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 severe acute respiratory syndrome coronavirus 2 (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 patients with COVID-19 and to 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 patients with COVID-19. Interestingly, we found that levels of fibroblast growth factor 21 mitokine correlate with COVID-19 disease severity and mortality. These data suggest that patients with COVID-19 have a compromised mitochondrial function and an energy deficit that is compensated by a metabolic switch to glycolysis. This metabolic manipulation by SARS-CoV-2 triggers an enhanced inflammatory response that contributes to the severity of symptoms in COVID-19. Targeting mitochondrial metabolic pathway(s) can help define novel strategies for COVID-19.
Keywords: COVID-19; SARS-CoV-2; glycolysis; mitochondrial dysfunction; mitokines.