Mitochondrial DNA is Early Marker of Severe COVID-19 Illness

Mitochondrial DNA (MT-DNA) levels assessed within a day of patients’ hospitalization for COVID-19 were highly elevated in those who ultimately died, required intensive care, intubation, or vasopressor or renal replacement therapy in comparison to those without these complications. After further validation, this testing, performed in about an hour using standard reverse transcription-polymerase chain reaction (rt-PCR) but without a DNA purification step, could give doctors a tool to know better when to implement treatments such as monoclonal antibodies.

Viral infections can trigger cellular necrosis, which releases MT-DNA and other MT-damage associated molecular patterns known to cause acute lung injury and systemic inflammation. With these pathologies found in COVID-19, the authors questioned whether elevated levels of circulating MT-DNA might be a risk factor for severe disease.

The blood samples of 97 patients with laboratory-confirmed SARS-CoV-2 infection admitted to Barnes-Jewish Hospital in St. Louis underwent two rounds of centrifugation to generate platelet poor plasma. The investigators then performed rt-PCR using a BioRad CFX-Connect instrument to measure MT-DNA levels.

The researchers found that MT-DNA levels were about 10-times higher in those who developed acute respiratory failure or eventually died. After multivariate analysis adjusting for age, sex, and comorbidities, MT-DNA remained an independent risk factor for mortality (2.24 adjusted odds ratio (OR); 1.28–4.16 95% confidence interval (CI); p value 0.015), intensive care admission (3.97 adjusted OR; 1.83–10.34 CI; p value 0.002), and intubation (8.48 adjusted OR; 3.48–27.33 CI; <0.0001 p value).

In comparison to other markers of inflammation typically measured in COVID-19 patients, including C-reactive protein, ferritin, lactase dehydrogenase, and D-dimer, MT-DNA levels yielded similar or improved area under the receiver operator characteristic (AUROC) for key outcomes (mortality and intensive care, similar AUROC of 0.68 and 0.75, respectively; intubation, superior AUROC at 0.86%).