Keywords
COVID-19, silent hypoxemia, renin-angiotensin system, SARS-CoV-2, bradykinin
For some time, researchers have struggled to understand the pathophysiology of “silent hypoxia” in coronavirus diseases (COVID-19) patients [1-3]. Based on the high ratio of 3.0 ± 2.1 of the shunt fractions to the fractions of gasless tissue as derived from the computed tomography scan findings in COVID-19 patients, Gattinoni et al [1]. were first to suggest pulmonary vasoplegia-induced hyperperfusion of non-aerated lung regions as the responsible pathophysiology. However, they did not offer a specific mechanism for this vasoplegia. Recently, Reynolds et al., using contrast-enhanced transcranial doppler (TCD), demonstrated a right-to-left shunt in COVID-19 patients [2]. As the severity of hypoxemia inversely correlated with the number of microbubbles detected and the prevalence of transpulmonary bubbles seen in this study was markedly higher than the prevalence of patent foramen ovale in the general population, Reynolds et al. concluded that pathological pulmonary vascular dilatation and not just a lack of hypoxic pulmonary vasoconstriction was a significant contributor to hypoxemia in COVID-19 patients with respiratory failure. However, once again no attempt was made to propose an explanation for this pathophysiological process, although the authors compared such the intense pulmonary vascular dilatation with that observed in hepatopulmonary syndrome [2]. Brito-Azevedo et al. also proposed intrapulmonary shunt, as evident using transthoracic saline contrast echocardiography (TTSCE), as an explanation for severe hypoxia despite preserved lung compliance in COVID-19 pneumonia [3]. They suggested a mechanism for the intrapulmonary shunt: SARS-Cov-2 infection-induced angiotensin II (Ang II)-mediated angiotensin converting enzyme (ACE) downregulation with upregulation of bradykinin-induced pulmonary vasodilation. This may correspond with the ‘bradykinin storm’ hypothesis that has been proposed by other researchers to explain the pulmonary manifestations of COVID-19 [4].