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Nitric Oxide for COVID-19
14 studies with >2,000 patients
Serious outcome risk
Nitric Oxide
Control
Significantly lower risk for hospitalization, cases, and viral clearance.
7 studies from 6 independent teams in 6 countries show significant benefit.
COVID-19 Nitric Oxide studies · October 2026
Nitric Oxide was adopted in 10 countries. Recent:
Maniscalco
Eby
Sarwal
Martins.
Covid Analysis Nitric Oxide reduces COVID-19 risk: real-time meta-analysis of 14 studies (Version 16)
Significantly lower risk is seen for hospitalization, cases, and viral clearance. 7 studies from 6 independent teams in 6 countries show significant benefit. Meta-analysis using the most serious outcome reported shows 35% [9‑54..
Mar 23
 Berra et al., NCT04305457 Nitric Oxide Gas Inhalation Therapy in Spontaneous Breathing Patients With Mild/Moderate COVID-19: a Randomized Clinical Trial
65% lower mortality (p=1) and 14% higher ventilation (p=1). Early terminated RCT 62 hosptialized patients, showing no significant difference with nitric oxide treatment.
Jan 9
 Martins et al., Viruses, doi:10.3390/v18010091 Broad-Spectrum Virucidal Activity of Nitric Oxide Nasal Spray (NONS) Against SARS-CoV-2 Variants and Major Respiratory Viruses
In vitro study showing broad-spectrum virucidal activity of nitric oxide nasal spray (NONS) against SARS-CoV-2 variants and major respiratory viruses. Authors found that NONS achieved >3 log10 reductions (>99.9% reduction) in viral infect..
Oct 13
2025
 Wright et al., Biochemistry Research International, doi:10.1155/bri/8846903 Nitric Oxide in the Treatment of COVID‐19: Nasal Sprays, Inhalants and Nanoparticles
Review of nitric oxide (NO) as a therapeutic for COVID-19, focusing on its administration as a nasal spray, inhalant, or via nanoparticles. Clinical trials on nitric oxide nasal spray (NONS) have shown it to be an effective and safe thera..
Mar 13
2025
 İdikut et al., Journal of Clinical Medicine, doi:10.3390/jcm14061931 Association of Endothelial Nitric Oxide Synthase Polymorphisms with Clinical Severity in Patients with COVID-19
Retrospective 178 COVID-19 patients examining the association between NOS3 genetic polymorphisms (G894T and 27-bp VNTR 4b/a) and disease severity. Overall, no statistically significant associations were found between NOS3 genotypes and CO..
Feb 11
2025
 Kurnik et al., Viruses, doi:10.3390/v17020244 Systolic Pulmonary Artery Pressure as Long-Term Mortality Predictor in Elderly Critically Ill with Severe COVID-19 Pneumonia
23% lower mortality (p=0.33). Retrospective 130 elderly (≥70 years) critically ill COVID-19 patients showing no significant difference in long-term mortality with nitric oxide.
Feb 6
2025
 Friedrich et al., ERJ Open Research, doi:10.1183/23120541.00006-2024 Inhaled nitric oxide for the treatment of COVID-19: an open-label, parallel, randomised controlled trial
50% lower need for oxygen therapy (p=0.09), no change in progression (p=1), and 36% shorter hospitalization (p=0.001). RCT 54 late stage hospitalized COVID-19 patients showing benefit with high-dose inhaled nitric oxide (iNO). Patients receiving 160 ppm iNO for 6 hours had significantly more days free of supplemental oxygen (11 vs 8 days, p=0.044) and sho..
Oct 26
2024
 Sánchez-García et al., Antioxidants, doi:10.3390/antiox13111301 Potential Beneficial Role of Nitric Oxide in SARS-CoV-2 Infection: Beyond Spike-Binding Inhibition
In vitro study showing that nitric oxide (NO) inhibits SARS-CoV-2 spike protein binding to ACE2 and reduces ACE2 enzymatic activity. Authors showed that NO donors DETA-NONOate (DETA-NO) and S-nitrosoglutathione (GSNO) significantly decrea..
Jul 26
2024
 Wolak et al., Scientific Reports, doi:10.1038/s41598-024-68055-w A safety evaluation of intermittent high-dose inhaled nitric oxide in viral pneumonia due to COVID-19: a randomised clinical study
64% lower need for oxygen therapy (p=0.03) and 41% shorter hospitalization (p=0.24). RCT 35 hospitalized patients with viral pneumonia (34 with COVID-19) showing improved recovery with high-dose inhaled nitric oxide (iNO) treatment. The treatment group received intermittent inhalations of 150 ppm iNO for 40 minutes, 4 tim..
Dec 15
2023
 Di Fenza et al., American Journal of Respiratory and Critical Care Medicine, doi:10.1164/rccm.202304-0637OC High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure Due to COVID-19: A Multicenter Phase II Trial
23% lower mortality (p=0.36), 30% lower progression (p=0.67), and 83% improvement (p=0.01). RCT 193 mechanically ventilated COVID-19 patients showing improved oxygenation at 48 hours but no difference in mortality with high-dose (80ppm) inhaled nitric oxide (NO) for 48 hours. The NO group had a higher proportion attaining PaO2/F..
Dec 15
2023
 Silva et al., Frontiers in Immunology, doi:10.3389/fimmu.2023.1284148 IFN-γ-mediated control of SARS-CoV-2 infection through nitric oxide
In vitro study showing that treatment with interferon-gamma (IFN-γ) inhibits SARS-CoV-2 infection in simian Vero E6 and human lung epithelial cell lines. The IFN-γ-triggered antiviral effect against SARS-CoV-2 is mediated through the endo..
Nov 1
2023
 Zhang et al., Medical Gas Research, doi:10.4103/2045-9912.385414 Saying No to SARS-CoV-2: the potential of nitric oxide in the treatment of COVID-19 pneumonia
Review of nitric oxide (NO) in the treatment of COVID-19. Authors summarizes evidence from in vitro studies suggesting NO has direct antiviral effects against SARS-CoV-2 as well as immune modulating and pulmonary protective effects. Small..
Oct 2
2023
 Zhao et al., Frontiers in Microbiology, doi:10.3389/fmicb.2023.1277552 Inhaled nitric oxide: can it serve as a savior for COVID-19 and related respiratory and cardiovascular diseases?
Review of inhaled nitric oxide (iNO) as a therapy for COVID-19 and related respiratory and cardiovascular diseases. Nitric oxide is an important signaling molecule produced by nitric oxide synthases that regulates various physiological pr..
Jun 27
2023
 Mekontso Dessap et al., Annals of Intensive Care, doi:10.1186/s13613-023-01150-9 Inhaled nitric oxide in patients with acute respiratory distress syndrome caused by COVID-19: treatment modalities, clinical response, and outcomes
Retrospective 300 COVID-19 ARDS ICU patients showing improved oxygenation (≥20% increase in PaO2/FiO2 ratio) within 6 hours for 46% of patients treated with inhaled nitric oxide (iNO).
Jun 24
2023
 Bryan et al., The American Journal of Medicine, doi:10.1016/j.amjmed.2023.05.021 The Efficacy of Nitric Oxide Generating Lozenges on Outcome in Newly Diagnosed COVID-19 Patients of African American and Hispanic Origin
1% higher progression (p=1) and 11% faster recovery (p=0.3). RCT 524 outpatients in the USA for a nitric oxide generating lozenge, showing no significant difference in combined hospitalization, ICU admission, intubation, dialysis, and death. There were only 3 events in each arm, all occuring in 202..
Feb 3
2023
 Yamasaki et al., Microorganisms, doi:10.3390/microorganisms11020397 Pleiotropic Functions of Nitric Oxide Produced by Ascorbate for the Prevention and Mitigation of COVID-19: A Revaluation of Pauling’s Vitamin C Therapy
Extensive review of vitamin C and nitric oxide focusing on the potential antiviral activity of vitamin C for SARS-CoV-2 via the production of nitric oxide. Authors note that vegetables are a major dietary source of nitrate, and that dieta..
Oct 3
2022
 Al Sulaiman et al., Critical Care, doi:10.1186/s13054-022-04158-y Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: a multicenter cohort study
40% higher mortality (p=0.1). Retrospective 815 COVID-19 ICU patients in Saudi Arabia, showing significant improvement in oxygenation within 24 hours with inhaled nitric oxide (iNO). There was no significant difference in mortality, and ICU and hospitalization time wa..
Aug 24
2022
 Oza et al., Nitric Oxide, doi:10.1016/j.niox.2022.08.003 Utility of NO and H2S donating platforms in managing COVID-19: Rationale and promise
Extensive review of the mechanisms of action and potential benefits of nitric oxide and hydrogen sulfide for SARS-CoV-2 and other viral infections.
Jul 7
2022
 Valsecchi et al., Obstetrics & Gynecology, doi:10.1097/AOG.0000000000004847 High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia
68% lower ventilation (p=0.08) and 39% lower ICU admission (p=0.28). Retrospective 71 hospitalized patients in Israel, 20 treated with inhaled nitric oxide, showing no significant differences.
Jun 29
2022
 Tandon et al., The Lancet Regional Health - Southeast Asia, doi:10.1016/j.lansea.2022.100036 SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial
68% greater improvement (p=0.08) and 20% improved viral clearance (p<0.0001). RCT with 153 patients treated with a nitric oxide nasal spray, and 153 placebo patients, showing faster viral clearance with treatment. NO generated by a nasal spray (NONS) self-administered six times daily as two sprays per nostril (0.45..
Jun 27
2022
 Poonam et al., PLOS ONE, doi:10.1371/journal.pone.0270646 Nitric oxide versus epoprostenol for refractory hypoxemia in Covid-19
14% lower mortality (p=0.1). Retrospective 103 mechanically ventilated patients, 41 treated with inhaled nitric oxide, and 62 with inhaled epoprostenol, showing no significant difference in outcomes.
May 31
2022
 Sarwal et al., Journal of Ayurveda and Integrative Medicine, doi:10.1016/j.jaim.2022.100586 Efficacy of Pranayama in Preventing COVID-19 in Exposed Healthcare Professionals: A Quasi-Randomized Clinical Trial
89% fewer cases (p=0.02). Quasi-randomized trial of 250 healthcare professionals (HCPs) exposed to COVID-19 in India showing benefit with a twice-daily Pranayama, including Bhramari Pranayama, which is a calming yoga breathing technique where a steady humming soun..
May 4
2022
 Strickland et al., The American Journal of Emergency Medicine, doi:10.1016/j.ajem.2022.04.052 Safety and practicality of high dose inhaled nitric oxide in emergency department COVID-19 patients
179% higher ventilation (p=1), 21% lower hospitalization (p=1), and 38% worse results (p=0.72). Early terminated RCT with 47 ER patients in the USA, less than 12 days of symptoms, showing no significant difference in outcomes with a single high-dose administration of inhaled nitric oxide by mask, 250ppm for 30 min.
Apr 30
2022
 Miller et al., Respiratory Therapy, 18:2, 2023 (date from earlier release of results) Epidemiological Analysis of Nitric Oxide Nasal Spray (VirX™) Use in Students Exposed to COVID-19 Infected Individuals
75% fewer cases (p<0.0001). Retrospective 625 high-risk university students in Thailand showing reduced SARS-CoV-2 infection rates with nitric oxide nasal spray prophylaxis. Among students exposed to infected individuals, those voluntarily using treatment (n=203) ha..
Jan 28
2022
 Akash et al., Frontiers in Drug Delivery, doi:10.3389/fddev.2023.1164671 (date from preprint) On a model-based approach to improve intranasal spray targeting for respiratory viral infections
Computational fluid dynamics study of nasal spray administration in 2 subjects showing 100x improvement in nasopharyngeal drug delivery using a new spray placement protocol. The study also found the optimal droplet size range for nasophar..
May 13
2021
 Winchester et al., Journal of Infection, doi:10.1016/j.jinf.2021.05.009 Clinical efficacy of nitric oxide nasal spray (NONS) for the treatment of mild COVID-19 infection
42% greater improvement (p=0.008) and 51% improved viral clearance (p=0.001). RCT with 40 nitric oxide and 40 placebo patients in the UK, showing faster viral clearance and greater improvement with treatment.
Apr 20
2021
 Moni et al., Infectious Microbes and Diseases, doi:10.1097/IM9.0000000000000079 (date from preprint) Clinical Efficacy of Inhaled Nitric Oxide in Preventing the Progression of Moderate to Severe COVID-19 and Its Correlation to Viral Clearance: Results of a Pilot Study
90% lower mortality (p=0.03), 90% lower ventilation (p=0.03), 42% greater improvement (p=0.47), and 64% faster viral clearance (p=0.005). RCT 29 ICU patients in India, showing improved clinical outcomes and faster viral clearance with inhaled nitric oxide treatment. The treatment group was younger (mean 54 vs. 66) and had more patients on NIV at baseline (29% vs. 18%).
Jan 31
2021
 Chandel et al., Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, doi:10.1177/11795484211047065 Inhaled Nitric Oxide via High-Flow Nasal Cannula in Patients with Acute Respiratory Failure Related to COVID-19
54% higher mortality (p=0.25) and 27% higher ventilation (p=0.26). Retrospective 272 acute respiratory failure patients in the USA treated with high-flow nasal cannula, 66 treated with inhaled nitric oxide, showing increased mortality with inhaled nitric oxide. There were significant differences in the u..
Nov 12
2020
 Abou-Arab et al., Critical Care, doi:10.1186/s13054-020-03371-x Inhaled nitric oxide for critically ill Covid-19 patients: a prospective study
Retrospective 34 ICU patients in France treated with inhaled nitric oxide, showing 65% had an increase in PaO2/FiO2 of >20% 30 min following administration.
Oct 31
2020
 Akaberi et al., Redox Biology, doi:10.1016/j.redox.2020.101734 Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro
In vitro study showing that nitric oxide can inhibit the replication of SARS-CoV-2 in Vero E6 cells, and identifying the SARS-CoV-2 main protease as a target for nitric oxide.
Jun 23
2020
 Hedenstierna et al., Nitric Oxide, doi:10.1016/j.niox.2020.06.005 Nitric oxide dosed in short bursts at high concentrations may protect against Covid 19
Hypothesis that reduced incidence of COVID-19 cases for smokers in some studies is due to bursts of high concentrations of nitric oxide during smoking.
Jan 31
2006
 Eby, G., Medical Hypotheses, doi:10.1016/j.mehy.2005.11.035 Strong humming for one hour daily to terminate chronic rhinosinusitis in four days: A case report and hypothesis for action by stimulation of endogenous nasal nitric oxide production
Case report of an outpatient showing significant symptomatic benefit with strong, low-pitch humming (a method to increase endogenous nitric oxide).
Aug 1
2003
 Maniscalco et al., European Respiratory Journal, doi:10.1183/09031936.03.00017903 Assessment of nasal and sinus nitric oxide output using single-breath humming exhalations
Physiological study of 10 healthy volunteers and a sinus/nasal model characterizing nasal nitric oxide (NO) output during humming exhalations. Humming caused a ~5-fold increase in nasal NO output compared to silent exhalation (2,233 vs. 4..
Jul 15
2002
 Weitzberg et al., American Journal of Respiratory and Critical Care Medicine, doi:10.1164/rccm.200202-138BC Humming Greatly Increases Nasal Nitric Oxide
Study of 10 healthy subjects showing that humming increased nasal nitric oxide (NO) levels 15 fold compared to quiet exhalation, likely due to increased sinus ventilation and gas exchange between the sinuses and nasal cavity. In a two-com..
Jun 1
1999
 Chatkin et al., Archives of Otolaryngology–Head & Neck Surgery, doi:10.1001/archotol.125.6.682 Nitric Oxide Accumulation in the Nonventilated Nasal Cavity
Analysis of nitric oxide concentrations in the nonventilated nasal cavity, showing increasing levels with time. Results indicate that nitric oxide levels can be increased with breathing techniques.