“Silent Hypoxemia” Leads to Vicious Cycle of Infection, Coagulopathy and Cytokine Storm in COVID-19: Can Prophylactic Oxygen Therapy Prevent It?

Abstract

Humankind is facing its worst pandemic of the twenty-first century, due to infection of a novel coronavirus named as SARS-CoV2, started from Wuhan in China. Till now, 15 million people are infected, causing more than 600,000 deaths. The disease, commonly known as, COVID-19, was initially thought to be associated with ARDS only, but later on revealed to have many unexplained and atypical clinical features like coagulopathy and cytokinemia, leading to multi-organ involvements. The patients also suffer from ‘ Silent Hypoxemia ’, where there is no immediate respiratory signs and symptoms even though alarmingly low SpO 2 level. We hypothesize that this covert hypoxemia may lead to molecular changes exacerbating coagulopathy and cytokine storm in COVID19 patients, which again, in turn, causes a vicious cycle of more hypoxemia/hypoxia and progression of the infection to more severe stages through HIF-1α dependent pathway. Although molecular mechanisms are yet to be substantiated by scientific evidence, hypoxemia remains an independent worsening factor in serious COVID 19 patients. Keeping all in mind, we propose that even in the early and asymptomatic cases, prophylactic oxygen therapy to be initiated to break the vicious cycle and to reduce the mortality in COVID 19 to save precious human lives.

Problems of Pathogenesis and Pathogenetic Therapy of COVID-19 from the Perspective of the General Theory of Pathological Systems (General Pathological Processes)

“…One of the main reasons for the development of SI and mortality in COVID-19 is hypoxemia linked with respiratory failure and systemic tissue hypoxia associated with several causes of impaired oxygen transport [ 63 , 64 , 65 , 66 ].…”

“…Similarly, hypoxemia/hypoxia is thought to be an independent risk factor for hospital mortality in the most critical forms of ARDS [ 63 , 64 , 65 , 66 ], as it is linked to the development of multiple organ failure and coagulopathy [ 63 , 64 , 65 , 66 ]. COVID-19 patients frequently develop hypoxemia without signs of breathlessness though their chest X-rays show diffuse pneumonia, and dangerous levels of blood oxygen are detected [ 63 ]. Meanwhile, low saturation values cause cascades of molecular changes in many tissues, which can trigger a chain of events that result in organ damage that can be fatal [ 63 ].…”

“…COVID-19 patients frequently develop hypoxemia without signs of breathlessness though their chest X-rays show diffuse pneumonia, and dangerous levels of blood oxygen are detected [ 63 ]. Meanwhile, low saturation values cause cascades of molecular changes in many tissues, which can trigger a chain of events that result in organ damage that can be fatal [ 63 ].…”

Hypoxia-dependent signaling in perioperative and critical care medicine

“…It is proposed that hypoxia induces Early Growth Response 1, which in turn regulate thrombus formation [137,138]. Moreover, HIFs or HIF targeted genes induces prothrombotic factors like PAI-1 and tissue factors, while antithrombotic factors like thrombomodulin, Protein S and TFPI [139][140][141][142][143]. However, the exact role of these pathways is yet to be elucidated in COVID-19 pathology.…”

Use of Antioxidants for the Neuro-Therapeutic Management of COVID-19

“…However, low levels of oxygen lead to damage in several tissues and it has been suggested that this can increase infection by up regulation of furin (via HIF-1α), a host enzyme required for cleaving the S protein of the SARS-CoV2 [ 27 , 28 ]. Hypoxemia has also been related to proinflammatory cytokines [ 29 ].…”