The COVID-19 pandemic is estimated to have caused over 4.6 million deaths so far. The predominant cause of mortality is pneumonia and severe acute respiratory distress syndrome. However, COVID-19 can cause multiple organ failure through cytokine release, microvascular and macrovascular thrombosis, endothelial damage, acute kidney injury and myocarditis.
Genome-wide association studies (GWAS) are used to identify genes and pathways that predispose to complex diseases like COVID-19, genetically validated drug targets are more likely to lead to approved drugs.
A recently published study by Downes and colleagues, published in the journal Nature genetics identified a gene that doubles the risks of respiratory failure and death from COVID-19 and could explain why people of south Asian heritage are more vulnerable to the disease.
The gene, which changes the way the lungs respond to infection, is the most important genetic risk factor identified so far and is carried by roughly 60% of people with south Asian backgrounds, compared with 15% of those with white European backgrounds. This could partially explain the excess deaths seen in some communities in the UK and the impact of COVID-19 in the Indian subcontinent.
A previous study identified a large portion of DNA that appeared to influence how severely ill people can get from COVID. The study by Downes and colleagues homed in on a single gene called LZTFL1, that according to their results doubles the risk of respiratory failure and death.
The gene acts as a switch to turn on a crucial defense mechanism that prevents SARS-CoV-2 from entering epithelial cells in the lung. In the high-risk version of the gene this response is blunted, allowing the virus to continue entering the cells, infecting them and damaging the lung.
The results could explain why these populations have been highly impacted by COVID-19, but some researchers think that it may also be caused by socioeconomic differences in these minority populations.
Hannah Devlin. (2021, Nov 4). Gene common in south Asian people doubles risk of Covid death, study finds. The Guardian. Retrieved from:
Downes, D.J., Cross, A.R., Hua, P. et al. Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus. Nat Genet 53, 1606–1615 (2021). https://doi.org/10.1038/s41588-021-00955-3