Potentially Useful Existing Drugs Suggested After GWAS Identification of Five Genes Associated with Most Severe Form of COVID-19; Work Called “Stunning Realization of the Promise of Human Genetics to Help Understand Critical Illness”

Existing drugs that could be repurposed to treat COVID-19 have been identified in a study highlighting genes linked to severe forms of the disease. Genes involved in antiviral immunity and lung inflammation have been pinpointed in the research, led by a scientist from the Roslin Institute of Scotland’s University of Edinburgh. The breakthrough should help doctors understand how COVID -19 damages lungs at a molecular level, and points towards existing drugs that could be effective against severe illness. Scientists studied the DNA of 2,700 patients in 208 intensive care units (ICUs) in the UK. Researchers from the GenOMICC (Genetics of Mortality in Critical Care) consortium--a global collaboration to study genetics in critical illness—used genome-wide association studies (GWAS) to compare the genetic information of COVID -19 patients in ICU with samples provided by healthy volunteers from other studies. The scientists found key differences in five genes--known as IFNAR2, TYK2, OAS1, DPP9, and CCR2--which may underlie why some people become severely sick with COVID -19, while others are not affected, or only moderately affected. Scientists were then able to predict the effect of drug treatments on patients, because some variations of the identified genes are known to respond in a similar way to particular drugs. For example, the scientists showed that a reduction in the activity of the TYK2 gene protects against COVID-19. A class of anti-inflammatory drugs called JAK inhibitors, which includes the drug baricitinib, produces this effect. The researchers also discovered that a boost in the activity of the gene INFAR2 could create protection, because it is likely to mimic the effect of treatment with interferon—a protein released by cells of the immune system to defend against viruses.