Hydroxychloroquine / Plaquenil and the Covid-19 / Coronavirus

[IThinkImTurningJapanese]

I found this essay on zinc lozenges and coronavirus that nicely separates fact from rumor: Can Zinc Lozenges Help with Coronavirus Infections?

Even our senses of smell and taste depend on enzymes that include zinc in their molecular structure.

Could that have something to do with Covid-19 causing sufferers to lose their sense of smell?

 

[pattismith]

Other new blue print from IHU Marseille




In vitro testing of Hydroxychloroquine and Azithromycin on SARS-CoV-2 shows synergistic effect

Julien Andreania,b, Marion Le Bideaua,b, Isabelle Duflota,b, Priscilla Jardota,b, Clara Rollanda,b, 3

Manon Boxbergera,b, Jacque Yaacoub Bou Khalila, Jean-Pierre Baudouin b, Nathalie Wurtza,b, 4

Jean-Marc Rolaina,b, Philippe Colsona,b, Bernard La Scolaa,b*, Didier Raoulta,b* 5

a IHU-Méditerranée Infection, Marseille, France 6

b MEPHI-AP-HM, Marseille, France 7



Abstract 13

Human coronaviruses SARS-CoV-2 appeared at the end of 2019 and led to a pandemic with 14

high morbidity and mortality. As there are currently no effective drugs targeting this virus, 15

drug repurposing represents a short-term strategy to treat millions of infected patients at low 16

costs. Hydroxychloroquine showed an antiviral effect in vitro. In vivo it also showed efficacy, 17

especially when combined with azithromycin in a preliminary clinical trial. Here we 18

demonstrate that the combination of hydroxychloroquine and azithromycin has a synergistic 19

effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human 20

lung.

 

[pattismith]

Discussion

In this present work, we could confirm a moderate effect of hydroxychloroquine alone on

SARS-CoV2 at low MOI as previously observed with the lowest concentrations used in a

prior study (19). The most striking observation was the synergistic effect of the combination

of hydroxychloroquine and azithromycin. As compared to other studies testing

hydroxychloroquine for which viral growth was evaluated at 48h, our conditions with

prolonged incubation time of 60 hours showed that this effect remained observable. As for

MOI, even at the higher MOI of 2.5, as compared to the data of Liu et al. where the highest

MOI was of 0.8, the effect of the combination to inhibit viral growth was observable.

Hydroxychloroquine has been demonstrated in vitro to inhibit replication of SARS-CoVs 1

and 2 (17;19). Concentrations of drugs for our study were based on the known cytotoxicity

drugs (50% of cytotoxicity, EC 50) and their effect on microorganisms (50% inhibitory

concentration, IC50).

With Zika virus, azithromycin showed activity with an IC 50 range

from 2.1 to 5.1 μM depending MOI (28) without notable effect on EC 50 at high

concentration (29). On Vero E6 it was shown that for hydroxychloroquine, EC 50 is close to

250 μM (249.50 μM), which is significantly above the concentrations we tested herein (19).

Against SARS-CoV 2, the IC 50 of hydroxychloroquine was determined to be 4.51, 4.06,

17.31, and 12.96 μM with various MOI of 0.01, 0.02, 0.2, and 0.8, respectively.

One of the main criticisms of previously published data was that drug concentrations for viral

inhibitionused in vitro are difficult to translate clinically due to side effects that would occur

at those concentrations. The synergy between azithromycin and hydroxychloroquine that we

observed herein is at concentrations achieved in vivo and detected in pulmonary tissues (35-

37). Our data are thus in agreement with the clinical efficacy of the combination of

hydroxychloroquine and azithromycin demonstrated by Gautret et al. (33). They support the

clinical use of this drug combination, especially at the early stage of the COVID-19 infection

before the patients have respiratory distress syndrome with associated cytokine storm and

become less treatable by any antiviral treatment.

 

[valentinelynx]

Could that have something to do with Covid-19 causing sufferers to lose their sense of smell?

I think that is more because the virus attacks the respiratory epithelium (outer surface) and we don't have much defense against it because of its novel nature. However, that the virus tends to enter through the nasopharynx may make it more susceptible to high levels of zinc in the region from sucking on zinc lozenges.

 

[Gemini]

Dr. Ian Lipkin is being treated with hydroxychloroquine (Plaquenil) for COVID-19

Thanks for posting information about Lipkin's treatment, @Wally.

Yesterday in his blog @Cort posted this link to an hourlong interview of Lipkin by Vincent Racaniello.

He indicates he felt better after the treatment but doesn't know if that was due to the treatment. Clinical trials are needed he says.

Interestingly, a friend offered to send him convalescent COVID-19 antibodies which he'd liked to have tried but his doctors chose to go with hydroxychloroquine without azithromycin instead.

www.microbe.tv/twiv/twiv-special-lipkin/

Also results of one recent nonrandomized trial of hydroxychloroquine with and without azithromycin:

 

[minimus]

One of my wife's friends is a PhD pharmacologist at NY Presbyterian Hospital who is a member of the hospital's Covid-19 response team.

Based on recommendations from S. Korea's CDC and then the initial French manuscript published sometime in mid-March, NY Presbyterian began using hydroxychloroquine + azithromycin on admitted Covid-19 patients about 9 days ago.

Yesterday, the pharmacologist was a bit discouraged, telling my wife that "the drugs are not working". Obviously, this is just a qualitative observation. It is not a randomized controlled study. She said NY Pres hospital now has 1300 admitted Covid patients and 300 on ventilators.

It is possible that the guidelines for hospital admission in NYC mean that patients are not starting these drugs until fairly late in the course of illness. Apparently, NYC hospitals do not admit patients with fever and cough alone. To be admitted, a patient has to present with shortness of breath, which I don't think is an early symptom of the illness except in patients with chronic lung diseases, congestive heart failure, or asthma.

 

[pattismith]

One of my wife's friends is a PhD pharmacologist at NY Presbyterian Hospital who is a member of the hospital's Covid-19 response team.

Based on recommendations from S. Korea's CDC and then the initial French manuscript published sometime in mid-March, NY Presbyterian began using hydroxychloroquine + azithromycin on admitted Covid-19 patients about 9 days ago.

Yesterday, the pharmacologist was a bit discouraged, telling my wife that "the drugs are not working". Obviously, this is just a qualitative observation. It is not a randomized controlled study. She said NY Pres hospital now has 1300 admitted Covid patients and 300 on ventilators.

It is possible that the guidelines for hospital admission in NYC mean that patients are not starting these drugs until fairly late in the course of illness. Apparently, NYC hospitals do not admit patients with fever and cough alone. To be admitted, a patient has to present with shortness of breath, which I don't think is an early symptom of the illness except in patients with chronic lung diseases, congestive heart failure, or asthma.

too late unfortunately...
Dr Raoult tested all the people coming to his hospital, even with mild symptoms, even no fever /no cough. The goal was to reduce the viral load and the excretion time, in order to reduce contagiosity and with the hope to protect people as much as possible from having a more severe form (as shown in his last study published 3 days ago). The idea to use this protocol in severe forms with people having already compromised heart function seems rather dangerous to me!

 

[andyguitar]

It is possible that the guidelines for hospital admission in NYC mean that patients are not starting these drugs until fairly late in the course of illness.

There is a clinical trial for hydroxychloroquine starting in the UK. Saw a news item about it last night. The lead researcher said he did'nt expect it to help those on ventilators. More likley to help in the early stage of the illness and prevent the need for ventilation.

 

[minimus]

too late unfortunately...
Dr Raoult tested all the people coming to his hospital, even with mild symptoms, even no fever /no cough. The goal was to reduce the viral load and the excretion time, in order to reduce contagiosity and with the hope to protect people as much as possible from having a more severe form (as shown in his last study published 3 days ago). The idea to use this protocol in severe forms with people having already compromised heart function seems rather dangerous to me!

Just to be clear, hydroxychloroquine and azithromycin are being started at NY Presbyterian as soon as patients are admitted, so long as they don't have abnormal EKGs and are not on contraindicated medications. As inpatients, they are initially monitored and get supplemental oxygen if they have air hunger or their oxygen saturation drops. According to my wife's friend, the drugs are not preventing progression from initial observation and supplemental oxygen to mechanical ventilation. Many of these patients have no comorbid conditions when admitted to the hospital.

Of course, I agree that these drugs might be beneficial if taken earlier in the course of illness.

On a related note, Dr. Cheney has said that 5 of his former ME/CFS patients have presumptive Covid-19. He said that the two with pulse oximeters have shown significant but temporary declines in oxygen saturation, with one patient dropping to 79%. However, none of these patients has had to be admitted to the hospital. So he is somewhat optimistic at this point that ME/CFS patients may not be at risk for severe illness.

 

[Wally]

There is a clinical trial for hydroxychloroquine starting in the UK. Saw a news item about it last night. The lead researcher said he did'nt expect it to help those on ventilators. More likley to help in the early stage of the illness and prevent the need for ventilation.

The misconceptions about the use of Vitamin C to treat illnesses is one of the reason that doctors from the U.S. traveled to China to advise medical professionals about using IV and oral Vitamin C as a treatment protocol “to try” for this virus. Whether used as a prophylactic or for a critically ill patient on a ventilator, they felt research and case studies supported trying this substance in the treatment of this coronavirus (SARS-CoV-2).

If you have not been following this thread at https://forums.phoenixrising.me/thr...apy-to-help-treat-coronavirus-patients.79430/ , the preliminary reporting out of China is that Vitamin C (oral and IV) has been having showing a positive effect as a treatment tool for the virus. The videos and other info. coming from China explain how it has been used both in a clinical trial and in other cases outside of the trial. However, there is concern that even the large dose (24 grams) being used in the trial may not be high enough for some patients who are critically ill.

Case reporting over the last 70 years has represented that the dose of IV Vitamin C, required in some situations, may need to be given in super high doses ranging anywhere between 50 to 200+ grams. (See, story of New Zealand farrier who was on an ECMO machine and the hospital treating him wanted to take him off life support, but within a few hours of starting a super high dose (50 grams) of Vitamin C, he showed signs of improvement not seen with other treatments that they had tried. (Story of New Zealand farmer and Vitamin C is located in a video linked at Post/Reply No. 23 at https://forums.phoenixrising.me/thr...apy-to-help-treat-coronavirus-patients.79430/

In this thread, at post/reply no. 260, https://forums.phoenixrising.me/thr...gainst-coronavirus.79014/page-13#post-2266181, I noted that John Hopkins (a well known and highly respected hospital and medical school in the U.S.) does not even mention in its current COVID-19 treatment guide that high dose Vitamin C is a treatment that is being trialed in China. In other trials, Vitamin C has been shown, even lower doses (as low as 1 to 2 grams) of oral or IV Vitamin, to have a positive effect on the treatment outcome of patients suffering from Sepsis, Influenza, Pneumonia, Common Cold (coronavirus) etc...

Perhaps, Vitamin C added to hydroxychloroquine and azithromycin might be reviewed to see if this combo could further improve the treatment outcome for critically ill patients. With no cures on the horizon for this illness, I just hope that more doctors will be willing to speak up with their own case studies and hypotheses about treatments that might help fight this virus.

https://medicaldialogues.in/amp/cri...-the-duration-of-mechanical-ventilation-64337

Critical care patients often have very low vitamin C plasma levels. In healthy people, 0.1 grams per day of vitamin C is usually sufficient to maintain a normal plasma level. However, much higher doses, in the order of grams per day, are needed for critically ill patients to increase their plasma vitamin C levels to within the normal range. Therefore, high vitamin C doses may be needed to compensate for the increased metabolism in critically ill patients.

Harri Hemilä from the University of Helsinki, Finland, and Elizabeth Chalker from the University of Sydney, Australia, carried out a systematic review of vitamin C for mechanically ventilated critical care patients. They identified 9 relevant controlled trials, and 8 of them were included in the meta-analysis.

On average, vitamin C administration shortened ventilation time by 14%, but the effect of vitamin C depended on the duration of ventilation. Patients who are more seriously ill require longer ventilation than those who are not as sick. Therefore, Hemilä and Chalker hypothesized that the effect of vitamin C might be greater in trials with sicker patients who need longer ventilation.

Vitamin C had no effect when ventilation lasted for 10 hours or less. However, in 5 trials including 471 patients who required ventilation for over 10 hours, dosage of 1 to 6 g/day of vitamin C shortened ventilation time on average by 25%.

"Vitamin C is a safe, low-cost essential nutrient. Given the strong evidence of benefit for more severely ill critical care patients along with the evidence of very low vitamin C levels in such patients, ICU patients may benefit from the administration of vitamin C. Further studies are needed to determine optimal protocols for its administration. Future trials should directly compare different dosage levels," says Dr. Hemilä.

 

[Wally]

Censoring of discussion re hydroxychloroquine on Twitter?

https://twitter.com/i/web/status/1244803489714315271

 

[minimus]

A new manuscript was published yesterday on the use of hydroxychloroquine in hospitalized Covid patients in China. Patients were on the mild end of the spectrum, in that their baseline oxygen saturation had to be above 93% for study inclusion.

The treatment consisted of 5 days of hydroxychloroquine 200mg twice a day for a total of 10 doses.

Treatment effects were positive and statistically significant though not really miraculous.

• Average time to resolution of fever was shortened by 1 day in the treated group relative to controls (2.2 vs 3.2 days)
• Average time to resolution of cough was also shortened by about 1 day (2.0 vs. 3.1 days).
• Chest CT images showed improvement in pneumonia in 81% of the treated group vs 55% of controls.
• No patients in the treated group progressed to severe illness vs. 13% of controls.

 

[pattismith]

thank you @minimus
The association hydroxychloroquine/azithromycin may be even better, according to Pr Raoult.

The true reason why the protocol is not used for mildly affected covid patients in France is very simple: these patients never reach hospitals as they are told to stay at home and to call for medical help only if they have problem breathing (!!), and so they are not tested (France doesn't have enough tests!!) and then how could they get treated….?
If this treatment really protect from evolution to severe illness, our management is a severe non sense...

 

[andyguitar]

If this treatment really protect from evolution to severe illness, our management is a severe non sense...

We have the same problem inUK. It's crazy!

 

[Wally]

A cardiologist from Mayo Clinic discusses the cardiac issues that can arise from the use of hydroxychlorinquine.

https://www.nbcnews.com/news/amp/ncna1178776

. . .Ackerman and his Mayo Clinic colleagues created a cardiac algorithm, published in Mayo Clinic Proceedings, to help physicians more safely prescribe hydroxychloroquine by identifying patients at greatest risk for drug-induced sudden cardiac death.

While hydroxychloroquine is likely to be safe for 90 percent of the population, Ackerman said, it could pose serious and potentially lethal risks to a small number of those susceptible to heart conditions, especially those with other chronic medical problems already on multiple medications. . . .

 

[pattismith]

"Using the algorithm developed by Dr. Ackerman and colleagues, the potential risk of drug-induced arrhythmias can be rated and used to modify treatment accordingly. For example, patients with a baseline QTc value greater than or equal to 500 milliseconds and those that experience an acute QTc reaction with a QTc greater than or equal to 60 milliseconds from baseline after starting treatment with one or more QTc-prolonging drugs are at greatest risk for drug-induced arrhythmias."

very interesting thank you!

A cardiologist from Mayo Clinic discusses the cardiac issues that can arise from the use of hydroxychlorinquine.

https://www.nbcnews.com/news/amp/ncna1178776

 

[pattismith]

Last blue print from Pr Raoult team

9 avril 2020
Early treatment of 1061 COVID-19 patients with hydroxychloroquine and azithromycin, Marseille, France


ABSTRACT

Background In a recent survey, most physicians worldwide considered that hydroxychloroquine (HCQ)
and azithromycin (AZ) are the two most effective drugs among available molecules against
COVID-19.
Nevertheless, to date, one preliminary clinical trial only has demonstrated its
efficacy on the viral load. Additionally, a clinical study including 80 patients was published,
and in vitro efficiency of this association was demonstrated.

Methods The study was performed at IHU Méditerranée Infection, Marseille, France. A cohort of 1061 COVID-19 patients, treated for at least 3 days with the HCQ-AZ combination and a follow-up of at least 9 days was investigated. Endpoints were death, worsening and viral shedding persistence.

Findings From March 3rd to April 9th, 2020, 59,655 specimens from 38,617 patients were tested for COVID-19 by PCR. Of the 3,165 positive patients placed in the care of our institute, 1061 previously unpublished patients met our inclusion criteria.

Their mean age was 43.6 years old and 492 were male (46.4%). No cardiac toxicity was observed. A good clinical outcome and virological cure was obtained in 973 patients within 10 days (91.7%).

Prolonged viral carriage at completion of treatment was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < 10-2) but viral culture was negative at day 10 and all but one were
PCR-cleared at day 15.
A poor outcome was observed for 46 patients (4.3%); 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).
Poor clinical outcome was significantly associated to older age (OR 1.11), initial higher severity (OR 10.05) and low hydroxychloroquine serum concentration.
In addition, both poor clinical and virological outcomes were associated to the use of selective beta-blocking agents and angiotensin II receptor blockers (P<0.05).

Mortality was significantly lower in patients who had received > 3 days of HCQ-AZ than in patients treated with other regimens both at IHU and in all Marseille public hospitals (p< 10-2)

 

[ebethc]

how does plaquenil work? is it an immunosuppressant?

 

[andyguitar]

Depends who you ask! Some say yes others no.

 

[pattismith]

how does plaquenil work? is it an immunosuppressant?

It seems it has antiviral activity (not yet proven in vivo, because it's not simple). Some says adding Zinc should give better response to the treatment.