Coronavirus (Covid-19) sepsis: revisiting mitochondrial dysfunction in pathogenesis, aging, inflammation, and mortality.
Inflamm Res
; 69(11): 1077-1085, 2020 Nov.
Article
in English
| MEDLINE | ID: covidwho-696688
ABSTRACT
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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Coronavirus Infections
/
Sepsis
/
Mitochondrial Diseases
/
Inflammation
/
Mitochondria
Type of study:
Prognostic study
/
Reviews
Topics:
Long Covid
Limits:
Humans
Language:
English
Journal:
Inflamm Res
Journal subject:
Allergy and Immunology
/
Pathology
Year:
2020
Document Type:
Article
Affiliation country:
S00011-020-01389-z
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