Rapid blood test identifies COVID-19 patients at high risk for serious diseases

One of the most disturbing aspects of the COVID-19 pandemic is the inability of doctors to predict which patients admitted to the hospital will develop serious illnesses, including complications involving the insertion of a breathing tube, kidney dialysis or other intensive care. need. Knowledge of the patient’s age and underlying medical conditions may predict such outcomes, but there are still surprises when younger, seemingly healthier patients experience serious complications that can lead to death.

Now scientists at the Washington University School of Medicine in St. Louis showed that a relatively simple and rapid blood test can be predicted within a day after hospitalization which patients with COVID-19 are most at risk for serious complications or death.

The study, published January 14 in JCI Insight, involved nearly 100 patients who had just been admitted to the hospital with COVID-19.

The blood test measures levels of mitochondrial DNA, a unique type of DNA molecule that normally lives inside the energy factories of cells. Mitochondrial DNA that leaks out of cells and into the bloodstream is a sign that a specific 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 deficient, and we know that some patients will get better without intensive treatments,” said co. – senior author Andrew E. Gelman, Ph.D., Jacqueline G. and William E. Maritz Endowed Chair in Immunology and Oncology in the Department of Surgery.

“There is so much we do not yet understand about this disease,” he added. “In particular, we need to understand why some patients, regardless of their age or underlying health in some cases, go into this hypinflammatory death coil. Our study suggests that tissue damage may be one cause of this coil, given the mitochondrial DNA released. itself an inflammatory molecule. ‘

According to the researchers, the test could serve as a way to predict the severity of diseases, as well as a tool to better design clinical trials, which can identify patients who could benefit from specific research treatments, for example. They also said they want to evaluate whether the test could be a way to monitor the effectiveness of new therapies. Presumably, effective treatments will 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 require dialysis or intubation or medication to prevent their blood pressure from dropping too low, would change how we want to trachea the patient, and it could change how we treat it much earlier in the disease, “said fellow senior author Hrishikesh S. Kulkarni, MD, an assistant professor of medicine.

The researchers, including co-authors Davide Scozzi, MD, Ph.D., a staff scientist, and Marlene Cano, Ph.D., a postdoctoral researcher, evaluated 97 patients with COVID-19 at Barnes-Jewish Hospital. . their mitochondrial DNA levels on the first day of their hospital stay. They found that mitochondrial DNA levels were much higher in patients who were eventually admitted to the ICU, intubated, or died. The researchers found that this association is maintained regardless of the patient’s age, gender, and underlying health conditions.

On average, mitochondrial DNA levels were approximately ten-fold 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 to those with lower levels.

Furthermore, the test predicted the results as well as better than existing markers of inflammation currently being measured in patients hospitalized with COVID-19. Most other markers of inflammation measured in patients with COVID-19, including those still under investigation, are, according to the researchers, general indications of systemic inflammation, rather than inflammation specific to cell death.

“Viruses can cause a type of tissue damage called necrosis, which is a violent, inflammatory response to the infection,” Gelman said. “The cell breaks open, releasing the contents, including mitochondrial DNA, which drives inflammation itself. In COVID-19 patients, there was anecdotal evidence of this type of cell and tissue damage in the lung, heart and kidney. We think it is possible. that measurements 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 can be performed quickly and easily in most hospital settings because it uses the same machinery as the standard PCR test for COVID-19. With the method they developed, mitochondrial DNA levels can be quantified directly in the blood. Without the need for intermediate steps to extract the DNA from the blood, the technique yielded results in less than an hour.

Before they can apply for approval from the Food and Drug Administration (FDA), scientists must verify that the test is accurate in a larger multi-center trial. They plan to expand the research to more sites.

The study used samples obtained from the School of Medicine’s COVID-19 biorepository, developed by co-authors Jane O’Halloran, MD, Ph.D., an assistant professor of medicine; Charles Goss, Ph.D., an instructor in biostatistics; and Phillip Mudd, MD, Ph.D., an assistant professor of emergency medicine.