HIF1A and Multiple Organ Failure: Numerous inter-related factors conspire to enhance the cytokine storm and multiple organ failure associated with COVID-19 disease severity and mortality, including elevated sPLA2-IIA, development of pro-inflammatory M1 macrophages, activation of HIF-1α, conversion to Warburg-type metabolism of immune cells, damage to mitochondria, massive release of cytokines, oxidative stress, etc. [117–120] (Fig. 1); each of these actions have been shown to be counteracted by melatonin.