Scientists at Washington University School of Medicine in St. Louis have found that a rapid blood test can predict which patients with coronavirus disease 2019 (COVID-19) have the highest risk of severe complications or death within a day of a hospital admission. Knowledge of a patient’s age and underlying medical conditions can help predict such outcomes, but there are still surprises when younger, healthier patients suffer severe complications that can lead to death, according to the researchers.

The study included approximately 100 patients newly admitted to the hospital with COVID-19. The blood test measures levels of mitochondrial DNA, which is a unique type of DNA molecule that normally resides inside the energy factories of cells. Mitochondrial DNA spilling out of cells and into the bloodstream is a sign that a particular type of violent cell death is taking place in the body, according to the study.

“Doctors need better tools to evaluate the status of COVID-19 patients as early as possible because many of the treatments—such as monoclonal antibodies—are in short supply, and we know that some patients will get better without intensive treatments,” said co-senior author Andrew E. Gelman, PhD, in a press release.

Gelman added that there are still significant knowledge gaps to overcome in the understanding of COVID-19.

“In particular, we need to understand why some patients, irrespective of their ages or underlying health in some cases, go into this hyperinflammatory death spiral,” Gelman said in a press release. “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.”

The researchers said that the test could serve as a way to predict disease severity as well as a tool to better design clinical trials, identifying patients who might, for example, benefit from specific investigational treatments. Further, the team said they would like to evaluate whether the test could serve as a way to monitor the efficacy of new therapies, since effective treatments would lower mitochondrial DNA levels, according to the study authors.

“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, that would change how we triage the patient, and it might change how we manage them much earlier in the disease course,” said co-senior author Hrishikesh S. Kulkarni, MD, in a press release.

The researchers evaluated 97 patients with COVID-19 at Barnes-Jewish Hospital, 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. Further, the researchers found this association held independently of a patient’s age, sex, and underlying health conditions.

Mitochondrial DNA levels were approximately 10 times higher in patients with COVID-19 who developed severe lung dysfunction or who eventually died. Those with elevated levels were approximately 6 times more likely to be intubated, 3 times more likely to be admitted to the ICU, and nearly twice as likely to die compared with those with lower levels.

The test predicted outcomes as well as or better than existing markers of inflammation currently measured in patients hospitalized with COVID-19. Most other markers of inflammation measured in patients with COVID-19, including those still under investigation, are general markers of systemic inflammation rather than inflammation specific to cell death, according to the study authors.

“Viruses can cause a type of tissue damage called necrosis that is a violent, inflammatory response to the infection,” Gelman said in a press release. “The cell breaks open, releasing the contents, including mitochondrial DNA, which itself drives inflammation. 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.”

The researchers emphasized that the test is quick and straightforward to perform in most hospital settings because it uses the same machinery that processes the standard PCR test for COVID-19. They said the method they developed allows mitochondrial DNA levels to be quantified directly in the blood. Without requiring intermediate steps to extract the DNA from the blood, the technique returned results in less than an hour.

The test will need to be verified in a larger, multi-center trial before it can be considered for approval by the FDA, according to the study authors.

REFERENCE
Rapid blood test identifies COVID-19 patients at high risk of severe disease. Washington University School of Medicine in St. Louis. https://medicine.wustl.edu/news/rapid-blood-test-identifies-covid-19-patients-at-high-risk-of-severe-disease/. Published January 15, 2021. Accessed January 18, 2021.