SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial
Monika Tandon, Wen Wu, Keith Moore, Stephen Winchester, Yuan-Po Tu, Christopher Miller, Rahul Kodgule, Amol Pendse, Shabbir Rangwala, Shashank Joshi
The Lancet Regional Health - Southeast Asia, doi:10.1016/j.lansea.2022.100036
Background Additional outpatient therapies which are readily accessible will be essential to reduce COVID-19 illness progression in high risk individuals. Especially as the virus continues to mutate with greater transmissibility despite increased global vaccination. Methods A randomized, double-blind, multicentre, parallel group, placebo-controlled phase III clinical trial evaluated the ability of nitric oxide (NO) to rapidly eradicate nasal SARS-CoV-2 RNA. Adults (18À70 years) with mild symptomatic COVID-19 were randomized, confirmed by laboratory SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) nasal swab. Randomisation was 1:1, NONS (N = 153) vs placebo (N = 153). NO generated by a nasal spray (NONS) was self-administered six times daily as two sprays per nostril (0Á45 mL of solution/dose) for seven days. Patients at high risk of illness progression, defined as unvaccinated, 45 years of age or having comorbidities, were the primary analysis population. Findings Overall, mean SARS-CoV-2 RNA concentrations (6¢96 log10 copies/mL in the NONS group and 7¢16 log10 copies/mL in the placebo group) were comparable at baseline. Primary endpoint mean treatment difference SARS-CoV-2 RNA change from baseline to the end of treatment (EOT) was -0¢52 copies/mL (SE 0¢202, 95% CI -0¢ 92 to -0¢12; p = 0¢010) with NONS compared to placebo. Secondary endpoint assessments demonstrated a greater proportion of patients receiving NONS (82¢8%) cleared SARS-CoV-2 (RT-PCR negative) by EOT compared to placebo (66¢7%, p = 0¢046), with no virus RNA detected a median of four days earlier compared to placebo (three vs seven days; p = 0¢044). Interpretation Use of NONS in patients recently infected with SARS-CoV-2 accelerates nasal virus clearance.
Supplementary materials Supplementary material associated with this article can be found in the online version at doi:10.1016/j.lan sea.2022.100036.
References
Fang, Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity, J Clin Invest
Friedland, Tucker, Goodall, In vivo (human) and in vitro inactivation of SARS-CoV-2 with 0.5% povidone-iodine nasal spray, Aust J Otolaryng,
doi:10.21037/ajo-21-40
Giarratana, Rajan, Kamala, Mendenhall, Giorgio, A sprayable Acid-Oxidizing solution containing hypochlorous acid (AOS2020) efficiently and safely inactivates SARS-Cov-2: a new potential solution for upper respiratory tract hygiene, Eur Archi Oto-Rhino-Laryngology,
doi:10.1007/s00405-021-06644-5
Hirabara, Serdan, Gorjao, SARS-COV-2 variants: differences and potential of immune evasion, Front Cell Infect Microbiol,
doi:10.3389/fcimb.2021.781429
Kerstr€ Om S, Gunalan, Keng, Tan, Mirazimi, Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected, Virology
Mccarthy, Rennick, Nambulli, Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape, Science
Moncada, Higgs, Endogenous nitric oxide: physiology, pathology, and clinical relevance, Eur J Clin Invest
Motozono, Toyoda, Zahradnik, SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity, Cell Host Microbe,
doi:10.1016/j.chom.2021.06.006
Pajon, Paila, Girard, Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial, Nat Med,
doi:10.1038/s41591-022-01679-5
Regev-Shoshani, Vimalanathan, Mcmullin, Road, Gay et al., Gaseous nitric oxide reduces influenza infectivity in vitro, Nitric Oxide
Weinreich, Sivapalasingam, Norton, REGEN-COV antibody combination and outcomes in outpatients with COVID-19, N Engl J Med,
doi:10.1056/NEJMoa2108163
Winchester, John, Jabbar, Isaac, Clinical efficacy of nitric oxide nasal spray (NONS) for the treatment of mild COVID-19 infection, J Infect,
doi:10.1016/j.jinf.2021.05.009
Yeh, Using trapezoidal rule for the area under a curve calculation
Yu, Sun, Shi, Wang, Zhao et al., SARSCoV-2 viral load in sputum correlates with risk of COVID-19 progression, Crit Care,
doi:10.1186/s13054-020-02893-8
Zou, Ruan, Huang, Liang, Huang et al., SARS-CoV-2 viral load in upper respiratory specimens of infected patients, N Engl J Med