Covid-19: Some individuals are genetically predisposed to severe disease

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  • Some individuals display severe Covid-19 symptoms
  • A new study suggests that these individuals are genetically predisposed to severe disease
  • This is due to the inherited makeup of their immune systems

In some people, Covid-19 infection causes severe disease accompanied by symptoms like high fever, severe cough, fatigue and shortness of breath. 

While it is known that certain underlying conditions can put one at risk for severe disease, it was only recently revealed in a new study that some people have a genetic predisposition to severe Covid-19. Findings were published in the journal Frontiers in Immunology

Fighting off viral infections

T-cells are vital for immune function – they are the part of the immune system that focuses on protecting the body from viral infections like Covid-19.

Human leukocyte antigen (HLA) class I molecules – a kind of cell-surface protein – also play a crucial role in developing an immune response to viral infections by revealing viral peptides (proteins) for T-cells to recognise and kill infected cells. 

The present study investigated the importance of HLA-I molecules to fight off Covid-19. 

“We explored whether HLA class I genotypes can be associated with the critical course of Coronavirus Disease-19 by searching possible connections between genotypes of deceased patients and their age at death,” the researchers explained. 

The ability of HLA-I molecules to present viral peptides depends largely on genetics, meaning that one inherits unique HLA-I molecules from one's parents.

Some people have genetic variants that are good at detecting a virus, which leads to immune cells easily destroying infected cells. Conversely, others have sets of HLA-I that are not good at detecting viruses, which means that they will tend to have more severe forms of disease.  

The interconnection between genotypes and Covid-19 severity

The researchers used machine learning to construct a model that can assess the ability of T-cell to respond to Covid-19 infection. 

The study involved 111 deceased patients, and 428 healthy individuals were identified with next-generation sequencing to act as the control group. 

“Deceased patients were split into two groups according to age at their time of death: 26 adult patients aged below 60 and 85 elderly patients over 60,” the researchers explain in their paper.

“With the use of HLA class I genotypes, we developed a risk score (RS) which was associated with the ability to present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides by the HLA class I molecule set of an individual.”

High-risk scores mean poor outcomes 

When HLA-I gene variants successfully presented viral peptides in an individual, they received a low-risk score, and vice versa. 

Results of the study indicate that the model used successfully depicts the link between genotypes and Covid-19 severity. The researchers observed higher risk scores in patients suffering from severe Covid-19, whereas scores were significantly lower in patients with milder symptoms.   

“In addition to the discovered correlations between the genotype and Covid-19 severity, the suggested approach also helps to evaluate how a certain Covid-19 mutation can affect the development of T-cell immunity to the virus.

For example, we will be able to detect groups of patients for whom infection with new strains of SARS-CoV-2 can lead to more severe forms of the disease,” said Alexander Tonevitsky, one of the affiliated researchers. 

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