Researchers from PrecisionLife have published a preprint study on medRxiv detailing their findings, which arose from a study that sought to identify genetic risk factors for sepsis especially in the context of COVID-19. The researchers sought to use their insights to identify existing drugs that might be used to treat life-threatening late-stage disease.
“Our high-resolution genomic analysis tools have allowed us to develop new insights into two serious and complex diseases for which new therapeutic options are urgently required,” PrecisionLife Co-founder and CEO Steve Gardner, PhD, said in a statement.
“We hope that these will lead to better understanding of what drives sepsis in COVID-19 patients and result in new ways to treat seriously ill patients,” added Gardner, the study’s corresponding author.
The researchers used datasets compiled by the UK Biobank to identify genes associated with sepsis, which has been seen in up to 59% of hospitalized COVID-19 patients, with a mortality rate of approximately 20%.
Investigators identified mutations in 70 sepsis risk genes, 61% of which were also present specifically in severe COVID-19 patients. Several of the disease associated genetic signatures found in both sepsis and severe COVID-19 patients have previously been linked to cancer, immune response, endothelial and vascular inflammation and neuronal signaling, PrecisionLife said.
Thirteen of the sepsis risk genes—which the study showed were also COVID risk genes—have been known to be druggable since they are targeted by active chemical compounds found in found in DrugBank or ChEMBL, and thus represent potential drug repurposing opportunities. The study identified 59 drug candidates known to be active against the 13 targets.
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“We will be using these new insights into the disease to investigate several novel therapeutic strategies that may help to reduce the high mortality rates currently observed in patients who develop sepsis both within and without the context of COVID-19,” the researchers concluded. “We continue to investigate the overlap between these sepsis-associated genetic signatures and those seen in COVID19-positive patients who present with life-threatening symptoms, including the development of viral sepsis.”
As more data from COVID-19 patients becomes available, that data may help lead to greater understanding into the mechanisms of late-stage disease and apparent clinical differences in patient responses to the SARS-CoV-2 virus, the investigators added.
According to PrecisionLife, previous studies failed to identify more than a handful of genetic variants that predispose individuals to developing sepsis.
