Genes can determine whether COVID-19 symptoms are serious
When some people are infected with coronavirus, they will only have mild or undetectable cases of COVID-19. Others will have severe symptoms and need to struggle with the help of a ventilator for several weeks if they can survive.
Despite the joint efforts of scientists around the world, doctors still do not know why this is so. Can genetic differences explain the differences in COVID-19 symptoms and severity?
To verify this, the researchers used computer models to analyze known genetic variations in the human immune system. Their modeling results indicate that, in fact, there are differences in people's DNA, which may affect their ability to respond to SARS-CoV-2 infection.
When the virus infects human cells, the body activates an anti-virus alert system. These alerts recognize virus intrusion and tell the immune system to send cytotoxic T cells (a type of white blood cell) to destroy infected cells, hoping to slow down the infection.
But not all alarm systems are the same. People have different versions of the same gene--called alleles--some of which are more sensitive to certain viruses or pathogens than others.
To test whether the different alleles of the alert system could explain certain areas of the SARS-CoV-2 immune response, the researchers first retrieved a list of all the proteins that make up the coronavirus from an online database.
They then used existing computer algorithms to predict the effectiveness of different versions of the anti-virus alert system to detect these coronavirus proteins.
Why it matters
The part of the alarm system that the researchers tested is called the Human Leukocyte Antigen System, or HLA for short. Everyone has multiple alleles that make up the HLA type. Each allele encodes a different HLA protein. These proteins are sensors of the alarm system. They are combined with various peptide chains to detect intruders. The peptide chains are the proteins that make up the coronavirus part, and these peptide chains are foreign to the body.
Once the HLA protein binds to the virus or viral fragment, it transports the invader to the cell surface. These "marked" infected cells will be killed by immune cells.
In general, the more viral polypeptides detected by human HLAs, the stronger the immune response. We think of it as a more sensitive sensor in an alarm system.
The researchers' modeling results predict that some HLA types can bind a large number of SARS-CoV-2 peptides, while other HLA types can only bind a few SARS-CoV-2 peptides. In other words, some sensors may be more suitable for SARS-CoV-2 than others. If this is true, then a person's HLA allele may be a factor that affects his immune system's immune response to COVID-19.
Because the study used only one computer model to make these predictions, they decided to use clinical information from the 2002-2004 SARS outbreak to test the results.
They found similarities in the effectiveness of alleles in identifying SARS and SARS-CoV-2. If the HLA allele does not seem to be good at identifying SARS-CoV-2, then it is also not good at identifying SARS. Their analysis predicts that an allele called B46: 01 is particularly harmful to SARS-CoV-2 and SARS-CoV. To be sure, previous research has shown that people who carry this allele are more likely to be infected with SARS virus and have a higher viral load than people who carry other HLA genes.
Based on their research, the researchers believe that mutations in the HLA gene are partly responsible for the huge differences in the severity of infection among many COVID-19 patients. These differences in HLA genes may not be the only genetic factors that affect the severity of COVID-19, but they may be an important part of this problem. It is necessary to further study how HLA types affect the severity of COVID-19 clinically, and to test these predictions through actual cases. Understanding how HLA type mutations affect the clinical course of COVID-19 can help identify people at high risk for the disease.
To the knowledge of the researchers, this is the first study to evaluate the relationship between viral proteins through a wide range of HLA alleles. Researchers currently know very little about the relationship between many other viruses and HLA types. In theory, researchers can repeat this analysis to better understand the genetic risks of many viruses that currently or may infect humans.
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