Summary of COVID-19 nasopharyngeal/oropharyngeal treatment studies
1. Choudhury et al., Effect of 1% Povidone Iodine Mouthwash/Gargle, Nasal and Eye Drop in COVID-19 patient
606 patient povidone-iodine early treatment RCT: 88% lower mortality (p=0.0006), 84% lower hospitalization (p<0.0001), and 96% improved viral clearance (p<0.0001).RCT 606 patients in Bangladesh for povidone iodine mouthwash/gargle, nasal drops and eye drops showing significantly lower death, hospitalization, and PCR+ at day 7.
Dec 2020, Bioresearch Communications, https://www.banglajol.info/index.php/BRC/article/view/54245, https://c19p.org/choudhury
1,123 patient SA58 prophylaxis RCT: 81% fewer symptomatic cases (p=0.0004) and 62% fewer cases (p=0.0001).
RCT 1,222 healthy adult workers in China showing SA58 (anti-SARS-CoV-2 monoclonal antibody) nasal spray reduced symptomatic COVID-19 by 81% and SARS-COV-2 infection by 62% compared to placebo when used as post-exposure prophylaxis within 72 hours of exposure. Efficacy was significantly lower when including participants who tested positive within 24 hours of first administration, suggesting SA58 is less effective once infection is established.
May 2023, Emerging Microbes & Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2023.2212806, https://c19p.org/song9
3. Almanza-Reyes et al., Evaluation of silver nanoparticles for the prevention of SARS-CoV-2 infection in health workers: In vitro and in vivo
231 patient AgNP prophylaxis RCT: 94% fewer cases (p<0.0001) and 49% improvement (p=0.003).RCT 231 healthcare workers showing significantly lower COVID-19 infection rates with silver nanoparticle (AgNPs) oral and nasal rinses. Authors also report in vitro experiments showing dose-dependent inhibition in cell cultures.
Aug 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256401, https://c19p.org/almanzareyes
4. de Gabory et al., Seawater nasal wash to reduce symptom duration and viral load in COVID-19 and upper respiratory tract infections: a randomized controlled multicenter trial
173 patient alkalinization early treatment RCT: 75% lower progression (p<0.0001), 24% faster recovery (p=0.02), and 37% improved viral clearance (p=0.54).RCT 355 adults with COVID-19 or other upper respiratory tract infections (URTIs). For COVID-19 patients there was lower progression and faster symptom resolution with alkaline seawater nasal wash (pH ~8) 4 times daily for 21 days. There was significantly lower transmission for patients with the delta variant and for patients with high viral load. The seawater nasal wash was safe and well-tolerated.
Feb 2024, European Archives of Oto-Rhino-Laryngology, https://link.springer.com/10.1007/s00405-024-08518-y, https://c19p.org/degabory
5. Winchester et al., Clinical efficacy of nitric oxide nasal spray (NONS) for the treatment of mild COVID-19 infection
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
50 patient curcumin late treatment RCT: 77% improved recovery (p=0.04), 92% lower need for oxygen therapy (p=0.01), 13% shorter hospitalization (p=0.92), and 10% improved viral clearance (p=0.77).
RCT 50 hospitalized patients in Israel, 33 treated with curcumin, vitamin C, artemisinin, and frankincense oral spray, showing improved recovery with treatment.
May 2022, J. Cellular and Molecular Medicine, https://onlinelibrary.wiley.com/doi/10.1111/jcmm.17337, https://c19p.org/hellou
7. da Silva Santos et al., Beneficial effects of a mouthwash containing an antiviral phthalocyanine derivative on the length of hospital stay for COVID-19: randomised trial
41 patient phthalocyanine late treatment RCT: 85% lower mortality (p=0.23), 92% lower ICU admission (p=0.02), and 54% lower hospitalization (p=0.03).RCT 41 patients in Brazil, 20 treated with a phthalocyanine derivative mouthwash, showing shorter hosptalization and lower ICU admission with treatment. One minute gargling/rinsing 5 times per day.
Oct 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-99013-5, https://c19p.org/dasilvasantos
8. Matsuyama et al., A prospective, randomized, open-label trial of early versus late povidone-iodine gargling in patients with COVID-19
279 patient povidone-iodine early treatment RCT: 69% improved viral clearance (p=0.03).RCT 430 COVID+ patients in Japan, showing significantly lower viral infectivity from culture, and significantly faster PCR viral clearance with PVP-I. For days 2-4 the study compares treatment with PVP-I vs. water (on day 5 both groups received PVP-I). Most patients were asymptomatic. 4 times per day mouthwashing and gargling with 20mL of 15-fold diluted PVP-I 7% or water.
Nov 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-24683-8, https://c19p.org/matsuyama
9. Gutiérrez-García et al., Nasopharyngeal and oropharyngeal rinses with neutral electrolyzed water prevents COVID‑19 in front‑line health professionals: A randomized, open‑label, controlled trial in a general hospital in Mexico City
163 patient hypochlorous acid prophylaxis RCT: 91% fewer symptomatic cases (p=0.004).RCT 170 front-line healthcare workers in Mexico showing significantly lower COVID-19 cases with neutral electrolyzed water (SES) nasal and oral rinses. Authors hypothesize that SES inactivates viral particles through its oxidizing potential, reducing viral load in the upper respiratory tract where SARS-CoV-2 initially establishes infection. HOCl is the primary active component of neutral electrolyzed saline.
Dec 2021, Biomedical Reports, http://www.spandidos-publications.com/10.3892/br.2021.1494, https://c19p.org/gutierrezgarcia
294 patient chlorhexidine late treatment RCT: 75% improved viral clearance (p<0.0001).
RCT 294 hospitalized patients in the USA, showing faster oropharyngeal viral clearance with chlorhexidine. Results were better with a combination of oropharyngeal rinse and posterior oropharyngeal spray compared with the rinse alone.
Apr 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jmv.26954, https://c19p.org/huang8
394 patient iota-carrageenan prophylaxis RCT: 80% fewer symptomatic cases (p=0.03).
Prophylaxis RCT with 394 healthcare workers, 196 treated with iota-carrageenan, showing significantly lower symptomatic cases with treatment. There were no deaths or hospitalizations. There was a significant number of PCR- symptomatic cases (7.6% treatment and 8.6% control). The two treatment cases occurred shortly after randomization - infection may have occurred before the start of treatment.
Apr 2021, Int. J. General Medicine, https://www.dovepress.com/efficacy-of-a-nasal-spray-containing-iota-carrageenan-in-the-postexpos-peer-reviewed-fulltext-article-IJGM, https://c19p.org/figueroa
12. Friedland et al., Phase II Trial of the Impact 0.5% Povidone‐Iodine Nasal Spray (Nasodine®) on Shedding of SARS‐CoV‐2
23 patient povidone-iodine early treatment RCT: 60% improved viral clearance (p=0.03) and 6% improved recovery.RCT 23 early COVID-19 outpatients showing significantly improved reduction in viral load and significantly faster viral clearance with povidone-iodine nasal spray compared to placebo. The study was underpowered due to low recruitment, enrolling only 23 patients from a target of 144. Authors report generally mild symptoms and a 6% benefit over placebo on symptom scores (AUC symptom score days 2-5) without statistical significance, but do not provide details. Notably, no benefit was seen for rapid antigen test positivity, which is unable to distinguish viable and non-viable virus. The relatively poor diagnostic information from viral positivity using methods that cannot distinguish viable virus may present misleading results in many COVID-19 studies. Treatment 8 times daily for a total of 20 doses.
Mar 2024, The Laryngoscope, https://onlinelibrary.wiley.com/doi/10.1002/lary.31430, https://c19p.org/friedland2
13. Seet et al., Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
1,354 patient povidone-iodine prophylaxis RCT: 45% fewer symptomatic cases (p=0.002) and 31% fewer cases (p=0.01).Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths.
Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seetp
114 patient ivermectin early treatment RCT: 63% improved recovery (p=0.0001) and 79% improved viral clearance (p=0.004).
RCT 114 patients, 57 treated with ivermectin mucoadhesive nanosuspension intranasal spray, showing faster recovery and viral clearance with treatment.
Jun 2021, Int. J. Nanomedicine, https://www.dovepress.com/clinical-biochemical-and-molecular-evaluations-of-ivermectin-mucoadhes-peer-reviewed-fulltext-article-IJN, https://c19p.org/aref
15. Karami et al., A Comparison of the Effects of Chlorhexidine and Sodium Bicarbonate Mouthwashes on COVID-19–Related Symptoms
76 patient chlorhexidine prophylaxis RCT: 61% lower progression (p=0.04) and 57% fewer cases (p=0.03).RCT 116 healthcare workers comparing 0.2% chlorhexidine mouthwash (n=36), 7.5% sodium bicarbonate mouthwash (n=40), and placebo (n=40) twice daily for 2 weeks, with symptoms followed for 4 weeks. There were lower symtoms and cases in both treatment groups, with statistical significance for chlorhexidine only. The treatments were stopped after two weeks, results may be better with continued use, more frequent use, and with the addition of nasal use.
Jan 2024, Iranian J. Nursing and Midwifery Research, https://journals.lww.com/jnmr/fulltext/2024/29010/a_comparison_of_the_effects_of_chlorhexidine_and.8.aspx, https://c19p.org/karami
16. Karaaltin et al., Effect of the povidone iodine, hypertonic alkaline solution and saline nasal lavage on nasopharyngeal viral load in COVID-19
60 patient povidone-iodine early treatment RCT: 83% improved viral load (p=0.007).RCT 120 outpatients in Turkey, showing improved reduction in viral load with PVP-I nasal irrigation. PVP-I prepared with hypertonic alkaline solution had better results. [Kreutzberger] show that SARS-CoV-2 requires acidic pH to infect cells, therefore alkalinization may add additional benefits. All patients received favipiravir. PVP-I 1% 4 times per day.
Oct 2022, Authorea, https://www.authorea.com/users/337860/articles/592062-effect-of-the-povidone-iodine-hypertonic-alkaline-solution-and-saline-nasal-lavage-on-nasopharyngeal-viral-load-in-covid-19?commit=bcb03d2ad8d86742ebd473271b70f5ab7211094d, https://c19p.org/karaaltin
17. Wang et al., Efficacy of nasal irrigation and oral rinse with sodium bicarbonate solution on virus clearance for COVID-19 patients
55 patient alkalinization late treatment RCT: 39% shorter hospitalization (p=0.0009).RCT 55 mild/moderate patients in China, showing shorter hospitalization with sodium bicarbonate nasal irrigation and oral rinsing. Oral rinse with 5% sodium bicarbonate solution three times daily. Nasal irrigation two times with the solution entering through one nostril and exiting from the other. 30-40mL of solution was used every time and irrigation was performed for at least 30s. Details of randomization are not provided.
Mar 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1145669/full, https://c19p.org/wang12
18. Tandon et al., SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial
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
134 patient phthalocyanine early treatment RCT: 29% improved recovery (p=0.02).
RCT 500 patients in Brazil, showing improved recovery with a phthalocyanine derivative mouthwash and toothpaste. Toothbrushing for 2 minutes, three times per day, and gargling/rising (5ml) for one minute, three times a day, for 7 days.
Dec 2021, J. Evidence-Based Dental Practice, https://www.sciencedirect.com/science/article/pii/S1532338222001002, https://c19p.org/poleti
20. Yilmaz et al., Effects of hypertonic alkaline nasal irrigation on COVID‐19
60 patient alkalinization early treatment RCT: 86% lower hospitalization (p=0.24) and 62% improved viral clearance (p=0.87).RCT 60 outpatients with mild COVID-19 showing improved viral clearance with hypertonic alkaline (pH 9.3) nasal irrigation. All patients received HCQ. The nasal irrigation group had no hospitalizations, while 3 patients in the control group required hospitalization, associated with viral load increase at day 3.
Nov 2021, Laryngoscope Investigative Otolaryngology, https://onlinelibrary.wiley.com/doi/10.1002/lio2.686, https://c19p.org/yilmaz4
57 patient sentinox early treatment RCT: 29% improved viral clearance (p=0.01).
RCT 57 mild COVID-19 patients showing non-significant viral load reduction with Sentinox (STX), a hypochlorous acid nasal spray. The proportion of COVID negative patients by day 5 was significantly higher in the STX-3 group than controls. Authors note that the results were likely driven by outliers with extreme baseline viral loads. When considering subjects with baseline cycle threshold values of 20-30, STX-3 showed a significant 2.01 log10 reduction. A complementary in vitro study demonstrated STX had ≥99.9% virucidal activity against various respiratory viruses including influenza, RSV, rhinovirus, adenovirus, parainfluenza, and seasonal coronavirus.
May 2022, Viruses, https://www.mdpi.com/1999-4915/14/5/1033, https://c19p.org/panatto
22. Aref et al., Possible Role of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Recovery of Post-COVID-19 Anosmia
96 patient ivermectin long COVID RCT: 74% faster recovery (p=0.0005).96 patient RCT showing faster resolution of post-COVID anosmia with an ivermectin nanosuspension nasal spray.
Sep 2022, Infection and Drug Resistance, https://www.dovepress.com/possible-role-of-ivermectin-mucoadhesive-nanosuspension-nasal-spray-in-peer-reviewed-fulltext-article-IDR, https://c19p.org/aref2
23. Arefin et al., Virucidal effect of povidone iodine on COVID-19 in the nasopharynx: an open-label randomized clinical trial
189 patient povidone-iodine early treatment RCT: 79% improved viral clearance (p=0.02).RCT with 189 patients showing significantly greater viral clearance with a single application of PVP-I. Authors recommend using PVP-I prophylactically in the nasopharynx and oropharynx. NCT04549376 [trialsjournal.biomedcentral.com].
May 2021, Indian J. Otolaryngology and Head & Neck Surgery, https://link.springer.com/article/10.1007/s12070-021-02616-7, https://c19p.org/arefin
24. Rengifo et al., A Mouthwash with Cetylpyridinium Chloride is reducing salivary SARS-CoV-2 viral load in +COVID-19
23 patient cetylpyridinium chloride late treatment RCT: 83% improved viral clearance (p=0.06).RCT 23 patients in Colombia, showing improved viral clearance with cetylpyridinium chloride plus chlorhexidine mouthwash.
May 2023, Revista Estomatologia, https://estomatologia.univalle.edu.co/index.php/revista_estomatologia/article/download/12669/15872, https://c19p.org/rengifo
621 patient povidone-iodine early treatment RCT: 91% lower hospitalization (p=0.06), 15% faster recovery (p=0.008), 68% improved viral clearance (p<0.0001), and 92% lower transmission (p<0.0001).
RCT with 200 patients and 421 contacts, with 100 patients and their contacts treated with nasal and oropharyngeal sprays containing povidone-iodine and glycyrrhizic acid, showing significantly faster viral clearance and recovery, and significantly lower transmission. SOC included vitamin C and zinc. The spray active ingredients included a compound of glycyrrhizic acid in the form of ammonium glycyrrhizate 2.5 mg/ml plus PVI 0.5% for oropharyngeal and dipotassium glycyrrhizinate 2.5 mg/ml plus PVI 0.5% for nasal spray. Patients were advised to concomitantly use oropharyngeal and nasal sprays 6 times per day. They were instructed to abstain from food, drink, and smoke for 20min, particularly after oropharyngeal spray. The oropharyngeal spray bottle contains an atomizer that ends with a long arm applicator to insert inside the mouth cavity and can be directed up, down, right, or left to cover the entire pharyngeal area.
Apr 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.863917/full, https://c19p.org/elsersy
3,368 patient SA58 prophylaxis study: 78% fewer cases (p=0.0001).
Prospective study of 3,368 medical personnel in China showing significantly lower COVID-19 cases with SA58 nasal spray use.
Dec 2023, China CDC Weekly, https://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2023.040, https://c19p.org/si
27. Sanchez-Gonzalez et al., Intranasal Chlorpheniramine Maleate for the treatment of COVID-19: Translational and Clinical Evidence
45 patient chlorpheniramine early treatment RCT: 87% lower hospitalization (p=0.08).Small RCT showing significantly improved recovery with intranasal chlorpheniramine maleate. Authors also perform an in vitro study showing efficacy with a highly differentiated three-dimensional model of normal, human-derived tracheal/bronchial epithelial cells.
Dec 2022, Medical Research Archives, https://esmed.org/MRA/index.php/mra/article/view/2752, https://c19p.org/sanchezgonzalez2
28. Miller et al., Epidemiological Analysis of Nitric Oxide Nasal Spray (VirX™) Use in Students Exposed to COVID-19 Infected Individuals
625 patient nitric oxide prophylaxis study: 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) had a 6.4% infection rate compared to 25.6% in the control group (n=422) (p<0.0001). Adverse events were limited to mild nasal burning or irritation in 11.4% of users, with no severe events reported. Authors note the study is limited by its retrospective, open-label nature and lack of randomization. Students who chose the treatment may have been more health-conscious or compliant with other protective measures. Authors are executives of the manufacturer.
Apr 2022, Respiratory Therapy, 2023, https://www.respiratorytherapy.ca/pdf/RT-18-2-Spring-2023-R17-web.pdf, https://c19p.org/miller
243 patient hypromellose prophylaxis study: 76% fewer cases (p=0.04).
Prospective observational study of 243 community members showing significantly lower SARS-CoV-2 infection with Taffix nasal spray during a high-risk mass gathering event. During the 14-day follow-up, 0% of per-protocol Taffix users (0/81) became infected compared to 10% of non-users (16/160). Among intention-to-treat users, 2.4% (2/83) became infected versus 10% in non-users. The study occurred during peak COVID-19 transmission in Bney Brak, Israel, where infection rates increased from 17.6% to 28.1% during the study period. Users may have been more health-conscious and careful with other protective measures. No adverse events were reported.
Apr 2021, Expert Review of Anti-infective Therapy, https://www.tandfonline.com/doi/full/10.1080/14787210.2021.1908127, https://c19p.org/shmuel
30. Guenezan et al., Povidone Iodine Mouthwash, Gargle, and Nasal Spray to Reduce Nasopharyngeal Viral Load in Patients With COVID-19: A Randomized Clinical Trial
24 patient povidone-iodine early treatment RCT: 63% improved viral load (p=0.25).RCT of PCR+ patients with Ct ≤20 with 12 treatment and 12 control patients, concluding that nasopharyngeal decolonization may reduce the carriage of infectious SARS-CoV-2 in adults with mild to moderate COVID-19. All patients but 1 had negative viral titer by day 3 (group not specified). There was no significant difference in viral RNA quantification over time. The mean relative difference in viral titers between baseline and day 1 was 75% [43%-95%] in the intervention group and 32% [10%-65%] in the control group. Thyroid dysfunction occurred in 42% of treated patients, with spontaneous resolution after the end of treatment. Patients in the treatment group were younger.
Feb 2021, JAMA Otolaryngol Head Neck Surg., https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2775984, https://c19p.org/guenezan
31. Di Domênico et al., Effectiveness of hydrogen peroxide as auxiliary treatment for hospitalized COVID-19 patients in Brazil: preliminary results of a randomized double-blind clinical trial
40 patient hydrogen peroxide late treatment RCT: 50% lower ICU admission (p=1), 6% greater improvement (p=0.91), and 7% higher hospital discharge (p=0.61).RCT very late treatment (>10 days from onset) comparing hydrogen peroxide + mint essence with water + mint essence, showing no significant differences.
Apr 2021, Epidemiology and Health, http://e-epih.org/journal/view.php?doi=10.4178/epih.e2021032, https://c19p.org/didomenico
32. Mukhtar et al., A Randomized trial on the regular use of potent mouthwash in COVID-19 treatment
92 patient hydrogen peroxide early treatment RCT: 86% lower mortality (p=0.24), 86% lower ventilation (p=0.24), and 18% improved viral clearance (p=0.16).RCT for mouthwash containing hydrogen peroxide 2% and chlorhexidine gluconate, showing higher discharge, shorter hospital stay, less intubation, and lower mortality with treatment.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.27.20234997v2, https://c19p.org/mukhtar
33. Jamir et al., Determinants of Outcome Among Critically Ill Police Personnel With COVID-19: A Retrospective Observational Study From Andhra Pradesh, India
266 patient povidone-iodine ICU study: 57% lower mortality (p=0.0004).Retrospective 266 COVID-19 ICU patients in India, showing significantly lower mortality with PVP-I oral gargling and topical nasal use, and non-statistically significant higher mortality with ivermectin and lower mortality with remdesivir. Note that the timing of treatment is not clear - authors note that patients "had been provided with bottles of commercially available povidone-iodine gargle (2% solution) as a preventive and adjuvant measure against COVID-19".
Dec 2021, Cureus, https://www.cureus.com/articles/73667-determinants-of-outcome-among-critically-ill-police-personnel-with-covid-19-a-retrospective-observational-study-from-andhra-pradesh-india, https://c19p.org/jamirp
34. Campione et al., Lactoferrin as Antiviral Treatment in COVID-19 Management: Preliminary Evidence
64 patient lactoferrin early treatment study: 47% faster viral clearance (p=0.0001).Small prospective study in Italy with 32 lactoferrin patients, 32 SOC, and 28 patients with no treatment, showing significantly faster viral clearance and improved recovery with treatment in unadjusted results. Oral and intranasal lactoferrin.
Oct 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/20/10985, https://c19p.org/campione
35. Reznikov et al., Identification of antiviral antihistamines for COVID-19 repurposing
azelastine prophylaxis study: 45% fewer cases (p=0.03).Retrospective 219,000 patients showing lower risk of COVID-19 with antihistamine H1RA use. In vitro study showing these drugs exhibit direct antiviral activity against SARS-CoV-2. Molecular docking suggests hydroxyzine and azelastine may exert antiviral effects by binding ACE2 and the sigma-1 receptor.
Jan 2021, Biochemical and Biophysical Research Communications, https://www.sciencedirect.com/science/article/pii/S0006291X20321409, https://c19p.org/reznikovazl
36. Ponphaiboon et al., Efficacy of Nasal Spray, Mouth Spray, and Mouthwash Containing Limonene, Cetylpyridinium Chloride, and Monolaurin in COVID-19 Management: A Double-Blind, Randomized, Placebo-Controlled Trial
116 patient cetylpyridinium chloride early treatment RCT: 36% improved recovery (p=0.006).RCT 120 low-risk COVID-19 patients showing improved recovery with nasal and oral formulations containing cetylpyridinium chloride, D-limonene, and monolaurin (the nasal formulation contained D-limonene and cetylpyridinium chloride, while the oral formulation contained D-limonene, monolaurin, and cetylpyridinium chloride). No patients progressed to severe disease. No adverse events were reported in either group during the 7 day treatment period or 1 month followup. Placebo contents are not specified - authors note only "a homogenized liquid carrier", however any liquid rinse may have some efficacy via mechanical clearance.
Sep 2025, MDPI AG, https://www.preprints.org/manuscript/202509.1594/v1, https://c19p.org/ponphaiboon2
37. Mohamed et al., Early viral clearance among COVID-19 patients when gargling with povidone-iodine and essential oils: a pilot clinical trial
10 patient povidone-iodine early treatment RCT: 86% improved viral clearance (p=0.17).Tiny RCT with 5 PVP-I patients, gargling 30 seconds, 3x per day, and 5 control patients (essential oils and tap water were also tested), showing improved viral clearance with PVP-I.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.07.20180448v1, https://c19p.org/mohamed
38. El-Badrawy et al., Efficacy and safety of nebulized Sodium Bicarbonate in adults with COVID-19 (SODIC): a randomized, single center, double-blinded, controlled trial
546 patient alkalinization late treatment RCT: 23% lower mortality (p=0.26) and 28% faster recovery (p<0.0001).RCT 546 patients showing significantly faster recovery and lower mortality with sodium bicarbonate (inhaled and nasal drops). The reduction in mortality is only statistically significant when excluding baseline critical cases. Authors hypothesize that treatment raises endosomal pH, potentially preventing SARS-CoV-2 attachment and entry into host cells. Inhalation of nebulized sodium bicarbonate 8.4% (5ml every 4h) 7:00am to 23:00pm every day for 30 days together with 8.4% nasal drops 4 times daily (three drops for each nostril).
Nov 2022, Current Therapeutic Research, https://www.sciencedirect.com/science/article/pii/S0011393X25000268, https://c19p.org/elbadrawy
39. Di Domênico et al., Hydrogen peroxide as an auxiliary treatment for COVID-19 in Brazil: a randomized double-blind clinical trial
128 patient hydrogen peroxide late treatment RCT: 34% lower ICU admission (p=1), 1% worse recovery (p=0.97), and 31% lower long COVID (p=0.54).RCT very late treatment (>9 days from onset) comparing hydrogen peroxide + mint essence with water + mint essence, showing no significant differences.
Aug 2021, Epidemiology and Health, http://e-epih.org/journal/view.php?doi=10.4178/epih.e2021051, https://c19p.org/didomenico2
40. Daneshfard et al., Effect of Sinamaz nasal drop on asymptomatic family members of COVID 19 patients: An open-label randomized controlled trial
173 patient nigella sativa prophylaxis RCT: 34% fewer symptomatic cases (p=0.006).RCT 173 family members of COVID-19 patients, showing lower incidence of COVID-19 symptoms with nasal drops containing nigella sativa oil and olea europaea oil. One drop in each nostril twice daily for 7 days.
Jul 2023, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/epdf/10.1002/ptr.7915, https://c19p.org/daneshfard
41. Valerio-Pascua et al., Chlorpheniramine Intranasal Spray to Accelerate COVID-19 Clinical Recovery in an Outpatient Setting: The ACCROS Trials
660 patient chlorpheniramine early treatment study: 54% faster recovery (p<0.0001).RCT and retrospective study of chlorpheniramine nasal spray for COVID-19. The retrospective study included 660 outpatients showing fewer days with general COVID-19 symptoms, cough, anosmia, and ageusia compared to standard of care alone. The RCT results are listed separately [Valerio-Pascua].
Oct 2022, Research Square, https://www.researchsquare.com/article/rs-2167465/v1, https://c19p.org/valeriopascua3b
42. Wang et al., Safety and Effectiveness of SA58 Nasal Spray against SARS-CoV-2 family transmission: an exploratory single-arm trial
432 patient SA58 prophylaxis study: 34% fewer cases (p<0.0001).Exploratory single-arm trial of 70 family contacts showing a protective effect of SA58 nasal spray against household SARS-CoV-2 transmission. The incidence of infection was 62.9% in the experimental group versus 94.8% in a contemporaneous control group (n=362), suggesting that SA58 nasal spray reduced transmission risk by 33.8% overall. Using SA58 at least three times daily showed better protection than once a day.
Mar 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.03.19.23287462, https://c19p.org/wang46
43. Amoah et al., Further observations on hydrogen peroxide antisepsis and COVID-19 cases among healthcare workers and inpatients
466 patient hydrogen peroxide prophylaxis study: 93% fewer cases (p=0.06).Retrospective 458 healthcare workers in Ghana, showing lower COVID-19 cases with hydrogen peroxide prophylaxis (oral and nasal rinse), without statistical significance.
Aug 2022, J. Hospital Infection, https://www.sciencedirect.com/science/article/pii/S0195670122001499, https://c19p.org/amoah
44. Brito-Reia et al., Population-based virucidal phthalocyanine gargling/rinsing protocol to reduce the risk of coronavirus disease-2019: a community trial
5,040 patient phthalocyanine prophylaxis study: 54% fewer cases (p=0.08).Comparison of two similar communities in Brazil, with one using a phthalocyanine derivative mouthwash, suggesting efficacy of the treatment in lowering COVID-19 cases. There was 54% lower risk of confirmed cases during the intervention in the treatment community, compared with 15% higher and 8% lower risk before and after the intervention. Gargle/rinse with 5mL of mouthwash containing phthalocyanine derivative for 1 minute, 3 to 5 times per day.
Nov 2021, German Medical Science GMS Publishing House, https://www.egms.de/en/journals/dgkh/2022-17/dgkh000426.shtml, https://c19p.org/britoreia
45. Sevinç Gül et al., Effect of oral antiseptics on the viral load of SARS-CoV-2: A randomized controlled trial
41 patient povidone-iodine early treatment RCT: 99% improved viral load (p=0.37) and 19% improved viral clearance (p=0.11).RCT with 21 PVP-I, 20 HOCl, and 20 saline patients gargling for 30 seconds and testing PCR Ct after 30 minutes, showing greater improvement with PVP-I and HOCl, without statistical significance. Ct values differ across testing platforms, however the reported Ct value difference can represent a large difference in viral load. For example, using the calibration included with the ct2vl converter, the reported difference in mean Ct values corresponds to a reduction in viral load of over 3x for PVP-I.
Jul 2022, Dental and Medical Problems, https://dmp.umw.edu.pl/en/ahead-of-print/150831/, https://c19p.org/sevincgul
46. El-Badrawy et al., Role of Sodium Bicarbonate as Adjuvant Treatment of Nonsevere Computed Tomography-identified COVID-19 Pneumonia: A Preliminary Report
182 patient alkalinization late treatment study: 57% lower mortality (p=0.37), 39% lower progression (p=0.52), and 19% improved recovery (p=0.03).Prospective study of 182 COVID-19 pneumonia patients, 127 treated with sodium bicarbonate inhalation and nasal drops, showing significantly faster recovery and improved CT scores with treatment. Authors note that contacts of index cases also received sodium bicarbonate treatment, with none reporting COVID-19. Inhalation of nebulized sodium bicarbonate 8.4% (5ml every 4h) 7:00am to 23:00pm every day for 30 days together with 8.4% nasal drops 4 times daily (three drops for each nostril).
Jun 2022, Indian J. Respiratory Care, https://www.ijrc.in/abstractArticleContentBrowse/IJRC/98/10/3/30725/abstractArticle/Article, https://c19p.org/elbadrawy2
47. Cegolon et al., Early Negativization of SARS-CoV-2 Infection by Nasal Spray of Seawater plus Additives: The RENAISSANCE Open-Label Controlled Clinical Trial
108 patient xylitol late treatment study: 32% improved viral clearance (p=0.05).108 patient prospective study showing improved viral clearance with Panthexyl nasal spray (a sterile hypertonic solution containing seawater, xylitol, panthenol and lactic acid).
Nov 2022, Pharmaceutics, https://www.mdpi.com/1999-4923/14/11/2502, https://c19p.org/cegolon
30 patient povidone-iodine early treatment RCT: 6% improved viral clearance (p=0.74).
Small mouth rinsing and gargling RCT with 15 1% PVP-I, 12 0.5% PVP-I, 15 3% hydrogen peroxide, 12 1.5% hydrogen peroxide, and 15 water patients, showing rapid improvement in Ct value in all groups, and no significant differences between groups.
Mar 2022, F1000Research, https://f1000research.com/articles/11-1238/v1, https://c19p.org/sulistyani
49. Sirijatuphat et al., A pilot study of 0.4% povidone-iodine nasal spray to eradicate SARS-CoV-2 in the nasopharynx
12 patient povidone-iodine early treatment study: 33% improved viral load (p=0.58).Small single-arm trial testing short-term viral load change after a single administration of three puffs of 0.4% PVP-I, showing lower viral titer at 3 minutes and 4 hours, not reaching statistical significance. Authors note that one reason for the lower change compared to in vitro results is that the spray administration may be less effective.
Aug 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.08.18.22278340, https://c19p.org/sirijatuphat3
50. Pablo-Marcos et al., Utility of mouth rinses with povidone-iodine and hydrogen peroxide in patients with COVID-19
71 patient hydrogen peroxide early treatment study: 12% improved viral clearance (p=0.67).Small prospective study with 31 patients gargling povidone-iodine, 17 hydrogen peroxide, and 40 control patients, showing lower viral load mid-recovery with povidone-iodine, without reaching statistical significance. Oropharyngeal only, and only every 8 hours for two days. Results may be better with the addition of nasopharyngeal use, more frequent use, and without the two day limit. Authors report only one of the 7 previous trials for PVP-I and COVID-19. Non-randomized study with no adjustments or group details. Some results in Figure 1 appear to be switched compared to the text and the labels in the figure. The viral clearance figures do not match the group sizes - for example authors report 62% PCR- for PVP-I at the 3rd test, however there is no number of 31 patients that rounds to 62%.
Oct 2021, Enfermedades Infecciosas y Microbiología Clínica, https://www.sciencedirect.com/science/article/pii/S0213005X21002950, https://c19p.org/pablomarcoshp
51. Zarabanda et al., The Effect of Povidone-Iodine Nasal Spray on COVID-19 Nasopharyngeal Viral Load in Patients: A Randomized Control Trial
24 patient povidone-iodine late treatment RCT: 27% worse recovery (p=1) and no change in viral clearance (p=1).Very late treatment (7 days from onset) RCT comparing 11 & 13 PVP-I (0.5% and 2%), and 11 saline spray patients in the USA, showing no significant differences. There was no control group (saline is likely not a placebo, showing efficacy in other trials). There are large unadjusted differences between groups, e.g. 7.1 days from onset for PVP-I versus 4.8 for saline. Baseline Ct was higher for PVP-I, providing less room for improvement. Authors note that they cannot determine if earlier use is more beneficial.
Oct 2021, Laryngoscope, https://onlinelibrary.wiley.com/doi/abs/10.1002/lary.29935, https://c19p.org/zarabanda
52. Bryan et al., The Efficacy of Nitric Oxide Generating Lozenges on Outcome in Newly Diagnosed COVID-19 Patients of African American and Hispanic Origin
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