New study reveals why different people experience varying intensity of COVID-19 symptoms

Over 41 million people in the world have been diagnosed with COVID-19 so far. Of these, over 30 million have recovered and more than 1.1 million have died.

While we know more about the disease now than we did a few months back, scientists are still not able to figure out why some people are less susceptible to SARS-CoV-2 and why people experience a varying intensity of the associated symptoms, ranging from being  asymptomatic to severely affected.

Now, a group of researchers at the University of Southern California claim that they have uncovered a possible reason for this variation.

The findings of their study, published in the journal Informatics in Medicine Unlocked, suggest the presence of certain genes and proteins that determine the susceptibility of a person to COVID-19 and the severity of disease once it is acquired.

An interplay between genes and proteins

Viruses are intracellular parasites meaning they need a living host to survive. Once inside your body, SARS-CoV-2 enters your body cells and takes over the cellular machinery to make copies of itself. The virus interacts with various proteins and genes inside the human body during this process.

For the study, the researchers investigated the expression profile of the human genes that interact with SARS-CoV-2, their variation by population, age and sex and in a normal (non-infected) population.

Gene expression: Most host genes interacting with SARS-CoV-2, particularly SFTPD, were highly expressed in the lungs, pointing to the unique susceptibility of the lung tissue. SFTPD is predicted to interact with SARS-CoV-2 spike protein. In contrast, blood that is less vulnerable to the infection has a different expression profile than that of the lungs. ACE2 and other proteases associated with viral entry in COVID-19 were expressed at higher levels in male gonads and gastrointestinal tract, suggesting the higher susceptibility of these tissues.

Splicing patterns: Human genome has various non-coding regions (those that do not produce proteins) interspersed with the coding regions (those that produce proteins). The non-coding regions help in the production of variable proteins depending on their need in body tissues by a process called splicing. During this process, introns or non-coding regions are removed from the coding regions or exons to make a single stretch of coding DNA. The researchers found that the splicing pattern was similar in the gastrointestinal tract and lungs, explaining why some people also experience digestive symptoms and weight loss.

Variation in population, gender, age

Not only in tissues but host genes interacting with SARS-CoV-2 were also found to be varying among the population. In particular, the researchers found the following genes to have major variation in expression in populations:

1. ACE2, CLEC4G, CLEC4M and CD209 - interact with the spike protein of SARS-CoV-2.

2. REEP6 - expressed in the olfactory epithelium

3. SLC27A2 and PKP2 - inhibit replication of the virus

4. PTGS2 - mediates fever response

Some proteases associated with SARS-CoV-2 entry into host cells also had multiple variants in different people. So did the SFTPD gene in the lungs.

Two genes called TIMM10 and ERGIC1 were expressed more in women than in men. The authors indicated that these genes are associated with the homeostasis of protein secretion in combating the virus.

The expression of about eight genes increased with age, suggesting the higher susceptibility of the elderly. ACE2 gene expression, in particular, was shown to increase slightly with every 10-year increase in age.

Some other genes that start to get expressed more with age include those responsible for hypoxia, uncontrolled inflammation or cytokine storm, oxidative stress and vitamin K biosynthesis. Low levels of vitamin K have been noted in COVID-19 patients and are associated with poor prognosis. Vitamin K deficiency promotes coagulopathy (impaired blood clotting leading to excessive blood clotting or bleeding), which is seen in severe COVID-19 patients.

Better treatment and prevention

In a news release by the University of Southern California, the researchers suggested that the findings of the study can be used to categorise risk groups and monitor disease progression in these groups. It could also help improve treatment efficiency and determine who needs to be given the vaccine first, once it is launched.

For more information, read our article on COVID-19. 

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