Quote from RobertBryant

Increased risk of using heart failure/arrest with..HCQ +Azithromycin(AZM)

Both HCQ and AZM prolong the QT interval.

However when HCQ is used with another drug(sulfasalazine which does not prolong the QT interval)

there is no increased risk of heart failure/arrest

Large retrospective study of rheumatoid arthritis users of HCQ ( not COVID patients)

medrxiv https://www.medrxiv.org/conten…04.08.20054551v1.full.pdf

Worryingly, significant risks are identified for combination users of HCQ+AZM even in the short-term as
proposed for COVID19 management, with a 15-20% increased risk of angina/chest pain and heart failure,
and a two-fold risk of cardiovascular mortality in the first month of treatment.

Display More

That study is useful but ONE BIG CAVEAT

The data comes from RA patients on long-term HCQ.

Presumably they all will have been screened for HCQ contra-indications before being put onto HCQ - e.g. cardiac arrhythmias or long QT interval? So these patients are selected as those likely to be safer.

I'm not sure because the RA doses of HCQ are relatively low, but even so I think you cannot compare these mortality rates with the mortality rates expected if all COVID patients are put onto HCQ? Need to screen for contraindications.

Quote from seven_of_twenty

Either remdesivir is not very effective for severe COVID-19 or it needs an added medication or the dose was not optimal.

Looks the same (in fact a bit better) as Kaletra where you posted a 10-20% effect. Remdesivir is a US drug and has been promoted by the US pharma mafia since day 1. I did post the same 1 month ago. Switzerland tried both and finally did give up Kaletra a few days ago because of the small effect. But even if the effect may be small (for both) if 1 out of 10 deaths can be prevented its still better than nothing. It's anyway used for severe cases only. Kaletra is cheap but Remdesivir is certainly not.

Quote from Shane D.

10 were transferred to intensive care units, 5 patients died (0.47%) (74-95 years old) and 31 required 10 days of hospitalization or more. Among this group, 25 patients are now cured and 16 are still hospitalized (98% of patients cured so far).

In Switzerland about 10% of the + cases need Hospitalization 4% die. This is 10x more than in Raoults summary. But we cannot easily compare statistics as e.g. Switzerland only reports ventilator cases as severe and others report all ICU cases like Boris getting Oxygen only as severe.

Quote from Navid

This is a population control game. And you are a character in their game...

We are all characters in the 5 eyes control game since along time (90ties...) . I know all the secrete back doors of NSA since day one and please do not believe that your PC,Mac, phone, tablet is not under control. It's just one more control and may be one reason they will not like it....

PS: We wrote the worlds first remote control active anti virus tool in 1987 for the MAC-OS...

Great documentary "Contagion" by the BBC on disease modelling and preparations for an outbreak. Its two years old but very relevant. Virus R = 2 to 3 approx.

A partcularly interesting part IMO is the role of superspreaders (often shop staff, bus drivers, teachers etc anec). The rate of disease progression if/when these people have immunity is discussed.

Its on bbc iplayer till Monday, or on youtube here:

The active favipiravir-ribofuranosyl-5-triphosphate has a remarkably similar tertiary molecular structure to remdesivir (minus two phosphates and substitution of the adenine group). So both are likely scooped up by the viral RNA dependent RNA polymerase resulting in either RNA sequence termination or defective virus RNA. Similar enzymes to hypoxanthine guanine phosphoribosyltransferase may grab the hydroxychloroquine molecule too resulting in another nonsense HCQ-ribofuranosyl-5-triphosphate active intermediiary to confuse and disrupt viral replication. The Zn ionophore and endosome pH raising properties may not be the only mechanisms involved in blocking viral replication. So which one to add to our anti bat virus combo? Well ease of administration does figure, a large molecule like remdesivir has to be injected. So favipiravir probably is the better candidate since this shows lower toxicity with similar clinical benefit. Probably cheaper too. The chloroquine + favipiravir (Avigan) combo is being tested in Indonesia at least, since their president had the foresight to order a vast quantity of both from China. Nobody that clever here, unfortunately. What about the phosphatase inhibitors? Maybe choose Lopinavir.

Mechanism of action[edit]

The mechanism of its actions is thought to be related to the selective inhibition of viral RNA-dependent RNA polymerase.^[7] Other research suggests that favipiravir induces lethal RNA transversion mutations, producing a nonviable viral phenotype.^[8] Favipiravir is a prodrug that is metabolized to its active form, favipiravir-ribofuranosyl-5'-triphosphate (favipiravir-RTP), available in both oral and intravenous formulations.^[9][10] Human hypoxanthine guanine phosphoribosyltransferase (HGPRT) is believed to play a key role in this activation process.^[11] Favipiravir does not inhibit RNA or DNA synthesis in mammalian cells and is not toxic to them.^[1] In 2014, favipiravir was approved in Japan for stockpiling against influenza pandemics.^[12] However, favipiravir has not been shown to be effective in primary human airway cells, casting doubt on its efficacy in influenza treatment.^[13]

So the ideal anti bat virus combo is, so far: Hydroxychloroquine 250 mg, Azithromycin 200 mg, Favipiravir 100mg, Lopinavir 50 mg, Zn SO4 100 mg. Twice daily? We can call it Anti-bat for short! Might work better than Z-pak. For Mass Drug Administration?

HCQ

I find the medical establishment views on this to be a bit weird. I agree with them that the current evidence for HCQ actually helping is pretty poor. Really just that one RCT from China. But the risks of using HCQ (after screening for contra-indications) are very low and even HCQ+AZT a risk of 0.1% is low. So giving that combo to say everyone with a risk > 5% of COVID mortality seems a good bet even if HCQ has a small positive effect. Specifically, on the basis of that one RCT that showed positive outcomes, that would be reasonable.

Having said that every new set of results from Raoult which is so weirdly reported it is meaningless makes his data look more and more suspect. And there is no likleihood that HCQ is a miracle cure, at best it is useful. Like remdesivir, and probably a few other things...

THH

India to export..360.000 HCQ tablets to USA + enough HCQ sulphate for 45 million tablets?

Plus other lakhs to 12 other countries

and I thought Dr Richard.. was a lone voice crying in the wilderness

https://www.indiatoday.in/indi…gnment-1665759-2020-04-11

Quote from THHuxleynew

And there is no likleihood that HCQ is a miracle cure

This is the pharma mafia meme. Nobody ever said this and only a dilettante would use HCQ alone - and there are more far dilettantes among doctors than you can imagine...

Even worse doing studies with HCQ alone on severe cases is a criminal act and I hope such doctors will loose their license. What we here did discuss is using a set of medication at an early stage possibly latest 3 days after first symptoms. But some countries do not even look at such cases. They like to see them as full blown victims only. This must change!

All people with classic symptoms, with age >65 absolute mandatory at age > 75 must be treated if they have a precondition - independent of a positive test as the death toll in this class is at least 10% versus 0.1 risk of medication.

We should not mix cases that absolutely need hospitalization, > 5% are serious positive ones even in Germany with the lowest death rate so far, with cases we can prevent from hospitalization.

Just one reminder in the class > 75 with preconditions and ventilation up to 80% will die!!

I thought I was too. Well we should see some progress soon. Just need a pharmacy to make up the Anti bat!

Any other suggestions to add? Maybe call it Z-pak Anti bat

https://www.preprints.org/manuscript/202004.0023/v1

Fascinating, with immediate suggestions for better clinical practice (if this is correct) and the type of work we need to find really good treatment of COVID. Worth reading the comments.

Kinins and Cytokines in COVID-19: A Comprehensive Pathophysiological Approach

Abstract

Most striking observations in COVID-19 patients are the hints on pulmonary edema (also seen on CT scans as ground glass opacities), dry cough, fluid restrictions to prevent more severe hypoxia, the huge PEEP that is needed while lungs are compliant, and the fact that anti-inflammatory therapies are not powerful enough to counter the severity of the disease. We propose that the severity of the disease and many deaths are due to a local vascular problem due to activation of B1 receptors on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2, a cell membrane bound molecule with enzymatic activity that next to its role in RAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the bradykinin receptor type 1 (B1). In contrast to bradykinin receptor 2 (B2), the B1 receptor on endothelial cells is upregulated by proinflammatory cytokines. Without ACE2 acting as a guardian to inactivate the ligands of B1, the lung environment is prone for local vascular leakage leading to angioedema. Angioedema is likely a feature already early in disease, and might explain the typical CT scans and the feeling of people that they drown. In some patients, this is followed by a clinical worsening of disease around day 9 due to the formation antibodies directed against the spike (S)-antigen of the corona-virus that binds to ACE2 that could contribute to disease by enhancement of local immune cell influx and proinflammatory cytokines leading to damage. In parallel, inflammation induces more B1 expression, and possibly via antibody-dependent enhancement of viral infection leading to continued ACE2 dysfunction in the lung because of persistence of the virus. In this viewpoint we propose that a bradykinin-dependent local lung angioedema via B1 and B2 receptors is an important feature of COVID-19, resulting in a very high number of ICU admissions. We propose that blocking the B1 and B2 receptors might have an ameliorating effect on disease caused by COVID-19. This kinin-dependent pulmonary edema is resistant to corticosteroids or adrenaline and should be targeted as long as the virus is present. In addition, this pathway might indirectly be responsive to anti-inflammatory agents or neutralizing strategies for the anti-S-antibody induced effects, but by itself is likely to be insufficient to reverse all the pulmonary edema. Moreover, we provide a suggestion of how to ventilate in the ICU in the context of this hypothesis.

Quote from Wyttenbach

We are all characters in the 5 eyes control game since along time (90ties...) . I know all the secrete back doors of NSA since day one and please do not believe that your PC,Mac, phone, tablet is not under control. It's just one more control and may be one reason they will not like it....

PS: We wrote the worlds first remote control active anti virus tool in 1987 for the MAC-OS...

Woah! For smartphones do signal or telegram allow for secure communications? Any tips on circumventing this?

Judging from our chemist's comments HCQ may already be a cytokine or bradykinin inhibitor so reducing pulmonary oedema. He also suggests melatonin to reduce ACE 2 receptors expression so decreasing viral attack sites but this would take a long time to kick in changing receptor protein synthesis the expression. A melatonin supplement has been suggested before.

Quote from Navid

fear mongering - spikes like that are known to occur when a bunch of old files are found or reports are quickly tallied.

there is even a name for this in epidemiology. direct from a physician in infectious disease.

Quote from oldguy

The additional deaths were added to April 2

April 4 - 7788 new cases and 1053 new deaths

April 3 -23060 new cases and 1120 new deaths April 3 the French Government reported 17,827 additional cases and 532 additional deaths from nursing homes that had not been reported previously

April 2 - 2116 new cases and 1355 new deaths in France, including 884 fatalities in nursing homes On April 2, France reported 884 additional deaths that have occurred in nursing homes over the past days and weeks [source]. The French Government did not include these deaths in their official count, as their count only takes into consideration deaths of hospitalized patients

notice their numbers do not include those who died at home.

taking out of context. That was not fear mongering, It was put in context which you seem to have ignored.

15-17% unseen infected in several independent studies. No herd immunity until 80 % infected and immune. So hand round the Z-pak anti Bat, Probably the only option for exit strategy. MDA.

Also the antibody tests have been notoriously unreliable - how do we know for sure all the milder cases were not due to another milder coronavirus, rhinovirus, or norovirus? That is, how selective is the antibody test for SARS Cov-2 as opposed to other common cold viruses? I don't believe this anecdotal symptomatology put round by the media, that 4 out of 5 cases are mild (so we don't have to worry). More likely if you catch the SARS Cov-2 virus for real it whacks you for six 100 % of the time! Read some of the case histories this is one heavy mother******* virus.

Quote from Dr Richard

Also the antibody tests have been notoriously unreliable - how do we know for sure all the milder cases were not due to another milder coronavirus, rhinovirus, or norovirus? That is, how selective is the antibody test for SARS Cov-2 as opposed to other common cold viruses? I don't believe this anecdotal symptomatology put round by the media, that 4 out of 5 cases are mild (so we don't have to worry). More likely if you catch the SARS Cov-2 virus for real it whacks you for six 100 % of the time! Read some of the case histories this is one heavy mother******* virus.

The symptoms are clear enough, and I know a number of people (students, lower risk) who have caught it and not suffered much, now fully well. Unfortunately there are also the less lucky ones, for whom it can disable or kill.

There is ample evidence that many more people catch this bug than the official case numbers. In this country you are only counted if you go to hospital and are tested. Otherwise you have a cough and temperature at home for a few days, get over it, and are one of the "mild" 4 out of 5 cases. I know a number of such people and am pretty sure most of them did have COVID.

The best guess figures so far of infection mortality rate around 0.66% are consistent with what people expected when we had much less evidence. They are not catastrophic (as SARS would have been, if more virulent). They are much much worse than influenza, and high enough to break health systems everywhere if the epidemic is uncontrolled: because unlike flu there is as yet no-one immune, and the disease has a much higher transmission rate than flu.

The real issue is that no-one can stand by while health systems are overwhelmed.

Quote from Navid

Woah! For smartphones do signal or telegram allow for secure communications? Any tips on circumventing this?

You are a dreamer... They may store anything you type/click etc. on your phone/computer and scramble - encode it. The stone age - offline solution in the 80ties was to space-fill it into excel/word documents...

by the way: Did you ever read the patriot act documents (all!!) .

Quote from THHuxleynew

Most striking observations in COVID-19 patients are the hints on pulmonary edema (also seen on CT scans as ground glass opacities), dry cough, fluid restrictions to prevent more severe hypoxia, the huge PEEP that is needed while lungs are compliant, and the fact that anti-inflammatory therapies are not powerful enough to counter the severity of the disease.

That's why the former linked paper "COVID-19__Attacks_the_1-Beta_Chain_of_Hemoglobin_and_Captures_the_Porphyrin_to_Inhibit_Human_Heme_Metabolism_v5.pdf" came to the conclusion that this is not a classical bacterial/viral inflammation. It's caused by excess iron that damages the tissues. The other conclusion was that intubation most of the time is counter productive and leads to more damage of the tissue.

The only thing that works is to protect the hemoglobin (its iron) and to block the virus.