Respiratory failure requiring hospitalisation, oxygen treatment and in severe cases, mechanical ventilation, is a devastating complication of SARS-CoV-2 infection. Although the combination of severe hypoxaemia with relatively preserved lung mechanics is not unique to COVID-19 Acute Respiratory Distress Syndrome (ARDS), and has also been described in non-COVID-19 ARDS, there are likely pathophysiological differences [1]. Pneumonitis, endotheliitis, microvascular thrombosis and lung perfusion dysregulation are induced by a significant cytokine release and coagulopathy in response to viral infection, and are thought to be responsible for the degree of severe hypoxaemia seen with COVID-19 ARDS [2-6]. Hypoxia-induced pulmonary vasoconstriction further worsens ventilation-perfusion mismatch as blood flow is restricted to poorly ventilated lung segments, resulting in increased alveolar dead space and severe hypoxaemia. Lastly, hypoxia-induced pulmonary vasoconstriction and the use of non-selective vasopressors may increase pulmonary vascular resistance leading to greater pulmonary hypertension and worsened right ventricular function. Clinical consideration of adjuvant therapeutic strategies aimed at pulmonary vasoconstriction may reverse these physiological changes and may therefore play a role in managing severe COVID-19 induced hypoxaemia [7-9].

The most used pulmonary vasodilators for refractory hypoxaemia are inhaled prostacyclins and inhaled nitric oxide (iNO). Inhaled prostacyclins, such as epoprostenol (iEpo), treprostinil, and iloprost, are potent systemic and pulmonary vasodilators, that act as endogenous inhibitors of platelet aggregation [10]. Their anti-thrombotic effect is attributed to the activation of intracellular adenylate cyclase and increased cyclic adenosine monophosphate in platelets. Inhaled NO is a selective pulmonary vasodilator with additional anti-inflammatory properties attributed to its inhibitory effect on neutrophil activation [11, 12]. Previously, inhaled pulmonary vasodilators have demonstrated no mortality benefit in ARDS and therefore are not recommended in routine practice [7, 8, 11, 13]. They may be used however as a rescue therapy.