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Summary of COVID-19 nitric oxide studies

Studies   Meta Analysis   Hide extended summaries

25 patient nitric oxide ICU RCT: 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%).

Apr 2021, Infectious Microbes and Diseases, https://journals.lww.com/10.1097/IM9.0000000000000079, https://c19p.org/moni

80 patient nitric oxide early treatment RCT: 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.

May 2021, J. Infection, https://www.journalofinfection.com/article/S0163-4453(21)00251-6/fulltext, https://c19p.org/winchester

193 patient nitric oxide ICU RCT: 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/FiO2 > 300 mmHg and reduced rates of neurologic symptoms at 90 days. NO was associated with faster viral clearance. No serious adverse events were reported with NO.

Dec 2023, American J. Respiratory and Critical Care Medicine, https://www.atsjournals.org/doi/10.1164/rccm.202304-0637OC, https://c19p.org/difenza

207 patient nitric oxide early treatment RCT: 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 (0.45mL of solution/dose) for seven days.

Jun 2022, The Lancet Regional Health - Southeast Asia, https://www.sciencedirect.com/science/article/pii/S2772368222000464, https://c19p.org/tandon

625 patient nitric oxide prophylaxis study: 75% fewer cases (p<0.0001).
PEP retrospective 625 university students in Thailand offered nitric oxide nasal spray, showing significantly lower cases for students that chose to use the treatment.

Apr 2022, SaNOtize, https://sanotize.com/clinical-trials-covid/, https://c19p.org/sanotizepep

71 patient nitric oxide late treatment study: 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.

Jul 2022, Obstetrics & Gynecology, https://journals.lww.com/10.1097/AOG.0000000000004847, https://c19p.org/valsecchi

103 patient nitric oxide ICU study: 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.

Jun 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270646, https://c19p.org/poonam

815 patient nitric oxide ICU study: 40% higher mortality (p=0.1).
Retrospective 815 COVID-19 ICU patients in Saudi Arabia, showing significant improvement in oxygenation. There was no significant difference in mortality, and ICU and hospitalization time was longer.

Oct 2022, Critical Care, https://ccforum.biomedcentral.com/articles/10.1186/s13054-022-04158-y, https://c19p.org/alsulaiman4

524 patient nitric oxide early treatment RCT: 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 2020, with zero events in 2021 or 2022. Recovery was 11% faster with treatment, without statistical significance. Authors note that a higher dose may have been more effective. Trials showing greater efficacy have used a nasal spray.

Jun 2023, The American J. Medicine, https://www.sciencedirect.com/science/article/pii/S0002934323003911, https://c19p.org/bryan

272 patient nitric oxide late treatment study: 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 usage of several other treatments between the groups.

Jan 2021, Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, http://journals.sagepub.com/doi/10.1177/11795484211047065, https://c19p.org/chandel

34 patient nitric oxide late treatment RCT: 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.

May 2022, The American J. Emergency Medicine, https://www.sciencedirect.com/science/article/pii/S0735675722002832, https://c19p.org/strickland
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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