Therapeutic Effects of Inhaled Nitric Oxide Therapy in COVID-19 Patients

Abstract

The global COVID-19 pandemic has become the largest public health challenge of recent years. The incidence of COVID-19-related acute hypoxemic respiratory failure (AHRF) occurs in up to 15% of hospitalized patients. Antiviral drugs currently available to clinicians have little to no effect on mortality, length of in-hospital stay, the need for mechanical ventilation, or long-term effects. Inhaled nitric oxide (iNO) administration is a promising new non-standard approach to directly treat viral burden while enhancing oxygenation. Along with its putative antiviral affect in COVID-19 patients, iNO can reduce inflammatory cell-mediated lung injury by inhibiting neutrophil activation, lowering pulmonary vascular resistance and decreasing edema in the alveolar spaces, collectively enhancing ventilation/perfusion matching. This narrative review article presents recent literature on the iNO therapy use for COVID-19 patients. The authors suggest that early administration of the iNO therapy may be a safe and promising approach for the treatment of COVID-19 patients. The authors also discuss unconventional approaches to treatment, continuous versus intermittent high-dose iNO therapy, timing of initiation of therapy (early versus late), and novel delivery systems. Future laboratory and clinical research is required to define the role of iNO as an adjunct therapy against bacterial, viral, and fungal infections.

High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia

“…[25][26][27] Due to its role in reducing ventilation-perfusion mismatching, iNO is used as a rescue therapy for hypoxemia in intubated and mechanically ventilated patients with hypoxic respiratory failure, both from COVID-19 and not. 8 Maternal hypoxemia is associated with an increased risk of miscarriage and fetal demise; thus, the Society for Maternal-Fetal Medicine COVID-19 task force recommends prompt reversal of hypoxemia and maintenance of an oxygen saturation greater than 95% in pregnant patients. 6 In a previous study, iNO was delivered to six nonintubated pregnant patients with severe COVID-19 pneumonia with the intent of increasing oxygenation.…”

The Endothelium and COVID-19: An Increasingly Clear Link Brief Title: Endotheliopathy in COVID-19

“…SARS-CoV-2’s tropism for endothelial cells leads to cell apoptosis, and thus a decrease in endothelial NO production [ 3 , 91 ]. Inhaled NO might be a therapeutic option in COVID-19 [ 92 ]. Inhaled NO has proven pulmonary vasodilation activity.…”

“…In vitro experiments have demonstrated that NO has antiviral activity against SARS-CoV-2 [ 93 ]. Although the modalities of inhaled NO administration (particularly the timing) still need to be explored, early initiation of this treatment might be promising [ 92 ].…”

High Doses of Inhaled Nitric Oxide as an Innovative Antimicrobial Strategy for Lung Infections

“…However, the lack of a larger clinical trial with patient-centered outcome as the primary endpoint precludes any further conclusion concerning iNO treatment in this patient population. More recently, due to the dramatic impact of the SARS-CoV-2 pandemic on the health system, several case series reported data on the treatment with iNO in patients with coronavirus disease 2019 (COVID-19) [ 77 ]. In all these studies, high-dose iNO (160–200 ppm) was delivered with intermittent regimens for 30 min per session twice daily.…”