25 Jan COVID-19: Circulating Mitochondrial DNA Can Help Predict Disease Severity
MedicalResearch.com Interview with:
Marlene Cano MD. PhD.
Post-Doctoral Research Fellow in Pulmonary Transplant Immunology
Division of Pulmonary and Critical Care
Department of Medicine
Washington University/Barnes-Jewish Hospital
Saint Louis, MO
MedicalResearch.com: What is the background for this study? How does this test differ from other tests for COVID-19?
Response: We know COVID-19 causes a wide spectrum of disease, and that while many develop only mild uncomplicated illness, others develop severe respiratory failure, multi-organ failure and death. These patients often require prolonged hospitalization, ICU level care and even mechanical intubation for respiratory support. However, we still do not have a great way to identify which patients are likely to develop severe disease. We felt it was important to have a test that could act as sort of a ‘biomarker’ that we could measure early in COVID-19 patients and would help predict which patients would develop severe disease. From prior work, we knew that mitochondrial DNA, which are proinflammatory molecules that are released into the circulation from damaged organs could be this such ‘biomarker’. So, we measured the levels of mitochondrial DNA circulating in the plasma of patients with COVID-19 at the time they first presented to the hospital. Then we investigated if higher levels of mitochondrial DNA indeed predict the development of more severe disease.
Currently there are no ‘biomarker’ tests specific for COVID-19. We do currently measure levels of other markers in the hospital that we feel might help us assess overall how sick patients may be, but these are very non-specific and assess only level of inflammation. This test instead can measure level of tissue injury.
MedicalResearch.com: What are the main findings?
Response: Patients who had higher levels of mitochondrial DNA circulating in the plasma at the time they presented to the hospital were more likely to develop severe COVID-19 disease. These patients were more likely to require ICU level care and to develop multiorgan failure requiring mechanical ventilation for respiratory support, vasopressor drugs for cardiovascular support or even dialysis for kidney failure. They were also more likely to die.
Other factors such as age and comorbidities were also found to be independent risk factors for the development of severe COVID-19 disease, much as in other studies. However, we found that mitochondrial DNA was also an independent risk factor after we accounted for age and comorbidities in these patients. Importantly, because mitochondrial DNA was elevated in patients with more severe disease it also provides a window into the possible mechanisms by which SARS-CoV-2 causes organ damage.
MedicalResearch.com: What should readers take away from your report?
Response: That we still do not completely understand the reasons why some patients have mild disease and others have severe disease. However, we can measure biomarkers such as this that are released by damaged organs as a surrogate for level of tissue injury. They can help inform clinicians which patients are more likely to become sicker and may require hospitalization or higher level of care even if they don’t quite appear as sick during initial presentation to the hospital. These can also guide us as to what are the mechanisms that cause tissue injury in COVID-19 that lead to severe disease
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Future research will need to explore how to streamline this test so that it can be performed widely by clinical labs at the time COVID-19 patients present to the hospital. It should also examine the additional value of adding this test to currently used scoring systems that help predict the risk of developing severe disease or death in other diseases, such as SOFA or APACHE scores. Finally, future studies will also focus on understanding the mechanisms by which SARS-CoV-2 causes organ damage that results in release of mitochondrial DNA.
Any disclosures? None of the authors have any conflict of interest or any disclosures.
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