Non-Cardiogenic Pulmonary Oedema as the first pathogenic feature in COVID-19 and potential benefit of nitrates in SARS-CoV-2 infection

Abstract
We wish to highlight a new hypothesis, that the early phase of COVID-19 is characterised by non-cardiogenic pulmonary oedema (‘leaky lungs’). We hypothesize that COVID-19 complications in lungs might progress through the initial stages of ‘leaky lungs’, to ‘cytokine storm’ and Acute Respiratory Distress Syndrome (ARDS ) , with high case fatality rates once ARDS sets in. SARS-CoV spike protein binding to Angiotensin Converting Enzyme 2 cell membrane receptors with down-regulation of the latter, followed by increased Angiotensin II, has been shown to increase pulmonary vascular permeability, potentially inducing pulmonary oedema. This hypothesis is supported by serial computerised tomographic scan findings on COVID-19 patients from China and post-mortem studies from around the world. Early attention and targeted treatment towards this pathological feature of non-cardiogenic pulmonary oedema may be of benefit, and warrants a clinical trial.