In conclusion, Ang II-mediated heterogenous pulmonary vasoconstriction
with microthrombotic perfusion defects but not pulmonary vasodilation is
likely the predominant mechanism for silent hypoxemia in early COVID-19
pneumonia. Our hypothesis is supported by the fact that the patients
with precapillary pulmonary hypertension and hypoxia often demonstrate
significant intrapulmonary arteriovenous shunt with increase in
alveolar-arterial PaO2 gradient [33]. This hypothesis is further
supported by the high incidence of raised PVR and right ventricular
dysfunction in early COVID-19 disease [34] and reports of lung
perfusion deficits that do not overlap with ground-glass opacities or
consolidation and are not associated with major vessel occlusion [10,
35]. Based on this model, we have previously advocated the beneficial
role of steroids and anticoagulant in the early to late stages of
COVID-19 [10] and this recommendation is now supported by more
clinical evidence [36, 37]. We strongly believe determining the
predominant pathophysiology ─ heterogenous pulmonary vasoconstriction
versus pulmonary vasodilation ─ has an important treatment implication:
early pulmonary vasoconstrictors versus vasodilators. Disappointingly,
no study has yet evaluated the role of NO therapy at an early stage of
COVID-19 disease and our recommendation on the use of early NO therapy
in the treatment of symptomatic high risk COVID-19 patients [10] is
still under debate [38, 39], the issue certainly warrants high
quality randomized clinical trials. Nonetheless, a recent multicentric
retrospective study comparing the outcome of COVID-19 disease in the
elderly population on antihypertensive with those who were not on any
antihypertensive therapy, authors identified significant benefits of ACE
inhibitors (ACEIs), AT1R blockers (ARBs) as well as calcium channel
blockers in reducing the severity and mortality of COVID-19 [40].
Our hypothesis of “epithelial-endothelial cross-talk” further raises
interest in the possible therapeutic role of ACEIs or ARBs in COVID-19.
Conflict of interest statement: None