Rapid Blood Test Identifies COVID-19 Patients at High Risk of Severe Disease
One of the most vexing aspects of the COVID-19 pandemic is doctors'
inability to predict which newly hospitalized patients will go on to
develop severe disease, including complications that require the
insertion of a breathing tube, kidney dialysis or other intensive care.
Knowledge of a patient's age and underlying medical conditions can help
predict such outcomes, but there are still surprises when younger,
seemingly healthier patients suffer severe complications that can lead
to death.
Now, scientists at Washington University School of
Medicine in St. Louis have shown that a relatively simple and rapid
blood test can predict -- within a day of a hospital admission -- which
patients with COVID-19 are at highest risk of severe complications or
death.
The study, published Jan. 14 in JCI Insight, involved nearly 100 patients newly admitted to the hospital with COVID-19.
The
blood test measures levels of mitochondrial DNA, 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.
"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, the Jacqueline G. and William E.
Maritz Endowed Chair in Immunology and Oncology in the Department of
Surgery.
"There's so much we still don't understand about this
disease," he added. "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. 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 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. They also said they would like to evaluate whether the test
could serve as a way to monitor the effectiveness of new therapies.
Presumably, effective treatments would lower mitochondrial DNA levels.
"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, an
assistant professor of medicine.
The researchers, including
co-first authors Davide Scozzi, MD, PhD, a staff scientist, and Marlene
Cano, PhD, a postdoctoral research scholar, 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. The researchers found this
association held independently of a patient's age, sex and underlying
health conditions.
On average, 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.
Further, 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
researchers.
"Viruses can cause a type of tissue damage called
necrosis that is a violent, inflammatory response to the infection,"
Gelman said. "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 also
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. 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.
Before they can
apply for approval from the Food and Drug Administration (FDA), the
scientists will need to verify that the test is accurate in a larger
multi-center trial. They have plans to expand the research to more
sites.
The study utilized samples obtained from the School of
Medicine's COVID-19 biorepository, which was developed by co-authors
Jane O'Halloran, MD, PhD, an assistant professor of medicine; Charles
Goss, PhD, an instructor in biostatistics; and Phillip Mudd, MD, PhD, an
assistant professor of emergency medicine.