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Other Treatments Global Adoption
Bromhexine COVID-19 studies. Bromhexine may be less effective for omicron due to the entry process moving towards TMPRSS2-independent fusion. Submit updates/corrections.
Aug 6
Early, Late, PrEP, PEP Covid Analysis (Preprint) (meta analysis)
Bromhexine for COVID-19: real-time meta analysis of 6 studies
Details   • Statistically significant improvements are seen for ventilation, ICU admission, and viral clearance. 4 studies from 4 independent teams in 3 different countries show statistically significant improvements in isolation (1 for the most se..
Jan 3
In Vitro Peacock et al., bioRxiv, doi:10.1101/2021.12.31.474653 (Preprint) (In Vitro)
In Vitro
The SARS-CoV-2 variant, Omicron, shows rapid replication in human primary nasal epithelial cultures and efficiently uses the endosomal route of entry
Details   In Vitro study showing that omicron can efficiently enter cells via the endosomal route, independent of TMPRSS2.
Jan 3
In Vitro Willett et al., medRxiv, doi:10.1101/2022.01.03.21268111 (Preprint) (In Vitro)
In Vitro
The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism
Details   In Vitro study showing that the entry process for omicron has moved towards TMPRSS2-independent fusion, indicating that TMPRSS2 inhibitors may be less effective for omicron.
Dec 20
PrEPPEP Tolouian et al., SSRN, doi:10.2139/ssrn.3989 (Preprint)
death, ↓32.9%, p=0.76
Bromhexine, for Post Exposure COVID-19 Prophylaxis: A Randomized, Double-Blind, Placebo Control Trial
Details   PEP RCT with 372 close contacts of COVID+ patients, 187 treated with bromhexine, showing significantly lower cases with treatment. IRCT20120703010178N22.
Apr 30
In Silico Sgrignani et al., Frontiers in Molecular Biosciences, doi:10.3389/fmolb.2021.666626
In Silico
Computational Identification of a Putative Allosteric Binding Pocket in TMPRSS2
Details   In Silico study of TMPRSS2 inhibition by camostat, nafamostat, and bromhexine, suggesting allosteric binding for bromhexine, compared to camostat and nafamostat which bind to the active site of TMPRSS2 forming covalent adducts.
Mar 15
Late Tolouian et al., J. Investig. Med., doi:10.1136/jim-2020-001747
death, ↓76.0%, p=0.43
Effect of bromhexine in hospitalized patients with COVID-19
Details   Small RCT with 100 patients, 48 with bromhexine added to SOC, showing slower viral- conversion but lower mortality and greater clinical improvement with bromhexine (not statistically significant with few deaths and very high recovery). Th..
Mar 8
PrEPPEP Mikhaylov et al., medRxiv, doi:10.1101/2021.03.03.21252855 (Preprint)
hosp., ↓80.0%, p=0.49
Bromhexine Hydrochloride Prophylaxis of COVID-19 for Medical Personnel: A Randomized Open-Label Study
Details   Small prophylaxis RCT with 25 treatment and 25 control health care worker, showing lower PCR+, symptomatic cases, and hospitalization with treatment, although not statistically significant with the small sample size.
Jan 31
In Vitro Carpinteiro et al., Journal of Biological Chemistry, doi:10.1016/j.jbc.2021.100701 (In Vitro)
In Vitro
Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells
Details   In Vitro study showing that ambroxol (a metabolite of bromhexine) inhibits SARS-CoV-2 infection.
Dec 31
Review Al-Kuraishy et al., Current Medical and Drug Research (Review) (Preprint)
The potential role of Bromhexine in the management of COVID-19: Decipher and a real game-changer
Details   Review article noting that bromhexine is a TMPRSS2 inhibitor with greater effect in lung tissue and attenuates the entry and proliferation of SARS‐CoV‐2.
Dec 3
Late Mareev et al., Кардиология, doi:10.18087/cardio.2020.11.n1440
no recov., ↓11.3%, p=0.47
Results of Open-Label non-Randomized Comparative Clinical Trial: “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)
Details   Prospective 103 PCR+ patients in Russia, 33 treated with bromexhine+spironolactone, showing lower PCR+ at day 10 or hospitalization >10 days with treatment. Bromhexine 8mg 4 times daily, spironolactone 25-50 mg/day for 10 days.
Sep 3
Early Li et al., Clinical and Translational Science, doi:10.1111/cts.12881
no disch., ↓75.0%, p=0.11
Bromhexine Hydrochloride Tablets for the Treatment of Moderate COVID‐19: An Open‐Label Randomized Controlled Pilot Study
Details   Tiny RCT with 12 bromhexine and 6 control patients showing non-statistically significant improvements in chest CT, need for oxygen therapy, and discharge rate within 20 days. Authors recommend a larger scale trial.
Jul 19
Early Ansarin et al., Bioimpacts, doi:10.34172/bi.2020.27
death, ↓90.9%, p=0.05
Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial
Details   RCT with 39 bromhexine and 39 control patients showing lower mortality, intubation, and ICU admission with treatment. The treatment group received bromhexine hydrochloride 8 mg three times a day for two weeks. All patients received SOC in..
May 26
Theory Depfenhart et al., Internal and Emergency Medicine, doi:10.1007/s11739-020-02383-3 (Theory)
Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?
Details   Proposal to use bromhexine to inhibit TMPRSS2-specific viral entry for prophylaxis and treatment of COVID-19.
Apr 30
Theory Habtemariam et al., Pharmacol. Res., doi:10.1016/j.phrs.2020.104853 (Theory)
Possible use of the mucolytic drug, bromhexine hydrochloride, as a prophylactic agent against SARS-CoV-2 infection based on its action on the Transmembrane Serine Protease 2
Details   Note on the potential use of bromhexine hydrochloride for prophylaxis of SARS-CoV-2, based on the role of TMPRSS2 in SARS-CoV-2 infection, and the TMPRSS2 inhibition of bromhexine hydrochloride.
Apr 22
Review Maggio et al., Pharmacol Res., doi:10.1016/j.phrs.2020.104837 (Review)
Repurposing the mucolytic cough suppressant and TMPRSS2 protease inhibitor bromhexine for the prevention and management of SARS-CoV-2 infection
Details   Proposal to use bromhexine for prophylaxis and treatment of COVID-19 based on TMPRSS2 inhibition, widespread clinical use, and supporting pharmacokinetic and safety data.
Mar 5
In Vitro Hoffman et al., Cell, doi:10.1016/j.cell.2020.02.052 (In Vitro)
In Vitro
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibito
Details   In Vitro study showing that SARS-CoV-2 uses ACE2 for entry and TMPRSS2 for S protein priming, and that TMPRSS2 inhibitor camostat blocked entry and may be an effective treaetment.
Please send us corrections, updates, or comments. Vaccines and treatments are both valuable and complementary. All practical, effective, and safe means should be used. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. Denying the efficacy of any method increases mortality, morbidity, collateral damage, and the risk of endemic status. 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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