Mimicking Gene–Environment Interaction of Higher Altitude Dwellers by Intermittent Hypoxia Training: COVID-19 Preventive Strategies

SIMPLE SUMMARY: Cyclooxygenase 2 (COX2) inhibitors have been demonstrated to protect against hypoxia pathogenesis in several investigations. In several studies, it has been shown that COX2 inhibitors guard against the pathogenesis of hypoxia. However, there are conflicting findings on COX inhibitors’ potency in treating COVID-19, and they have drawbacks. As a result, therapeutic COX2 inhibition may not always be beneficial, and further research into potential downstream mediators for hypoxic environment adaptability is required. According to research, those who are used to the lower oxygen levels at altitude may be more resistant to the negative effects of COVID-19. It indicates that COVID-19 poses a greater risk to people who live at lower elevations. It has been demonstrated that the COX2 pathway’s downstream molecules adapt in people who live at high altitudes, which may help to explain why these people have a decreased prevalence of COVID-19 infection. Intermittent hypoxia training can be used to imitate the gene-environment interactions found in people who live at higher altitudes (IHT). It appears that COX-2 adaptation brought on by hypoxia exposure at altitude or IHT serves a significant therapeutic purpose. In this article, we highlight some of the most significant common genes associated with the pathophysiology of COVID-19 and hypoxia. We propose a common pathway between COVID-19 pathogenesis and hypoxia that influences apoptosis, proliferation, the immune system, and metabolism. We also emphasize the importance of researching people who reside at higher elevations to mimic their gene-environment interactions and contrast the results with IHT. Finally, we suggest COX2 as an upstream target for evaluating IHT’s efficacy in preventing or mitigating the consequences of COVID-19 and other oxygen-related pathological conditions in the future. ABSTRACT: Cyclooxygenase 2 (COX2) inhibitors have been demonstrated to protect against hypoxia pathogenesis in several investigations. It has also been utilized as an adjuvant therapy in the treatment of COVID-19. COX inhibitors, which have previously been shown to be effective in treating previous viral and malarial infections are strong candidates for improving the COVID-19 therapeutic doctrine. However, another COX inhibitor, ibuprofen, is linked to an increase in the angiotensin-converting enzyme 2 (ACE2), which could increase virus susceptibility. Hence, inhibiting COX2 via therapeutics might not always be protective and we need to investigate the downstream molecules that may be involved in hypoxia environment adaptation. Research has discovered that people who are accustomed to reduced oxygen levels at altitude may be protected against the harmful effects of COVID-19. It is important to highlight that the study’s conclusions only applied to those who regularly lived at high altitudes; they did not apply to those who occasionally moved to higher altitudes but still lived at lower altitudes. COVID-19 appears to be more dangerous to individuals residing at lower altitudes. The downstream molecules in the (COX2) pathway have been shown to adapt in high-altitude dwellers, which may partially explain why these individuals have a lower prevalence of COVID-19 infection. More research is needed, however, to directly address COX2 expression in people living at higher altitudes. It is possible to mimic the gene–environment interaction of higher altitude people by intermittent hypoxia training. COX-2 adaptation resulting from hypoxic exposure at altitude or intermittent hypoxia exercise training (IHT) seems to have an important therapeutic function. Swimming, a type of IHT, was found to lower COX-2 protein production, a pro-inflammatory milieu transcription factor, while increasing the anti-inflammatory microenvironment. Furthermore, Intermittent Hypoxia Preconditioning (IHP) has been demonstrated in numerous clinical investigations to enhance patients’ cardiopulmonary function, raise cardiorespiratory fitness, and increase tissues’ and organs’ tolerance to ischemia. Biochemical activities of IHP have also been reported as a feasible application strategy for IHP for the rehabilitation of COVID-19 patients. In this paper, we aim to highlight some of the most relevant shared genes implicated with COVID-19 pathogenesis and hypoxia. We hypothesize that COVID-19 pathogenesis and hypoxia share a similar mechanism that affects apoptosis, proliferation, the immune system, and metabolism. We also highlight the necessity of studying individuals who live at higher altitudes to emulate their gene–environment interactions and compare the findings with IHT. Finally, we propose COX2 as an upstream target for testing the effectiveness of IHT in preventing or minimizing the effects of COVID-19 and other oxygen-related pathological conditions in the future.