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

• Published in: Inflammation research Vol. 69; no. 11; pp. 1077 - 1085
• Main Author: Shenoy, Santosh
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.11.2020
• Subjects: Aging; Allergology; Biomedical and Life Sciences; Biomedicine; Coronavirus Infections - complications; Coronavirus Infections - mortality; Coronavirus Infections - pathology; COVID-19; Dermatology; Humans; Immunology; Inflammation - etiology; Inflammation - mortality; Inflammation - pathology; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial Diseases - etiology; Mitochondrial Diseases - mortality; Mitochondrial Diseases - pathology; Neurology; Pandemics; Pharmacology/Toxicology; Pneumonia, Viral - complications; Pneumonia, Viral - mortality; Pneumonia, Viral - pathology; Review; Rheumatology; Sepsis - etiology; Sepsis - mortality; Sepsis - pathology; Sirtuins; HIF-α; Mitochondrial dysfunction; Covid-19; Viral replication; DAMP
• ISSN: 1023-3830; 1420-908X; 1420-908X
• DOI: 10.1007/s00011-020-01389-z

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.