Scientists explore role of immunocompromised in generating Covid-19 variants

As variants of the SARS-CoV-2 virus that causes Covid-19 have appeared over the past several months, scientists have sought to understand how they come to be. Some have been looking into the role that individuals with compromised immune systems may play in spurring the mutations of the virus that create new variants.

Patients waiting for vaccinations against Covid-19 near Johannesburg, South Africa, August 30, 2021.
Patients waiting for vaccinations against Covid-19 near Johannesburg, South Africa, August 30, 2021. © Sipiwe Sibeko, Reuters/File

Who is the Omicron variant's patient zero? Detected for the first time in South Africa, the variant formally known as B.1.1.529 sparked immediate concern in the international community. Indeed, Omicron's unprecedented number of mutations – more than 30 compared with the original strain of this coronavirus – present two potential threats: that it could be particularly contagious and that it might prove resistant to existing vaccines.

While governments around the world have set out to bolster restrictions to stem Omicron's spread, scientists have set about tracing the origins of the "super mutant" variant to understand how it came into being.

Among the theories put forward, some researchers are looking at mutations that appeared in one infected patient with a compromised immune system. Over the course of several months, they have studied the effect of a possible link between the emergence of variants of the highest concern and immune systems weakened in patients who are, for example, suffering from cancer, waiting for an organ transplant or living with untreated HIV.

"When a patient is immune-compromised, the virus will remain in their system for a very long time, sometimes several months, compared to just a few days in the average person," Morgane Bomsel, a virologist at the CNRS and the Cochin Institute in Paris, told FRANCE 24. "His immune defence system is too weak and he can't manage to rid himself 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 following 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 under 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.

It bears noting that SARS-CoV-2, like all viruses, has a genetic makeup that replicates itself. But sometimes errors insinuate themselves into that process. Those are known as mutations. In most cases, they have no repercussions, but some can modify the transmissibility or the virulence of a virus. The variant is therefore that new version of the virus accounting for those assorted modifications.

"Among immunocompromised patients, the immune system will not manage to beat the virus, but it will still fight against it. That will provoke what we call selection pressure," Vincent Maréchal, a professor of virology at Sorbonne University, told FRANCE 24.

In short, in the battle between the immune system and the virus, the latter will be forced to evolve and will retain only the mutations that allow it to continue to reproduce and to resist. As a result, only the most dangerous of mutations will remain – those able to escape the neutralising power of antibodies. It is that virus, with its mutations, that will be passed along if the patient infects somebody else.

"With such an impressive number of mutations, the Omicron variant very probably found its origin in an immunocompromised patient," Maréchal said.

"But this isn't the first time this hypothesis has been raised. It was also put forward for the British and Beta variants," Bomsel noted.

Fertile ground in South Africa

South Africa, for its part, could be fertile ground for just the sort of process that creates variants owing in particular to the AIDS epidemic. Seven million individuals are living with AIDS in the country, which represents 12 percent of the total population, or 19 percent of 15-to-45-year-olds.

Moreover, the rate of those individuals actually receiving treatment remains very low, just 57 percent in 2017. "So there is a high proportion of immune-compromised people in a country with low (Covid-19) vaccine coverage and where the virus is circulating heavily," Maréchal explained. "That is clearly a situation where variants can appear."

It is not the first time that South Africa has detected a new Covid-19 variant before anywhere else. Prior to the Omicron variant, two others had been dubbed "South African" variants before those names were changed; first, the Beta variant and then C.1.2.

"But that can be explained, first of all, by the fact that the country conducts a lot of sequencing, which is what enables it to identify variants on its soil," Maréchal explained. "It doesn't necessarily mean that the patient zero (of the Omicron variant) is in South Africa."

The geographic origin of Omicron remains unclear for the moment – several countries, including some in Europe, have since identified cases that pre-date the announcement of its discovery in South Africa. A September article in the journal Science suggested however that the earlier Beta variant did most likely first appear in South Africa.

That study said that Beta, which was isolated for the first time in October 2020, is thought to have been detected for the first time in AIDS patients in Nelson Mandela Bay. The process is said to have been expedited by the lack of means allocated to AIDS treatment in that area. Indeed, the region figures among those with the world's highest concentrations of individuals both infected with HIV and deprived of the appropriate treatment for it.

Using data analysis comparing all the variants in the Beta line detected around the world, the study's authors discovered that 90 percent of those variants' ancestors hailed from South Africa. The first in the line therefore in all likelihood first appeared in Nelson Mandela Bay.

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

'Variants can appear anywhere'

South Africa should nevertheless not be called out, Maréchal insisted: "What this shines a light on above all is what happens when two pandemics meet and the need to not forget the fight against AIDS amid Covid-19."

"But we have clearly seen over the past two years that variants can appear everywhere. From Brittany to India to the United Kingdom," he insisted. "There are surely many factors to take into account. There are still a lot of things about variants that we don't understand."

While the search continues to grasp the mechanisms at work in the emergence of these variants, the virologist puts forward one other hypothesis. "Perhaps the variants emerge more easily in certain locations as a function of socio-cultural and healthcare contexts," he suggested. "In that case, we need to identify those areas and put monitoring into place in order to see these things coming ahead of time."

This article has been translated from the original in French.

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