Heterogeneous Perfusion in COVID-19 and High Altitude Pulmonary Edema: A Review of Two Cases Followed by Implications for Hypoxic Pulmonary Vasoconstriction, Thrombosis Development, Ventilation Perfusion Mismatch and Emergence of Treatment Approaches

Abstract

Coronavirus disease 2019 (COVID-19) has been compared to high altitude pulmonary edema (HAPE). Multiple similarities between the two conditions were drawn in the past. This article seeks to further clarify potential underlying mechanisms related to hypoxia and pulmonary vascular responses. It does so by looking at perfusion imaging of patients with COVID-19 and comparing them with patterns observed in HAPE and hypoxic exposure. Two separate clinical cases are reviewed. The salient aspect of each case that is emphasized is the perfusion scintigraphy results that revealed heterogeneous perfusion patterns in both patients. Heterogeneous or non-homogeneous perfusion is also observed in HAPE. A detailed clinical course of each patient is described. Medications utilized to treat the conditions are outlined as well as laboratory parameters and clinical findings. Interestingly, both of these patients were treated with calcium channel blockers and this class of medications is utilized to prevent HAPE as well. Discussion following the case presentations attempts to contextualize possible implications of this and other studies on the broader pathophysiology of COVID-19 disease. Findings related to pathophysiologic patterns and treatment strategies are also described. Micro-thrombi formation has been reported in both COVID-19 and HAPE as well and may be an accessory complication of perfusion compromise. In a separate study, vasodilatation with calcium channel blocker (CCB) therapy has been associated with improved mortality in COVID-19 and potential pathophysiologic mechanisms were previously presented. This case report provides further clinical findings that support the notion that perfusion deficits are an integral component of hypoxia in COVID-19. It also advances the basis for use of vasodilator therapy as part of treatment regimens in COVID-19. Vasodilators may improve micro-perfusion. In this way, oxygenation may be promoted by decreasing impedance and improving flow via the alveolar-capillary unit.

Hyperbaric oxygen as an adjuvant treatment for patients with COVID-19 severe hypoxaemia: a randomised controlled trial

“… 7 Hypoxaemia correction and hyperoxia generation could trigger an anti-inflammatory effect that, in turn, could lead to a clinical improvement in patients with hypoxaemic severe pneumonia associated with COVID-19. 5 8 In case studies, HBO 2 therapy has proved to be effective and safe in patients with COVID-19 pneumonia. 9 10 In patients that received HBO 2 therapy, SpO 2 increased, tachypnoea resolved and inflammatory markers decreased.…”

“…2 Impaired oxygen diffusion leads to a drop in oxygen levels, which produces hypoxaemia and further inflammation. [3][4][5] In severe pneumonia caused by COVID-19, impaired oxygen diffusion leads to hypoxaemia and lower level of oxygenhaemoglobin saturation. [3][4][5] Oxygen administrated at higher pressure increases the partial pressure of oxygen in the haematoalveolar exchange, increasing gas diffusion through an altered alveolar membrane which, under the hyperbaric environment, produces a larger amount of…”

“…Hypoxaemia has been independently associated with in-hospital mortality in patients with COVID-19; in moderate to critically ill patients, oxygen saturation (SpO 2 ) of more than 90% with oxygen supplementation indicate a very high likelihood of survival, while values below 90%, despite normobaric oxygen supplementation, have been associated with a high mortality risk 2. Impaired oxygen diffusion leads to a drop in oxygen levels, which produces hypoxaemia and further inflammation 3–5. In severe pneumonia caused by COVID-19, impaired oxygen diffusion leads to hypoxaemia and lower level of oxygen–haemoglobin saturation 3–5…”

“…Impaired oxygen diffusion leads to a drop in oxygen levels, which produces hypoxaemia and further inflammation 3–5. In severe pneumonia caused by COVID-19, impaired oxygen diffusion leads to hypoxaemia and lower level of oxygen–haemoglobin saturation 3–5…”

Case Studies in Physiology: Temporal variations of the lung parenchyma and vasculature in asymptomatic COVID-19 pneumonia: a multispectral CT assessment

“…Such vascular pathophysiology is unique to COVID-19 pneumonia, given an increasing observation of severe hypoxemia even in patients with normal lung compliance (6). The similarity of regional hypoperfusion in COVID-19 to cases of high-altitude pulmonary edema (HAPE) have been noted (29), suggesting a role for pulmonary vasodilators. When compared to healthy controls and matched patients with acute respiratory distress syndrome, COVID-19 patients showed significantly reduced blood volume in small caliber blood vessels on CT (31) and loss of smaller vessels (as detected by CT) has been show to serve as a predictor of survival (20).…”