Update on the Treatment of Covid-19
COVID19 - CORONAVIRUS, 10 Aug 2020
Please note: This is a recommendation to authorities and physicians. Patients are asked to consult a doctor.
4 Aug 2020 – SPR has updated its Covid-19 early treatment protocol and has added bromhexine. Bromhexine is a simple over-the-counter mucolytic cough medication that inhibits cellular TMPRSS2 protease and thus blocks SARS-CoV-2 cell entry via ACE2 cell receptors.
Several groups have already proposed bromhexine as an early or prophylactic treatment for Covid-19. An Iranian group recently reported a decrease in intensive care treatments of 82%, a decrease in intubations of 89%, and a decrease in deaths of 100% in a trial with 78 patients.
For further information on bromhexine see the reference section on the protocol page.
In view of a possible renewed increase in infection rates, early or prophylactic treatment of people at high risk or high exposure (including health care workers) should be of paramount importance to reduce hospitalizations and deaths.
Immunological and serological studies show that most people develop no symptoms or only mild symptoms when infected with the new coronavirus, while some people may experience a more pronounced or critical course of the disease.
Based on the available scientific evidence and current clinical experience, the SPR Collaboration recommends that physicians and authorities consider the following Covid-19 treatment protocol for the early treatment of people at high risk or high exposure (see references below).
- Zinc (50mg to 100mg per day)º
- Hydroxychloroquine (400mg per day)*º
- Quercetin (500mg to 1000mg per day)º
- Bromhexine (50mg to 100mg per day)º
- Azithromycin (up to 500mg per day)*
- Heparin (usual dosage)*
*) Prescription only (in most countries)
º) Also prophylactically (for high-risk persons)
Note: Quercetin may be used in addition to or as a replacement of hydroxychloroquine (HCQ). Contraindications for HCQ (e.g. favism or heart problems) and azithromycin must be observed.
Zinc/HCQ/AZ: US physicians reported an 84% decrease in hospitalization rates, a 50% decrease in mortality rates among already hospitalized patients (if treated early), and an improvement in the condition of patients within 8 to 12 hours. Italian doctors reported a decrease in deaths of 66%.
Bromhexine: Iranian doctors reported in a study with 78 patients a decrease in intensive care treatments of 82%, a decrease in intubations of 89%, and a decrease in deaths of 100%. Chinese doctors reported a 50% reduction in intubations.
Mechanisms of action
Zinc inhibits RNA polymerase activity of coronaviruses and thus blocks virus replication. Hydroxychloroquine and quercetin support the cellular absorption of zinc and have additional anti-viral properties. Bromhexine inhibits the expression of the cellular TMPRSS2 protease and thus the entry of the virus into the cell. Azithromycin prevents bacterial superinfections. Heparin prevents infection-related thromboses and embolisms in patients at risk. (See scientific references below).
See also: Illustration of the mechanisms of action of HCQ, quercetin and bromhexine
The early treatment of patients as soon as the first typical symptoms appear and even without a PCR test is essential to prevent progression of the disease. Zinc, HCQ, quercetin and bromhexin may also be used prophylactically for people at high risk or high exposure (e.g. for health care workers).
In contrast, isolating infected high-risk patients at home and without early treatment until they develop serious respiratory problems, as often happened during lockdowns, may be detrimental.
The alleged or actual negative results with hydroxychloroquine in some studies were based on delayed use (intensive care patients), excessive doses (up to 2400mg per day), manipulated data sets (the Surgisphere scandal), or ignored contraindications (e.g., favism or heart disease).
Early treatment based on the above protocol is intended to avoid hospitalization. If hospitalization nevertheless becomes necessary, experienced ICU doctors recommend avoiding invasive ventilation (intubation) whenever possible and using oxygen therapy (HFNC) instead.
The efficacy of HCQ against SARS coronaviruses was established in 2005 in the wake of the SARS-1 epidemic. The efficacy of zinc in blocking RNA replication of coronaviruses was discovered in 2010 by world-leading SARS virologist Ralph Baric. The efficacy of HCQ in supporting the cellular uptake of zinc was discovered in 2014 as part of cancer research. The efficacy of the flavonoid quercetin in supporting the cellular uptake of zinc was also discovered in 2014. The efficacy of bromhexine in blocking cell entry of coronaviruses was established in 2017.
- EVMS Critical Care Covid-19 Management Protocol (Paul Marik, MD, June 2020)
- Study: Effect of Zinc Salts on Respiratory Syncytial Virus Replication (Suara & Crowe, AAC, 2004)
- Study: Zinc Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture (Velthuis et al, PLOS Path, 2010)
- Study: Zinc for the common cold (Cochrane Systematic Review, 2013)
- Study: Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients (Carlucci et al., MedRxiv, May 2020)
- Review: Does zinc supplementation enhance the clinical efficacy of chloroquine/ hydroxychloroquine to win today’s battle against COVID-19? (Derwand & Scholz, MH, 2020)
- Review: Zinc supplementation to improve treatment outcomes among children diagnosed with respiratory infections (WHO, Technical Report, 2011)
- Article: Can Zinc Lozenges Help with Coronavirus Infections? (McGill University, March 2020)
- Studies: Overview of more than 50 international HCQ studies (com)
- Study: Chloroquine is a potent inhibitor of SARS coronavirus infection and spread (Vincent et al., Virology Journal, 2005)
- Study: Chloroquine Is a Zinc Ionophore (Xue et al, PLOS One, 2014)
- Study: Physicians work out treatment guidelines for coronavirus (Korean Biomedical Review, February 2020)
- Study: Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia (Guangdong Health Commission, February 2020)
- Study: Clinical Efficacy of Chloroquine derivatives in COVID-19 Infection: Comparative meta-analysis between the Big data and the real world (Million et al, NMNI, June 2020)
- Study: Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19 (Arshad et al, Int. Journal of Infect. Diseases, July 2020)
- Study: COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin (Scholz et al., Preprints, July 2020)
- Study: Effectiveness of HCQ in COVID-19 disease (Monforte et al., IJID, July 2020)
- Protocol: Advisory on the use of HCQ as prophylaxis for SARS-CoV-2 infection (Indian Council of Medical Research, March 2020)
- Review: White Paper on Hydroxychloroquine ( Simone Gold, AFD, July 2020)
- Article: The Key to Defeating COVID-19 Already Exists. We Need to Start Using It. (Professor Harvey A. Risch, Newsweek, July 2020)
- Article: Using Hydroxychloroquine and Other Drugs to Fight Pandemic (Yale School of Medicine)
- Article: Moroccan Scientist: Morocco’s Chloroquine Success Reveals European Failures (Morocco World News, June 2020) Zemmouri believes 78% of Europe’s coronavirus-related deaths could have been avoided if European states had mirrored Morocco’s chloroquine strategy.
- Article (IT): Covid: None of my patients are dead, and only 5% had to be hospitalized (Italia Oggi, June 2020) Dr. Cavanna treated the affected by the virus by intervening promptly and at home.
- Study: Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells (Ling Yi et al., Journal of Virology, 2004)
- Study: Zinc Ionophore Activity of Quercetin and Epigallocatechin-gallate: From Hepa 1-6 Cells to a Liposome Model (Dabbagh et al., JAFC, 2014)
- Study: Quercetin as an Antiviral Agent Inhibits Influenza A Virus Entry (Wu et al, Viruses, 2016)
- Study: Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (Biancatelli et al, Front. in Immun., June 2020)
- Report: EVMS Critical Care Covid-19 Management Protocol (Paul Marik, MD, June 2020)
- Study: TMPRSS2: A potential target for treatment of influenza virus and coronavirus infections (Wen Shen et al., Biochimie Journal, 2017)
- Letter: Repurposing the mucolytic cough suppressant and TMPRSS2 protease inhibitor bromhexine for the prevention and management of SARS-CoV-2 infection (Maggio and Corsini, Pharmacological Research, April 2020)
- Study: Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy? (Depfenhart et al., Internal and Emergency Medicine, May 2020)
- Study: Bromhexine Hydrochloride: Potential Approach to Prevent or Treat Early Stage COVID-19 (Stepanov and Lierz, Journal of Infectious Diseases and Epidemiology, June 2020)
- Study: TMPRSS2 inhibitors, Bromhexine, Aprotinin, Camostat and Nafamostat as potential treatments for COVID-19 (Arsalan Azimi, Drug Target Review, June 2020)
- Trial: Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial (Ansarin et al., BioImpacts, July 2020): “There was a significant reduction in ICU admissions (2 out of 39 vs. 11 out of 39), intubation (1 out of 39 vs. 9 out of 39) and death (0 vs. 5) in the bromhexine treated group compared to the standard group.”
- Commentary: The versatile heparin in COVID‐19 (Thachil, JTH, April 2020)
- Study: Anticoagulant Treatment Is Associated With Decreased Mortality in Severe Coronavirus Disease 2019 Patients With Coagulopathy (Tang et al, JTH, May 2020)
- Study: Autopsy Findings and Venous Thromboembolism in Patients With COVID-19 (Wichmann et al., Annals of Internal Medicine, May 2020)
- Article: Anticoagulation Guidance Emerging for Severe COVID-19 (Medpage Today)
- Article: Aspirin may prevent blood clots in COVID-19, study shows (Knowridge Science)
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