Perspective - (2024) Volume 15, Issue 4
Received: 02-Jul-2024, Manuscript No. IPTB-24-14945; Editor assigned: 05-Jul-2024, Pre QC No. IPTB-24-14945 (PQ); Reviewed: 19-Jul-2024, QC No. IPTB-24-14945; Revised: 26-Jul-2024, Manuscript No. IPTB-24-14945 (R); Published: 23-Aug-2024
The COVID-19 pandemic has revealed significant variations in the severity of symptoms among those infected with the SARSCoV- 2 virus. While some individuals experience mild or asymptomatic cases, others develop severe and life-threatening conditions. These disparities have led scientists to investigate the underlying genetic factors that may influence the severity of COVID-19. One of the most promising areas of research is the study of genetic variants, particularly coding variants, which can provide insights into the biological mechanisms that affect disease outcomes.
Genetic variants and their classification
Genetic variants are differences in the DNA sequence that occur among individuals in a population. These variants can affect how genes function and how proteins are produced, influencing an individual’s susceptibility to diseases, including COVID-19. Genetic variants are typically classified based on their frequency in the population:
Common variants: These occur in more than 5% of the population. While individually they may have a small effect on disease risk, their combined impact can be significant.
Low-frequency variants: These occur in 1%-5% of the population. They can have moderate effects on disease risk.
Rare variants: These occur in less than 1% of the population. They often have a more substantial impact on disease risk but are less likely to be identified due to their low occurrence.
Ultra-rare variants: These occur in less than 0.1% of the population. These variants can have profound effects on health but are challenging to study due to their rarity.
The role of genetic variants in COVID-19 severity
Research into the genetic underpinnings of COVID-19 severity has identified several key areas where genetic variants play a role:
Immune response genes
The immune system is critical in fighting off viral infections and variations in immune response genes can influence how effectively an individual can respond to SARS-CoV-2.
Common variants: Studies have shown that common variants in the genes encoding cytokines and chemokines, which are signaling molecules involved in the immune response, can affect COVID-19 severity. For example, variants in the gene encoding Interleukin-6 (IL-6) have been associated with severe inflammatory responses in COVID-19 patients.
Rare and ultra-rare variants: Rare and ultra-rare variants in genes involved in the interferon response, such as TLR7, have been linked to severe COVID-19. Interferons are crucial for antiviral defense and deficiencies due to genetic variants can lead to a poor immune response to the virus.
ACE2 and TMPRSS2 genes
The SARS-CoV-2 virus enters human cells by binding to the ACE2 receptor and requires the protease TMPRSS2 to facilitate this process.
Common variants: Variants in the ACE2 gene can influence the receptor’s expression and function, potentially affecting viral entry and disease severity.
Rare and ultra-rare variants: Rare variants in TMPRSS2 have been identified that might alter the protease's activity, impacting the efficiency of viral entry and replication.
Blood clotting and cardiovascular genes
Severe COVID-19 is often associated with blood clotting disorders and cardiovascular complications.
Common variants: Genetic variants in clotting factor genes such as F5 and F2 have been linked to an increased risk of thrombosis in COVID-19 patients.
Rare and ultra-rare variants: Rare variants in genes involved in endothelial function, such as those affecting the nitric oxide pathway, can predispose individuals to severe cardiovascular complications in COVID-19.
Genomic studies and findings
Several large-scale genomic studies have been conducted to identify genetic variants associated with COVID-19 severity:
Genome-Wide Association Studies (GWAS): GWAS have identified several loci associated with severe COVID-19, including regions on chromosomes 3 and 9. These studies primarily focus on common variants and have revealed genes involved in immune response and lung function.
For example, a locus on chromosome 3 containing the gene SLC6A20 has been associated with severe respiratory failure in COVID-19 patients.
Whole-Exome Sequencing (WES) and Whole-Genome Sequencing (WGS): WES and WGS studies have been instrumental in identifying rare and ultra-rare coding variants. These studies sequence the entire exome or genome, providing a comprehensive view of an individual’s genetic makeup.
Rare variants in genes such as IFNAR2 and OAS1, which are involved in the antiviral response, have been linked to severe COVID-19 outcomes.
Candidate gene studies
These studies focus on specific genes of interest based on prior knowledge of their biological functions.
Variants in the gene encoding the Surfactant Protein D (SFTPD), important for lung function and immune defense, have been associated with increased COVID-19 severity.
The study of common, low-frequency, rare and ultra-rare coding variants has provided valuable insights into the genetic factors that influence COVID-19 severity. These findings have significant implications for personalized medicine, drug development and public health strategies. As research continues, it is crucial to address the challenges of diversity, environmental interactions and functional validation to fully understand the genetic underpinnings of COVID-19 and improve outcomes for affected individuals. By leveraging genetic information, we can enhance our preparedness for future pandemics and develop more effective interventions to combat infectious diseases.
Citation: Saha A (2024) Normal to Ultra-Rare Coding Variants Contribute to COVID-19 Severity. Transl Biomed. Vol.15 No.4: 033
