Hypoxia: A key feature of COVID-19 launching activation of HIF-1 and cytokine storm

Abstract

COVID-19, disease caused by the new coronavirus, SARS-CoV-2, appeared in the end of 2019 and was rapidly spread in most countries. This respiratory virus has different symptoms from moderate to severe, and results in lung pneumonia following acute respiratory distress syndrome (ARDS) and patient’s death in severe cases. ARDS is a severe form of acute lung injury that is caused by high inflammatory response of the innate immunity cells. Hypoxia is the common feature in the inflammatory sites with having various impacts on this condition by induction of some factors such as hypoxia inducible factor-1α (HIF-1α). HIF-1α regulates some important cellular processes including cell proliferation, metabolism and angiogenesis. Furthermore, this factor is activated during the immune responses and plays important roles in the inflammation site by inducing pro-inflammatory cytokines production through immune cells. So, in this study the possible effect of the HIF-1α on the COVID-19 pathogenesis with emphasizes on its role on innate immunity response has been discussed.

Genetic and epigenetic regulation of the non-muscle myosin light chain kinase isoform by lung inflammatory factors and mechanical stress

“…While HIF-1α drives LPS-induced IL-1β [ 63 ], TNF, IL-12, and VEGF expression [ 64 ], HIF1α has been postulated to reduce VILI via A2B receptor regulation [ 65 , 66 ]. We have shown HIF-2α, and to a lesser extent HIF-1α, are involved in transcriptional regulation of the ARDS/VILI DAMP, eNAMPT, [ 64 , 67 , 68 ]. Our current studies demonstrate that HIF-1α and HIF-2α accumulation (elicited by PHD2 inhibition) to also significantly increase nm MYLK promoter activities with HIF-1α induction more rapid and HIF-2α induction more delayed.…”

Hypoxia-inducible factor (HIF): The link between obesity and COVID-19

“…In obese patients with COVID-19 the interplay between systemic hypoxia (due to lung injury), ATH, and cyclic hypoxia lead to a canonical activation of HIF-1ɑ. The subsequent effect of HIF-1α (explained in section 3) might explain why obesity increases the risk of cytokine storm in COVID-19 infected patients ( Jahani, Dokaneheifard, and Mansouri 2020a ).…”

“…The names and uses of the medications acting at each level have been discussed in Table 1 ( Jahani, Dokaneheifard, and Mansouri 2020b ). Despite the encouraging results of such drugs, there are no ongoing trials about their repurposing for the treatment of COVID-19 treatment.…”

An Integrated Approach of the Potential Underlying Molecular Mechanistic Paradigms of SARS-CoV-2-Mediated Coagulopathy

“…Earlier studies have also revealed an alternative strategy of coagulation development during hypoxia by Toll-like receptors 3 (TLR3) mediated NF-κB/ AP-1 signalling in endothelial cells in response to the viral infections [ 89 ]. Hypobaric hypoxia mediates TF activation and deposition of fibrin via TLR3 signalling [ 76 ].…”