A number of existing COVID-19 variants could have the potential to evade the immune system’s response in specific populations and minorities, a new study examining the immune system’s cytotoxic T cell response in the human body has found.
The peer-reviewed study entitled “Predicted impact of the viral mutational landscape on the cytotoxic response against SARS-CoV-2” was authored by Antonio Martín-Galiano of the Carlos III Health Institute, Spain and his research team, and was published in the PLOS Computational Biology journal on February 10 of this year.
The cytotoxic T cell is an effector cell that destroys virus-infected cells, tumor cells or tissue grafts in the human body as part of the overall immune system response. More specifically, it is an immune response that does not require antibodies and is therefore crucial in neutralizing SAR-CoV-2 infection in those without them.
The study examines the possibility that existing COVID-19 mutations could have developed the ability to evade the cytotoxic T cell response, as well as the likelihood of further mutations evolving and developing this ability.
The human T cell response is genetically encoded by human leukocyte antigen (HLA) molecules and therefore differs from group to group around the world as a result.
This, combined with the fact that there are thousands of possible epitopes – the portion of a foreign protein that is capable of stimulating an immune response – in the SAR-CoV-2 pathogens meant that it would not be feasible to track every single human immune response to every single viral variant. Instead, the research team developed a computational strategy to approach this issue.
In the first stage of the study, the research team determined the full set of epitopes from the original strain of COVID-19, first detected in Wuhan, China.
In doing so, they discovered 1,222 epitopes of SARS-CoV-2 that were associated with the main HLA subtypes, accounting for the HLA molecules of around 90% of the population. Therefore, they determined that at least 9 out of 10 people could launch a T cell response to the original coronavirus strain.
With this knowledge in hand, the research team then continued on to the next stage, working to determine whether or not the statistic changed as the virus evolved. The possibility of this occurring was high, as viruses are continuously evolving and are able to produce cytotoxic escape variants by reducing the effectiveness of, or even entirely deleting, HLA molecules.
In order to assess this possibility, the research team examined 117,811 COVID-19 isolates, looking to find mutations of the original Wuhan reference strain epitopes. All-in-all, the researchers found that 47% of the epitopes had mutated in at least one existing isolate. Many of these mutations were responsible for the deletion or alteration of HLA molecules, as they had suspected.
Following this, they set out to determine the exact nature of these alterations and deletions, examining whether or not there was a pattern as to which HLA types they targeted, which would allow them to understand if certain populations would be more vulnerable to this type of immune system evasion.
By analyzing the different HLA gene variants and finding which ones were more susceptible to cytotoxic T cell evasion, the team was able to find recurring patterns in certain regions of the world.
It was with this method that they discovered that populations in sub-Saharan Africa, and East and Southeast Asia may be more susceptible to the coronavirus putting pressure on the cytotoxic T cell response, making them unable to launch an immune response.
While the findings are significant when it comes to understanding the individual immune response to COVID-19, the researchers have indicated that at present, the accumulation of these mutations in independent isolates is too low to threaten the global human population. This means that currently, no COVID-19 variant exists that could bypass the cytotoxic T cell response entirely in all HLA subtypes.
However, what the research has shown is that certain communities and populations are more vulnerable to this phenomenon. This knowledge will allow for closer monitoring and a greater understanding of what could be causing local outbreaks and how to prevent them.
“Given the slow pace of vaccination in some geographic regions, enhanced primary infection by strains that evade immune detection might worsen the significant health and socioeconomic burden caused by the COVID-19 pandemic,” explains the author of the study.
“The knowledge acquired here may help to understand the current status of the human cytotoxic defense in the context of the pandemic and to promptly identify emerging strains that require close monitoring.”