How Genes Influence The Risk of Severe COVID-19?

Coronavirus disease 2019 (COVID-19) is a highly contagious, potentially fatal respiratory illness caused by the coronavirus (SARS-CoV). It was first identified in Wuhan, China, in December 2019, and later rapidly spread worldwide. On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a pandemic disease.

How is COVID-19 Transmitted?

COVID-19 is likely to transmit through:

1. Respiratory droplets when an infected person coughs or sneezes
2. By touching surfaces contaminated by the virus and then touching the eyes, nose, or mouth.
3. From close contact with an infected person.

Signs and Symptoms

The symptoms of COVID-19 can vary in severity - from very mild to severe illness.

In about 80% of affected people, it causes only mild symptoms.

Some common symptoms include:

1. Shortness of breath or breathing difficulties
2. Fever or chills
3. Cough
4. Fatigue
5. Muscle or body aches
6. Headaches
7. Sore throat
8. Loss of taste or smell
9. Congestion or runny nose
10. Nausea or vomiting

These symptoms may appear between two and fourteen days after exposure to the virus. Children have similar but usually milder symptoms than adults. Older adults and people with severe underlying medical conditions like heart or lung disease or diabetes are at higher risk of more serious complications from COVID-19.

According to the Chinese Center for Disease Control (CCDC), COVID-19 death cases were already suffering from 10.5% cardiovascular disease, 7.3% for diabetes, 6.3% for chronic respiratory disease, 6.0% for hypertension, and 5.6% for cancer.

Role of Genetics in COVID-19

Genes can determine an individual’s susceptibility to infectious diseases such as COVID-19. They also influence the chances of developing complications from these infections.

Some individuals who get infected remain asymptomatic. Some may develop mild symptoms, while others experience severe symptoms that require hospitalization. These inter-individual differences might be influenced by both genetic and non-genetic factors (environmental/lifestyle).

Research studies have documented that the SARS-CoV-2 virus enters the body by interacting with the ACE2 protein present on the outer surface of certain cells. Certain variants of the?ACE2?gene may prevent the SARS-CoV-2 virus from entering cells, thus decreasing a person’s vulnerability to the virus. Variants in?LZTFL1, ABO, ACE2, HLA, DPP9, OAS3, IFNAR2, TYK2, and other genes have also been correlated with COVID-19 severity.

A recent genome-wide association study of COVID-19 has shown a significant association of?COVID-19 severity with a multigene locus at 3p21.31 and the ABO blood group locus at 9q34.2.

The?LZTFL1?Gene

The?LZTFL1?gene contains instructions to produce a protein widely expressed in the cytoplasm (the fluid that fills the cells) and cilia (hair-like projection found on the surface of the cells). It is involved in protein trafficking (transport) to the ciliary membrane. It functions as a tumor suppressor by interacting with E-cadherin and the actin cytoskeleton, thereby regulating the transition of epithelial cells to mesenchymal cells [ECM].

rs11385942 and COVID-19 Severity

The rs11385942 is an indel (insertion-deletion) variation located in the intronic region of the?LZTFL1?gene. Studies have shown that the frequency of minor risk allele (A) was higher among patients receiving mechanical ventilation than those receiving supplemental oxygen only. This finding indicates that this risk allele confers a predisposition to the most severe forms of COVID-19.

The?ABO?Gene

The?ABO?gene contains instructions to produce an enzyme called glycosyltransferase that transfers specific sugar residues to?H substance?and is responsible for the formation of antigens in blood groups A and B. Certain variants in the?ABO?gene are associated with an?increased risk for certain cancers and cardio-cerebrovascular disease.

Furthermore, recent studies have documented that blood groups may play a key role in determining the susceptibility and severity of COVID-19. According to a study,?people with an A blood group are associated with an increased risk of acquiring COVID-19, whereas people with an O blood group are associated with a lower risk.

rs657152 and COVID-19 Severity

The rs657152 is a C>A polymorphism in the?ABO?gene, which may influence several biological molecules, including LDL cholesterol, liver-derived alkaline phosphatase, and interleukin-6, thus contributing to the occurrence and development of the disease.

Based on a GWAS that studied COVID-19 severity,?the rs657152 risk allele (A) was significantly associated with a higher risk of a severe COVID infection.

rs657152 and COVID-19 Severity

The rs657152 is a C>A polymorphism located in the intronic region of the?ABO?gene, which may influence several biological molecules, including LDL cholesterol, liver-derived alkaline phosphatase, and interleukin-6, thus contributing to the occurrence and development of the disease.

Based on a GWAS that studied COVID-19 severity,?the rs657152 risk allele (A) was significantly associated with a higher risk of a severe COVID infection.

Summary

1. Coronavirus disease 2019 (COVID-19) is defined as an illness caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
2. COVID-19 can be transmitted through respiratory droplets, touching contaminated surfaces and touching your mouth, and from close contact with the affected person.
3. Some signs and symptoms of COVID-19 are coughs, fatigue, fever, shortness of breath, and loss of smell and taste.
4. A person's genetic makeup can influence, to an extent, influences the risk of catching COVID-19, as well as the severity of the disease.
5. The virus enters the body by interacting with the ACE2 protein produced by the ACE2 gene.
6. In some individuals, the ACE2 gene produces a higher number of ACE2 proteins and increases both the risk and severity of COVID-19.
7. Other genes like ABO, LZTFL1, and HLA have also been correlated with COVID-19 severity.

First appeared in https://www.xcode.life/covid-19/how-does-genetics-infulence-the-risk-of-severe-covid-19/