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

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, hyperinflammatory 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.

Implications of Oxidative Stress and Potential Role of Mitochondrial Dysfunction in COVID-19: Therapeutic Effects of Vitamin D

“…SARS-CoV-2 infection may produce multiple free radicals such as H 2 O 2 , O 2 •− and •OH, among the most prominent. Interactions between SARS-CoV-2 proteins and host cell mitochondrial proteins cause the loss of membrane integrity and mitochondrial dysfunction, which provokes an exacerbated increase in ROS production [159]. Although a certain level of ROS is important in the regulation of immune response and the elimination of virus, its exacerbated production may destroy many cell components in both virus-infected cells and normal cells, causing multiple organ failure [160].…”

Relationship between the dynamic changes of serum 2019-nCoV IgM/IgG and patient immunity after 6 month hospital discharge

“…Presently, due to the lack of effective antiviral drugs [ 3 ] and vaccines [ 4 ], convalescent plasma therapy [ 5 ] and specific human monoclonal antibodies [ 6 ], the treatment of COVID-19 remains the greatest challenge for medical staff and scientific researchers [ 7 ]. As a novel coronavirus, the dynamic immunity to and pathogenesis of this disease in the human body are unclear [ 8 – 10 ].…”

Daylight is critical to preserve 5-methoxytryptophol levels in suspected and confirmed COVID-19 patients

“…Another effect of COVID-19 infection is that it causes mitochondrial dysfunction and thus triggers the formation of reactive oxygen species (ROS), thus causing oxidative stress [17] . At this point, it is thought that the hyperinflammatory response developed due to viral invasion is the most important factor causing mitochondrial damage [18] . It is thought that this situation may play a role in triggering multiple organ failure [19] .…”