A number of variants of SARS-CoV-2 have emerged from immunocompromised hosts, research shows. The variants of concern – including B.1.1.7, a variant first identified in Kent – are believed to have been the result of long-term infection in people with weakened immune systems.
Persistent infections in people who are immunocompromised can cause the virus to mutate more often because a person’s immune system cannot clear the virus as quickly as a healthy person’s immune system.
Authors Professor Wendy Barclay, Dr Thomas Peacock, Professor Julian Hiscox and Rebekah Penrice-Randal explain the importance of monitoring genetic changes in SARS-CoV-2 for future control of the virus: “As more and more variants appear , we improve our picture of their shared similarities and differences and can better predict what other newer variants will look like. Putting all this information together will also help us design booster vaccines that protect against as many variants as possible or design targeted diagnostics. “, they declared.
Their review examines where the mutations occurred, what part of the virus they affect, and how the resulting variants might impact vaccination efforts. According to the authors, mutations in SARS-CoV-2 are expected as the virus adapts to humans. “The sequencing of seasonal human coronaviruses has not been done on a scale like SARS-CoV-2, especially when it is believed to have initially spread to humans. SARS-CoV-2 is at the start of its journey in humans while other human coronaviruses have been around, in some cases, for many decades, ”they said.
Variants with the same or similar mutations have emerged independently in different countries: “SARS-CoV-2 is probably still finding its way into humans in terms of optimal infection and transmission. ‘epidemic and massive sequencing efforts will identify concomitant mutations’ Basically the virus is under the same kinds of selection pressures wherever you are in the world, and the epidemic was sown by the same original virus », Explained the authors.
Mutations of particular interest include those in the spike protein. This protein allows the virus to enter host cells and is the primary target of the immune system, including the immunity generated by all current SARS-CoV-2 vaccines.
Mutations in the gene that codes for the peak could change the shape of the protein, allowing it to no longer be recognized by the immune system. Because this protein is so important for the entry of SARS-CoV-2, favorable mutations are more likely to succeed and create new dominant variants of the virus.
Changes that give the virus an advantage can quickly become dominant. For example, a mutation, named D614G, was found in 80% of SARS-CoV-2 viruses sequenced just four months after its first detection. Now viruses without the D614G mutation are commonly seen only in parts of Africa.
Another mutation, N501Y, is found in the B.1.1.7 variant of SARS-CoV-2. It is believed that this mutation is the result of infection of an immunocompromised individual and may help make the virus more contagious. Infections with this variant have a higher death rate. In the UK, B.1.1.7 has become the dominant variant within three months and is now responsible for over 90% of infections there.
Significant mutations in spike proteins discussed in the review include:
In February 2020, a mutation was detected in the SARS-CoV-2 spike protein and named D614G. This mutation makes SARS-CoV-2 more infectious, but does not make the virus more harmful. This increase in infectivity led to a significant advantage in terms of fitness and in four months, 80% of the SARS-CoV-2 viruses sequenced worldwide were found to carry the mutation. Today, only parts of Africa have circulating viruses without the D614G mutation.
Despite initial concerns, D614G has no effect on vaccine efficacy and in some cases viruses with the D614G mutation are more easily cleared by antibodies to SARS-CoV-2.
By mid-2020, reports of mink infected by humans became common. In mink, the virus spike protein typically developed two mutations called Y435F and N501T. These mutations allow stronger binding of the virus to human receptor cells. Viruses carrying these mutations have been found in a cluster of human infections in Denmark, believed to originate from mink. Worryingly, this variant was able to infect people who had previously been infected with SARS-CoV-2 and who were believed to have some immunity to the virus. As a result, 17 million mink were slaughtered.
The Y435F mutation has also been reported to have developed in an immunocompromised person, possibly as a result of chronic infection with the virus allowing them to adapt.
In December 2020, a highly transmissible variant of the virus was isolated in Kent, UK. This variant, named B.1.1.7, contained a mutation in the spike protein called N501Y. Not only does this mutation make the virus more contagious, it has also been found to have a higher death rate. In the UK, B.1.1.7 is now the dominant variant and is responsible for over 90% of infections.
The N501Y mutation was found to have little effect on immunity to both vaccines and previous infections.
The mutation in the spike protein E484K has appeared in recent months, once in South Africa and at least twice in Brazil. Variants with the E484K mutation are able to evade the immune system of vaccinated and previously infected individuals.
It is believed that this mutation was due to high levels of immunity in the population, which led to mutations in the spike protein to escape the immune system. In Brazil, there have been several reports of healthcare workers and others with antibodies to SARS-CoV-2 reinfected with variants with the mutant E484K, raising concerns about vaccine protection against this virus. variant.
The review also examines mutations that modify other parts of the virus, such as ORF8, an accessory protein believed to suppress the host’s immune system. Viruses with a deletion in the gene that codes for ORF8 have been found to cause less severe clinical disease.
The review authors called for increased global efforts to monitor SARS-CoV-2 mutations. Currently, the UK and Denmark are disproportionately sequencing the SARS-CoV-2 genome. Regular surveillance of the virus allows early identification of emerging variants and allows researchers to identify associated mutations.
“Although genomic surveillance in Europe and the United States is quite strong, it is becoming clear in large parts of the world that we simply have no idea what variants are circulating. These are starting to appear in Europe in the form of imports or community epidemics. Better surveillance in a wider range of countries would allow us to better assess the risks of what the next stage of the pandemic might look like, ”the authors said. “If we are to monitor the emergence, spread and ongoing importation of potential mutants to escape vaccines, we must continue this effort or risk further waves of pandemic and vaccine failure.” In addition, understanding the genomic epidemiology of the virus as early as possible will allow us to rapidly develop updated vaccine boosters. “
Professor Alain Kohl, Deputy Editor-in-Chief of Journal of General Virology said: “The emergence of SARS-CoV-2 variants is one of the great challenges of the ongoing pandemic. This review article summarizes our current knowledge and understanding of the evolution of the virus, as well as its consequences – for example in terms of vaccination. It is of great interest to anyone who wants to know more about the history of this virus and what the future holds. “