Coronavirus COVID-19 Update: Hydroxychloroquine and Other Treatments

Guided_by_Voices · Apr 4, 2020

There also seems to be some of the "just one thing" fallacy going on too. For example, I believe some of the Doctors reporting success with this were giving it with a number of other things including zinc, and if zinc turns out to be partially how it works and people are low on zinc (as many people are) then it might not be as effective

Rock H. Johnson · Apr 4, 2020

Guided_by_Voices said:
There also seems to be some of the "just one thing" fallacy going on too. For example, I believe some of the Doctors reporting success with this were giving it with a number of other things including zinc, and if zinc turns out to be partially how it works and people are low on zinc (as many people are) then it might not be as effective

I agree seeing that the quines and others like dietary plant polyphenols such as the flavonoids quercetin (QCT) and epigallocatechin-gallate act as antioxidants and as signaling molecules all are Zinc ionophores. The effect of them as the signal to insert the zinc into the cell and stop the virus from replicating....as I simply understand.

Nelson Vergel · Apr 5, 2020

"We focused on fourteen phenolic compounds grouped according to their chemical structure, including the flavonoids quercetin (QCT), epigallocatechin-3-gallate (EGCG)(FROM GREEN TEA), luteolin (LUT), narin- genin (NAR), phloretin (PHLO), genistein (GEN), catechin hydrate (CAT HYD), rutin (RUT) and dihydroquercetin or taxifolin (TAX); the phenolic acids gallic acid (GAL), tannic acid (TAN) and caffeic acid (CAF); the stilbene resveratrol (RSV); and other polyphenols such as catechol (CAT). Two different zinc ionophore agents, clioquinol and pyrithione, were used to compare the ionophore activity of the selected polyphenols"

sammmy · Apr 5, 2020

One problem of the French study by Gautret is that out of 26 patients on hydroxychloroquine treatment, 3 were transferred to intensive care units (on days 2,3,4 after starting treatment), and one patient died on day 3. No patients dropped from the control (non treated) group.

However, the groups were not statistically equivalent: the treatment group self-selected the hydroxychloroquine treatment because they were significantly older (mean age 51.2 years) than the control group (mean age 37.3 years). Also, 30% of the treatment group had lower track infection (pneumonia) vs only 12.5% in the control group.

Hydroxychloroquine is an immune suppressor - it reduced immune inflammation by also reduces the number of lymphocytes (seen it in a HIV study). I wonder if it is best if it is combined with something that increases lymphocytes such as isoprinosine or thymosine alpha-1. I've tried both compounds myself and they do increase lymphocytes significantly.

Nelson Vergel · Apr 5, 2020

Randomized Controlled Trials in Progress (Thanks to Medscape)

COVID-19 RCTs

Therapy	Trial Name	Proposed # of Patients	Participating Countries	Primary Completion Date
Remdesivir RCTs
Remdesivir	Mild/Moderate 2019-nCoV Remdesivir RCT	308	China	April 10, 2020
Remdesivir	Severe 2019-nCoV Remdesivir RCT	453	China	April 3, 2020
Remdesivir	Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734) in Participants With Moderate Coronavirus Disease (COVID-19) Compared to Standard of Care Treatment	600	US, Hong Kong, South Korea, Singapore, Taiwan	May 1, 2020
Remdesivir	Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734) in Participants With Severe Coronavirus Disease (COVID-19)	400	US, Hong Kong, South Korea, Singapore, Taiwan	May 1, 2020
Remdesivir	Adaptive COVID-19 Treatment Trial (ACTT) (NIH supported)	440	US, Japan, South Korea, Singapore	April 1, 2023
Remdesivir, lopinavir-ritonavir, interferon, hydroxychloroquine	DisCoVeRy: Trial of Treatments for COVID-19 in Hospitalized Adults	3100	France	March 1, 2023
Lopinavir/Ritonavir RCTs
Lopinavir-ritonavir, anakinra, macrolides, corticosteroids, interferon	REMAP-CAP: A randomised, embedded, multi-factorial, adaptive platform trial for community-acquired pneumonia	No maximum	Canada and 13 other countries (Australia, NZ, UK, "a dozen EU countries"), 50 sites	End April/Early May 2020
Lopinavir-ritonavir, hydroxychloroquine	Comparison of lopinavir-ritonavir or Hydroxychloroquine in Patients With Mild Coronavirus Disease (COVID-19)	150	South Korea	May 1, 2020
Lopinavir-ritonavir, hydroxychloroquine, remdesivir	CATCO: Canadian Treatments for COVID-19 trial - Canadian Arm of the WHO SOLIDARITY trial	440	Canada plus 45 countries so far	March 18, 2022
Lopinavir-ritonavir, interferon, Chinese medicine	Treatment and Prevention of Traditional Chinese Medicines (TCMs) on 2019-nCoV Infection	150	China	January 22, 2021
Lopinavir-ritonavir, oseltamivir, arbidol hydrochloride	A Prospective/Retrospective, Randomized Controlled Clinical Study of Antiviral Therapy in the 2019-nCoV Pneumonia	400	China	June 1, 2020
Lopinavir-ritonavir, ribavirin, interferon	Lopinavir/ Ritonavir, Ribavirin and IFN-beta Combination for nCoV Treatment	70	Hong Kong	January 31, 2022
Remdesivir, lopinavir-ritonavir, interferon, hydroxychloroquine	DisCoVeRy: Trial of Treatments for COVID-19 in Hospitalized Adults	3100	France, Belgium, German, the Netherlands, Spain, Sweden, UK	March 1, 2023
Lopinavir-ritonavir	A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe COVID-19	199	China	February 3, 2020
Lopinavir-ritonavir	CORIPREV-LR: COVID-19 Ring-based Prevention Trial With Lopinavir-Ritonavir	1220	Canada	March 31, 2021
Other Antiviral RCTs
Arbidol (antiviral), bromhexine hydrochloride (mucolytic), interferon	Evaluating the Efficacy and Safety of Bromhexine Hydrochloride Tablets Combined With Standard Treatment/ Standard Treatment in Patients With Suspected and Mild Novel Coronavirus Pneumonia (COVID-19)	60	China	April 15, 2020
Darunavir, cobicistat	DACO-nCoV: Efficacy and Safety of Darunavir and Cobicistat for Treatment of Pneumonia Caused by 2019-nCoV	30	China	August 31, 2020
Favipiravir, oseltamivir, protease-inhibitor combinations	THDMS-COVID19: Various Combination of Protease Inhibitors, Oseltamivir, Favipiravir, and Hydroxychloroquine for Treatment of COVID19: A Randomized Control Trial (THDMS-COVID19)	80	Thailand	October 31, 2020
Investigational Immunotherapy RCTs
Lopinavir-ritonavir, anakinra, macrolides, corticosteroids, interferon	REMAP-CAP: A randomised, embedded, multi-factorial, adaptive platform trial for community-acquired pneumonia	No maximum	Canada and 13 other countries (Australia, NZ, UK, "a dozen EU countries"), 50 sites	End April/Early May 2020
Bevacizumab	BEST-RCT: Bevacizumab in Severe or Critically Severe Patients With COVID-19 Pneumonia-RCT	118	China	June 30, 2020
Emapalumab, anakinra	Efficacy and Safety of Emapalumab and Anakinra in Reducing Hyperinflammation and Respiratory Distress in Patients With COVID-19 Infection.	54	Italy	July 1, 2020
CD24Fc	SAC-COVID: CD24Fc as a Non-antiviral Immunomodulator in COVID-19 Treatment	230	US	May 1, 2021
Tocilizumab, favipiravir	Favipiravir Combined With Tocilizumab in the Treatment of Corona Virus Disease 2019	150	China	May 1, 2020
"PD-1 blocking antibody", thymosin	Immunoregulatory Therapy for 2019-nCoV	120	China	April 30, 2020
Sarilumab	CORIMUNO-19 - SARI: Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Sarilumab Trial -	180	France	March 26, 2021
Sarilumab	Evaluation of the Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19	400	US	March 16, 2021
ASC09F, ritonavir, oseltamivir	A Randomized, Open, Controlled Clinical Study to Evaluate the Efficacy of ASC09F and Ritonavir for 2019-nCoV Pneumonia	60	China	May 1, 2020
Tocilizumab	COVACTA: A Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia	330	US	August 31, 2021
Tocilizumab, sarilumab	TOCIVID: Anti-il6 Treatment of Serious COVID-19 Disease With Threatening Respiratory Failure	200	Denmark	June 1, 2021
Human Product RCTs
Convalescent plasma	CSSC-OO1: Efficacy and Safety Human Coronavirus Immune Plasma (HCIP) vs. Control (SARS-CoV-2 Non-immune Plasma) Among Adults Exposed to COVID-19	150	US	December 31, 2022
Stem cells	Study of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Novel Coronavirus Severe Pneumonia	48	China	June 30, 2020
Stem cells	Treatment With Mesenchymal Stem Cells for Severe Corona Virus Disease 2019 (COVID-19)	90	China	December 31, 2020
Natural-killer cells	NK Cells Treatment for Novel Coronavirus Pneumonia	30	China	September 30, 2020
Vitamin C RCTs
Vitamin C (high-dose IV)	LOVIT: Lessening Organ Dysfunction With VITamin C	800	Canada	December 31, 2021
Vitamin C (high-dose IV)	Vitamin C Infusion for the Treatment of Severe 2019-nCoV Infected Pneumonia	140	China	September 30, 2020
(Hydroxy)Chloroquine RCTs
Chloroquine, azithromycin	ACT COVID19: Anti-Coronavirus Therapies to Prevent Progression of Coronavirus Disease 2019 (COVID-19) Trial	1500	Canada "+ international"	September 30, 2020
Hydroxychloroquine	COVID-19 PEP: Post-Exposure Prophylaxis / Preemptive Therapy for SARS-Coronavirus-2	3000	Canada, US	April 21, 2020
Hydroxychloroquine	Efficacy and Safety of Hydroxychloroquine for Treatment of Pneumonia Caused by 2019-nCoV (HC-nCoV )	30	China	February 25, 2020
Hydroxychloroquine	Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial	62	China	February 28, 2020
Hydroxychloroquine	Hydroxychloroquine Post Exposure Prophylaxis for Coronavirus Disease (COVID-19) [includes treatment of early symptoms]	1600	US	March 1, 2021
Hydroxychloroquine, azithromycin	Safety and Efficacy of Hydroxychloroquine Associated With Azithromycin in SARS-CoV2 Virus (Coalition Covid-19 Brasil II)	440	Brazil	August 30, 2020
Other RCTs
Chinese medicine	Yinhu Qingwen Decoction for the Treatment of Mild/Common CoVID-19	300	China	January 1, 2021
Chinese medicine	Yinhu Qingwen Granula for the Treatment of Severe CoVID-19	116	China	March 30, 2021
Chinese medicine, N-acetylcysteine (cysteine supplement)	Treatment of Pulmonary Fibrosis Due to 2019-nCoV Pneumonia With Fuzheng Huayu	136	China	December 1, 2022
Colchicine	COLCORONA: Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA)	6000	Canada	September 1, 2020
Immunoglobulin	The Efficacy of Intravenous Immunoglobulin Therapy for Severe 2019-nCoV Infected Pneumonia	80	China	April 30, 2020
Interferon, arbidol hydrochloride	A Prospective/Retrospective, Randomized Controlled Clinical Study of Interferon Atomization in the 2019-nCoV Pneumonia	100	China	June 1, 2020
Losartan	Losartan for Patients With COVID-19 Not Requiring Hospitalization	516	US	April 1, 2021
Losartan	Losartan for Patients With COVID-19 Requiring Hospitalization	200	US	April 1, 2021
Methylprednisolone	Steroids-SARI: Glucocorticoid Therapy for Novel Coronavirus Critically Ill Patients With Severe Acute Respiratory Failure	80	China	April 25, 2020
Methylprednisolone	The Efficacy of Different Hormone Doses in 2019-nCoV Severe Pneumonia	100	China	June 1, 2020
Methylprednisolone	Efficacy and Safety of Corticosteroids in COVID-19	400	China	May 1, 2020
Nitric oxide gas	NoCovid: Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID-19	240	US, China, Italy	April 1, 2021
Nitric oxide gas	NOSARSCOVID: Nitric Oxide Gas Inhalation in Severe Acute Respiratory Syndrome in COVID-19	200	US, China, Italy	March 21, 2021
PUL-042 inhalation solution	PUL-042 Inhalation Solution to Reduce the Severity of COVID-19 in Adults Positive for SARS-CoV-2 Infection	100	US	September 1, 2020
Tetrandrine	TT-NPC: Tetrandrine Tablets Used in the Treatment of COVID-19	60	China	March 1, 2021

Guided_by_Voices · Apr 5, 2020

Note that a study is testing "thymosin" which is presumably Thymosin Alpha One although Thymosin Beta 4 has also been suggested to have beneficial properties. It is still available from one of our well-known sources, miraculously enough.

charile12 · Apr 6, 2020

Metformin combined with chloroquine can be deadly. @Nelson Vergel any other info on this? I could imagine many folks on Metformin including myself.

Abstract
Guided by the principle of primum non nocere (first do no harm), we report a cautionary note on the potential fatal toxicity of chloroquine (CQ) or hydroxychloroquine (HCQ) in combination with anti-diabetic drug metformin. We observed that the combination of CQ or HCQ and metformin, which were used in our studies as potential anti-cancer drugs, killed 30-40% of mice. While our observations in mice may not translate to toxicity in humans, the reports that CQ or HCQ has anti-COVID-19 activity, the use of CQ resulting in toxicity and at least one death, and the recent Emergency Use Authorization (EUA) for CQ and HCQ by the US Food and Drug Administration (FDA) prompted our report. Here we report the lethality of CQ or HCQ in combination with metformin as a warning of its potential serious clinical toxicity. We hope that our report will be helpful to stimulate pharmacovigilance and monitoring of adverse drug reactions with the use of CQ or HCQ, particularly in combination with metformin.

Fatal toxicity of chloroquine or hydroxychloroquine with metformin in mice

Guided by the principle of primum non nocere (first do no harm), we report a cautionary note on the potential fatal toxicity of chloroquine (CQ) or hydroxychloroquine (HCQ) in combination with anti-diabetic drug metformin. We observed that the combination of CQ or HCQ and metformin, which were...

www.biorxiv.org

Nelson Vergel · Apr 6, 2020

charile12 said:
Metformin combined with chloroquine can be deadly. @Nelson Vergel any other info on this? I could imagine many folks on Metformin including myself.

Abstract
Guided by the principle of primum non nocere (first do no harm), we report a cautionary note on the potential fatal toxicity of chloroquine (CQ) or hydroxychloroquine (HCQ) in combination with anti-diabetic drug metformin. We observed that the combination of CQ or HCQ and metformin, which were used in our studies as potential anti-cancer drugs, killed 30-40% of mice. While our observations in mice may not translate to toxicity in humans, the reports that CQ or HCQ has anti-COVID-19 activity, the use of CQ resulting in toxicity and at least one death, and the recent Emergency Use Authorization (EUA) for CQ and HCQ by the US Food and Drug Administration (FDA) prompted our report. Here we report the lethality of CQ or HCQ in combination with metformin as a warning of its potential serious clinical toxicity. We hope that our report will be helpful to stimulate pharmacovigilance and monitoring of adverse drug reactions with the use of CQ or HCQ, particularly in combination with metformin.

Fatal toxicity of chloroquine or hydroxychloroquine with metformin in mice

Guided by the principle of primum non nocere (first do no harm), we report a cautionary note on the potential fatal toxicity of chloroquine (CQ) or hydroxychloroquine (HCQ) in combination with anti-diabetic drug metformin. We observed that the combination of CQ or HCQ and metformin, which were...

www.biorxiv.org

Crazy high dose of each!! For a 100 Kg human, these would amount to 6000 mg per day of hydroxychloroquine and 25,000 mg per day of Metformin.

Nelson Vergel · Apr 6, 2020

Ophthalmologic safety of long-term hydroxychloroquine sulfate treatment

Rynes, Richard I

The American Journal of Medicine, 1983, Vol.75(1), pp.35-39

The fear of retinal toxicity has been a major factor limiting the use of chloroquine and hydroxychloroquine. Patients reported to develop retinal toxicity with visual loss usually took daily dosages higher than those currently in use. Toxicity with low dosages (for example, 250 mg per day chloroquine or 400 mg per day hydroxychloroquine) usually reveals pigment abnormalities; associated loss of vision is rare. When 99 patients treated with hydroxychloroquine for more than one year were studied prospectively, four patients showed evidence of retinal toxicity; none developed visual loss, and all abnormalities were completely reversible after drug discontinuation. All persons receiving antimalarials should be evaluated by an ophthalmologist at baseline and every six months thereafter. ∗ ∗ The manufacturer's recommendation is that Ophthalmologic examinations be made every three months during long-term therapy.

COVID-19 PROTOCOLS BEING STUDIED (all short term treatment):

University of Minnesota Post Exposure Study:

200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Some Chinese studies:

400 mg per day for 5 days

This drug is pretty safe for short term use.

Cataceous · Apr 6, 2020

Thanks to "cujet" at PeakTestosterone for this one:

COVID-19:Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism

The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory caused by the novel coronavirus. The virus is the positive-strand RNA one with high homology to bat coronavirus. The pathogenic mechanism of the new coronavirus is still unclear, which is a significant obstacle to the...

chemrxiv.org

The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory infection caused by the novel coronavirus. The virus is a positive-strand RNA virus with high homology to bat coronavirus. In this study, conserved domain analysis, homology modeling, and molecular docking were used to compare the biological roles of certain proteins of the novel coronavirus. The results showed the ORF8 and surface glycoprotein could bind to the porphyrin, respectively. At the same time, orf1ab, ORF10, and ORF3a proteins could coordinate attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide. The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images. The mechanism also interfered with the normal heme anabolic pathway of the human body, is expected to result in human disease. According to the validation analysis of these finds, chloroquine could prevent orf1ab, ORF3a, and ORF10 to attack the heme to form the porphyrin, and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress. Favipiravir could inhibit the envelope protein and ORF7a protein bind to porphyrin, prevent the virus from entering host cells, and catching free porphyrins. Because the novel coronavirus is dependent on porphyrins, it may originate from an ancient virus. Therefore, this research is of high value to contemporary biological experiments, disease prevention, and clinical treatment.

Nelson Vergel · Apr 6, 2020

Some interesting algorithms here

Initial Treatment Algorithm for Hospitalized, Non–Severe COVID-19 Patients

sammmy · Apr 6, 2020

Nelson Vergel said:
Crazy high dose of each!! For a 100 Kg human, these would amount to 6000 mg per day of hydroxychloroquine and 25,000 mg per day of Metformin.

Presumably, mice doses are converted to human doses by division by 6 so the human dose is 10mg/kg, which for a typical 70kg human is around 700mg dose. They say somewhere in the article that the mouse dose corresponds to the usual human doses.

sammmy · Apr 6, 2020

Cataceous said:
Thanks to "cujet" at PeakTestosterone for this one:

COVID-19:Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism

The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory caused by the novel coronavirus. The virus is the positive-strand RNA one with high homology to bat coronavirus. The pathogenic mechanism of the new coronavirus is still unclear, which is a significant obstacle to the...

chemrxiv.org

This is a computer simulation not an actual genetic research. The pneumonia in COVID-19 is actually caused by infiltrating neutrophils which wreak havoc on the lung tissue. Chloroquine probably suppresses neutrophil numbers and behavior so that is the most route of its action against pneumonia. Not clear if a direct anti-viral effect plays any role in vivo.

DragonBits · Apr 6, 2020

So why don't they give this to Boris johnson, PM of England who is in intensive care??

IMO this was given to people who were going to recover anyway, so I will believe this a little more if they have given it to the PM of England.

But if you are drowning, many people will grab on to anything.

sammmy · Apr 6, 2020

Hopefully Trump will send some Remdesivir for Boris Johnson.

Hydroxychloroquine is not shown to help if started late when the patient is already on oxygen.

fifty · Apr 7, 2020

You think the PM of England needs medical treatment from the US?

sammmy · Apr 7, 2020

I think the PM of England will need an actual treatment, not just being watched to die on ventilator. His best bets are Remdesivir which happens to be a US drug and/or blood with antibodies from people that already had coronavirus.

DragonBits · Apr 7, 2020

sammmy said:
I think the PM of England will need an actual treatment, not just being watched to die on ventilator. His best bets are Remdesivir which happens to be a US drug and/or blood with antibodies from people that already had coronavirus.

So far the PM is getting oxygen but not on require a ventilator. At least not yet.

I don't think there are any good treatments, but I would try blood with antibodies as the most likely helpful.

Any treatment that had any kind of good success we would already know about since the USA is the world leader in cases of covid and there are plenty of opps to try a treatment.

Nelson Vergel · Apr 7, 2020

Results from a Controlled Trial of Hydroxychloroquine for COVID-19

A placebo-controlled trial of hydroxychloroquine in patients hospitalized with COVID-19 finds the drug shortened time to recovery, possibly lessened severity.

www.contagionlive.com