Potential roles of nitric oxide in COVID-19: A perspective

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a beta-coronavirus closely linked to the SARS coronavirus. COVID-19 patients present with hypoxemia linked to acute respiratory distress syndrome (ARDS). Reversing the hypoxemia prevalent in COVID-19 requires advanced mechanisms that facilitate the transportation of oxygen from alveoli to blood, as increased supplemental oxygen does not always lead to optimal oxygen saturation. Clinical and experimental evidence suggest a significant role for inhaled Nitric Oxide (NO) as a selective vasodilator, which has shown to restore oxygenation by helping to normalise shunts and ventilation/perfusion mismatch. NO has demonstrated the ability to suppress the replication of a respiratory corona virus, which is unique for NO among other vasodilators. These suggest a potentially significant role for NO in the clinical management of COVID-19, warranting urgent investigations into optimal methods of harnessing its potential in restoring pulmonary physiology. Introduction The pathophysiological conditions and clinical evidence associated with COVID-19 are rapidly being established, supporting the development of therapeutic solutions [1,2]. COVID-19 patients present with respiratory characteristics of acute respiratory distress syndrome (ARDS), which in accordance with The Berlin definition includes; new or worsening respiratory symptoms within one week of symptom onset; bilateral opacities on chest imaging not fully explained by effusions, atelectasis or nodules; respiratory failure from lung edema not fully explained by cardiac failure or fluid overload; and finally oxygenation impairment [3]. However, the ARDS presented with COVID-19 is recognised to be atypical as an alarmingly majority do not experience breathlessness and have relatively good lung compliance, whilst presenting with hypoxia [4-6]. Supplemental oxygen can partially improve oxygen saturation. However, hypoxaemia due to shunt does not respond well to supplemental oxygen [7]. High levels of supplemental oxygen can be toxic but can be prevented by titrating [8]. Invasive mechanical ventilation, which is considered when addressing the most severe cases continues to be associated with a higher incidence of adverse outcomes [9]. Therefore, there is currently an incentive to explore alternative methods of optimal management of patients in addition to widely practiced prone positioning [10]. Methods of reducing pulmonary resistance and resolving oxygenation with noninvasive therapy are of interest [11]. Hypoxia is known to cause vasodilation in systemic arteries whilst causing vasoconstriction in pulmonary arterioles. Nitric Oxide (NO) has a major role in regulating hypoxia and in healthy conditions it was found that NO can mediate adaptive mechanisms including modulation of vasodilation. Hypoxia regulation in extreme conditions such as high altitudes has shown a strong link to NO, with large populationbased studies demonstrating NO upregulation as a physiological response [12]. Exhaled NO measurements associated with a range of respiratory disease conditions demonstrate specific variations in NO downregulation that correspond to an identifiable role in NO [13]. NO is a gaseous molecule and is primarily known for its role in regulating vascular compliance via cGMP pathway [14]. It is synthesised *Correspondence to: Achala de Mel, Centre for Translational Medicine and Therapeutics William Harvey Research Institute, Queen Mary University of London, NuTissu Ltd, UK, E-mail: demelach@gmail.com