Five genes associated with the most severe form of COVID-19 have been identified by researchers at the University of Edinburgh, highlighting potential treatments, according to a report in Nature (11 December 2020).
The team from the GenOMICC consortium — a global collaboration studying genetics in critical illness — analysed the DNA of 2,244 patients admitted to intensive care units (ICU) with COVID-19 in the UK. They compared the genetic information from these patients with samples provided by healthy volunteers from other studies, such as UK Biobank, Generation Scotland and 100,000 Genomes.
The researchers found key differences in five genes — IFNAR2, TYK2, OAS1, DPP9 and CCR2 — and used their findings to predict the effect of drug treatments on patients.
For example, they found that a reduction in the activity of the TYK2 gene protected against COVID-19 and that anti-inflammatory JAK inhibitors, such as baricitinib, could mimic this effect. They also found that boosting the activity of the gene INFAR2 with interferon could also protect against COVID-19.
“Just like in sepsis and influenza, in COVID-19, damage to the lungs is caused by our own immune system, rather than the virus itself,” explained Kenneth Baillie, the study’s chief investigator.
“Our genetic results provide a roadmap through the complexity of immune signals, showing the route to key drug targets.
“Our results immediately highlight which drugs should be at the top of the list for clinical testing.”
- 1Pairo-Castineira E, Clohisey S, et al. Genetic mechanisms of critical illness in Covid-19. Nature Published Online First: 11 December 2020. doi:10.1038/s41586-020-03065-y