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].