Identifying Host Genetic Factors in COVID-19 with NGS

22 October 2020 Roche

As the novel coronavirus SARS-CoV-2 continues to spread, Roche has remained committed to understanding the mechanism by which the virus interacts with the human genome and improving healthcare response to COVID-19. By using next-generation sequencing (NGS), scientists can become more informed about how host genetic factors play a role in disease severity and susceptibility. 

Coronaviruses (CoV), which are named after the crown-like spikes on its surface, are a large family of zoonotic viruses that can be transmitted between animals and people.1,2 The current, novel coronavirus disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Identifying host genetic factors could lead to improved diagnostics and treatments not only for COVID-19 but also for other viruses that will emerge in the future.

Host Genetic Factors & NGS

It is unclear why COVID-19 causes such a broad spectrum of illness in patients. Some patients will be asymptomatic. While in others, the disease is deadly. With a wide range of symptom severity, comorbidity risk, and immune response, human genetic variation may contribute to such differences. NGS enables researchers to sequence and analyze genomic information, and could help determine which host genetic factors impact susceptibility and severity of COVID-19.3

Researchers have begun to evaluate the molecular genetics of the virus, specifically how SARS-CoV-2 targets host tissues and gene expression in cells. For example, scientists have used single-cell RNA-sequencing (scRNA-seq) datasets to evaluate the target SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2), which is how SARS-CoV-2 internalizes into epithelial cells in the lungs and other organs.4

Numerous host genetic factors could play a role in SARS-CoV-2 susceptibility and COVID-19 severity,3-8 including:

  • HLA (Human leukocyte antigen)

  • Gene variants in ACE2, APOE (Apolipoprotein E) e4 allele, interferon-induced transmembrane protein-3

  • Innate immunity factors

  • ABO blood group

  • Other unknown genetic polymorphisms

Furthermore, international collaborations look to evaluate other molecular genetic determinants and variations such as virus-specific T-cell receptor (TCR) sequences, cytokine and chemokine profiling, and humoral immunological signature of the human virome.7

By identifying specific host genetic factors with NGS to determine disease susceptibility and severity, more reliable and efficient diagnostic tests and treatment strategies can be developed. 

Roche’s Commitment to NGS during COVID-19

“The ingenuity of NGS has led to rapidly understanding SARS-CoV-2; detecting the presence of the virus, tracking viral spread and understanding human vulnerabilities,” said William LaRochelle PhD, Clinical Science Director at Roche Sequencing Solutions. “NGS enables better decision-making during disease management and tremendously contributes to therapeutic and vaccine development by enhancing our understanding of the underlying pathways of how the virus impacts human health.”

Roche has remained steadfast in battling this global pandemic, and supporting scientists and healthcare providers with a broad portfolio of NGS products to study COVID-19. Identifying host genetic factors could help unravel the molecular mechanisms behind SARS-CoV-2 infection and stop the transmission of COVID-19.

Related article:
Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series.

 

References

  1. https://www.niaid.nih.gov/diseases-conditions/coronaviruses. Accessed August 2020.
  2. https://www.cdc.gov/coronavirus/types.html. Accessed August 2020.
  3. The COVID-19 Host Genetics Initiative. Eur J Hum Genet. 2020;28: 715–718.
  4. Ziegler C. et al. Cell. 2020 May 28;181(5): 1016–1035.e19.
  5. Kuo C-L. et al. J Gerontol A Biol Sci Med Sci. 2020 May 26;glaa131.
  6. Zhang Y. et al. J Infect Dis. 2020 Jun 16;222(1):34-37.
  7. https://www.niaid.nih.gov/research/immune-response-covid-19. Accessed August 2020.
  8. Ellinghaus D. et al. N Engl J Med. 2020 Jun 17;NEJMoa2020283.