Will the new omicron variant cause severe disease or just a runny nose?

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  • Carl Bergstrom
    Theoretical and evolutionary biologist
Commuters And Heathrow Airport Ahead Of U.K. Tightening Coronavirus Rules
Commuters And Heathrow Airport Ahead Of U.K. Tightening Coronavirus Rules

Virulence is the ability of a pathogen to wreak damage on those it infects, and it is on news of the virulence or lethality of omicron that the world now anxiously awaits.

If the news is positive and the new variant turns out to be milder than earlier strains, expect the latest round of restrictions to be quickly unwound. We’ll breathe a global sigh of relief and get on with learning to live with the virus again.

If, on the other hand, this variant – already thought (but not proven) to be more transmissible than its predecessors – is more deadly we will not be in a good place. Even less so if it has the combination of mutations needed to bypass our hard-won immunity or at least dilute it.

Meaghan Kall, lead epidemiologist in Covid-19 at the UK Health Security Agency (HSA), says scientists will need to track “several hundred” confirmed omicron cases from start to finish to fully answer the question – a process that could take up to six weeks.

“All [UK] systems & teams are on standby to run the analysis, but my sense is we are still a long way from that number”, she said at the weekend. “So we depend on South Africa.”

Early reports from there are mixed. Hospitalisations are up sharply in the worst affected province, Gauteng, quadrupling from 134 admissions two weeks ago to 580 in the seven days to the end of last week.

On a more positive note, primary care doctors in South Africa are reporting that symptoms in the omicron patients they have seen are unusual but mild. They warn that may yet change as the virus works its way into older age groups but, for the moment at least, there is nothing especially frightening or out of the ordinary.

In the absence of hard data, some of the world’s best evolutionary biologists have been doing the rounds, explaining the Darwinian pressures the virus faces and what that might mean for us – its principle animal host and reservoir.

Importantly, they say we should not be seduced by the idea that gains in the virus’s transmissibility necessarily mean a decline in its virulence.

It is true that several forms of the common cold – a coronavirus – have evolved into little more than a runny nose. But the exact opposite can be true, and often is.

“Viruses do not inevitably evolve to become less virulent over time. If this has happened with omicron – and it's too early to tell whether it has – it would be a matter of good fortune,” Tweeted Professor Carl Bergstrom, a theoretical and evolutionary biologist at the University of Washington in Seattle.

“Many viruses do not attenuate [reduce in force] over time. Influenza remains far worse than a common cold. Measles, even more so. Smallpox, worse yet”.

Prof Bergstrom also warned against the related idea that viruses evolve to become less virulent “to keep their hosts alive and thereby transmit more”.

“This is unlikely to be a factor for Covid, where death occurs weeks after the transmission ceases”, he noted.

Prof Francois Balloux, director of the UCL Genetics Institute, and a professor of computational biology at University College London, agrees.
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“Viruses kill host cells and damage host tissues when replicating [inside us]. Thus, a pathogen that is better at replicating within hosts, spreads more virions in the environment, and hence transmits better AND generally tends to be intrinsically more virulent”, he said.

This was true of the alpha and delta variants. Both are more transmissible and more dangerous than the original virus. The natural reproduction rate of the virus has grown from a median estimate of 2.79 in spring 2020 to 5.08 with delta today. Meanwhile, studies show the risk of ending up in hospital in the UK and dying has also increased as the virus has evolved.

But alpha and delta emerged at a time when immunisation through natural infection and vaccination was low. With immunisation now high and increasing around the world, the selective pressures on the virus are changing – and so is the way it evolves.

The substantial number of mutations seen in the spike of omicron suggest the virus is now focused on ducking human immunity, so it can continue to spread. But as far as virulence is concerned, things could still go either way.

“A virus replicating in the upper airways could be highly transmissible yet fairly benign to its host”, noted Prof Balloux. But “a viral strain replicating within organs (lungs, kidneys) is expected to cause extensive damage”.

He added: “If we're unlucky, omicron's ability to (re-)infect immunised hosts doesn't significantly impact its high replication rate (and the damage it causes to host tissues).

“If we're a bit lucky, its ability to (re-)infect immunised hosts does reduce its replication rate, and hence would be expected to cause on average less severe symptoms, send fewer people into hospital and reduce fatality rates”.

As we wait to discover how nasty or otherwise omicron turns out to be, there is one other oddity of viral evolution to keep in mind – its penchant for randomness.

Prof Bergstrom flags an academic paper published in 1994 which found that viral evolution can be “short sighted”, with pathogens becoming much more dangerous without gaining any particular advantage from it. Bacterial meningitis is a classic example.

“To paraphrase and generalise [the study], virulence is often not so much a matter of evolutionary fine-tuning as a matter of ‘shit happens’,” said Prof Bergstrom.

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