Genetic factors that put some people at higher risk for severe illness and death due to Covid-19 infection have been identified by a global study of 57,000 people – including more than 50 patients in Ireland.
The global Genetics of Mortality in Critical Care Consortium, which includes St Vincent’s University Hospital (SVUH) in Dublin, found 16 genetic variants in people with severe Covid-19 that impacted on blood clotting, the immune response and the inflammation response. The findings were reported in the journal, Nature.
"This is additional information to identify the patients with the highest risk of death, those we need to keep in hospital for longer, or admit to the ICU sooner," says Prof Alistair Nichol, critical care consultant at SVUH, a co-author of the study led by the University of Edinburgh and Genomics England.
Nichol, who is director of the Irish Critical Care Clinical Trials Network at University College Dublin, led the local arm of the global study funded by the Health Research Board.
In the longer term, this landmark study – the first to link genes with outcomes across all critical care patients – opens the door to identifying which patients will respond best to existing treatments for severe Covid-19 as well as identifying new treatment options.
Clotting abnormalities
The study found a gene variant that disrupts a molecule critical for the immune response called interferon alpha-10. The presence of this gene increased risk of severe disease, and researchers believe treating patients with the gene with interferon can improve outcomes.
The study also found other genetic variants that control Factor 8 – a critical protein responsible for blood clotting. The absence of the variants for Factor 8 is associated with the presence of the most common form of haemophilia and may explain clotting abnormalities seen in many severe Covid-19 cases.
The pinpointing of genetic factors that put people at risk for Covid-19 opens the door to the development of new drugs or therapies that can neutralise such factors.
There are still people getting severely ill with the virus in Ireland, with 51 people on Tuesday being treated in ICU.
This study allows the identification of novel or repurposed therapeutics to improve outcomes in critically-ill Covid patients, says Nichol. “[It] gives us a much greater range of targets for the future. Covid will be with us for a long time, and we need to increase our range of therapeutics.”
In the future, a better understanding of the genetic factors that put people at greater risk of ending up in ICU with Covid-19 could herald the application of “precision medicine” to such critically ill people. But it would require development of a cheap, point-of-care, genomic test.
‘Risk of death’
“We could identify patients who would be at higher risk of death,” he points out. “We could use whole genome sequencing; this could be another determinant that doctors at the beside could take into consideration when making clinical decisions.”
SVUH is in negotiation with four other hospitals that are interested in joining the study. It is important that Irish patients take part in international research studies like this one, Nichol says, so doctors can have greater confidence its findings are applicable here. “This collaboration is another example of how scientists and clinicians have collaborated together to deliver important results in a time sensitive manner to improve outcomes.”
“We are able to see the goals of precision medicine in these results. Precision medicine hopes to tailor therapies not only to patients’ condition but also to their genetic and phenotypic responses to therapy,” he adds.