The research on hydroxychloroquine as a treatment for COVID19. And other therapeutics

Hydroxychloroquine and COVID-19

Emerging evidence about this medicine | Updated 5 June 2020
In response to international interest in the use of hydroxychloroquine for the prevention and treatment of COVID-19, the disease caused by the virus SARS-CoV-2, we look at emerging evidence, current guidelines and whether hydroxychloroquine is actually a ‘miracle drug’ that will save lives during this pandemic.

Australian hydroxychloroquine COVID-19 treatment trial

On 21 April 2020, the Australasian COVID-19 trial (ASCOT) was launched. The trial aims to generate clinical evidence about treatments that can be applied during the pandemic to reduce mortality or the need for mechanical ventilation in hospitalised but not yet critically ill patients with COVID-19. A key feature of the trial is that it will be applying an 'adaptive' methodology that will allow evidence about treatments to be continually updated with new information as it becomes available, while at the same time maintaining trial integrity.

The first treatments to be trialled are lopinavir/ritonavir and hydroxychloroquine. Both medicines are already in use for the treatment of other conditions.

What is the COVID-SHIELD Trial?

The COVID-SHIELD Trial is looking to see if hydroxychloroquine (the medication under investigation) can help prevent COVID-19. The medication under investigation for this trial is already prescribed in Australia for conditions such as lupus and rheumatoid arthritis.
We are looking for health care workers in Australia who are at significant risk of illness by the new coronavirus to take part in the trial. COVID-19 is a condition caused by the new coronavirus (SARS-CoV-2), presenting as fever, cough and shortness of breath. More serious cases require hospital admission and the need for assisted ventilation, with a risk of death.
In this trial, participants will be randomly assigned to receive hydroxychloroquine or matching placebo daily. This will allow us to see if hydroxychloroquine is better than placebo in preventing COVID-19 and if hydroxychloroquine reduces the severity and duration of COVID-19 symptoms.
About 2,250 health care workers in Australia will take part in the trial.

Hydroxychloroquine and COVID-19

Why was the use of hydroxychloroquine stopped in the Solidarity Trial?

On 17 June 2020, WHO announced that the hydroxychloroquine (HCQ) arm of the Solidarity Trial to find an effective COVID-19 treatment was being stopped.
The trial's Executive Group and principal investigators made the decision based on evidence from the Solidarity trial, UK's Recovery trial and a Cochrane review of other evidence on hydroxychloroquine.
Data from Solidarity (including the French Discovery trial data) and the recently announced results from the UK's Recovery trial both showed that hydroxychloroquine does not result in the reduction of mortality of hospitalised COVID-19 patients, when compared with standard of care.

From Australia's TGA - Therapeutic Goods Administration:

New restrictions on prescribing hydroxychloroquine for COVID-19

24 March 2020

In recent days there has been considerable focus on the potential for hydroxychloroquine and the similar compound chloroquine (which is not marketed in Australia) to help in treating COVID-19.
Hydroxychloroquine is used for treatment of malaria and certain autoimmune diseases.
Recent reports of increased off-label prescribing of medicines containing hydroxychloroquine have raised concerns that this will create a potential shortage of this product in Australia.
Clinical trials are underway around the world examining their potential to treat COVID-19. However, these medicines pose well-known serious risks to patients including cardiac toxicity (potentially leading to sudden heart attacks), irreversible eye damage and severe depletion of blood sugar (potentially leading to coma).
Given the limited evidence for effect against COVID-19, as well as the risk of significant adverse effects, the TGA strongly discourages the use of hydroxychloroquine outside of its current indications at this time other than in a clinical trial setting or in a controlled environment in the treatment of severely ill patients in hospital.
To limit use of hydroxychloroquine to currently approved indications, there have been new restrictions placed on who can initiate therapy using it. Only certain types of specialists will be able to prescribe hydroxychloroquine to new patients (see information for health professionals below). General practitioners and other medical practitioners (e.g. hospital Resident Medical Officers (RMOS) and doctors in training) can continue to prescribe repeats for hydroxychloroquine to patients in line with the registered indications for patients in whom the medication was prescribed prior to 24 March 2020. From 24 March 2020, general practitioners and doctors in training can only prescribe these medicines for continued treatment of patients where initial treatment has been authorised by one of the specialists.

 

Three big studies dim hopes that hydroxychloroquine can treat or prevent COVID-19

Praised by presidents as a potential miracle cure and dismissed by others as a deadly distraction, hydroxychloroquine was spared a seeming death blow last week. On 4 June, after critics challenged the data, The Lancet suddenly retracted a paper that had suggested the drug increased the death rate in COVID-19 patients, a finding that had stopped many clinical trials in their tracks. But now three large studies, two in people exposed to the virus and at risk of infection and the other in severely ill patients, show no benefit from the drug.

“We’d be better off shifting our attention to drugs that might actually work.” 

On 5 June, researchers in the United Kingdom announced the results from the largest trial yet, Recovery, in a press release. In a group of 1542 hospitalized patients treated with hydroxychloroquine, 25.7% had died after 28 days, compared with 23.5% in a group of 3132 patients who had only received standard care. “These data convincingly rule out any meaningful mortality benefit,” wrote the investigators.

Hydroxychloroquine for the Prevention of Covid-19 — Searching for Evidence

Some researchers have promoted chloroquine and hydroxychloroquine for the treatment and prevention of illness from a variety of microorganisms, including SARS-CoV.  Hydroxychloroquine can inhibit replication of SARS-CoV-2 in vitro. Some observational studies have suggested benefits of hydroxychloroquine for the treatment of Covid-19, whereas other treatment reports have described mixed results...

The advocacy and widespread use of hydroxychloroquine seem to reflect a reasonable fear of SARS-CoV-2 infection. However, it would appear that to some extent the media and social forces — rather than medical evidence — are driving clinical decisions and the global Covid-19 research agenda...

The results reported by Boulware et al. are more provocative than definitive, suggesting that the potential prevention benefits of hydroxychloroquine remain to be determined...

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19

Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care.

NIH COVID19 Treatment Guidelines

Overall Recommendations

• The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of chloroquine or hydroxychloroquine for the treatment of COVID-19, except in a clinical trial (AII).
• The Panel recommends against the use of high-dose chloroquine (600 mg twice daily for 10 days) for the treatment of COVID-19 (AI).

FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems

Does not affect FDA-approved uses for malaria, lupus, and rheumatoid arthritis 

July 1, 2020 Update: A summary of the FDA review of safety issues with the use of hydroxychloroquine and chloroquine to treat hospitalized patients with COVID-19 is now available. This includes reports of serious heart rhythm problems and other safety issues, including blood and lymph system disorders, kidney injuries, and liver problems and failure.

Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19

Annotation by Ian Breakspear, Naturopath and Senior Lecturer at Endeavour College of Natural Health:

This study by Arshad et al, is a retrospective observational study which is interesting. The study does indicate those treated with HCQ had a lower mortality rate. It gives no indication as to whether the patients had reduced or zero viral loads after administration (however this is not a major limitation - regardless of viral loads, a reduction in mortality rate is a good thing! It just means we need to then also understand whether it reduces the pathophysiological consequences of the disease, or kills the infection or both - which we don't know yet). In addition to the HCQ or HCQ + azithromycin, both corticosteroids and tocilizumab were used for most patients (which they controlled for in their statistical analysis, but I find it interesting people are not talking about these medications as part of treatment, and just focusing on the HCQ). 

Some limitations I see are: 

1) Only first admission for each patient was included in the data, and subsequent admissions were not included. It would be valuable to know what the numbers of subsequent admissions were, if they were COVID-19 related, and outcomes. To me this is really important. If they had severe disease in their initial admission, were discharged (i.e. not a fatality) and then subsequently readmitted (even if they survived the second readmission) then that says to be that the value of the treatment is quite limited. 

 2) The authors themselves point out a limitation in that it wasn't randomised or blinded. I don't think that this is a big issue, it just points out that ideally we need to also conduct randomised and blinded studies, to have a better understanding of whether these results are just correlation, or if there is an actual causative link between HCQ usage and reduced mortality. However what I find interesting is that some outlets (like the Christian Broadcasting Network) are reporting this study as a randomised double blind study, which it is not. 

 3) The authors also point out their results need to be interpreted with caution (good scientific practice) and "should not be applied to patients treated outside of hospital settings" which was the opposite of what the "America's Frontline Doctors" press conference was saying.

Global HC Q studies. PrEP, PEP, and early treatment studies show high effectiveness, while late treatment shows mixed results.

This  link it is an interesting clustering of available HCQ studies. It is pointing in the direction that perhaps prophylactic usage or early stage usage may result in improved outcomes. The limitation here is it is mixing together different outcome measures (mortality rates, severity of symptoms, infection rates, etc). However it is great to see as an early attempt at weighing the evidence.

Everything you need to know about the COVID-19 therapy trials

There are thousands of clinical trials investigating treatments and preventative measures for COVID-19.

 

World-first COVID-19 antiviral therapy developed in Brisbane and US targets virus in the body

 

Israel claims new covid treatments could be a ‘game-changer’

After being faced with yet another surge in Covid-19 cases, experts in this country have been working on new ways to beat covid.

 

 

A major ivermectin study has been withdrawn, so what now for the controversial drug?

 

Huge study supporting ivermectin as Covid treatment withdrawn over ethical concerns

The preprint endorsing ivermectin as a coronavirus therapy has been widely cited, but independent researchers find glaring discrepancies in the data.

The study found that patients with Covid-19 treated in hospital who “received ivermectin early reported substantial recovery” and that there was “a substantial improvement and reduction in mortality rate in ivermectin treated groups” by 90%.

But the drug’s promise as a treatment for the virus is in serious doubt after the Elgazzar study was pulled from the Research Square website on Thursday “due to ethical concerns”. Research Square did not outline what those concerns were.

 

Wait for the Principle Trial ...

What now for ivermectin?

Professor Andrew McLachlan reviews the medication and its potential against COVID-19 in the wake of a major study being withdrawn.

What now for ivermectin?

Professor Andrew McLachlan reviews the medication and its potential against COVID-19 in the wake of a major study being withdrawn.

Hydroxychloroquine side effects and contra-indication

Read this first:

The White Coat Summit at Capital Hill. Lots of white coats. Lots of agenda

(With thanks to the brilliant Claire Chapman who sourced the following.)

Want some hydroxychloroquine?

CONTRAINDICATIONS
Hydroxychloroquine is contraindicated in:

patients with pre-existing maculopathy of the eye;
patients with known hypersensitivity to 4-aminoquinoline compounds;
long-term therapy in children;
children under 6 years of age.

4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Hydroxychloroquine is not effective against chloroquine-resistant strains of P. falciparum.
Patients should be warned to keep hydroxychloroquine out of the reach of children, as small children are particularly sensitive to 4-aminoquinolines.
Hydroxychloroquine should be used with caution, or not at all, in patients with severe gastrointestinal, neurological or blood disorders. If such severe disorders occur during therapy, hydroxychloroquine should be stopped. Periodic blood counts are advised.
When used in patients with porphyria or psoriasis, these conditions may be exacerbated. Hydroxychloroquine should not be used in these conditions unless in the judgement of the physician, the benefit to the patient outweighs the possible risk.
Chronic cardiac toxicity
Cases of cardiomyopathy resulting in cardiac failure, in some cases with fatal outcome, have been reported in patients treated with hydroxychloroquine. Clinical monitoring for signs and symptoms of cardiomyopathy is advised and hydroxychloroquine should be discontinued if cardiomyopathy develops. Chronic toxicity should be considered when conduction disorders (bundle branch block / atrio-ventricular heart block) as well as biventricular hypertrophy are diagnosed.

Hypoglycaemia
Hydroxychloroquine has been shown to cause severe hypoglycaemia including loss of consciousness that could be life threatening in patients treated with and without anti-diabetic medications. Patients treated with hydroxychloroquine should be warned about the risk of hypoglycaemia and the associated clinical signs and symptoms. Patients presenting with clinical symptoms suggestive of hypoglycaemia during treatment with hydroxychloroquine should have their blood glucose level checked and treatment reviewed as necessary.

QT interval prolongation
Hydroxychloroquine prolongs the QTc interval and should not be used in patients receiving drugs known to prolong the QT interval, e.g. class IA and III antiarrhythmics, tricyclic antidepressants, antipsychotics, some anti-infectives due to increased risk of ventricular arrhythmia (see Section 4.5 Interactions with other medicines and other forms of interactions and Section 4.9 Overdose).
Hydroxychloroquine should be used with caution in patients with congenital or documented acquired QT prolongation and/or known risk factors for prolongation of the QT interval such as:
cardiac disease, e.g., heart failure, myocardial infarction
proarrhythmic conditions, e.g., bradycardia (< 50 bpm)
a history of ventricular dysrhythmias
uncorrected hypokalaemia and/or hypomagnesaemia
The magnitude of QT prolongation may increase with increasing concentrations of the drug. Therefore, the recommended dose should not be exceeded (see Section 4.5 Interactions with other medicines and other forms of interactions and Section 4.8 Adverse effects (Undesirable effects)).

Ophthalmological
Irreversible retinal damage has been observed in some patients who had received long-term or high-dosage 4-aminoquinolone therapy for discoid and systemic lupus erythematosus or rheumatoid arthritis. Retinopathy has been reported to be dose related. Exceeding the recommended daily dose sharply increases the risk of retinal toxicity.
If there is any indication of abnormality in the visual field or retinal macular areas (such as pigmentary changes, loss of foveal reflex), or any visual symptoms (such as light flashes and streaks) which are not fully explainable by difficulties of accommodation or corneal opacities, hydroxychloroquine should be discontinued immediately and the patient closely observed for possible progression. Retinal changes (and visual disturbances) may progress after cessation of therapy. (See Section 4.8 Adverse effects (Undesirable effects))
Concomitant use of hydroxychloroquine with drugs known to induce retinal toxicity, such as tamoxifen, is not recommended.
Before starting treatment with hydroxychloroquine, all patients should have a careful complete examination of both eyes which includes slit lamp microscopy for corneal changes, fundoscopy, visual acuity, central visual field and colour vision. A complete eye examination before treatment will determine the presence of any visual abnormalities, either coincidental or due to the disease, and establish a baseline for further assessment of the patient's vision.
Ophthalmological testing should be conducted at 6-monthly intervals in patients receiving hydroxychloroquine at a dose of not more than 6 mg/kg body weight per day.
Ophthalmological testing should be conducted at 3–4 monthly intervals in the following circumstances:
dose exceeds 6 mg/kg ideal (lean) body weight per day. Using absolute body weight, as a guide to dosage, could result in an overdosage in the obese;
significant renal impairment;
significant hepatic impairment;
elderly;
complaints of visual disturbances;
duration of treatment exceeds 8 years.
Corneal changes often subside on reducing the dose or on interrupting therapy for a short period of time, but any suggestion of retinal change or restriction in the visual field is an indication for complete withdrawal of the drug.
The use of sunglasses in patients exposed to strong sunlight is recommended, as this may be an amplifying factor in retinopathy.

Skin Reactions
Pleomorphic skin eruptions (morbilliform, lichenoid, purpuric), itching, dryness and increased pigmentation sometimes appear after a few months of therapy. The rash is usually mild and transient. If a rash appears, hydroxychloroquine should be withdrawn and only started again at a lower dose.
Patients with psoriasis appear to be more susceptible to severe skin reactions than other patients.
Other monitoring on long term treatments
Patients on long-term therapy should have periodic full blood counts. If evidence of abnormalities such as agranulocytosis, aplastic anaemia, thrombocytopenia or leukopenia becomes apparent, and cannot be attributed to the disease being treated, hydroxychloroquine should be discontinued.
All patients on long-term therapy with hydroxychloroquine should be questioned and examined periodically, including the testing of knee and ankle reflexes, to detect any evidence of muscular weakness. If weakness occurs discontinue the drug.

Miscellaneous
Gastrointestinal disturbances such as nausea, anorexia, abdominal cramps or rarely vomiting, occur in some patients. The symptoms usually stop on reducing the dose or temporarily stopping the drug.
Muscle weakness, vertigo, tinnitus, nerve deafness, headache and nervousness have been reported less frequently.
In the treatment of rheumatoid arthritis, if objective improvement (such as reduced joint swelling, increased mobility) does not occur within six months, hydroxychloroquine should be discontinued. Safe use of hydroxychloroquine in the treatment of juvenile rheumatoid arthritis has not been established.
Suicidal behaviour has been reported in very rare cases in patients treated with hydroxychloroquine.
Extrapyramidal disorders may occur with hydroxychloroquine.
Also observe caution in patients with gastrointestinal, neurological, or blood disorders, in those with a sensitivity to quinine and in glucose-6-phosphate dehydrogenase deficiency.
Use in hepatic impairment
Observe caution in patients with hepatic disease, in whom a reduction in dosage may be necessary, as well as in those taking medicines known to affect the organ.
Use in renal impairment
Observe caution in patients with renal disease, as well as in those taking medicines known to affect the organ. A reduction in dosage may be necessary.
Use in the elderly
See Section 4.4 Special warnings and precautions for use – Ophthalmological.

Paediatric use
No data available.
Effects on laboratory tests
No data available.

4.5 INTERACTIONS WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTIONS
It has been suggested that 4-aminoquinolines are pharmacologically incompatible with monoamine oxidase inhibitors.
Concomitant hydroxychloroquine and digoxin therapy may result in increased serum digoxin concentrations. Consequently, serum digoxin concentrations should be closely monitored in patients receiving concomitant therapy.
As hydroxychloroquine may enhance the effects of a hypoglycaemic treatment, a decrease in doses of insulin or antidiabetic drugs may be required.
Drugs known to prolong QT interval / with potential to induce cardiac arrhythmia: Hydroxychloroquine should not be used in patients receiving drugs known to prolong the QT interval, e.g., Class IA and III antiarrhythmics, tricyclic antidepressants, antipsychotics, some anti-infectives due to increased risk of ventricular arrhythmia (see Section 4.4 Special precautions and warnings for use and Section 4.9 Overdose). Halofantrine should not be administered with hydroxychloroquine.
Increased plasma cyclosporin levels have been reported when cyclosporin and hydroxychloroquine are co-administered.
Hydroxychloroquine can lower the convulsive threshold. Co-administration of hydroxychloroquine with other antimalarial known to lower the convulsion threshold (e.g. mefloquine) may increase the risk of convulsions.
The activity of antiepileptic drugs might be impaired if co-administered with hydroxychloroquine.
In a single-dose interaction study, chloroquine has been reported to reduce the bioavailability of praziquantel. It is not known if there is a similar effect when hydroxychloroquine and praziquantel are co-administered. Per extrapolation, due to the similarities in structure and pharmacokinetic parameters between hydroxychloroquine and chloroquine, a similar effect may be expected for hydroxychloroquine.
There is a theoretical risk of inhibition of intra-cellular α-galactosidase activity when hydroxychloroquine is co-administered with agalsidase.

4.6 FERTILITY, PREGNANCY AND LACTATION
Effects on fertility
There are no animal data on hydroxychloroquine action on fertility. A study in male rats after 30 days of oral treatment at 5 mg/day of chloroquine showed a decrease in testosterone levels, weight of testes, epididymis, seminal vesicles and prostate.
In another rat study with chloroquine the male fertility rate was decreased after 14 days of intraperitoneal treatment at 10 mg/kg/day.
There are no data in humans.
Use in pregnancy
Category D
Hydroxychloroquine crosses the placenta. Data are limited regarding the use of hydroxychloroquine during pregnancy. It should be noted that 4-aminoquinolines in therapeutic doses have been associated with central nervous system damage, including ototoxicity (auditory and vestibular toxicity, congenital deafness), retinal haemorrhages and abnormal retinal pigmentation. Hydroxychloroquine should be avoided in pregnancy except when, in the judgement of the physician, the potential benefits outweigh the potential hazards.
The use of hydroxychloroquine in the treatment of malaria or suppression of malaria in high risk situations may be justified if the treating physician considers the risk to the foetus is outweighed by the benefits to the mother and foetus.
Use in lactation
Hydroxychloroquine is excreted in breast milk and it is known that infants are extremely sensitive to the toxic effects of 4-amonioquinones. In one study, the daily HCQ exposures to infant from breast milk were estimated to be less than 2% of the maternal dose (after bodyweight correction).
Although hydroxychloroquine is excreted in breast milk, the amount is insufficient to confer any protection against malaria to the infant. Separate chemoprophylaxis for the infant is required.
There are very limited data on the safety in the breastfed infant during long-term hydroxychloroquine treatment; the prescriber should assess the potential risks and benefits of use during breastfeeding, according to indication and duration of treatment.

4.7 EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Patients should be warned about driving and operating machinery since hydroxychloroquine can impair visual accommodation and cause blurring of vision. If the condition is not self-limiting, the dosage may need to be temporarily reduced.

4.8 ADVERSE EFFECTS (UNDESIRABLE EFFECTS)
Note:
very common: ≥ 1/10 (≥ 10%)
common: ≥ 1/100 and < 1/10 (≥ 1% and < 10%)
uncommon: ≥ 1/1000 and < 1/100 (≥ 0.1% and < 1%)
rare: ≥ 1/10,000 and < 1/1000 (≥ 0.01% and < 0.1%)
very rare: < 1/10,000 (< 0.01%)
not known: frequency cannot be estimated from the available data
Eye Disorders
Common:
blurring of vision
Uncommon:
corneal changes, retinal changes, retinopathy with changes in pigmentation and visual field defects. In its early form, it appears reversible on discontinuation of hydroxychloroquine. If allowed to develop, there may be a risk of progression even after treatment withdrawal.
Patients with retinal changes may be asymptomatic initially, or may even have scotomatous vision with paracentral, pericentral ring types, temporal scotomas and abnormal colour visions.
Corneal changes including oedema and opacities have occurred from three weeks (infrequently) to some years after the beginning of therapy. They are either symptomless or may cause disturbances such as halos, blurring of vision or photophobia. They may be transient or are reversible on stopping treatment. Should these types of corneal changes occur with hydroxychloroquine, it should be either stopped or temporarily withdrawn.
Not known:
cases of maculopathies and macular degeneration have been reported and may be irreversible.
Reversible extra-ocular muscle palsies and temporary blurring of vision due to interference with accommodation have also been noted.
Retinal changes such as abnormal macular pigmentation and depigmentation (sometimes described as a "bull's eye"), pallor of the optic disc, optic atrophy and narrowing of the retinal arterioles have been reported.
Originally, the condition was thought to be progressive and irreversible, but more recent evidence suggests that routine ophthalmological examinations may detect retinal changes, especially pigmentation, at an early and reversible stage when there is no apparent visual disturbance.
Much evidence suggests that there is a threshold of dosage above which retinopathy appears. These results seem to correlate more with daily dosage than with a cumulative dose, although the risk increases with increased duration of treatment.
Before starting treatment with hydroxychloroquine, all patients should have a careful complete examination of both eyes which includes slit lamp microscopy for corneal changes, fundoscopy, visual acuity, central visual field and colour vision, repeated at six month intervals during therapy (see Section 4.4 Special warnings and precautions for use – Opthalmological).
Any adverse changes in the ocular findings or the appearance of scotoma, night blindness or other retinal changes require immediate discontinuation of hydroxychloroquine; these patients should not subsequently receive any pharmacologically similar drugs.
Ear and Labyrinth Disorders
Uncommon: vertigo, tinnitus
Not known: hearing loss
Immune System Disorders
Not known: urticaria, angioedema, bronchospasm
Blood and Lymphatic System Disorders
Rare: bone marrow depression, anaemia, aplastic anaemia, leukopenia, thrombocytopenia.
Very rare: agranulocytosis.
Psychiatric Disorders
Common: affect lability
Very rare: psychosis, suicidal behaviour, nightmares
Nervous System Disorders
Common: headache
Uncommon: nerve deafness, nervousness, dizziness.
Rare: convulsions, neuromyopathy.
Very rare: nystagmus, ataxia
Not known: extrapyramidal disorders such as dystonia, dyskinesia, tremor.
Musculoskeletal and Connective Tissue Disorders
Uncommon: sensory motor disorders
Not known: absent or hypoactive deep tendon reflexes, muscle weakness or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups (muscle weakness may be reversible after drug discontinuation, but recovery may take many months). Depression of tendon reflexes and abnormal nerve conduction studies.
Very rare: extraocular muscle palsies.
Gastrointestinal Disorders
Very common: abdominal pain, nausea
Common: diarrhoea, vomiting
Metabolism and Nutrition Disorders
Common: anorexia
Not known: hypoglycaemia
Hydroxychloroquine may exacerbate porphyria.
Hepatobiliary Disorders
Uncommon: abnormal liver function tests.
Very rare: fulminant hepatitis.
Cardiac Disorders
Rare: cardiomyopathy which may result in cardiac failure, and in some cases a fatal outcome (see section 4.4 Special warnings and precautions for use)
Chronic toxicity should be considered when conduction disorders (bundle branch block / atrio-ventricular heart block) as well as biventricular hypertrophy are diagnosed.
Not known: QT interval prolongation in patients with specific risk factors, which may lead to arrhythmia (torsade de pointes, ventricular tachycardia) (See Section 4.4 Special warnings and precautions for use and 4.5 Interactions with other medicines and other forms of interactions).
Skin and Subcutaneous Tissue Disorders
Common: skin rashes, alopecia, pruritus.
Uncommon: pigmentary changes, bleaching of hair
Very rare: bullous eruptions such as acute generalized exanthematous pustulosis (AGEP), exfoliative dermatitis and erythema multiforme, Stevens-Johnson syndrome, Drug rash with Eosinophilia and Systemic Symptoms (DRESS syndrome), toxic epidermal necrolysis, photosensitivity.
Miscellaneous
Rare: exacerbation or precipitation of porphyria and attacks of psoriasis.
Very rare: weight loss, lassitude.

The White Coat Summit at Capital Hill. Lots of white coats. Lots of agenda

READ THIS FIRST

First, well-meaning friends and colleagues, who understandably have concerns about medical monopoly breathlessly shared this 'white coat summit at capitol hill' video that claimed to "correct" disinformation - which is classic projection of the type Jared Yates Sexton describes HERE.

As a natural skeptic, I had my concerns.

White coats? What - when not even seeing patients?

Breitbart? Are you kidding me? That outlet is synonymous with alt-right misogyny.

As far right fundamentalist friends shared the heck out it, surpassed only by left-wing alternative health, non-mainstream friends and Insta-famous wellness/success 'influencers'.

I thought just wait. 3 days and the fact-checkers will catch up.

It took ONE day.

First came a few Facebook posts urging caution:

1. Peter Ravn Rasmussen

 "For any of you seeing news about today's Breitbart-sponsored "press conference" on the SCOTUS steps, please be aware of the following facts:

1. "America's Frontline Doctors" didn't exist two weeks ago. Their internet domain name was registered on the 16th of July. It's a newly-created propaganda front, and has no actual medical institutional provenance.

2. The people in the white coats (labeled "America's Frontline Doctors" to make sure you knew they were American frontline doctors) are not actually frontline doctors. Some of them aren't even physicians. To be fair, the ones who aren't physicians didn't actually claim that they were. They just stood there in their white coats (labeled "America's Frontline Doctors").

3. The right-wing media coverage of this is almost universally copied from the same script. Someone fed a text to the right-wing media, and they just ran it.

4. The social media coverage is, similarly, dominated by bots that all say pretty much the same things, often verbatim. Again, there's a script which is being copied ad nauseam.

5. There's going to be more of this kind of thing. It serves to weaken the influence of actual medical professionals' voices in the Republican political effort to pretend that COVID-19 is a negligible problem.

The smell of Republican ratfuckery is all over this thing."

2.Melissa Stout:

"I need your attention. You've seen the video Trump shared of doctors claiming scientists don't want you to know that Hydroxychloroquine cures COVID-19. So I did some digging on the doctors to see if they're credible. Here's what I found:

Dr. Immanuel has no privileges at any Texas hospital and claims that scientists are developing a vaccine to make you an atheist, modern medical treatments contain alien DNA, and miscarriage, endometriosis, and infertility are caused by having sex with demons in your dreams. It gets worse.

- Licensing: http://www.tmb.state.tx.us/page/look-up-a-license

- Some of her views: https://archive.fo/G7wtb

She claims masks are unnecessary and she and all her medical staff take Hydroxychloroquine to prevent COVID-19, but she wears a mask in her videos promoting her Fire Power Ministry -- just not when she's trying to influence public health policy. Among her Fire Power Ministry services are conversion therapy and removing generational curses from your placenta.

When you search for her clinic, it shows her religious gift shop in a strip mall. In her posts and videos, *she Photoshops her clinic sign over the actual sign next door*. She "runs" another clinic in Katy, TX OUT OF AN OLD HOME but again the sign says it's her ministry. Look at the photos! Would you trust this person with your health?

- First location: https://g.co/kgs/s3tXpu

- Second location: https://g.co/kgs/dsb8uv

Each doctor in the video is wearing a white coat with an "America's Frontline Doctors" logo. They are organized by the "Tea Party Patriots". AFD's site was created right before the video, on July 16, less than two weeks ago, so Breitbart could say, "We're here with America's frontline doctors." Not exactly an established group. The AFD site runs out of that strip mall. The listed phone number leads to a website called "Southern Flare [sic] Urgent Care" with another photoshopped clinic encouraging anyone with COVID to pay for virtual treatment.

In the video, she says she's saving the lives of patients who are about to die from COVID-19. On her page, she says she accepts patients with mild cases.

She set up a GoFundMe for any future legal issues she may have. (GoFundMe appears to be down now.)

Dr. Simone Gold, with America's Frontline Doctors, claimed to be affiliated with Centinela Hospital (they have confirmed she is not a current staff member), and inferred she was affiliated with Cedars-Sinai ER -- who has clarified that she is not.

Dr. Gold has 4 reviews, at least one of which was made today and simply thanks her for being so "brave" in the video.

Dr. Jeff Barke is a Qanon conspiracy theorist who was busted in a drug sting. He is affiliated with an online school that was recently sued for fraud and was under investigation for preying on seniors. He's a member of a group that funds Republican candidates, and the Orange County Republican Central Committee. He said COVID-19 is no more dangerous than the flu, when US flu deaths are at 34,000/year and US COVID-19 deaths are at 150,000.

Dr. Barke founded a religious charter school using right-wing curriculum developed by Betsy DeVos-linked Hillsdale College. A charter school PAC gave his wife's campaign $245,000. Guess who is leading the fight to reopen Orange County schools during a pandemic.

- Charter school: https://orangecountyclassicalacademy.org/board-of-directors

A leaked audio of a Republican conference shows the Trump administration was fed a list of 27 pro-Trump doctors who could be "activated" on TV to "spread the message" of reopening the country as soon as possible. Tea Party Patriots, who organized the AFD event, was involved. Is this what the GOP means by "paid actors"? This video got 14 million views in ONE NIGHT and was promoted by Prager U, Breitbart, Turning Point USA, and the PRESIDENT. The person who is supposed to be LEADING while Americans are dying.

- Leaked audio: https://apnews.com/4ee1a3a8d631b454f645b2a8d9597de7

*As I don't have the luxury of being paid to share my opinions, I'd like to reiterate this information is just what I've found online, it's available to everyone, and should not be taken as absolute fact without individual verification*

If you find more on the other speakers leave a comment, but your girl is tired so this is all I'm doing for now."

3. Phil Collins

I truly didn’t think that any of the people I actually know would ride this video wave of Dr. Stella Immanuel without at least typing her name into Google after noticing the Breitbart emblem at the bottom of the video...but alas, here we are.

It is nice, she is passionate, and she makes you want to believe that this could be true. A simple Google search of Dr. Stella Immanuel would have also shown you a few things about her medical history and her clinic in a strip mall that sits next to the church she runs. I’ll list a few below:

- She argues that Gynecological problems (endometriosis, infertility, impotence, ovarian cysts, molar pregnancies) are the work of “demons” and “witches” that you have sex with in your sleep.

- The Illuminati has sent witches to destroy the world via Gay marriage, abortion, and children’s toys.

-She claims the government has pinpointed religion in DNA and that the government has created a vaccine to “destroy” that part of your DNA.

-She claims patients are being treated using “Alien DNA” and that the country is being run by “reptiles”.

-She has preached from her church hatred of the LGBTQ community, saying after the SCOTUS decision to legalize gay marriage that the LGBTQ community would start marrying and raping children, called it “homosexual terrorism” and praised one of her members for disowning his transgender daughter.

-There is records of her saying she supports “corporal punishment” for children.

-AND she has hypocritically said to wear masks up until the moment she was in front of video cameras.

Furthermore this entire event was staged by the Right leaning Tea Party Patriots, backed financially by wealthy Republicans, and streamed on Breitbart; in case you have forgotten, Steve Bannon runs Breitbart, Breitbart is labeled nationalist media, nationalists = white supremacists.

I want to believe that my friends are smarter than reposting media from a White Supremacists media company, I want to believe that. I want to believe my friends are smarter than seeing the first impassioned doctor shout “THERES A CURE!” and holding on to that as a new life line. I really really want to believe that we all understand that there is no “cure” for Covid-19 and media like this is incredibly dangerous for the young folks who think this is all a hoax anyway.

Come on friends. Be smarter.

*Update: the website for America’s Frontline Doctors Summit, has been removed.

 

Then - the inevitable flurry of articles:

 

Hydroxychloroquine: Why a video promoted by Trump was pulled on social media

 

 

Astral sex and alien DNA: Who is the doctor behind the misleading COVID-19 video shared by Donald Trump?

This is from a Christian magazine. (NOTE: we are not ALL right-wing fundamentalists - and guess what? Loads of us aren't even American. Just like the vast majority of Muslims are not extremists, fundamentalists, or terrorists.)

 

A Doctor Promoted by Trump Is Also Concerned About the Side Effects of Having Sex With Demons

 

Trump Shares Messages Calling Dr. Fauci A ‘Fraud,’ Promoting Hydroxychloroquine

 

How Quack Doctors And Powerful GOP Operatives Spread Misinformation To Millions

"A group calling itself “America’s Frontline Doctors” spread false information about COVID-19 with the help of Facebook, right-wing media and President Trump."

 

Who Are ‘America’s Frontline Doctors’, the Pro-Trump, Pro-Hydroxychloroquine Weirdos Banned From Social Media?

 

Dark money and PAC's coordinated 'reopen' push are behind doctors' viral hydroxychloroquine video

"The virality of the video underscores the difficulty in moderating coronavirus misinformation as treatments and public health responses have become more political."

Immanuel has been a vocal supporter of Trump on social media since 2016, and used Facebook and Twitter to spread conspiracy theories, including that the coronavirus was manufactured in China. She also operates the religious organization "Fire Power Ministries" from her Houston clinic, where she posts videos expressing extreme beliefs, including falsely attributing medical issues such as miscarriage, gynecological problems and impotence as stemming from spiritual possession by demon spirits.

(PAC = political action committee)

 Finally, a few pithy comments I gleaned:

* "A lot of the tweets and RTs about this seem to have a fair amount of anti-Semitism to them. Stuff about "Jewish media" and "Jewish remdesivir" and the like."

* "I did watch the video and she lost me when she said we don’t need controlled clinical trials. She said none of the 350 patients that she saw in her office had died, and that was enough evidence for her that HCQ works. I’ve never seen a reputable doctor put anecdotal evidence over controlled trials. She is a GP. Perhaps she would have a different opinion if she were an ER doc or worked in the ICU. To push HCQ as a “cure” is irresponsible and potentially deadly."

  Also worth considering the experience of patients who actually need to take this drug: 

"The side effects are shocking even using it for rheumatoid atheist it’s a double sword. Help with pain... or lose my hair & suffer kidney dysfunction."

This is by Ian Breakspear, one of Australia's leading Naturopaths and Senior Lecturer at Endeavour College of Natural Health:

Ian Breakspear

: 

"So this “America’s Frontline Doctors” video has been doing the rounds, and it’s a little concerning to see some people taking it seriously. I’ve had some colleagues ask me about it. It is somewhat understandable that members of the public might take it seriously, as they are using classic techniques of manipulation – such as wearing white coats to make them look authoritative, medical and scientific (when they are out in the open and not in a health care or lab setting where they may be needed), blending truth and fiction together to make it hard to tell what is what, and also using quite emotional language in some cases.

However the credibility of the information provided, and the way it is provided, is highly suspect. Below I discuss why. For those who wish to see the recorded press conference first hand, I’m not linking to the video because it keeps getting removed from social media (which I am fine with given how misleading it is), but the transcript can be read here: https://www.rev.com/blog/transcripts/americas-frontline-doctors-scotus-press-conference-transcript/amp

The biggest thing people are focusing on is a claim from some of the doctors that they have the cure for COVID-19, including hydroxychloroquine, azithromycin, and zinc.

As we know, hydroxychloroquine was been postulated as a treatment since the early stages of this pandemic, however ongoing research has indicated that the initially published positive results were not able to be duplicated. This is the value of science – that a claim needs to be rigorously investigated and show consistently – not just once – that it holds up to scrutiny. And so far hydroxychloroquine has not held up under that scrutiny, especially in more highly symptomatic cases of COVID-19 – which of course are the ones for which we are really hoping for a successful treatment.

Now looking at some of the specific statements:

Dr. Stella Immanuel: (06:46)

“So right now, I came here to Washington DC to say, America, nobody needs to die. The study that made me start using hydroxychloroquine was a study that they did under the NIH in 2005 that say it works. Recently, I was doing some research about a patient that had hiccups and I found out that they even did a recent study in the NIH, which is our National Institute … that is the National … NIH, what? National Institute of Health. They actually had a study and go look it up. Type hiccups and COVID, you will see it. They treated a patient that had hiccups with hydroxychloroquine and it proved that hiccups is a symptom of COVID. So if the NIH knows that treating the patient would hydroxychloroquine proves that hiccup is a symptom of COVID, then they definitely know the hydroxychloroquine works.”

There are whole lot of issues here:

1) As far as we know SARS-CoV-2 didn’t exist in 2005, so there could not have been published research showing the efficacy of a drug on killing that particular virus.

2) How can treating a patients for hiccups successfully with hydroxychloroquine (HQ) actually prove that hiccups are a symptom of COVID-19, let alone that HQ is a cure for COVID-19? It is scientifically nonsensical. Whilst hiccups have been recorded as an atypical symptom of COVID-19, in the single patient case report (full text here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165082/ ) the authors state the patient initially only presented with a 4 day history of hiccups and 4 month history of weight loss. Testing revealed the patient was positive for SARS-CoV-2, was treated with HQ for a few days, and discharged. There was no information given as to the out-patient follow up of this individual, no subsequent testing to determine if the virus had been cleared. The authors don’t even make the slightest hint that HQ successfully treated HQ – they are merely pointing out the need to be alert to unusual symptoms in patients who otherwise may not have the classic COVID-19 clinical picture.

3) The fact that this doctor can’t even seem to say the full name of the American NIH without assistance, does not fill me with confidence.

Simone Gold: (11:02)

“My gosh. Dr. Immanuelle also known as warrior. Before I introduce the next guest, I just want to say that I wish all doctors that are listening to this bring that kind of passion to their patients. And the study that Dr. Immanuel was referring to is in Virology, which talks about a SARS viral epidemic that affects the lungs that came from China. And they didn’t know what would work. The study showed that chloroquine would work. It sounds exactly like it could have been written three months ago, but in fact, that’s study in Virology, which was published by the NIH, the National Institute of Health when Dr. Anthony Fauci was the director. Again, the official publication of the NIH, Virology, 15 years ago showed that chloroquine … we use hydroxychloroquine, it’s the same … little safer … works. They proved this 15 years ago when we got this novel coronavirus, which is not that novel, it’s 78% similar to the prior coronavirus, which is not that novel. It’s 78% similar to the prior version. The COV-1, not surprisingly. It works.”

Yes this study on chloroquine and SARS-CoV-1 exists - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1232869/

However it is an entirely in-vitro study. It is not a study done on humans, but instead cell cultures in laboratory conditions. It certainly is not reporting success of chloroquine in humans infected and symptomatic with SARS-CoV-1, or in humans as a prevention for infection from this virus.

Also the statement that SARS-CoV-2 is not that novel, but in fact 78% similar to SARS-CoV-1 (which I haven’t personally verified so not sure if that number is correct), is bizarre. Humans and chimpanzees are 98% similar in genetic code, so I think 78% similarity is far from proof positive that treatment for one virus is going to work for another virus in the same family.

Speaker 9: (27:45)

“Yeah, that’s a great question. Because the whole political situation has driven the fear towards this drug. So let’s address that. This drug is super safe. It’s safer than aspirin, Motrin, Tylenol. It’s super safe. All right.”

I don’t know what planet they are on, but I have seen patients with adverse reactions to HQ (when it is prescribed for other, more well-established, indications). The adverse reactions are well known and well documented, and have been for many years. Like all medicines its risk needs to be weighed against its benefit. So far the research across the world is not indicating a positive benefit vs risk in treating patients who are severely symptomatic with COVID-19.

In addition to just this snapshot of bizarre statements, I’d encourage you to dig a little deeper into some of the bizarre statements around diseases made by Dr Immanuel long before COVID-19 as part of her “Fire Power Deliverance Ministries with Dr Stella Immanuel”.

Finally, if these doctors truly feel that they have the cure for COVID-19, then why have they not published? They are claiming to have hundreds of cases, surely they could publish a case series? Even if they claim that they are being blocked from publication in mainstream journals, then take it upon yourselves to publish detailed case reports on your own websites, etc. It’s not hard to get information out there in today’s world. Give us the details, the dosages, the patient histories, etc, so that we can review this information properly.

I’m not sure what this group’s agenda is, and they may have some legitimate ideas worthy of investigation. But in my opinion their unprofessional behaviour is not doing them any service, and a lot of their statements are emotive, unscientific rubbish."

Before you wonder if the failure of our medicos in Australia to widely recommend Hydroxychloroquine for the treatment of COVID19, please carefully read this list of side effects and cautions. Just possibly, their caution and reservations might NOT because they are just "totally brain-washed by Left-wing MSM, un-woke sheeple." Who knew!!?

Hydroxychloroquine side effects and contra-indications

The Research (so far) on Hydroxychloroquine as a therapeutic for COVID19