In August last year, an immuno-suppressed woman in Italy contracted Covid-19. Unlike most patients, her body struggled to rid itself of the virus. She had cancer, which doctors were treating with chemotherapy, and for more than six months, her immune system and the coronavirus waged an internal war. By March, she was Covid-negative, but in that time the virus had accrued more than 20 mutations.
"The virus is mutating all the time,” says Ed Rybicki, a virologist at the University of Cape Town in South Africa. But it is more likely to mutate “if the virus is not cleared quickly enough”.
The latest variant, Omicron, which has now been detected in at least 77 countries, has more than 50 mutations. One theory for this rapid leap in mutations is that the virus mutated in an immuno-suppressed person. If these scientists are right, the variant could have evolved in one of the many immunosuppressed people in the world. Experts argue that, to curb this possible source of variants, public health authorities have to redouble their efforts to vaccinate people with compromised immune systems –– and that they may need multiple vaccinations, rather than the three currently being recommended.
As viruses spread, they naturally mutate. What has scientists concerned about Omicron is the high number of mutations it developed in such a short period of time. There are currently three major theories as to how this could have happened: that the variant evolved in an immuno-suppressed person; that it jumped to animals, which then reinfected people with a heavily-mutated virus; and that the virus was circulating and evolving in an isolated group of people, before being reintroduced to the general population as a new variant.
Researchers first detected Omicron in South Africa and Botswana in November, fuelling speculation that the variant had evolved in one of the almost eight million people currently living with HIV in those countries. If left untreated, HIV damages the immune system, killing the cells that fight diseases such as Covid. An untreated HIV-positive person could develop a persistent infection, which could give the coronavirus time to mutate.
To develop a Covid infection that would allow significant viral evolution in a single individual, a person would have to have a “profoundly immune-suppressed”, says Marvin Hsiao, a virologist at the University of Cape Town.
There is an example of an HIV-positive woman, who –– like the Italian patient with cancer –– had a Covid infection for more than six months. In that time, the virus evolved a number of mutations, some of them on the spike protein.
Scientists are particularly interested in the virus’ spike protein, which is how it latches onto human cells. In the case of Omicron, the majority of its mutations are on this protein.
“That is a position that is a classic ‘immune escape’ mutation,” says Gonzalo Bello, a virologist who worked to identify and map the spread of the Gamma variant in Brazil. As a person’s immune system tries to eradicate the virus, the virus mutates to avoid it, often on this protein. Omicron’s mutations are not spread throughout the virus’ genome, but are concentrated in the spike protein, Bello says. Previous variants of concern, such as Delta which rapidly overtook other strains but now looks set to be overtaken by Omicron, also had mutations on that protein.
Epidemiologist and HIV specialist Salim Abdool Karim, based in South Africa, emphasises that the three variant origin theories are speculation, without concrete evidence. But even if Omicron had evolved inside an immuno-compromised individual, he doubts it was an HIV-positive person in South Africa.
Based on genetic analysis, Omicron’s “ancestor” –– the lineage of the virus that accrued the mutations –– was in circulation in about September last year, says Adbool Karim, who chairs the World Health Organisation’s HIV and hepatitis scientific and technical advisory group.
A person would have had to be ill with Covid for about a year, before infecting someone else with their version of the virus. Even if they had mild Covid symptoms, that person would have likely ended up in the healthcare system with another disease such as TB, he says.
Furthermore, the virus’ ability to evolve in an immuno-suppressed person does not mean that variant will necessarily take hold in the general population, Adbool Karim and Hsiao caution. Viral evolution in an individual will not necessarily yield a new variant of concern, like Omicron.
“The virus can evolve a lot, but if it only helps (the virus) in that particular person and doesn’t do anything for everyone else, then it is just a phenomenon we observe,” Hsiao says.
In the case of the Italian lymphoma patient, researchers who studied her case say that her long isolation in hospital may have curbed the spread of a possible variant, although it is not certain whether it could have outcompeted other types of the coronavirus already in circulation.
The search is on for Omicron’s origin, but experts are not hopeful that they will find the first person who contracted the variant –– whether the immuno-suppressed person it evolved in, the individual who caught it from an animal, or the isolated population where it mutated.
In the case of an immuno-suppressed individual, finding the source is almost impossible, says Adbool Karim. “It’s a single person –– one person who was infected and then became the source of the next wave of infections.”
How can we stop it happening?
One way to curb future possible variants is to increase vaccinations, they say. With less of the virus in circulation, it has fewer opportunities to replicate. However, this can be tricky when it comes to immuno-suppressed people, says Abdool Karim.
Officials advise that people with compromised immune systems receive a booster jab, but these three vaccinations may not be enough to protect them.
The OCTAVE study, whose initial findings were published in August in theBritish Medical Journal, looked at how 600 people in the United Kingdom with weakened immune systems responded to two shots of a Covid vaccine. Four in 10 people generated lower levels of antibodies than healthy people.
“You’re worried about the same group who don’t produce antibodies when they’re naturally infected,” says Abdool Karim. “They don’t produce it with vaccines either. You have got to give them multiple shots –– however many they need before they have a proper immune response.”
That would be logistically complicated, but offers the prospect of shutting down an avenue via which the coronavirus could continue to evolve and reinfect people.
Sarah Wild @sarahemilywild is a freelance science journalist who splits her time between South Africa and the UK