Scientists explore role of immunocompromised in the generation of Covid-19 variants

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As variants of the SARS-CoV-2 virus that cause Covid-19 have emerged in recent months, scientists have sought to understand how they came about. Some have looked at the role that people with weakened immune systems can play in stimulating mutations in the virus that create new variants.

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

As governments around the world set out to tighten restrictions to stem the spread of Omicron, scientists set out to trace the origins of the “super mutant” variant to understand how it came about.

Among the theories advanced, some researchers are looking at mutations that have appeared in an infected patient with a weakened immune system. For several months, they studied the effect of a possible link between the emergence of variants of the most concern and the weakening of the immune system in patients, for example with cancer, awaiting a transplant. organ or living with HIV.

“When a patient is immunocompromised, the virus will stay in their system for a very long time, sometimes several months, compared to just a few days in the average person,” said Morgane Bomsel, virologist at CNRS and at the Cochin Institute. in Paris, told FRANCE 24. “His immune defense system is too weak and he cannot 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 on immunosuppressive therapy following a transplant has remained positive for Covid-19 for more than six months.

In December 2020, doctors in the United States brought to light a similar case of a patient on immunosuppressive therapy who died of a Covid-19 infection that had lasted for 154 days. “And all the while, the virus can build up a whole bunch of mutations and create a variant,” Bomsel explained.

Covid-19 – Scientists: Sequencing variant key to slow spread

It should be noted that SARS-CoV-2, like all viruses, has a genetic makeup that replicates. But sometimes mistakes creep into this process. These are known as mutations. In most cases, they have no impact, but some can change the transmissibility or virulence of a virus. The variant is therefore this new version of the virus representing these various modifications.

“In immunocompromised patients, the immune system will not be able to overcome the virus, but it will fight it anyway. This will cause what is called selection pressure,” Vincent Maréchal, professor of virology at FRANCE 24, told FRANCE 24 Sorbonne University.

In short, in the battle between the immune system and the virus, the latter will be forced to evolve and will only keep the mutations that allow it to continue to reproduce and to resist. 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 someone else.

“With such an impressive number of mutations, the Omicron variant most likely originated in an immunocompromised patient,” Maréchal said.

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

Fertile land in South Africa

South Africa, on the other hand, could be fertile ground for just the type of process that creates variations due in particular to the AIDS epidemic. Seven million people are living with AIDS in the country, which represents 12% of the total population, or 19% of 15-45 year olds.

In addition, the rate of these people actually receiving treatment remains very low, barely 57% in 2017. “There is therefore a high proportion of immunocompromised people in a country with low vaccination coverage (Covid-19) and where the virus circulates. strongly ”, explained Maréchal. “This is clearly a situation where variations can appear.”

This is not the first time South Africa has detected a new variant of Covid-19 before anywhere else. Prior to the Omicron variant, two more had been dubbed “South African” variants before these names were changed; first, the beta variant, then C.1.2.

“But this is explained first of all by the fact that the country does a lot of sequencing, which allows it to identify variants on its soil”, explained Maréchal. “This does not necessarily mean that patient zero (of the Omicron variant) is in South Africa.”

The geographic origin of Omicron remains uncertain for now – several countries, including some in Europe, have since identified cases that predate its discovery in South Africa. A September article in the journal Science, however, suggested that the earlier beta variant most likely first appeared in South Africa.

This study indicated that Beta, which was first isolated in October 2020, was first detected in AIDS patients in Nelson Mandela Bay. The process would have been accelerated by the lack of resources allocated to the treatment of AIDS in this area. Indeed, the region has one of the highest concentrations in the world of people both infected with HIV and deprived of appropriate treatment.

Using analysis of data comparing all the beta lineage variants detected around the world, the study authors found that 90 percent of the ancestors of these variants were from South Africa. The first of the line therefore probably appeared for the first time in Nelson Mandela Bay.

The virus then spread rapidly to 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 Reunion in the Indian Ocean near Madagascar.

“Variants can appear anywhere”

South Africa should not, however, be questioned, insisted Maréchal: “What this highlights above all is what happens when two pandemics meet and the need not to forget the fight against AIDS in the middle of Covid-19. “

“But we have seen these last two years that variants can appear everywhere. From Brittany to India via the United Kingdom”, he insisted. “There are surely a lot of factors to consider. There is still a lot about the variants that we don’t understand.”

While research continues to grasp the mechanisms at work in the emergence of these variants, the virologist advances another hypothesis. “Perhaps the variants emerge more easily in certain places depending on the socio-cultural and health contexts,” he suggested. “In that case, we have to identify those areas and put in surveillance to see these things coming ahead.”

This article has been translated from the original into French.

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