Can Hyperperfusion of Nonaerated Lung Explain COVID-19 Hypoxia?

Early stages of the novel coronavirus disease (COVID-19) have been associated with 'silent hypoxia' and poor oxygenation despite relatively small fractions of afflicted lung. Although it has been speculated that such paradoxical findings may be explained by impairment of hypoxic pulmonary vasoconstriction in infected lungs regions, no studies have confirmed this hypothesis nor determined whether such extreme degrees of perfusion redistribution are physiologically plausible. Here, we present a mathematical model which provides evidence that the extreme amount of pulmonary shunt observed in patients with early COVID-19 is not plausible without hyperperfusion of the relatively small fraction of injured lung, with three-fold increases in regional perfusion to afflicted regions. Although underlying perfusion heterogeneity (e.g., due to gravity or pulmonary emboli) exacerbated existing shunt in the model, the reported severity of hypoxia in early COVID-19 patients could not be replicated without considerable reduction of vascular resistance in nonoxygenated regions.