Targeting long-term cardiopulmonary complications of Covid-19 with dietary nitrate

Background:

Long-term cardiovascular pulmonary and muscular symptoms after Covid-19 infection is common, even in younger individuals. Endothelial dysfunction after Covid-19 is one element that mechanistically could be explained by inflammation, oxidative stress and reduced nitric oxide (NO) bioavailability. Normally, NO is generated by specific enzymes in the vasculature where it regulates blood flow and protects the endothelium.

We and others have shown that NO signaling can be enhanced by dietary intake of inorganic nitrate, an anion highly present in certain vegetables. Human studies have shown beneficial effects of nitrate on vascular function, oxidative stress and mitochondrial efficiency. These findings suggest that dietary nitrate supplementation could have a therapeutic role in counteracting post Covid-19 cardiovascular and pulmonary dysfunction.

Aims:

To explore the hypothesis that increased intake of inorganic nitrate will improve endothelial dysfunction in patients with long-term post Covid-19 cardiopulmonary symptoms. To investigate the hypothesis that this effect is coupled to improved exercise capacity and muscular efficiency. Workplan:

In a four-week proof-of-concept study, we will administer inorganic nitrate in the form of concentrated beetroot juice. Similar juice devoid of nitrate is used as placebo. Young to middle aged subjects (n=40) with long-term post Covid 19 symptoms will be included.

Before and at the end of the study period we will analyze vascular function (flow-mediated vasodilation as major endpoint, pulse wave velocity and blood pressure), lung function/inflammation (spirometry, exhaled NO) and exercise tolerance together with muscle function. Blood and urine samples are analyzed for NO metabolites and biomarkers of endothelial injury, oxidative stress and inflammation.

Significance:

Vascular dysfunction due to abrogated NO signaling may be an underlying cause behind long-term cardiovascular, pulmonary and muscular symptoms after Covid-19 infection. The use of dietary nitrate to increase NO bioactivity may improve vascular function and blood flow regulation to provide relief in patients with post Covid-19 complications.