Summary of COVID-19 alkalinization studies

1. 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

2. Mody et al., Effect of 8.4% Soda-Bicarbonate Steam Inhalation on the Course of Disease in Mild to Moderate Cases of Covid-19

60 patient alkalinization late treatment RCT: 64% greater improvement (p=0.0007).
RCT 60 hospitalized patients in India, showing significantly greater clinical improvement with inhaled sodium bicarbonate. Nasal and oral inhalation of nebulized 50ml 8.4% sodium bicarbonate for 5 minutes twice daily for 5 days.
Mar 2021, Acta Scientific Orthopaedics, https://actascientific.com/ASOR/ASOR-04-0290.php, https://c19p.org/mody2

3. Pantazopoulos et al., A Hypertonic Seawater Nasal Irrigation Solution Containing Algal and Herbal Natural Ingredients Reduces Viral Load and SARS-CoV-2 Detection Time in the Nasal Cavity

56 patient alkalinization late treatment RCT: 42% improved viral clearance (p=0.04).
RCT 56 severe COVID-19 patients, showing significantly decreased viral load with Sinomarin Plus Algae nasal irrigation. Sinomarin Plus Algae is a hypertonic seawater solution with algal and herbal natural ingredients with a pH of 7.5-8 [sinomarin.com]. The treatment group received nasal irrigation every 4 hours, 16 hours per day, for 2 days. Nasopharyngeal swabs were taken at baseline and 48 hours later to measure viral load. The treatment group showed a significant increase in cycle threshold values, indicating decreased viral load, while no difference was seen in the control group. The treatment was well tolerated with only mild adverse effects. Alkalinization is one possible mechanism of action - SARS-CoV-2 requires acidic pH for infection [Kreutzberger] and the solution has pH 7.5-8. Other possible mechanisms include antiviral activity of ingredients (e.g., fucoidan from Undaria pinnatifida) and physical removal of viral particles.
Jul 2023, J. Personalized Medicine, https://www.mdpi.com/2075-4426/13/7/1093, https://c19p.org/pantazopoulos

4. 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

5. 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

6. Soares et al., Preliminary observation of the use of sodium bicarbonate solution as an adjunct in the treatment of coronavirus 2019 disease (COVID-19): prognosis improvement in patients requiring intensive care

76 patient alkalinization ICU study: 76% lower mortality (p=0.0001).
Analysis of 76 ICU patients in Brazil, 44 treated with bronchoalveolar lavage using 3% sodium bicarbonate, showing significantly lower mortality with treatment. Bronchoalveolar lavage with 10ml of sodium bicarbonate solution directly into the tube (closed circuit), 500μl for each lung segment, followed by aspiration of the solution, performed every 6 hours for 7 days.
Dec 2021, Brazilian J. Development, https://brazilianjournals.com/ojs/index.php/BRJD/article/view/40521, https://c19p.org/soares

7. Kalayan et al., Safety and Efficacy of Nebulised Anti-Inflammatory Solution of Alkaline Hypertonic Ibuprofen (AHI) for Treatment of SARS-Cov-2 Infection: A Compassionate Study with a Comparator Arms

99 patient alkalinization late treatment study: 79% lower mortality (p=0.0009).
Retrospective 99 COVID-19 patients in Argentina showing significantly lower mortality with inhaled alkaline hypertonic ibuprofen (AHI) treatment. The treatment has a pH of 8.5. 3 times daily for 7-10 days.
Dec 2022, European J. Respiratory Medicine, https://europeanjournalofrespiratorymedicine.com/safety-and-efficacy-of-nebulised-anti-inflammatory-solution-of-alkaline-hypertonic-ibuprofen-ahi-for-treatment-of-sars-cov-2-infection-a-compassionate-study-with-a-comparator-arms, https://c19p.org/kalayanph

8. Salva et al., Reversal of SARS-CoV2-Induced Hypoxia by Nebulized Sodium Ibuprofenate in a Compassionate Use Program

501 patient alkalinization late treatment study: 45% lower mortality (p=0.009) and 14% shorter hospitalization (p<0.0001).
Retrospective 383 hospitalized COVID-19 patients in Argentina showing signifcantly lower mortality and shorter hospital stay with nebulized sodium ibuprofenate compared to 195 contemporaneous controls. The treatment appears to be the same as detailed in [Kalayan], which reports a pH of 8.5. [Kreutzberger] showed that SARS-CoV-2 requires an acidic pH (between 6.2-6.8) for membrane fusion and cell entry, even when the viral spike protein is primed by proteases like TMPRSS2. Efficacy seen here may be more due to alkalinization, which shows more consistent higher efficacy than ibuprofen in studies to date. Baseline SpO2 was significantly different for the patients on mechanical ventilation at baseline.
Aug 2021, Infectious Diseases and Therapy, https://link.springer.com/10.1007/s40121-021-00527-2, https://c19p.org/salvaph

9. Calonico et al., Causal Inference During a Pandemic: Evidence on the Effectiveness of Nebulized Ibuprofen as an Unproven Treatment for COVID-19 in Argentina

5,416 patient alkalinization late treatment study: 49% lower mortality (p=0.01).
Retrospective 5,146 hospitalized COVID-19 patients in Argentina, showing lower mortality associated with nebulized ibuprofen (NaIHS) treatment. Doubly robust inverse probability weighting estimators were used to control for confounding. Authors emphasize the need for randomized controlled trials. The treatment appears to be the same as detailed in [Kalayan], which reports a pH of 8.5. [Kreutzberger] showed that SARS-CoV-2 requires an acidic pH (between 6.2-6.8) for membrane fusion and cell entry, even when the viral spike protein is primed by proteases like TMPRSS2. Efficacy seen here may be more due to alkalinization, which shows more consistent higher efficacy than ibuprofen in studies to date.
May 2022, National Bureau of Economic Research, http://www.nber.org/papers/w30084.pdf, https://c19p.org/calonicoph

10. Delić et al., Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial

94 patient alkalinization ICU RCT: 23% lower mortality (p=0.13).
RCT mechanically ventilated patients in Croatia, 42 treated with sodium bicarbonate inhalation, and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-caused ventilator-associated pneumonia. ICU mortality results are from [repozitorij.mefst.unist.hr].
May 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/6/1118, https://c19p.org/delicph

11. Karami et al., A Comparison of the Effects of Chlorhexidine and Sodium Bicarbonate Mouthwashes on COVID-19–Related Symptoms

80 patient alkalinization prophylaxis RCT: 45% lower progression (p=0.14) and 39% fewer cases (p=0.16).
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/karamiph

13. El-Badrawy et al., A randomized controlled trial of adjuvant inhalable sodium bicarbonate role in treatment of COVID-19

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. 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, Research Square, https://www.researchsquare.com/article/rs-2214180/v1, https://c19p.org/elbadrawy

14. 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

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