The novel coronavirus, SARS-CoV-2 was first reported in Wuhan, China in December 2019. The virus quickly spread globally causing the WHO to declare a worldwide pandemic crisis in March 2020. In a desperate attempt to find a treatment./prevention many different medications and other therapies have been explored to determine the efficacy in the prevention and treatment of COVID-19, the disease caused by the virus SARS-CoV-2. One such treatment being explored is inhalation of nitric oxide gas. In an article published May 2020 in the journal Microbes and Infection the authors discuss the possibility of inhalation nitric oxide gas as a viable treatment and possible prevention.1
Currently a clinical trial is underway to explore the benefits of inhalation nitric oxide gas in severe acute respiratory in COVID-19 (NCT04306393). At the time of this writing the trial is currently recruiting. However, during the 2002-2003 SARS epidemic inhaled NO was tested in six patients, beneficial effects were observed. The beneficial effects observed were decreased pulmonary hypertension, improved arterial oxygenation, and reduced spread and density of lung infiltration. Other possible options to increase NO levels in people other than inhalation gas includes NO donor molecules (arginine, citrulline, nitroglycerin), phosphodiesterase inhibitors such as Viagra, and nitrate rich foods such as leafy green vegetables, beetroots and herbal spices.
NO is a reactive oxygen species and is continually produced by epithelial cells of the paranasal sinuses. The rationale for exploring NO as a treatment/prevention strategy stems from the fact that NO plays a major role in pulmonary and cardiovascular physiology. NO induces vasodilatory and bronchodilatory effects, it also activates ciliary movement and mucus secretions which increases removal of dust and viral particles. Some studies suggest nasally produced NO represents the bodies endogenous defense against respiratory viruses as higher basal levels of exhales NO are associated with fewer symptoms of the common cold.
Important to note, high levels of NO are currently used as biomarkers for eosinophilic airway inflammation in asthmatic people. Some authors have proposed that NO may contribute to tissue damage during airway inflammation. It remains to be seen whether increased levels of NO will produce antiviral effects in COVID-19 patients. On the other hand, low NO levels may facilitate SARS-CoV-2 infection and development of COVID-19 in some patients.
Nasal NO levels are reduced in individuals that smoke or consume alcohol, caffeine, or corticosteroids, as well as those that mouth breath. Mouth breathing has been associated with a plethora of health issues. Though most people report breathing through the nose, mouth breathing may occur during talking, exercise and sleep. People with allergies, congestion or nasal obstruction are more likely to breathe through their mouth. Mouth breathing reduces the beneficial effects of NO leading to unobstructed viral replication, therefore mouth breathing may worsen the symptoms of COVID-19.
The authors conclude by stating, “The studies described here suggest that therapies designed to increase airway NO levels via gas inhalation and donor molecules may improve oxygenation and produce health benefits in COVID-19 subjects. In addition, limiting the lifestyle factors that reduce endogenous NO levels in the airway- such as mouth breathing and smoking- may also help to reduce SARS-CoV-2 viral load and symptoms of COVID-19 pneumonia by promoting more efficient antiviral defense mechanisms in the respiratory tract. In the absence of effective treatments targeting SARS-CoV-2, we believe that these strategies should be considered and tested to prevent or treat COVID-19.”
- Martel J, Ko YF, Young JD, Ojcius DM. Could nasal nitric oxide help to mitigate the severity of COVID-19? Microbes Infect. 2020 May-Jun;22(4-5):168-171. doi: 10.1016/j.micinf.2020.05.002. Epub 2020 May 6. PMID: 32387333; PMCID: PMC7200356.