, you have a real chance of becoming predominant in the new community.

Time is of the essence, according to the new study: even for a new variant equipped with transmission superpowers, the first super-spreader event must occur within a month of its arrival for the variant to establish itself.

That’s a lot of narrow windows and a lot of high hurdles, and the likelihood that a new variant will remove all of these obstacles is actually quite small, the researchers concluded. And that should give people a bit of hope.

But then there is the reality: at least five new “worrying variants” have apparently overcome these forbidden opportunities within about six months.

That suggests something rather ominous: there are likely many more such variations, each looking for their happy break. While few variants will get it, it only takes one or two with the right set of mutations to prolong or escalate the pandemic – or undermine the vaccines and drugs that could end it.

The team’s model was released this week on MedRxiv, a website where researchers share their research and get feedback from colleagues. In this respect, its results are provisional.

For researchers hoping to see around the next corner of the pandemic, such a modeling exercise is more than idle speculation.

The coronavirus that causes COVID-19 is known to mutate constantly, but almost always in ways that do not significantly change its behavior. So it would be nice to know how these variants are born and whether there are still many similar ones. And if so, it would be helpful to know how to fill them quickly.

“Phenomenological” modeling studies like this one collect the wildly unpredictable spread patterns buried in pandemic data, combine them with well-documented cases of super-spreader events, and drop a new actor playing by slightly different rules. Then they play over and over again what happens next in computer models that function as digital test tubes.

One thing that researchers are increasingly certain is that those who have compromised immune systems are more likely to have the coronavirus adopting not just one but a variety of mutations. These genetic changes could make it even more difficult to fight the virus with drugs, masks, and vaccines.

A model like this does not provide calibrated measurements of how effective an intervention like universal masking can stop the spread. No predictions are made about the next phase of the pandemic. However, it does offer insights into how a virus behaves in a variety of circumstances, as well as probabilistic estimates that can sharpen the intuition of public health officials.

“We will most likely develop new variants in addition to the new ones,” said Dr. Joshua T. Schiffer, who led the modeling team at Fred Hutch. “And those who will win are the ones who dodge the vaccine or transmit it more easily.”

These variants don’t have a name yet and may not appear for months, added Schiffer. But when they do emerge, they will face the same harsh early experiences.

After going through thousands of scenarios, the team concluded that variants with potentially frightening spread and disease patterns are likely to occur frequently over the course of a pandemic of the size of one. After all, there are dozens of branches in the SARS-CoV-2 family tree, and any of them could have been a chance for genetic mischief. With the punishing rate of wear and tear on new varieties, it takes unfortunate ones to be born around the world every day to have so many branches.

Periods with high transmission seem to create an “all-comer-welcome” atmosphere for variants. So if the infections increase, even a variant that is more non-communicable than those already in circulation has a better chance of getting involved, as the modeling shows. And a genetic variant that arrives in that department with a biological advantage is even more likely to be successful.

A clinical laboratory scientist processes upper respiratory tract samples from patients suspected of having COVID-19.

All of these newcomers still face great opportunities. But when the variations are plentiful, and when carefree companies give them the chance of an early superspreader event, it is reasonable to assume that at least one or two will be able to gain a foothold to take off.

Their influence on the trajectory of the pandemic will be a genetic roll of the dice.

In the meantime, the research offers some actionable advice for both experts and the general public.

The most effective way to reduce the number of new variants is to prevent “large waves of infection” from occurring at all, write the authors of the study. A rise is not only an ideal environment for generating new variants, but also offers many possibilities for an overarching event.

And that means we all have a role to play by wearing masks, practicing social distancing, avoiding large gatherings, and taking other precautions that can take away the happiness of a new variant that it needs.

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More information:
Ashish Goyal et al. Early super-spreader events are a likely determinant for the prevalence of the novel SARS-CoV-2 variant MedRxiv (2021). DOI: 10.1101 / 2021.03.23.21254185

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