To the Editor:I have read the article entitled “COVID-19 Lung Injury and High Altitude Pulmonary Edema: A False Equation with Dangerous Implications” by Luks and Swenson published April 24, 2020 (1).Although the authors’ knowledge about high-altitude pulmonary edema (HAPE) is beyond reproach, contained in this article are unproven assumptions with regard to the pathophysiology underlying coronavirus disease 2019 (COVID-19) lung disease. The authors posit that the natural evolution of COVID-19 involves “alveolar flooding, atelectasis, severely diminished lung compliance, ventilation–perfusion mismatch and right-to-left shunt.” This has not been scientifically confirmed and is based on a presumption of equivalency between COVID-19 lung and known alveolar disorders leading to acute respiratory distress syndrome. I find this presumed equivalency to be the most dangerous of possible false equations.In the face of a pandemic in which so many practicing physicians admit to honest bewilderment, at some point, we must be allowed to fall back on scientific principles that are governed by natural law. The equation of motion of the respiratory system is one such principle. Relying on that natural truth, it seems highly unlikely that a disease that causes such a severe level of hypoxemia due to alveolar collapse/filling, which is to say hypoxemia defined by loss of functional lung volume, could present with normal or near-normal pulmonary compliance.Presuming to know what is unknown is more detrimental to medical advancement than voicing the notion that COVID-19lung disease may involve pathophysiologic mechanisms similar to those that are believed to underlie HAPE. In light of a most striking and unusual similarity, progressive hypocapnic hypoxemia manifesting clinically as hypoxemia out of proportion to dyspnea, it seems reasonable to initiate a debate about whether what is used to treat one might be effective in treating the other.I do appreciate the authors’ concern and their imparted wisdom. If COVID-19 is a problem of impaired rather than exaggerated pulmonary vasoconstriction, the treatment of COVID-19 with medications used to treat HAPE may cause harm. We should heed their caution. However, we should not retreat from a study of the similarities between high-altitude hypoxemia and COVID-19hypoxemia. A comparison of the two may yet yield answers to questions of great clinical import. For example, in COVID-19lung disease, a hypoxemic condition that progresses over several days in which many patients do not appear to be in distress, what is more injurious: accepting a lower oxygen saturation as measured by pulse oximetry or initiating invasive mechanical ventilation?With great respect for the authors’ well-meaning concern to avoid patient harm, let me be clear about mine: I am concerned that the alveolar filling/collapse, low-compliance pulmonary disease being seen in the intensive care unit is predominantly due to ventilator-induced lung injury rather than to the natural evolution of COVID-19 disease. That is not to say that this iatrogenic lung injury, if confirmed by further data, is avoidable. We are tasked with preserving life, and it is highly likely that to maintain oxygenation at viable levels for life, we must injure lungs along the way and then do our best to heal them, as we are.I suspect that in the coming months, new research will show that COVID-19mortality is caused by vascular endothelial rather than alveolar epithelial dysfunction. This will likely lead to intense debate over alterations to currently adopted ventilation strategies that have historically been used to treat alveolar filling/collapse disease. To safely ventilate COVID-19 lungs, our oxygenation and ventilation targets may need to change. Given their experience in treating a condition of well-tolerated hypoxemia leading to pulmonary vascular dysfunction, these authors are precisely the experts we will need to help redefine those targets. I look forward to once again hearing and heeding their concerns.