HIF-1α contributing to COVID-19 infections and poor prognosis in cancer patients – A hypothesis

Abstract

In 2019, a new coronavirus (SARS-CoV-2) infecting Humans first identified in Wuhan, China, has caused the worst pandemic of the 21st century. This virus infection leads to the clinical symptoms that may range from asymptomatic condition to life-threatening illness. The insights from the recent studies suggest that SARS-CoV-2 requires a host enzyme, Furin to activate receptor-binding domain (RBD) of its S protein. Upon binding of RBD to host cell membrane-bound Angiotensin Convertase Enzyme 2 (ACE2), it facilitates the entry of virus in the host cell. Evidence from the literature also suggests that HIF-1α (Hypoxia-inducible factor 1-α) is one of the factors regulating the expression of Furin. In addition, it is also well documented that the interior of solid tumours, which grow very fast, leads to the hypoxic tumour microenvironment, resulting in overexpression and release of HIF-1α. The SARS-CoV-2 infected patients with severe tissue damage and inflammatory injury also suffer from tissue hypoxia. So, we hypothesize that hypoxic condition due to tumour microenvironment in cancer patients upregulates the HIF-1α, leading to increased expression of Furin. Upon infection of cancer patients with SARS-CoV-2 having increased Furin expression in the cells due to upregulation of HIF-1α, leads to the entry of a greater number of SARS-CoV-2 virus in these cells resulting in severe infection. The vicious cycle of the virus infection in which virus is more easily invaded into surrounding tissue leads to the involvement of multiple organs and ultimately poor prognosis in the disease outcome. Therefore, we suggest evaluating the expression of HIF-1α in SARS-CoV-2 infections at an early phase of infection particularly in patients with comorbidities like solid malignancies as well as patients having signs and symptoms of hypoxia. It is also suggested that continuous monitoring of the SpO2 level and early institution of preventive O2 therapy at an early stage in these patients may lead to lesser morbidity as well as mortality in COVID-19 patients.