Abstract
Early stages of the novel coronavirus disease (COVID-19) are associated with silent hypoxia and poor oxygenation despite relatively minor parenchymal involvement. Although speculated that such paradoxical findings may be explained by impaired hypoxic pulmonary vasoconstriction in infected lung regions, no studies have determined whether such extreme degrees of perfusion redistribution are physiologically plausible, and increasing attention is directed towards thrombotic microembolism as the underlying cause of hypoxemia. Herein, a mathematical model demonstrates that the large amount of pulmonary venous admixture observed in patients with early COVID-19 can be reasonably explained by a combination of pulmonary embolism, ventilation-perfusion mismatching in the noninjured lung, and normal perfusion of the relatively small fraction of injured lung. Although underlying perfusion heterogeneity exacerbates existing shunt and ventilation-perfusion mismatch in the model, the reported hypoxemia severity in early COVID-19 patients is not replicated without either extensive perfusion defects, severe ventilation-perfusion mismatch, or hyperperfusion of nonoxygenated regions.
Highlights
Stages of the novel coronavirus disease (COVID-19) are associated with silent hypoxia and poor oxygenation despite relatively minor parenchymal involvement
Given a certain fraction of injured lung (Finj) with impaired oxygen transport, what increase in regional blood flow and vasodilation would be necessary to manifest a ratio of shunt fraction (Fshu) to Finj around 3? Could a ratio of this magnitude be explained by impaired oxygen equilibration? What roles might gravitational gradients and thromboembolic perfusion defects play? In the present study we use a mathematical model of perfusion and oxygen transport to address these questions with the goal of determining if the impaired hypoxic pulmonary vasoconstriction (HPV) and microemboli hypotheses can potentially explain the hypoxemia of early COVID-19, or whether we need to look for an alternative explanation
The predicted response of the model with 17% Finj to supplemental oxygen is shown in Fig. 7 for several possible scenarios including altered HPV in the injured lung, extensive perfusion defect in the noninjured lung, and venous admixture caused by ventilation-perfusion mismatching in the noninjured lung
Summary
Stages of the novel coronavirus disease (COVID-19) are associated with silent hypoxia and poor oxygenation despite relatively minor parenchymal involvement Speculated that such paradoxical findings may be explained by impaired hypoxic pulmonary vasoconstriction in infected lung regions, no studies have determined whether such extreme degrees of perfusion redistribution are physiologically plausible, and increasing attention is directed towards thrombotic microembolism as the underlying cause of hypoxemia. In the present study we use a mathematical model of perfusion and oxygen transport to address these questions with the goal of determining if the impaired HPV and microemboli hypotheses can potentially explain the hypoxemia of early COVID-19, or whether we need to look for an alternative explanation. Conditions representing critical care patients are available as supplementary material, with increased Finj (Supplementary Figs. 5–9), increased FiO2 (Supplementary Fig. 10), and increased mixed venous oxygen tension (e.g., owing to venovenous extracorporeal membrane oxygenation) (Supplementary Fig. 11)
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