Coronavirus (Covid-19) sepsis: revisiting mitochondrial dysfunction in pathogenesis, aging, inflammation, and mortality

Inflamm Res. 2020 Nov;69(11):1077-1085. doi: 10.1007/s00011-020-01389-z. Epub 2020 Aug 7.


Background: Decline in mitochondrial function occurs with aging and may increase mortality. We discuss mitochondrial contribution to Covid-19 sepsis, specifically the complex interaction of innate immune function, viral replication, hyper-inflammatory state, and HIF-α/Sirtuin pathways.

Methods: Articles from PubMed/Medline searches were reviewed using the combination of terms "SARS-CoV-2, Covid-19, sepsis, mitochondria, aging, and immunometabolism".

Results: Evidence indicates that mitochondria in senescent cells may be dysfunctional and unable to keep up with hypermetabolic demands associated with Covid-19 sepsis. Mitochondrial proteins may serve as damage-associated molecular pattern (DAMP) activating innate immunity. Disruption in normal oxidative phosphorylation pathways contributes to elevated ROS which activates sepsis cascade through HIF-α/Sirtuin pathway. Viral-mitochondrial interaction may be necessary for replication and increased viral load. Hypoxia and hyper-inflammatory state contribute to increased mortality associated with Covid-19 sepsis.

Conclusions: Aging is associated with worse outcomes in sepsis. Modulating Sirtuin activity is emerging as therapeutic agent in sepsis. HIF-α, levels of mitochondrial DNA, and other mitochondrial DAMP molecules may also serve as useful biomarker and need to be investigated. These mechanisms should be explored specifically for Covid-19-related sepsis. Understanding newly discovered regulatory mechanisms may lead to the development of novel diagnostic and therapeutic targets.

Keywords: Covid-19; DAMP; HIF-α; Mitochondrial dysfunction; Sirtuins; Viral replication.

Publication types

  • Review

MeSH terms

  • Aging
  • COVID-19
  • Coronavirus Infections / complications*
  • Coronavirus Infections / mortality
  • Coronavirus Infections / pathology*
  • Humans
  • Inflammation / etiology*
  • Inflammation / mortality
  • Inflammation / pathology*
  • Mitochondria / metabolism*
  • Mitochondria / pathology*
  • Mitochondrial Diseases / etiology*
  • Mitochondrial Diseases / mortality
  • Mitochondrial Diseases / pathology*
  • Pandemics
  • Pneumonia, Viral / complications*
  • Pneumonia, Viral / mortality
  • Pneumonia, Viral / pathology*
  • Sepsis / etiology*
  • Sepsis / mortality
  • Sepsis / pathology*