Scientists explore the role of immunosuppressed people in generating Covid-19 variants

As variants of the SARS-CoV-2 virus that causes Covid-19 have appeared in recent months, scientists have tried to understand how they are produced. Some have been investigating the role that people with compromised immune systems can play in stimulating mutations in the virus that create new variants.

Who is patient zero of the Omicron variant? First detected in South Africa, the variant formally known as B.1.1.529 caused immediate concern in the international community. In fact, the unprecedented number of Omicron mutations, more than 30 compared to the original strain of this coronavirus, presents two potential threats: that it could be particularly contagious and that it could prove resistant to existing vaccines.

While governments around the world have set out to tighten restrictions to stop the spread of Omicron, scientists have set out to trace the origins of the “super mutant” variant to understand how it arose.

Among the theories presented, some researchers are analyzing the mutations that appeared in an infected patient with a compromised immune system. Over several months, they have studied the effect of a possible link between the appearance of variants of greatest concern and a weakened immune system in patients who, for example, suffer from cancer, await an organ transplant or live with untreated diseases . HIV

“When a patient is immunosuppressed, the virus will stay in their system for a long time, sometimes several months, compared to just a few days in the average person,” Morgane Bomsel, virologist at CNRS and the Cochin Institute. in Paris, he told FRANCE 24. “His immune defense system is too weak and he can’t get rid of the virus.”

Selection pressure

According to a study published last month in the journal Nature Communications, a 58-year-old man with a history of kidney disease and under immunosuppressive treatment after a transplant remained Covid-19 positive for more than six months.

In December 2020, doctors in the United States brought to light a similar case of a patient undergoing immunosuppressive treatment who died after a Covid-19 infection that had lasted 154 days. “And during all that time, the virus can accumulate a whole series of mutations and create a variant,” Bomsel explained.

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It should be noted that SARS-CoV-2, like all viruses, has a genetic makeup that replicates itself. But sometimes mistakes creep into that process. Those are known as mutations. In most cases, they have no impact, but some can modify the transmissibility or virulence of a virus. Therefore, the variant is the new version of the virus that explains those varied modifications.

“Among immunosuppressed patients, the immune system will not be able to defeat the virus, but it will continue to fight it. That will cause what we call selection pressure,” Vincent Maréchal, professor of virology at Sorbonne University, told FRANCE 24.

Ultimately, in the battle between the immune system and the virus, the latter will be forced to evolve and will only retain the mutations that allow it to continue reproducing and resisting. As a result, only the most dangerous mutations will remain: those capable of escaping the neutralizing power of antibodies. It is this virus, with its mutations, that will be transmitted if the patient infects another person.

“With such an impressive number of mutations, the Omicron variant most likely found its origin in an immunosuppressed patient,” Maréchal said.

“But this is not the first time this hypothesis has been raised. It was also put forward for the British and Beta variants,” Bomsel noted.

Fertile land in South Africa

South Africa, for its part, could be fertile ground for the kind of process that creates variants due, in particular, to the AIDS epidemic. Seven million people are living with AIDS in the country, which represents 12 percent of the total population, or 19 percent of people aged 15 to 45 years.

Also, the rate of people actually receiving treatment is still very low, just 57 percent in 2017. “So there is a high proportion of immunosuppressed people in a country with low vaccine coverage (Covid-19) and where the virus is circulating to a large extent, “explained Maréchal. “That is clearly a situation in which variants can appear.”

It is not the first time that South Africa has detected a new variant of Covid-19 earlier than anywhere else. Before the Omicron variant, two others had been called “South African” variants before those names were changed; first, the Beta variant and then C.1.2.

“But that can be explained, in the first place, by the fact that the country performs a lot of sequencing, which is what allows it to identify variants in its soil,” explained Maréchal. “It doesn’t necessarily mean that patient zero (of the Omicron variant) is in South Africa.”

Omicron’s geographic origin remains unclear at the moment: Several countries, including some in Europe, have since identified cases prior to the announcement of its discovery in South Africa. However, a September article in the journal Science suggested that the earlier Beta variant likely first appeared in South Africa.

That study said that Beta, which was first isolated in October 2020, is believed to have been first detected in AIDS patients in Nelson Mandela Bay. The process is said to have been accelerated by the lack of resources allocated to AIDS treatment in that area. In fact, the region ranks among those with the highest concentrations of people infected with HIV and deprived of adequate treatment.

Using data analysis comparing all variants of the Beta line detected around the world, the study authors found that 90 percent of the ancestors of those variants came from South Africa. Therefore, the first of the line appeared for the first time in Nelson Mandela Bay.

The virus then quickly spread through other provinces in South Africa before spreading to neighboring countries. In March 2021, it became the dominant virus in southern Africa, as well as in the French overseas departments of Mayotte and La Réunion in the Indian Ocean near Madagascar.

‘Variants can appear anywhere’

However, South Africa should not be denounced, Maréchal insisted: “What this sheds light above all is what happens when two pandemics are found and the need not to forget the fight against AIDS in the midst of Covid-19.”

“But we have seen clearly in the last two years that variants can appear everywhere. From Britain to India to the UK,” he insisted. “Surely there are many factors to consider. There are still many things about the variants that we do not understand.”

Although the search continues to understand the mechanisms that operate in the appearance of these variants, the virologist presents another hypothesis. “Perhaps the variants arise more easily in certain places depending on the sociocultural and health contexts,” he suggested. “In that case, we have to identify those areas and put a follow-up in place to see these things come ahead of time.”

This article has been translated from the original in French.