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.