Scientists have developed a rapid blood test that can predict within a day of hospitalisation which patients with COVID-19 are at the highest risk of severe complications or death, an advance that may help identify those who may best benefit from specific investigational treatments.
The test, described in the journal JCI Insight, measures levels of mitochondrial DNA — a unique type of genetic material that normally resides inside the energy factories of cells.
According to the researchers from the Washington University School of Medicine at St. Louis in the US, mitochondrial DNA spilling out of cells and into the bloodstream indicates that a type of violent cell death is taking place in the body.
“Doctors need better tools to evaluate the status of COVID-19 patients as early as possible because many of the treatments are in short supply, and we know that some patients will get better without intensive treatments,” said study co-author Andrew E. Gelman.
“We need to understand why some patients, irrespective of their ages or underlying health in some cases, go into this hyperinflammatory death spiral. Our study suggests that tissue damage may be one cause of this spiral, since the mitochondrial DNA that is released is itself an inflammatory molecule,” Gelman added.
Viruses are known to cause a type of tissue damage called necrosis that is a violent, inflammatory response to the infection, the researchers said, adding that this may lead to cells breaking open and releasing their contents including mitochondrial DNA.
“In COVID-19 patients, there has been anecdotal evidence of this type of cell and tissue damage in the lung, heart and kidney. We think it’s possible that measures of mitochondrial DNA in the blood may be an early sign of this type of cell death in vital organs,” Gelman explained.
The scientists believe the new test could help predict disease severity and also act as a tool to better design clinical trials — identifying patients who might benefit from specific investigational treatments.
“We will need larger trials to verify what we found in this study, but if we could determine in the first 24 hours of admission whether a patient is likely to need dialysis or intubation or medication to keep their blood pressure from dropping too low,” said Hrishikesh S. Kulkarni, another co-author of the research.
In the study, the researchers assessed 97 patients with COVID-19, measuring their mitochondrial DNA levels on the first day of their hospital stays.
They found that mitochondrial DNA levels were much higher in patients who eventually were admitted to the ICU, intubated or died.
According to the study, this association held independently of a patient’s age, sex and underlying health conditions.
It noted that mitochondrial DNA levels were about tenfold higher in patients with COVID-19 who developed severe lung dysfunction or eventually died.
Those with elevated levels were almost six times more likely to be intubated, three times more likely to be admitted to the ICU and almost twice as likely to die compared with those with lower levels, the scientists said.
They said the test could also predict outcomes as well as, or better than, existing markers of inflammation currently measured in patients hospitalised with COVID-19.
According to the scientists, the test is quick to perform, returning results in less than an hour, and uses the same machinery that processes the standard PCR test for COVID-19.
They said the method allows mitochondrial DNA levels to be quantified directly from patient blood samples without requiring intermediate steps to extract the DNA from the blood.
The researchers hope to verify that the test is accurate in a larger multi-center trial before applying for approval from the US Food and Drug Administration.