COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm

Figure 1

Mechanisms that lead to acute respiratory distress syndrome (ARDS) and mortality following SARS-CoV-2 infection are shown. The cells of the innate immune response secrete increasing amounts of cytokines. The cells that normally protect against a cytokine storm lose this ability leading to a runaway positive feedback loop of cytokine production. Abbreviations: 11β-HSD1 and 11β-HSD2: 11β-hydroxysteroid dehydrogenase types 1 and 2; ACE2: angiotensin-converting enzyme 2; AEC I and AEC II: alveolar epithelial cell types I and II; DCs: dendritic cells; FOXO1: forkhead box O1 transcription factor; FOXO3: forkhead box O3 transcription factor; HIF-1α: hypoxia-inducible factor 1 alpha; IFN: interferon; IL-6: interleukin-6; IRF3: IFN-regulatory factor 3; NAD(H): nicotinamide adenine dinucleotide; NADP(H): nicotinamide adenine dinucleotide phosphate; ONOO^-: peroxynitrite; PGC1-α: PPARG coactivator 1-alpha; PDK1 and PDK4: pyruvate dehydrogenase kinases 1 and 4; RLR: retinoic acid-inducible gene I-like receptors; RNS: reactive nitrogen species; ROS: reactive oxygen species; SOD: superoxide dismutase; TGF-β: transforming growth factor-β; TNF-α: tumor necrosis factor-alpha.