Ômicron: why it is important to discover the origin of the variant

When scientists working in South Africa discovered the omicron, some features of this coronavirus variant soon came to attention.

The first and most important was the large number of mutations this version of the virus carried — a combination of mutations that had not yet been detected by a global network of researchers that monitor the pathogen’s genetic changes.

“The omicron came up with something completely different,” says Richard Lessells, an infectious disease specialist at the University of KwaZulu-Natal in South Africa and part of the team that first detected the variant in late November.

Scientists believe the omicron may have evolved from a single person with a weakened immune system in sub-Saharan Africa — possibly someone with untreated HIV — and then spread to more than 40 countries.

Although there are at least two other possible explanations for the emergence of this variant, the hypothesis that it started from “a single individual” is supported by a significant part of the scientific community.

Why discovering variant origin is important

While we are not yet sure where omicron came from, its existence was first reported to the WHO (World Health Organization) on 24 November.

But knowing where and when a variant appears is important for scientists and health managers, as this information can define areas of social isolation and travel restrictions (which, however, are in some circumstances judged to be ineffective by experts).

The sooner a new variant is detected, the more time we have to determine its severity: is it more transmissible? Does it replicate faster in the body of an infected person? Does it lead to gravity more often?

The “how” is equally crucial: if the omicron did indeed evolve in a single patient with a compromised immune system, monitoring individuals like this would become extremely important in combating Covid-19.

“Today, we have more data suggesting a link between variants and immunocompromised people with chronic coronavirus infections,” says Larry Corey, a virologist at the Fred Hutchinson Cancer Research Center in the United States.

“But these people have not (yet) been placed as an important component of Covid’s prevention strategies.”

How could the variant have evolved in a single person?

Scientists say they have some clues to making “sound assumptions” about how the omicron came about.

Lessells points out that the omicron differs substantially from the variants existing so far.

“Genetic analysis showed she’s on an entirely different branch of the family tree.”

There were no records of the most recent intermediate mutations found in omicron — the closest version, says Lessells, dated mid-2020.

That gap suggests that this mutation-ridden variant evolved off the radar, according to François Balloux, a professor of computational systems biology at University College London in England.

“She came out of nowhere,” says Balloux.

And the variant is very, very different. Analysis has shown that she has 50 mutations, more than 30 of them in the protein spike, a part of the virus that defines how it interacts with the body’s defense tools.

As a comparison, the delta variant had only seven mutations in the protein. spike.

While most people can eliminate the Sars-Cov-2 virus from their bodies in a short period of time, in people with weakened immune systems — such as those with HIV or cancer, or transplant recipients — the infection can be very longer, as shown by several studies around the world.

Upon encountering lesser resistance in the host, the virus ends up incorporating mutations that, in other situations, would only appear with a wide circulation in the population. Chronic infection made possible by a weakened immune system gives the virus more room to maneuver.

In December 2020, researchers at Cambridge University, England, warned that they had found, in samples from a cancer patient in the UK who had died of Covid-19 in August, the emergence of an important mutation also seen in alpha, the first “concern variant” recognized by the WHO.

This classification is used to describe the coronavirus variations that pose the greatest risk to public health.

The patient died 101 days after being diagnosed with Covid-19.

“A typical coronavirus infection lasts only seven days, and that is not enough time for the virus to adapt and evolve, as the immune system is fighting it,” explains Professor Ravi Gupta, from the Institute of Therapeutic and Immunology, to the BBC. Cambridge Infectious Diseases, leader of the immunocompromised patient study.

In June, Lessells and his colleagues announced the results of analyzing the case of a woman in South Africa who had an untreated HIV infection.

After several steps of genetic analysis, the researchers found “significant changes” in the evolution stages of the virus.

And that could indicate the beginning of a public health crisis: In an article published in early December in the journal Nature, Lessells and other authors estimated that about 8 million people with HIV in sub-Saharan Africa are not receiving effective antiretroviral treatments —a number that includes people who have never been tested for the disease.

This scenario is fertile ground for new variants.

Other explanations

Scientists say there are two other plausible hypotheses for the emergence of the omicron.

One would be animal origin, in which the virus would have infected an unknown animal population and mutated before re-infecting humans — as it did with the original Sars-CoV-2 virus, according to a WHO report released in March.

However, Larry Corey points out that genetic analysis of the omicron so far suggests that it evolved into a human.

Balloux says his team has not found any “silver bullets” to support the animal transmission hypothesis.

A second possibility for the origin of omicron is that the variant evolved not within an individual, but from a population for which there is not much genetic monitoring, as is the case in many African countries, before reaching South Africa.

Brazilian biologist and independent researcher Atila Iamarino believes that this could be the case for omicron.

Iamarino sees parallels with the emergence of another strain of concern, gamma, which caused an explosion of infections in Manaus in early 2021.

“The same hypothesis that the virus evolved in a single person with a weakened immune system was raised when the gamma was detected”, recalls the biologist.

“Later it was proven that intermediate strains were circulating undetected and accumulating mutations as they spread through the local population.”

The biologist believes that further research may reveal a similar script in the case of omicron.

“The pieces fit together. The omicron was detected on a continent with less testing and monitoring than the rest of the world.”

“The omicron may have been circulating in Africa for much longer than we believe today.”

Will we ever find patient zero?

Proponents of the “one person” hypothesis have been careful not to discount these alternatives altogether, but believe the weight of evidence is in their favor.

If this hypothesis is confirmed, would it be possible to find one day the first person to have suffered an infection by the omicron variant?

“Patient zero” is a term used to refer to the first human being infected with a viral or bacterial disease.

For Covid-19, scientists have so far not been able to identify this individual for either the omicron or other variants.

Richard Lessells believes that it is very unlikely that omicron patient zero will ever be found — and reckons that this lack of knowledge could be a good thing.

“We don’t want to increase the stigma and discrimination that people living with HIV are exposed to”, says the scientist.

Instead, Lessells argues that the “one person” hypothesis should be one more reason to speed up Covid-19 vaccination in Africa.

The Our World in Data platform, a collaboration between the University of Oxford and an educational organization, estimated in mid-November that less than 7% of Africans were fully vaccinated, while globally the number is 40%.

Michael Head, senior researcher in global health at the University of Southampton in the UK, believes that we must pay more attention to this uneven distribution of vaccines if we are to prevent the emergence of variants.

“Like anything with Covid, there will be a number of factors that contribute to the emergence of new variants, but inequality in vaccination is definitely one of the main reasons. I believe omicron is a consequence of this inequality in Africa.”

“If a person is not vaccinated, they are more likely to be sick more severely and for a longer period of time,” explains Head.

“It also means the virus is more likely to develop new mutations, which increases the risk of a new strain of worry and the need to learn another letter of the Greek alphabet.”