Nitric Oxide Therapies in Viral Respiratory Diseases

Nitric oxide (NO) has emerged as a multifaceted agent in the management of viral respiratory infections, combining direct antiviral activity with modulation of pulmonary haemodynamics and immune responses. Endogenously produced in the airway epithelium and vascular endothelium, NO mediates smooth muscle relaxation, improves ventilation–perfusion matching and exerts broad-spectrum antimicrobial effects. In the context of influenza, SARS-CoV and SARS-CoV-2, laboratory studies have shown that NO donors can disrupt viral entry processes and inhibit replication. Clinically, inhaled nitric oxide (iNO) has been deployed as a rescue therapy in acute respiratory distress syndrome (ARDS) due to viral pneumonia, aiming to enhance oxygenation and reduce ventilator requirements. Innovations include intermittent high-dose regimens to maximise antiviral potential, combination protocols with vasoactive agents to correct perfusion defects and exploration of donor compounds to extend systemic effects. While case series and observational cohorts report improvements in arterial oxygenation, the impact on survival and long-term outcomes remains uncertain. Ongoing research seeks to define optimal dosing strategies, identify responder phenotypes and integrate NO therapies with antiviral and anti-inflammatory regimens. These advances carry global significance as adaptable interventions in current and future viral outbreaks, offering a potential bridge between supportive care and targeted antiviral treatment.

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Nitric Oxide Therapies in Viral Respiratory Diseases publication trend

The graph below shows the total number of articles in nitric oxide therapies in viral respiratory diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Nitric oxide (NO): A gaseous signalling molecule that induces vascular relaxation, modulates immune responses and exhibits antiviral activity.

Inhaled nitric oxide (iNO): Administration of NO gas via the airway to target pulmonary vasculature and improve oxygenation in respiratory failure.

Acute respiratory distress syndrome (ARDS): A severe form of respiratory failure characterised by diffuse lung inflammation, hypoxaemia and decreased lung compliance.

PaO₂/FiO₂ ratio: The ratio of arterial oxygen partial pressure to fractional inspired oxygen, used to assess the severity of hypoxaemia.

NO donor: A pharmacological compound that releases nitric oxide or related species to exert systemic or local effects.

References

1. Potential Beneficial Role of Nitric Oxide in SARS-CoV-2 Infection: Beyond Spike-Binding Inhibition. Antioxidants (2024).
2. Inhaled nitric oxide in patients with acute respiratory distress syndrome caused by COVID-19: treatment modalities, clinical response, and outcomes. Annals of Intensive Care (2023).
3. Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: a multicenter cohort study. Critical Care (2022).
4. Unraveling the impact of nitric oxide, almitrine, and their combination in COVID-19 (at the edge of sepsis) patients: a systematic review. Frontiers in Pharmacology (2024).
5. Rescue therapy with inhaled nitric oxide and almitrine in COVID-19 patients with severe acute respiratory distress syndrome. Annals of Intensive Care (2020).
6. Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia. Nitric Oxide (2021).