SARS-COV-2 INFECTING ENDOTHELIAL CELLS, BIOCHEMICAL ALTERATIONS, AUTOPSY FINDINGS AND OUTCOMES IN COVID-19, SUGGEST ROLE OF HYPOXIA-INDUCIBLE FACTOR-1

Researchers around the world have experienced the dual nature of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), 'tragically lethal in some people while surprisingly benign in others'. There have been congregating studies of the novel coronavirus disease (COVID-19), a disease that mainly attacks the lungs but also has mystifying effects on the heart, kidneys and brain. Researchers are also gathering information to ascertain why people are dying of COVID-19, whether it is solely a respiratory disorder, a coagulation disorder or multi-organ failure. Alterations in laboratory parameters like lactate, ferritin and albumin have been established as risk factors and are associated with outcomes, yet none have not been sub stantiated with a scientific biochemical rationale. SARSCoV-2 affects the alveolar type II epithelial cells which significantly disturbs its surfactant homeostasis, deprives Na,K-ATPase of ATP, thereby disturbing the alveolar lining fluid which then gradually decreases the alveolar gaseous exchange initiating the intracellular hypoxic conditions. This activates AMP-activated kinase, which further inhibits Na,K-ATPase, which can progressively cause respiratory distress syndrome. The virus may infect endothelial cell (EC) which, being less energetic, cannot withstand the huge energy requirement towards viral replication. There fore glycolysis, the prime energy generating pathway, must be mandatorily upregulated. This can be achieved by Hypoxia-inducible factor-1 (HIF-1). However, HIF-1 also activates transcription of von Willebrand factor, plasmino-gen activator inhibitor-1, and suppresses the release of thrombomodulin. This in turn sets off the coagulation cas-cade that can lead to in-situ pulmonary thrombosis and micro clots. The proposed HIF-1 hypothesis justifies various features, biochemical alteration, laboratory as well as autopsy findings such as respiratory distress syndrome, increased blood ferritin and lactate levels, hypoalbumine-mia, endothelial invasion, in-situ pulmonary thrombosis and micro clots, and multi-organ failure in COVID-19.