In 2019, a new coronavirus (SARS-CoV-2) was identified in China and had
rapidly spread across the world. Its associated disease, coronavirus disease 2019
(COVID-19), has led to millions of deaths in 2020-2021. Studies have been
demonstrating that SARS-CoV-2 induces a systemic hyperinflammatory state, which is
associated with a decreased cytotoxic capacity and impaired Type I interferon (IFN)
response. Moreover, iron dysfunction/hyperferritinemia in association with
hyperinflammation leads to oxidative stress and apoptosis. Altogether, these cellular
events contribute to COVID-19 severity. In viral infections, systemic and cellular
alterations can promote mitochondrial dysfunction. In this regard, dysfunctional
mitochondria can trigger the immune response, leading to the release of mitochondrial
damage-associated molecular patterns, including mitochondrial DNA (mtDNA) and
reactive oxygen species (mtROS). mtDNA is known to promote a beneficial antiviral
response; however, sustained nocive stimuli, such as SARS-CoV-2, could turn this
response into oxidative stress and exacerbated inflammation leading to tissue injury. In
addition, mtDNA can be released into the extracellular space and induce a
proinflammatory state in neighboring cells. Here, we highlight the potential role of
mtDNA as an important marker of hyperinflammation in the progress of COVID-19.
Furthermore, we briefly discuss the role of mtROS and its interactions with the
mitochondrial antiviral signaling (MAVS), which can also contribute to COVID-19
immunopathogenesis.
Keywords: Coronavirus, COVID-19, Immune response, Inflammation, Mitochondrial DNA.