Management implications
High permeability can be viewed as a form of ‘leaky lungs” in the early
phase of DAD. SARS-CoV spike protein binding to ACE2, with
downregulation of the latter, followed by increased angiotensin II, has
been shown to increase pulmonary vascular permeability, potentially
inducing pulmonary oedema ( 10 ).
Alveolar oedema per se will drive cytokine release, due to hypoxia and
hypercarbia in the alveolus, leading to ARDS, complicating the initial
pulmonary oedema caused by the virally driven high capillary
permeability. Nitric oxide as a pulmonary vasodilator is thought to
improve hypoxemia in patients on mechanical ventilators, but does not
improve survival in non-COVID related ARDS.
The dynamics of capillary permeability, on theoretical grounds ,
suggests that pulmonary venous dilatation induced by nitroglycerin would
rebalance hydrostatic forces and reduce pulmonary oedema. Glyceryl
trinitate patches should improve hypoxemia in non-cardiogenic pulmonary
oedema, as it does with cardiac pulmonary oedema. Randomised clinical
trials on the potential benefits of therapy in early phase of COVID-19
are urgently needed.
Early intervention with CPAP may have a positive impact on pulmonary
oedema of both cardiogenic and non-cardiogenic origin.
We hypothesize that COVID-19 that the first pulmonary pathogenic feature
in COVID-19 is non-cardiogenic pulmonary oedema ( ‘leaky lungs’ ), which
if dealt with it at an early stage appropriately, will limit the
progression of disease. Further work looking at therapeutic targets, and
the potential repurposing of widely used intervention strategies,
earlier within the disease trajectory, may halt this cascade, and
improve patient outcomes.