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New COVID-19 study identifies variants that could escape our immune response

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In a new COVID-19 study, scientists discovered changes in the virus that causes Coronavirus that could let it evade the immune system in certain groups of people.

SARS-CoV-2 strains currently in circulation, as well as future variants that may emerge, have the ability to evade the immune system’s cytotoxic T cell response in some people.

Antonio Martn-Galiano of the Carlos III Health Institute in Spain and colleagues came at this conclusion in a new modeling study published today in PLOS Computational Biology.

HLA molecules encode the T cell response in humans; this means that different people have distinct HLAs, which are trained to recognize invading infections based on different components, or “epitopes,” of the pathogens.

With thousands of distinct HLA molecules in the human population and thousands of possible epitopes in any particular virus, it’s impossible to test every human HLA allele’s immune response to every viral variant in an experimental setting.

Computational methods, on the other hand, can make this process easier.

Researchers determined the whole collection of epitopes from an original reference strain of SARS-CoV-2 from Wuhan, China, in the current study. The researchers detected 1,222 SARS-CoV-2 epitopes associated with major HLA classes, representing over 90% of the human population; these 1,222 epitopes can trigger a T cell response to COVID-19 in at least 9 out of every 10 people.

The researchers then used a computer program to look for changes in these epitopes in 118,000 different SARS-CoV-2 isolates from around the world that were described in a National Center for Biotechnology Information (NCBI) dataset. They discovered that at least one existing strain had mutated 47 percent of the epitopes. Existing isolates exhibited mutations in numerous epitope locations in certain cases, but cumulative mutations for any given HLA allele type never affected more than 15% of epitopes. When the researchers looked at susceptible alleles and the geographic origins of their respective escape isolates, they discovered that they co-existed in some areas, such as Sub-Saharan Africa and East and Southeast Asia, implying that the cytotoxic T cell response may be under genetic pressure in these areas.

“The accumulation of these changes in independent isolates is still too low to threaten the global human population,” the authors add. “Our protocol has identified mutations that may be relevant for specific populations and warrant deeper surveillance.”

However, “unnoticed SARS-CoV-2 mutations” may in the future “threaten the cytotoxic T response in human subpopulations,” according to Martn-Galiano.

Source: 10.1371/journal.pcbi.1009726

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