Mitochondrial metabolic manipulation by SARS-CoV-2 in peripheral blood mononuclear cells of patients with COVID-19

Abstract

The COVID-19 pandemic has been the primary global health issue since its outbreak in December 2019. Patients with metabolic syndrome suffer from severe complications and a higher mortality rate due to SARS-CoV-2 infection. We recently proposed that SARS-CoV-2 can hijack host mitochondrial function and manipulate metabolic pathways for their own advantage. The aim of the current study was to investigate functional mitochondrial changes in live peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, decipher the pathways of substrate utilization in these cells and corresponding changes in the inflammatory pathways. We demonstrate mitochondrial dysfunction, metabolic alterations with an increase in glycolysis and high levels of mitokine in PBMCs from COVID-19 patients. Interestingly, we found that levels of FGF-21 mitokine correlate with COVID-19 disease severity and mortality. These data suggest that COVID-19 patients have compromised mitochondrial function and an energy deficit which is compensated by a metabolic switch to glycolysis. This metabolic manipulation by SARS-CoV-2 triggers an enhanced inflammatory response which contributes to severity of symptoms in COVID-19. Targeting mitochondrial metabolic pathway(s) can help define novel strategies for COVID-19.

SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function

“…Interestingly, pathways involved in RNA processing and chromatin accessibility (i.e., histone modification) were upregulated together with the response to viral infection, suggesting that SARS-CoV-2 may induce broad epigenetic reprogramming of the host to promote its own replication (Figures 4E and S4A; Tables S1 and S3) (Banerjee et al, 2020). In addition, we observed that genes involved in mitochondrial function and energy production were downregulated (Figures 4F and S4B; Tables S2 and S4), indicating that SARS-CoV-2 might promote a shift toward a glycolytic metabolism by suppressing mitochondrial oxidative phosphorylation, which could also favor its replication (Ajaz et al, 2021;Icard et al, 2021).…”

The central role of mitochondrial fitness on antiviral defenses: An advocacy for physical activity during the COVID-19 pandemic

“…While very few experimental data are available on the effect of mitochondrial fitness on infection with SARS-CoV-2 (e.g. there may be deficits in mitochondrial respiration in peripheral blood mononuclear cells of COVID-19 patients 71 ), several pieces of evidence suggest mitochondrial integrity to be crucial for the general anti-viral host defense 51 72 . In the following sections these arguments are discussed for the individual components of mitochondrial fitness.…”

Mitochondrial Functionality in Inflammatory Pathology-Modulatory Role of Physical Activity

“…In fact, some viruses are able to alter the innate immune system in cells by increasing DRP1 s616 phosphorylation [ 68 ], which ultimately results in mitochondrial fragmentation and dysfunction [ 66 ]. Additionally, peripheral mononuclear cells showed altered mitochondrial metabolism by SARS-CoV-2 in patients with COVID-19 [ 69 ]. Moreover, the authors proposed that disease severity was positively associated with the degree of mitochondrial dysfunction in peripheral mononuclear cells [ 69 ].…”

“…Additionally, peripheral mononuclear cells showed altered mitochondrial metabolism by SARS-CoV-2 in patients with COVID-19 [ 69 ]. Moreover, the authors proposed that disease severity was positively associated with the degree of mitochondrial dysfunction in peripheral mononuclear cells [ 69 ].…”