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High levels of mitochondrial DNA potential marker for severe COVID-19

Mitochondrial DNA is inflammatory nucleic acids released by damaged organs and could represent a potentially useful marker for the identification of patients who develop more severe COVID-19 infection.

Research has shown that viral infections are able to trigger cellular necrosis. This effect both inhibits further viral replication but is also associated with the release of damage associated molecular patterns (DAMPs), which are essentially “danger” molecules which activate the innate immune system. This ultimately drives the expression of inflammatory cytokines which is an important feature of infections. Mitochondrial DNA (MT-DNA) is one such DAMPs and has been shown to be elevated in the plasma of patients with acute respiratory distress syndrome (ARDS) and the multi-organ dysfunction seen during sepsis. Given the association between MT-DNA and ARDS, researchers from the Division of Cardio-thoracic Surgery, Washington University School of Medicine in the US, wondered if the presence of elevated levels of MT-DNA could be a marker for the development of severe COVID-19. The authors used cell-free plasma from patients with confirmed COVID-19 and measured levels of MT-DNA within the first 24 hours of presentation at an emergency department. The primary outcome for the study was mortality and the authors used multivariate regression to determine whether MT-DNA levels were independent of other known risk factors for COVID-19.

In total, 97 adults were included in the study with a median age of 65 years and with just over half (55.7%) who were male. The primary outcome of mortality was observed in 25.8% of the subjects who were generally older, smokers and with a higher incidence of co-morbidities. In addition, 56.7% of participants required admission to an intensive care unit. After adjustment for independent risk factors of death, e.g., age, sex and co-morbidities, the authors found that circulating levels of MT-DNA were associated with an increased risk of mortality (odds ratio, OR = 2.24, 95% CL 1.29 – 4.16, p = 0.006). Higher levels of MT-DNA were also associated with a greater risk of requiring intensive care admission and intubation.

Commenting on their findings, the authors noted that high levels of circulating MT-DNA are an early and independent risk factor for severe illness and mortality in those hospitalised with COVID-19. They concluded that MT-DNA measurement early in the disease course appears to predict survival status and the requirement for intensive care and called for further studies to examine their findings.

Scozzi D et al. Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19. JCI Insight 2021