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COVID-19 can evolve to a severe lung compromise with life-threatening hypoxemia. The mechanisms involved are not fully understood. Their understanding is crucial to improve the outcomes. Initially, past-experience lead to the implementation of standardized protocols assuming this disease would be the same as SARS-CoV. Impulsive use of ventilators in extreme cases ended up in up to 88% fatality. We compare medical and physiological high altitude acute and chronic hypoxia experience with COVID-19 hypoxemia. A pathophysiological analysis is performed based on literature review and histopathological findings. Application of the Tolerance to Hypoxia formula = Hemoglobin/PaCO₂ + 3.01 to COVID-19, enlightens its critical hypoxemia. Pneumolysis is defined as progressive alveolar-capillary destruction resulting from the CoV-2 attack to pneumocytes. The adequate interpretation of the …