How do COVID variants emerge?

This article was originally posted on 15th April 2021, and updated on 30th November.

Since its first appearance in Wuhan, China, SARS-CoV2 has been acquiring random mutations. In recent months several new variants – such as omicron – have been observed. Some of those cause significant changes in how the virus behaves, including how contagious or deadly it is.

Mutations happen all the time and are entirely random. “It’s just what viruses do,” says Professor Gilda Tachedjian, a virologist at the Burnet Institute and president of the Australian Virology Society.

If we sequenced all the virus particles – virions – from someone infected with SARS-CoV2, we’d find that each particle is slightly different. That’s because when viruses make copies of themselves, they make mistakes. Most of these go completely unnoticed. Others confer advantages to the virus and gradually become predominant.

Some experts hypothesise that mutations might happen more frequently in immunosuppressed people, and is one possible origin of the recent omicron variant. But how does this happen?

How do variants arise in immunicompromised people?

In early February, a study published in Nature reported the case of a 70-year-old man admitted to hospital in the UK, who had tested positive for SARS-CoV2. He was infected for over 100 days before he died. The man was immunocompromised. He had lymphoma and had previously received chemotherapy treatment.

Researchers from Cambridge University who followed the patient noticed that the virus evolved rapidly after the man received plasma therapy – an infusion of plasma taken from people who have recovered from COVID-19, and thus contains antibodies against SARS-CoV2. The virus produced “escape mutations” that helped it to evade detection by the antibodies in the plasma.

While random changes in any viral genetic sequence are normal over the course of an infection, this patient presented a pattern that attracted the researchers’ attention. Multiple new mutations appeared in the patients after he received the first plasma infusions. These became dominant but vanished two weeks later when antibody levels had diminished.

But when the patient received his final plasma dose, the mutant strains were detected again. The research team suggest that the mutations occurred in response to the plasma therapy. This phenomenon is called selective pressure – when an external cause reduces the chance of survival, the virus mutates to escape.

The rapid evolution of the virus has been documented in other patients. A 45-year-old Boston man undergoing immunosuppressive therapy was hospitalised with a COVID-19 infection that recurred for 154 days until he died.

Perhaps even more worrying is that such rapid viral evolution has been also reported in an immunocompromised patient who remained asymptomatic over several months.

“If the person has a robust immune system, the virus will replicate, but eventually the immune system will shut it down,” says Tachedjian. “In an immunocompromised individual, the virus is turning over for months.

“It comes back to that ability of the virus to replicate, to introduce mutations, and then to evolve so that it’s able to escape the weak immune response that immunocompromised individual might have.”

If this hypothesis is true, it might have implications for vaccination programs. People with compromised immune systems, such as cancer patients or people undergoing immunosuppressive therapies, should be among the first to be vaccinated.

Scientists have still not figured out how, when and in whom this viral evolution happen. But in the wake of these new variants, rapid global vaccination is even more urgent.

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