Genetic variation can play a role in determining which patients will develop severe illness from COVID-19 and which patients experience milder symptoms. Previous studies leveraging next generation sequencing technologies have identified some variants associated with more severe cases, which can aid in developing more effective therapeutic and diagnostic strategies for tackling the disease. Now, the largest-ever study of genetic COVID-19 risk, conducted by researchers from the Genetics of Susceptibility and Mortality in Critical Care (GenOMICC) Consortium, led by University of Edinburgh in partnership with Genomics England, has revealed 16 new variants associated with severe cases, leveraging data from more than 57,000 whole genome sequences.
The study involved the sequencing of genomes from 7,491 COVID-19 patients in 224 intensive care units across the United Kingdom, as well as 1,630 genomes of patients with mild COVID-19 cases. The other 48,400 genome sequences used in the study, from people who had not had COVID-19, came from Genomic England’s 100,000 Genomes Project, in which the genomes of 100,000 people with a rare disease or cancer were sequenced between 2014 and 2018. Comparing the genomes from this large pool of patients allowed the researchers to create a precise map and identify genetic variation linked to the severity of COVID-19 illness.
The result was the identification of 16 new genetic variants associated with severe illness, as well as the confirmation of seven other genetic variations already associated with COVID-19 severity in previous studies. One of the newly-discovered variants disrupts interferon alpha-10, a key messenger molecule in immune system signaling, and the researchers found this single variant was enough to increase a patient’s risk of severe disease. This highlights the gene’s key role in immune system function and suggests that treating patients with interferon may be a possible avenue for managing the disease in its early stage. Additionally, variations in genes that control levels of Factor 8, a central component of blood clotting, were also found to be associated with COVID-19 severity. This may explain some clotting abnormalities that have been seen in severe cases of COVID-19, the researchers said. The results of the study were published recently in Nature.
“Strategically, we’re at a point where genomic science is becoming an integral part of the national infrastructure in routine healthcare,” said Dr. Rich Scott, study co-author and chief medical officer at Genomics England. “This study illustrates the value of whole genome sequencing to detect rare and common variants that influence critical illness requiring intensive care. It represents a major leap forward in our understanding of how our genetic makeup influences severe illness with Covid-19.”