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Coronavirus Drug: French Researcher Reports Successful Trial Using Malaria Medicine

Early treatment of COVID-19 patients with hydroxychloroquine & azithromycin: A retrospective analysis of 1061 cases in Marseille

Postby smix » Wed May 13, 2020 1:24 am

Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France
Science Direct - Travel Medicine and Infectious Disease

URL: https://www.sciencedirect.com/science/a ... 3920302179
Category: healthNews
Published: May 5, 2020

Description: Abstract
Background
In France, the combination hydroxychloroquine (HCQ) and azithromycin (AZ) is used in the treatment of COVID-19.
Methods
We retrospectively report on 1061 SARS-CoV-2 positive tested patients treated with HCQ (200 mg three times daily for ten days) + AZ (500 mg on day 1 followed by 250 mg daily for the next four days) for at least three days. Outcomes were death, clinical worsening (transfer to ICU, and >10 day hospitalization) and viral shedding persistence (>10 days).
Results
A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 years – range 14–95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74–95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity. Five patients are still hospitalized (98.7% of patients cured so far). PClinO was associated with older age (OR 1.11), severity at admission (OR 10.05) and low HCQ serum concentration. PClinO was independently associated with the use of selective beta-blocking agents and angiotensin II receptor blockers (p < .05). A total of 2.3% of patients reported mild adverse events (gastrointestinal or skin symptoms, headache, insomnia and transient blurred vision).
Conclusion
Administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with very low fatality rate in patients.
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Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study
Science Direct - Travel Medicine and Infectious Disease

URL: https://www.sciencedirect.com/science/a ... 3920301319
Category: healthNews
Published: April 11, 2020

Description: Abstract
Background
We need an effective treatment to cure COVID-19 patients and to decrease virus carriage duration.
Methods We conducted an uncontrolled, non-comparative, observational study in a cohort of 80 relatively mildly infected inpatients treated with a combination of hydroxychloroquine and azithromycin over a period of at least three days, with three main measurements: clinical outcome, contagiousness as assessed by PCR and culture, and length of stay in infectious disease unit (IDU).
Results
All patients improved clinically except one 86 year-old patient who died, and one 74 year-old patient still in intensive care. A rapid fall of nasopharyngeal viral load was noted, with 83% negative at Day7, and 93% at Day8. Virus cultures from patient respiratory samples were negative in 97.5% of patients at Day5. Consequently patients were able to be rapidly discharged from IDU with a mean length of stay of five days.
Conclusion
We believe there is urgency to evaluate the effectiveness of this potentially-life saving therapeutic strategy at a larger scale, both to treat and cure patients at an early stage before irreversible severe respiratory complications take hold and to decrease duration of carriage and avoid the spread of the disease. Furthermore, the cost of treatment is negligible.
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PDF: Original Article



Beneficial effect of the hydroxychloroquine-azithromycin combination in elderly patients with covid-19: results of an observational study
Science Direct

URL: https://www.sciencedirect.com/science/a ... 4220300771
Category: healthNews
Published: June 9, 2020

Description: Summary
Sixty-eight patients, all over 65 years of age and diagnosed PCR-positive for covid-19, received the hydroxychloroquine / azithromycin combination between March 27 and May 1, 2020.Dosages of hydroxychloroquine and azithromycin were in accordance with the protocol of the Institut Hospitalo-Universitaire de Marseille. The mean age was 86.4 ± 8.2 years, mean BMI was 22.8 ± 5.2 kg/m2. Nineteen patients were overweight (BMI greater than 25 kg / m2), four of whom were obese (BMI greater than 30 kg / m2). Seven patients had renal impairment of less than 30 mL / min.The survey of associated conditions indicated that about 51.5% of patients had high blood pressure while 28% had heart disease. Of these, 16.2% had diabetes. Only one patient had asthma and one had COPD.Two patients had to stop their treatment after 3 and 9 days of dual therapy respectively due to QTc prolongation. The objective of our study was to evaluate the efficacy of the hydroxychloroquine-azithromycin combination in elderly subjects with covid-19.During the study period, 7 of the 68 patients studied died. All deaths occurred due to severe respiratory complications of the disease. The remaining patients were considered cured after clinical signs disappeared 21 days after the PCR+ test.
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PDF: Early treatment of COVID-19 patients with hydroxychloroquine & azithromycin: A retrospective analysis of 1061 cases in Marseille



Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis
Science Direct - Travel Medicine and Infectious Disease

URL: https://www.sciencedirect.com/science/a ... 3920302817
Category: healthNews
Published: June 25, 2020

Description: Abstract
Background
In our institute in Marseille, France, we initiated early and massive screening for coronavirus disease 2019 (COVID-19). Hospitalization and early treatment with hydroxychloroquine and azithromycin (HCQ-AZ) was proposed for the positive cases.
Methods
We retrospectively report the clinical management of 3,737 screened patients, including 3,119 (83.5%) treated with HCQ-AZ (200 mg of oral HCQ, three times daily for ten days and 500 mg of oral AZ on day 1 followed by 250 mg daily for the next four days, respectively) for at least three days and 618 (16.5%) patients treated with other regimen (“others”). Outcomes were death, transfer to the intensive care unit (ICU), ≥10 days of hospitalization and viral shedding.
Results
The patients’ mean age was 45 (sd 17) years, 45% were male, and the case fatality rate was 0.9%. We performed 2,065 low-dose computed tomography (CT) scans highlighting lung lesions in 592 of the 991 (59.7%) patients with minimal clinical symptoms (NEWS score = 0). A discrepancy between spontaneous dyspnoea, hypoxemia and lung lesions was observed. Clinical factors (age, comorbidities, NEWS-2 score), biological factors (lymphocytopenia; eosinopenia; decrease in blood zinc; and increase in D-dimers, lactate dehydrogenase, creatinine phosphokinase, and C-reactive protein) and moderate and severe lesions detected in low-dose CT scans were associated with poor clinical outcome. Treatment with HCQ-AZ was associated with a decreased risk of transfer to ICU or death (Hazard ratio (HR) 0.18 0.11–0.27), decreased risk of hospitalization ≥10 days (odds ratios 95% CI 0.38 0.27–0.54) and shorter duration of viral shedding (time to negative PCR: HR 1.29 1.17–1.42). QTc prolongation (>60 ms) was observed in 25 patients (0.67%) leading to the cessation of treatment in 12 cases including 3 cases with QTc> 500 ms. No cases of torsade de pointe or sudden death were observed.
Conclusion
Although this is a retrospective analysis, results suggest that early diagnosis, early isolation and early treatment of COVID-19 patients, with at least 3 days of HCQ-AZ lead to a significantly better clinical outcome and a faster viral load reduction than other treatments.
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Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time
Science Direct - International Journal of Antimicrobial Agents

URL: https://www.sciencedirect.com/science/a ... 7920303125
Category: healthNews
Published: August 2, 2020

Description: Abstract
Introduction
Interest of anti-infective agents in COVD-19 showed discrepant results. However, there is no evaluation about the impact in changes of practices on the prognosis over time.
Methods
Single center, retrospective study, conducted from March 5th to April 25th 2020, in adults hospitalized in a medicine ward for a COVID-19. Patient characteristics were compared between 2 periods (before/after March 19th) considering French guidelines issued by learned societies. Aim of the study was to evaluate how medical care impacted unfavorable outcome, namely admission in intensive care unit (ICU) and/or death.
Results
One hundred thirty-two patients were admitted, mean age was 59.0 ± 16.3 years, mean CRP level was 84.0±71.1 mg/L, 46% had a lymphocyte count<1000/mm3. When prescribed, anti-infective agents were lopinavir-ritonavir (n=12), azithromycin (AZI) (n=28) and AZI combined with hydroxychloroquine (HCQ) (n=52). Between the 2 periods we noted a significant decrease of ICU admission, from 43% to 12% (p<0.0001). Delays until transfer in ICU were similar between periods (p=0.86). Pulmonary CT-scan were significantly more performed (from 50% to 90%, p<0.0001), as oxygen-dependency (53% vs 80%, p=0.001) and prescription of AZI±HCQ (from 25% to 76%, p<0.0001) were greater over time. Multivariate analyses showed a reduction of unfavorable outcome in patients receiving AZI±HCQ (HR=0.45, 95%IC [0.21-0.97], p=0.04), especially among an identified category of individuals (lymphocyte≥1000/mm3 or CRP≥100 mg/L).
Conclusion
The present study revealed a significant decrease of admission in ICU over time probably related to multiple factors, including a better indication of pulmonary CT-scan, of oxygen therapy, and a suitable prescription of anti-infective agents.
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Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients with COVID-19: A Nationwide Observational Study of 8075 Participants
Science Direct - International Journal of Antimicrobial Agents

URL: https://www.sciencedirect.com/science/a ... via%3Dihub
Category: healthNews
Published: August 24, 2020

Description: Abstract
Background
Hydroxychloroquine (HCQ) has been largely used and investigated as therapy of COVID-19 across various settings, at total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use of low-dose HCQ (2400 mg in total over five days) was recommended for hospitalized patients with COVID-19.
Methods
We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19 hospital surveillance data. Patients treated either with HCQ alone and supportive care (HCQ group) were compared to patients treated with supportive care only (no-HCQ group) using a competing risks proportional hazards regression with discharge alive as competing risk, adjusted for demographic and clinical features with robust standard errors.
Results
Of 8075 patients with complete discharge data on 24th of May and diagnosed before the 1st of May, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the multivariable analysis, the mortality was lower in the HCQ group compared to the no-HCQ group (adjusted hazard ratio [HR] 0.684, 95% confidence interval [CI] 0.617–0.758). Compared to the no-HCQ group, mortality in the HCQ group was reduced both in patients diagnosed ≤ 5 days (n=3975) and > 5 days (n=3487) after symptom onset (adjusted HR 0.701, 95% CI 0.617–0.796 and adjusted HR 0.647, 95% CI 0.525–0.797, respectively).
Conclusions
Compared to supportive care only, low-dose HCQ monotherapy was independently associated with lower mortality in hospitalized patients with COVID-19 diagnosed and treated early or later after symptom onset.
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COVID-19 outpatients: early risk-stratified treatment with zinc plus low-dose hydroxychloroquine and azithromycin: a retrospective case series study
Science Direct - International Journal of Antimicrobial Agents

URL: https://www.sciencedirect.com/science/a ... 7920304258
Category: healthNews
Published: October 26, 2020

Description: Abstract
The aim of this study was to describe the outcomes of patients with coronavirus disease 2019 (COVID-19) in the outpatient setting after early treatment with zinc, low-dose hydroxychloroquine and azithromycin (triple therapy) dependent on risk stratification. This was a retrospective case series study in the general practice setting. A total of 141 COVID-19 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the year 2020 were included. The main outcome measures were risk-stratified treatment decision and rates of hospitalisation and all-cause death. A median of 4 days [interquartile range (IQR) 3–6 days; available for n = 66/141 patients] after the onset of symptoms, 141 patients (median age 58 years, IQR 40–67 years; 73.0% male) received a prescription for triple therapy for 5 days. Independent public reference data from 377 confirmed COVID-19 patients in the same community were used as untreated controls. Of 141 treated patients, 4 (2.8%) were hospitalised, which was significantly fewer (P < 0.001) compared with 58 (15.4%) of 377 untreated patients [odds ratio (OR) = 0.16, 95% confidence interval (CI) 0.06–0.5]. One patient (0.7%) in the treatment group died versus 13 patients (3.4%) in the untreated group (OR = 0.2, 95% CI 0.03–1.5; P = 0.12). No cardiac side effects were observed. Risk stratification-based treatment of COVID-19 outpatients as early as possible after symptom onset using triple therapy, including the combination of zinc with low-dose hydroxychloroquine, was associated with significantly fewer hospitalisations.
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PDF: Article
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Press Release:
NEW YORK, Oct. 29, 2020 /PRNewswire/ -- Dr. Vladimir Zelenko and team announced today that a retrospective study analyzing his patient data was accepted for publication after a rigorous peer review process.1 The study finds that early intervention and treatment of high-risk patients with COVID-19 resulted in significantly fewer hospitalizations and deaths. The treatment consisting of zinc, low-dose hydroxychloroquine, and azithromycin, is also referred to as "The Zelenko Protocol."

This study is unique because only HIGH RISK out-patients were treated with the triple-drug regimen. High-risk patients are those that have a 5% to 10% chance of dying from COVID-19. This category includes patients who are older than 60, who are younger than 60 but have other medical issues, or who have trouble breathing. All identified high-risk outpatients were treated at their initial visit, most within the first five days of the onset of symptoms. All these patients had laboratory confirmation of COVID-19 infection.

This retrospective analysis is the product of the unique collaboration of three doctors with a rare synergy of industry, academia, and clinical medicine. Dr. Roland Derwand is a German physician and life science industry expert. Professor Martin Scholz is an independent consultant and adjunct professor for experimental medicine at Heinrich Heine University, Düsseldorf, Germany. Drs. Derwand and Scholz were the first to draw attention to "The Zelenko Protocol" in their published hypothesis paper about the importance of combining zinc with hydroxychloroquine as a method for treating COVID-19.

"What differentiates this study is that patients were diagnosed very early with COVID-19 in an outpatient setting, and only high-risk patients were treated early on," said Dr. Derwand. "Unfortunately, we seem to have forgotten common medical knowledge - that we want to treat any patient with an infectious disease as soon as possible. Dr. Zelenko treated his high-risk patients immediately with the three-drug regimen to ensure sufficient efficacy. He correctly didn't wait for the disease to further develop."

Following the rigorous peer review process, Dr. Zelenko said: "It's unfortunate that much of the media coverage surrounding hydroxychloroquine has been negative. These three medications are affordable, available in pill form, and work in synergy against COVID-19." According to Dr. Zelenko: "Hydroxychloroquine's main role is to allow zinc to enter the cell and inhibit the virus' reproduction. And azithromycin prevents secondary bacterial infection in the lungs and reduces the risk of pulmonary complications."

The third author, Professor Scholz added: "This is the first study with COVID-19 outpatients that shows how a simple-to-perform outpatient risk stratification allows for rapid treatment decisions shortly after onset of symptoms. The well-tolerated 5-day triple therapy resulted in a significantly lower hospitalization rate and less fatalities with no reported cardiac side effects compared with relevant public reference data of untreated patients. The magnitude of the results can substantially elevate the relevance of early use, low-dose hydroxychloroquine, especially in combination with zinc. This data can be used to inform ongoing pandemic response policies as well as future clinical trials."

1) Derwand, R., Scholz, M., Zelenko, V. COVID-19 outpatients – early risk-stratified treatment with zinc plus low dose hydroxychloroquine and azithromycin: a retrospective case series study. Int. J. Antimicrob. Agents (2020), doi: https://doi.org/10.1016/j.ijantimicag.2020.106214
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Dr. Zelenko: Making a Difference with Hydroxychloroquine & Zinc

Postby smix » Sun May 17, 2020 1:46 am

Dr. Zelenko: Making a Difference with Hydroxychloroquine & Zinc
The New American

URL: https://www.thenewamerican.com/usnews/h ... quine-zinc
Category: healhNews
Published: May 14, 2020

Description: Dr. Vladimir Zelenko M.D., a Board Certified family practitioner from Monroe, New York., discusses protocol of hydroxychloroquine, zinc, and azithromycin in effectively combating COVID-19 among his patients in New York, and in Honduras, Australia, and Israel. Dr. Zelenko also explains what President Trump can and should do to win the global war against in the novel coronavirus in the United States and to reopen the economy today.





Hydroxychloroquine Dr. Zelenko: “We Are at a Pivotal Moment”
The New American

URL: https://www.thenewamerican.com/usnews/h ... tal-moment
Category: healhNews
Published: May 19, 2020

Description: Throughout the plague-ridden spring of 2020, one aspect of the mainstream narrative has remained consistent: There is no treatment for COVID-19. So it is best, and mandated by government decree, that everyone stay locked down in their homes, that business (except for those of the largest variety) are non-essential and should be shut down, and that life should be restricted as much as possible. Much of this is dangerous and unprecedented, and it is in part based on a complete untruth. The notion that there is no treatment available for COVID-19 is simply not true, as several doctors in the United States and abroad have developed treatment protocols that they say are working. Among these is Dr. Vladimir Zelenko. Practicing in a community on the outskirts of New York City, the epicenter of the pandemic outbreak in the United States, Dr. Zelenko has gained international fame for his work in treating COVID-19 patients with a three drug treatment consisting of hydroxychloroquine, azithromycin, and zinc. Heavily promoted early on by President Trump, but panned by the mainstream media and politicized almost to extinction in the United States, the treatment as administered by Dr. Zelenko seems to have had noteworthy success. In an interview with The New American’s Christian Gomez, Dr. Zelenko described how he decided on the course of treatment as well as why and how he believes it has proven effective in saving lives. “I started studying the basic science of how this virus works,” Dr. Zelenko said in the video interview made available on YouTube. “So like all viruses, a virus cannot replicate or grow on its own, it needs to get inside a cell and when it goes inside a cell it steals the resources of the cell and uses those resources to replicate, to reproduce. And in the process of doing so it kills the cell,” he continued. “So it turns out that zinc, it’s well-known that it inhibits viral replication and specifically in the cytoplasm, in the inside of the cell there is an enzyme ... and it’s used by the virus to make copies of its genetic material so that it makes more virus. So this enzyme is essential to viral growth. Turns out that zinc inhibits that enzyme, it deactivates the enzyme and so it makes it very difficult if not impossible for the virus to grow. The problem that we have with zinc is that it doesn’t get into the cell at all because its like oil and water. Zinc is a positive charged ion that is dissolved in the plasma and the cell membrane is essentially cholesterol — it’s made up of a phospholipid bilayer essentially. So what that is, is oil and water. So even though zinc is effective against the viral growth, it cannot get into the place where the virus is. So what does hydroxychloroquine do? In this case, it’s nothing more than opening a door, a channel, a zinc transport channel, it’s called a zinc ionophore, and it allows for zinc to go from outside the cell to the cytoplasm, to inside the cell. Thats all it does.” There is research, however, that indicates chloroquine/hydrochloroquine may have a direct antiviral properties. In work published in the journal Antiviral Research in May, researchers Franck Touret of Aix Marseille Université and Xavier de Lamballerie of Émergence des Pathologies Virales noted: “The in vitro antiviral activity of chloroquine has been identified since the late 1960’s and the growth of many different viruses can be inhibited in cell culture by both chloroquine and hydroxychloroquine, including the SARS coronavirus.” With viral replication seemingly inhibited by Dr. Zelenko’s treatment protocol, the disease is slowed in its progression, or possibly prevented from progressing entirely. Importantly, however, according to Dr. Zelenko, treatment needs to begin early, before the virus has replicated to such an extent that its growth can no longer be successfully inhibited. “The sooner you deal with it, the easier it is to treat it,” Dr. Zelenko noted, pointing out that this is in keeping with normal medical practice, which generally advises that it is better to catch and treat problems early in their progression. In the interview, Dr. Zelenko noted that patients having symptoms should visit a doctor early, and that their symptoms should lead to treatment immediately, even before COVID-19 test results are obtained. “The key is to initiate treatment on day 4 or 5, immediately, even before you get the results of the test,” he emphasized. “I’ll tell you why: because it takes three days to get the results of the test. If you come to my office on day five, I do the test and I wait til day eight for you to get the result, at that point the virus is out of control, so we’re stuck. If we had a test that could be done in the office and get some accurate results right away that would be different, but we don’t. So what happens is when we see a patient we have a very narrow window of opportunity to initiate treatment and get rid of this virus early.” Reacting to critics who have characterized results obtained with his treatment protocol as “anecdotal” and therefore insufficient, Dr. Zelenko pointed out that entire nations have seen success when the protocol has been used. “The entire country of Honduras, for example, has been using my protocol,” he pointed out. “I actually set them up. Their ministry of health, their president, reached out to me a few weeks ago. I helped them develop the protocol. They actually reached out to President Trump, if you recall, and the president actually made a statement during a news conference that he spoke to the president of Honduras and they’re seeing remarkable results of the use of essentially my protocol. Number one, that’s an entire country. Then, if you look at Brazil, and by the way I spoke to the ministry of health of Brazil and maybe I will be speaking to the president of Brazil today, I was essentially asked to lead or collaborate with Brazil’s Covid-19 response and I’m in the process of doing so. But they have a medical system, subsystem, called Prevent, and this system treats around a million people and they treated a thousand patients with a variation of my protocol and they found a 95 percent reduction in hospitalizations.” Moreover, he pointed to the nation of Israel and compared results there with the situation in New York City. “If you look at the country of Israel, which I helped set their policy, they have had, it’s a nation of 9 million people — its essentially the same size of New York City in population — and they had 280 deaths. Compare that to New York, which is also around 9 million people, and the deaths are up to 15,000.” In fact, as of May 18, Israel has seen 272 deaths from more than 16,000 cases, with more than 13,000 recovered, according to Worldometers.info. This despite the fact that experts predicted far, far worse. According to Haaretz, the model that was “one of the key documents that has influenced policymakers” in the country predicted up to between 8,600 and 21,000 deaths in Israel. Currently, researchers remain divided over the use of hydroxychloroquine, though some clinical studies destined for peer-review have begun. The Henry Ford Health System, for instance, has begun one such study, called “Will Hydroxychloroquine Impede or Prevent COVID-19” (WHIP COVID-19). The effort “is a randomized, double-blind study designed to produce a scientific answer to the question: Does it work?” the Ford Health System says in its description of the study. In his interview with The New American, Dr. Zelenko indicated that he too is working with researchers on another study to be reported in peer-reviewed journals at some point. Still, controversy swirls even on this point. According to the Times of Israel, journalist Jerome Corsi, once investigated by the Mueller witch hunt, has come to the attention of federal prosecutors again for an email he inadvertently sent to one of them that was intended for Dr. Zelenko. “Corsi said he mistakenly sent an email meant for Dr. Vladimir ‘Zev’ Zelenko to federal prosecutor Aaron Zelinsky because they are similar names in his address book,” the Times of Israel reported. Zelinsky worked on the Mueller effort and “was one of the prosecutors who had been investigating Corsi,” the paper reported, noting that the email sent by Corsi to Zelinsky apparently made reference to “FDA-approved randomized” testing. “The prosecutor responded to the email by asking Corsi if he had an attorney, and then told Corsi’s lawyer that he had checked a government website of approved clinical trials and found no mention of Zelenko,” the paper said. According to Salon, “Zelinsky is currently investigating coronavirus-related crimes in Maryland as part of Attorney General William Barr's efforts to respond to fraudsters and price-gougers taking advantage of the health crisis.” Dubious political intrigues aside, health outcomes obtained by Dr. Zelenko and others in using hydroxychloroquine for the treatment of COVID-19 strongly suggest that properly conducted studies of the drug and protocols based on it for treatment of COVID-19 should be conducted to ascertain the details of effectiveness and means of action of the drug. For Dr. Zelenko, we are now at an important point where successful treatment of COVID-19 can make a significant difference in the outcome for society as a whole. A second wave of the virus, he said, is likely, and when it comes, the correct response will be to “treat someone early, and treat for prevention the high risk population” to limit the impact. In conclusion, he told The New American’s Christian Gomez: “We are now at a very pivotal moment in history where depending on political will and policy we could turn this thing around and essentially end the global crisis.”
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Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the...

Postby smix » Sun May 17, 2020 2:10 am

Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20081059v1
Category: healthNews
Published: April 26, 2020

Description: Abstract
Background Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. Method In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events.
Results A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose.
Conclusions Although randomised trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.



Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20054551v1
Category: healthNews
Published: April 10, 2020

Description: Abstract
Background: Hydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin. Methods: New user cohort studies were conducted including 16 severe adverse events (SAEs). Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 days. Self-controlled case series (SCCS) were conducted to further establish safety in wider populations. Separately, SAEs associated with hydroxychloroquine-azithromycin (compared to hydroxychloroquine-amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (CalHRs) according to drug use. Estimates were pooled where I2<40%.
Results: Overall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included. No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR2.19 [1.22-3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02-1.45])
Conclusions: Short-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19.



Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20040758v3
Category: healthNews
Published: April 10, 2020

Description: Abstract
Aims: Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. However, evidence regarding its effects in patients is limited. This study aims to evaluate the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19.
Main methods: From February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ. Key findings: For the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 31) compared with the control group (54.8%, 17 of 31). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group.
Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia.



Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20073379v1
Category: healthNews
Published: May 1, 2020

Description: Abstract
Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high mortality. The most urgent thing is to find effective treatments. Objective: To determine whether hydroxychloroquine application may be associated with a decreased risk of death in critically ill COVID-19 patients and what is potential mechanism. Design, Setting and Patients: This retrospective study included all 568 critically ill COVID-19 patients who were confirmed by pathogen laboratory tests despite antiviral treatment and had severe acute respiratory distress syndrome, PAO2/FIO2 <300 with need of mechanical ventilation in Tongji Hospital, Wuhan, between February 1 of 2020 to April 8 of 2020. All 568 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them additionally received oral hydroxychloroquine (HCQ) treatment (200 mg twice a day for 7-10 days). Primary endpoint is mortality of patients, and inflammatory cytokines levels were compared between hydroxychloroquine and non-hydroxychloroquine (NHCQ) treatments.
MAIN OUTCOMES AND MEASURES: In-hospital death and hospital stay time (day) were obtained, level of inflammatory cytokine (IL-6) was measured and compared between HCQ and NHCQ treatments. RESULTS: The median age of 568 critically ill patients is 68 (57, 76) years old with 37.0% being female. Mortalities are 18.8% (9/48) in HCQ group and 45.8% (238/520) in NHCQ group (p<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4 - 14) days for the HCQ and NHCQ groups, respectively (p<0.05). The level of inflammatory cytokine IL-6 was significantly lowered from 22.2 (8.3-118.9) pg/mL at the beginning of the treatment to 5.2 (3.0-23.4) pg/ml (p<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group.
CONCLUSIONS AND RELEVANCE: Hydroxychloroquine treatment is significantly associated with a decreased mortality in critically ill patients with COVID-19 through attenuation of inflammatory cytokine storm. Therefore, hydroxychloroquine should be prescribed for treatment of critically ill COVID-19 patients to save lives.



Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20081059v1
Category: healthNews
Published: May 4, 2020

Description: Abstract
Background Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. Method In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events.
Results A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose.
Conclusions Although randomised trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.



Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20080036v1
Category: healthNews
Published: May 8, 2020

Description: Abstract
Background: COVID-19 has rapidly emerged as a pandemic infection that has caused significant mortality and economic losses. Potential therapies and means of prophylaxis against COVID-19 are urgently needed to combat this novel infection. As a result of in vitro evidence suggesting zinc sulfate may be efficacious against COVID-19, our hospitals began using zinc sulfate as add-on therapy to hydroxychloroquine and azithromycin. We performed a retrospective observational study to compare hospital outcomes among patients who received hydroxychloroquine and azithromycin plus zinc versus hydroxychloroquine and azithromycin alone.
Methods: Data was collected from electronic medical records for all patients being treated with admission dates ranging from March 2, 2020 through April 5, 2020. Initial clinical characteristics on presentation, medications given during the hospitalization, and hospital outcomes were recorded. Patients in the study were excluded if they were treated with other investigational medications. Results: The addition of zinc sulfate did not impact the length of hospitalization, duration of ventilation, or ICU duration. In univariate analyses, zinc sulfate increased the frequency of patients being discharged home, and decreased the need for ventilation, admission to the ICU, and mortality or transfer to hospice for patients who were never admitted to the ICU. After adjusting for the time at which zinc sulfate was added to our protocol, an increased frequency of being discharged home (OR 1.53, 95% CI 1.12-2.09) reduction in mortality or transfer to hospice remained significant (OR 0.449, 95% CI 0.271-0.744).
Conclusion: This study provides the first in vivo evidence that zinc sulfate in combination with hydroxychloroquine may play a role in therapeutic management for COVID-19.



Hydroxychloroquine plus azithromycin: a potential interest in reducing in-hospital morbidity due to COVID-19 pneumonia (HI-ZY-COVID)?
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20088757v1
Category: healthNews
Published: May 11, 2020

Description: Abstract
Introduction: Hydroxychloroquine (HCQ) with or without azithromycin is currently still debated as a potential treatment for the COVID-19 epidemic. Some studies showed discrepant results. However, timing for the treatment initiation and its setting (in-hospital or out-patient) are not consistent across studies.
Methods: Monocentric retrospective study conducted from 2th March to 17th April 2020, in adults hospitalized in a tertiary hospital for COVID-19. Patients characteristics were compared between groups depending on the therapy received (HCQ/azithromycin taken ≥ 48 hours or other treatment). Outcomes were evaluated from admission, by the need for intensive care unit (ICU) support and/or death. Univariate analyses were performed using non-parametric tests and confirmed by a multiple logistic regression using Pearson correlation test.
Results: Among 132 patients admitted for COVID-19 in the medicine ward, 45 received HCQ/azithromycin ≥ 48 hours, with a favorable outcome in 91.1% of cases (OR=6.2, p=0.002) versus others regimen (n=87). Groups were comparable at the baseline in terms of age, sex, comorbidities, extend in thoracic imaging, and severity. Among patients that required to be transferred to ICU (n=27) (for mechanical ventilation), median delay for transfer was 2 days (IQR 1-3). We report only 1 patient that presented an adverse event (a prolonged QT interval on EKG) that required to discontinue HCQ.
Conclusion: The present study suggests a potential interest of the combination therapy using HCQ/azithromycin for the treatment of COVID-19 in in-hospital patients.



Systematic Review and Meta-analysis of the Effectiveness and Safety of Hydroxychloroquine in COVID-19.
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20093831v2
Category: healthNews
Published: May 14, 2020

Description: Abstract
Backgrounds. Since COVID-19 outbreak, various agents have been tested but no proven effective therapies have been identified. This has led to a lot of controversies among associated researches. Hence, in order to address the issue of using hydroxychloroquine (HCQ) in treating COVID-19 patients, we conducted a systematic review and meta-analysis.
Methods. A thorough search was carried out to find relevant studies in MEDLINE, medRxiv, PubMed, Cochrane Database, China Academic Journals Full-text Database and Web of Science. Two investigators independently reviewed 274 abstracts and 23 articles. The trials which evaluated HCQ for treatment of COVID-19 were included for this systematic review. Two investigators assessed quality of the studies and data extraction was done by one reviewer and cross checked by the other.
Results. Five trials involving 677 patients were included while conducting the meta-analysis. Compared with the control group, HCQ with or without azithromycin (AZI) showed benefits in viral clearance of SARS-CoV-2 (odds ratio (OR) 1.95, 95% CI 0.19-19.73) and a reduction in progression rate (OR 0.89, 95% CI 0.58-1.37), but without demonstrating any statistical significance. This systematic review has also suggested a possible synergistic effect of the combination therapy which included HCQ and AZI. However, the use of HCQ was associated with increased mortality in COVID-19 patients.
Conclusions. The use of HCQ with or without AZI for treatment of COVID-19 patients, seems to be effective. The combination of HCQ and AZI has shown synergistic effects. However, mortality rate was increased when the treatment was conducted with HCQ.



Treatment Response to Hydroxychloroquine, Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First Report on the Pharmacological Outcomes from South Korea
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20094193v1
Category: healthNews
Published: May 18, 2020

Description: Abstract
Background: No consensus or evidence-based guideline currently exists for pharmacological therapy against Coronavirus Disease 2019 (COVID 19). While South Korea has been relatively successful in managing the pandemic, its management of confirmed cases and treatment outcomes have not been reported to date. Methods: A retrospective cohort study of the 358 laboratory-confirmed SARS CoV 2 or COVID 19 patients was conducted. Of these patients, 270 adult patients met inclusion criteria and were included in our analyses. The primary endpoints were time to viral clearance and clinical improvement. The mean duration to viral clearance and clinical improvements were displayed as bar-plots to visualize treatment responses.
Results: Ninety-seven moderate COVID 19 patients were managed with hydroxychloroquine (HQ) plus antibiotics (n = 22), lopinavir/ritonavir (Lop/R) plus antibiotics (n = 35), or conservative treatment (n = 40). Time to viral clearance, as signified by negative conversion on PCR, after initiation of treatment was significantly shorter with HQ plus antibiotics compared to Lop/R plus antibiotics (hazard ratio [HR], 0.49; 95% confidence interval [95% CI], 0.28 to 0.87) or conservative treatments (HR, 0.44; 95% CI, 0.25 to 0.78). Hospital stay duration after treatment was also shortest for patients treated with HQ plus antibiotics compared to other treatment groups. Subgroup analysis revealed that mean duration to viral clearance was significantly reduced with adjunctive use of antibiotics compared to monotherapy (HR 0.81, 95% CI, 0.70 to 0.93). While both HQ and Lop/R showed side effects including nausea, vomiting, and elevation of liver transaminases, none were serious.
Conclusion: This first report on pharmacological management of COVID 19 from South Korea revealed that HQ with antibiotics was associated with better clinical outcomes in terms of viral clearance, hospital stay, and cough symptom resolution compared to Lop/R with antibiotics or conservative treatment. The effect of Lop/R with antibiotics was not superior to conservative management. The adjunct use of the antibiotics may provide additional benefit in COVID 19 management but warrants further evaluation.



Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20066902v1
Category: healthNews
Published: May 22, 2020

Description: Abstract
Importance: Patients in long-term care facilities (LTCF) are at a high-risk of contracting COVID-19 due to advanced age and multiple comorbidities. Without effective treatments, outbreaks in such facilities will become commonplace and will result in severe morbidity and mortality. The effectiveness of doxycycline (DOXY) and hydroxychloroquine (HCQ) combination therapy in high risk COVID-19 patients in long-term care facilities is not yet understood.
Objective: The goal of this analysis is to describe outcomes after use of DOXY-HCQ combination in high-risk COVID-19 patients in LTCF.
Design: Case-series analysis. Setting: Three (3) LTCFs in New York. Participants: From March 19 to March 30, 2020, fifty-four (54) patients, residents of three (3) LTCFs in New York and diagnosed (confirmed or presumed) with COVID-19, were included in this analysis. Exposure: All patients who were diagnosed (confirmed or presumed) with COVID-19 received DOXY-HCQ combination therapy along with standard of care. Main Outcomes and Measures: Patients characteristics, clinical recovery, radiological improvements, medication side-effects, hospital transfer, and death were assessed as outcome measures.
Results: A series of fifty-four (54) high-risk patients, who developed a sudden onset of fever, cough, and shortness of breath (SOB) and were diagnosed or presumed to have COVID-19, were started with a combination of DOXY-HCQ and 85% (n=46) patients showed clinical recovery defined as: resolution of fever and SOB, or a return to baseline setting if patients are ventilator-dependent. A total of 11% (n=6) patients were transferred to acute care hospitals due to clinical deterioration and 6% (n=3) patients died in the facilities. Naive Indirect Comparison suggests these data were significantly better outcomes than the data reported in MMWR (reported on March 26, 2020) from a long-term care facility in King County, Washington where 57% patients were hospitalized, and 22% patients died.
Conclusion: The clinical experience of this case series indicates DOXY-HCQ treatment in high-risk COVID-19 patients is associated with a reduction in clinical recovery, decreased transfer to hospital and decreased mortality were observed after treatment with DOXY-HCQ.



Pre exposure Hydroxychloroquine use is associated with reduced COVID19 risk in healthcare workers
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20116806v1
Category: healthNews
Published: June 12, 2020

Description: Abstract
Abstract Background: While several trials are ongoing for treatment of COVID-19, scientific research on chemoprophylaxis is still lacking even though it has potential to delay the pandemic allowing us time to complete research on vaccines.
Methods: We have conducted a cohort study amongst Health Care Workers (HCW) exposed to COVID-19 patients, at a tertiary care center in India where there was an abrupt cluster outbreak within on duty personnel. HCWs who had voluntarily taken hydroxychloroquine (HCQ) prior to exposure were considered one cohort while those who had not were considered to be another. All participants with a verifiable contact history were tested for COVID-19 by rtPCR. The two cohorts were comparable in terms of age, gender, comorbidities and exposure. The primary outcome was incidence rates of rtPCR positive COVID-19 infection amongst HCQ users and non - users.
Results: 106 healthcare workers were examined in this cohort study of whom 54 were HCQ users and rest were not. The comparative analysis of incidence of infection between the two groups demonstrated that voluntary HCQ usage was associated with lesser likelihood of developing SARS-CoV-2 infection, compared to those who were not on it, X2=14.59, p<0.001. None of the HCQ users noted any serious adverse effects.
Conclusions: This study demonstrated that voluntary HCQ consumption as pre-exposure prophylaxis by HCWs is associated with a statistically significant reduction in risk of SARS-CoV-2. These promising findings therefore highlight the need to examine this association in greater detail among a larger sample using Randomised Controlled Trials (RCT).



A short therapeutic regimen based on hydroxychloroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissions and complications.
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20101105v1
Category: healthNews
Published: June 12, 2020

Description: Abstract
The new SARS-CoV-2 infection named COVID-19 has severely hit our Health System. At the time of writing this paper no medical therapy is officially recommended or has shown results in improving the outcomes in COVID-19 patients. With the aim of diminishing the impact in Hospital admissions and reducing the number of medical complications, we implemented a strategy based on a Hospital Home-Care Unit (HHCU) using an easy-to-use treatment based on an oral administration regimen outside the hospital with hydroxychloroquine (HCQ) plus azithromycin (AZM) for a short period of 5 days.
Patients and methods: Patients ≥ 18 years old visiting the emergency room at the Hospital Universitario San Pedro de Logrono (La Rioja) between March, 31st and April, 12th diagnosed with COVID-19 with confirmed SARS-CoV-2 infection by a specific PCR, as follows: Patients with pneumonia (CURB ≤ 1) who did not present severe comorbidities and had no processes that contraindicated this therapeutic regime. Olygosimptomatic patients without pneumonia aged ≥ 55 years. Patients ≥ 18 years old without pneumonia with significant comorbidities. We excluded patients with known allergies to some of the antimicrobials used and patients treated with other drugs that increase the QTc or with QTc >450msc. The therapeutic regime was: HCQ 400 mg every twice in a loading dose followed by 200 mg twice for 5 days, plus AZM 500 mg on the first day followed by 250 mg daily for 5 days. A daily telephone follow-up was carried out from the hospital by the same physician. The end-points of our study were: 1.- To measure the need for hospital admission within 15 days after the start of treatment. 2.- To measure the need to be admitted to the intensive care unit (ICU) within 15 days after the start of the treatment. 3.- To describe the severity of the clinical complications developed. 4.- To measure the mortality within 30 days after starting treatment (differentiating if the cause is COVID-19 or something else). 5.-To describe the safety and adverse effects of the therapeutic regime.
Results: During the 13 days studied a total of 502 patients were attended in the emergency room due to COVID-19. Forty-two were sent at home; 80 were attended by the HHCU (patients on this study) and 380 were admitted to the Hospital. In our series there were a group of 69 (85.18%) patients diagnosed with pneumonia (37 males and 32 females). Most of them, 57 (82.60%) had a CURB65 score of <1 (average age 49) and 12 (17.40%) a CURB score of 1 (average age 63). Eighteen (22.50%) of the pneumonia patients also had some morbidity as a risk factor. 11 patients (13.75%) without pneumonia were admitted to the HHCU because comorbidities or age ≥ 55 years. Six patients with pneumonia had to be hospitalized during the observation period, 3 of them because side effects and 3 because of worsening. One of these patients, with morbid obesity and asthma, had clinical worsening needing mechanical ventilation at ICU and developed acute distress respiratory syndrome. With the exception of the patient admitted to the ICU, the rest of the patients were discharged at home in the following 8 days (3 to 8 days). Twelve patients (15%), 11 of whom had pneumonia, experienced side effects affecting mainly the digestive. In another patient a QTc interval prolongation (452 msc) was observed. In total 3 of these patients had to be admitted in the Hospital, 2 because of vomiting and 1 because a QTc interval lengthening. None of the patients needed to stop the HCQ or AZM and all the 80 patients finished the therapeutic strategy. From the group without pneumonia only a patient developed diarrhea that did not require hospitalization or stop the medication.
Conclusions: Our strategy has been associated with a reduction in the burden of hospital pressure, and it seems to be successful in terms of the number of patients who have developed serious complications and / or death. None of the patients died in the studied period and only 6 have to be admitted in conventional hospitalization area.



Chloroquine, but not hydroxychlorquine, prolongs the QT interval in a primary care population
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20135475v2
Category: healthNews
Published: June 22, 2020

Description: Abstract
Background: Chloroquine (CQ) and Hydroxychloroquine (HCQ) have recently been suggested as treatment for the current Corona Virus Disease 2019 (COVID-19) pandemic. However, despite their long-term use and only few case reports on adverse effects, CQ and HCQ are listed as a known risk of the lethal ventricular arrhythmia Torsade de Pointes and their cardiac safety profile is being questioned. Thus, we aimed to investigate the electrocardiographic and mortality effects of CQ and HCQ in a primary care population.
Methods: We used Danish health care registers and electrocardiograms (ECGs) from primary care to define three studies. 1) A paired study of subjects with ECGs before and during use of CQ/HCQ, 2) a matched ECG study of subjects taking CQ/HCQ compared to controls, and 3) a mortality study on people taking HCQ matched to control. In both matched studies, we adjusted for connective tissue diseases, use of QT-prolonging drugs, and cardiac disease. We used the QTc interval as the marker for electrocardiographic safety. In the mortality study, cases were followed from first claimed prescription until 300 days after estimated completion of the last prescription. 95% confidence intervals follow estimates in parenthesis.
Results: Use of CQ was associated with a 5.5 (0.7;10) ms increase in QTc in the paired study (n=10). In the matched study (n=28, controls=280), QTc was insignificantly increased in subjects taking CQ by 4.7 (-3.4;13) ms. With a ΔQTc of 1.0 (-5.6;7.5), use of HCQ was not associated with an increased QTc in the paired study (n=32). In the matched study (n=172, controls=1,720), QTc also was not different between groups (p=0.5). In the mortality study (n=3,368), use of HCQ was associated with a hazard ratio of 0.67 (0.43;1.05).
Conclusions: In subjects free of COVID-19, we found a small increase in QTc associated with use of chloroquine, but not hydroxychloroquine. We found no increased mortality associated with use of hydroxychloroquine.



Chronic treatment with hydroxychloroquine and SARS-CoV-2 infection.
medRxiv

URL: https://www.medrxiv.org/content/10.1101 ... 20056507v1
Category: healthNews
Published: June 29, 2020

Description: Abstract
Background: Hydroxychloroquine sulphate (HCQ) is being scrutinized for repositioning in the treatment and prevention of SARS-Cov-2 infection. This antimalarial drug is also chronically used to treat patients with autoimmune diseases.
Methods: By analyzing the Portuguese anonymized data on private and public based medical prescriptions we have identified all cases chronically receiving HCQ for the management of diseases such as systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases. Additionally, we have detected all laboratory confirmed cases of SARS-CoV-2 infection and all laboratory confirmed negative cases in the Portuguese population (mandatorily registered in a centrally managed database). Cross linking the two sets of data has allowed us to compare the proportion of HCQ chronic treatment (at least 2 grams per month) in laboratory confirmed cases of SARS-CoV-2 infection with laboratory confirmed negative cases.
Results: Out of 26,815 SARS-CoV-2 positive patients, 77 (0.29%) were chronically treated with HCQ, while 1,215 (0.36%) out of 333,489 negative patients were receiving it chronically (P=0.04). After adjustment for age, sex, and chronic treatment with corticosteroids and/or immunosuppressants, the odds ratio of SARS-CoV-2 infection for chronic treatment with HCQ has been 0.51 (0.37-0.70).
Conclusions: Our data suggest that chronic treatment with HCQ confer protection against SARS-CoV-2 infection.



A New Model of SARS-CoV-2 Infection Based on (Hydroxy) Chloroquine Activity
bioRxiv

URL: https://www.biorxiv.org/content/10.1101 ... 2.232892v1
Category: healthNews
Published: August 2, 2020

Description: Abstract
Chloroquine and hydroxychloroquine (H)CQ are well known anti-malarial drugs, while their use against COVID-19 is more controversial. (H)CQ activity was examined in tissue culture cells to determine if their anti-viral benefits or adverse effects might be due to altering host cell pathways. Metabolic analysis revealed (H)CQ inhibit oxidative phosphorylation in mitochondria, likely by sequestering protons needed to drive ATP synthase. This activity could cause cardiotoxicity because heart muscle relies on beta oxidation of fatty acids. However, it might also explain their therapeutic benefit against COVID-19. A new model of SARS-CoV-2 infection postulates virus enters host cell mitochondria and uses its protons for genome release. Oxidative phosphorylation is eventually compromised, so glycolysis is upregulated to maintain ATP levels. (H)CQ could prevent viral infection and/or slow its replication by sequestering these protons. In support of this model other potential COVID-19 therapeutics also targeted mitochondria, as did tobacco smoke, which may underlie smokers’ protection. The mitochondria of young people are naturally more adaptable and resilient, providing a rationale for their resistance to disease progression. Conversely, obesity and diabetes could exacerbate disease severity by providing extra glucose to infected cells dependent on glycolysis. The description of (H)CQ function presented here, together with its implications for understanding SARS-CO-V2 infection, makes testable predictions about disease progression and identifies new approaches for treating COVID-19.
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Chinese study finds hydroxychloroquine useful in controlling Covid mortality

Postby smix » Sun May 17, 2020 2:45 am

Chinese study finds hydroxychloroquine useful in controlling Covid mortality
India Today

URL: https://www.indiatoday.in/india/story/c ... 2020-05-02
Category: healthNews
Published: May 2, 2020

Description: As some Western studies found hydroxychloroquine ineffective as a potential Covid-19 therapy, a new Chinese research has reported that the anti-malarial drug brought down mortality rates significantly among critical coronavirus patients. The latest preprint study -- which means it's not yet peer-reviewed -- is based on the clinical analysis of 568 Covid-19 cases at Tongji Hospital in Wuhan, the initial epicentre of the pandemic, between February 1 and April 8. Funded by China's Ministry of Science and Technology, Nature Science Foundation and Ma Yun Foundation, the research is sent to the Science China Life Sciences journal for peer-reviewing. According to this research, all patients under the clinical analysis received comparable basic treatments, including antiviral and antibiotic drugs, and 48 of them received oral HCQ therapy for seven-ten days additionally. The mortality rate in the HCQ group stood at 18.8 percent against 43.5 percent in the non-HCQ group, the study noted. "Hydroxychloroquine treatment is significantly associated with a decreased mortality in critically-ill Covid-19 patients," the researchers wrote. The study claims to "demonstrate that hydroxychloroquine application is associated with a decreased risk of death in critically-ill Covid-19 patients without obvious toxicity". It recommends that "hydroxychloroquine should be considered a primary option to apply to treat critically-ill Covid-19 patients, which could save lives during the current Covid-19 pandemic". The Chinese researchers, however, also suggest that despite their findings, the randomized double-blind-control study was needed to provide stronger evidence.
Mixed Results Elsewhere
Turkey, which has made HCQ a part of standard Covid-19 treatment, has more than a million cases but has managed to keep the number of deaths much less than in the European countries. Encouraged by the results, Turkey is now relaxing some of the lockdown measures. HCQ treatment, said Istanbul University President Nuri Aydin, is "one of the main steps" in Covid-19 treatment. "...the second is isolation," news reports quoted Dr Aydin as having said. In the US, the Association of American Physicians and Surgeons found there are "about 90 percent chances of HCQ helping Covid-19 patients". But another retrospective study associated with the US veterans claimed that the treatment had no positive effect on the 97 patients given HCQ doses. In another study published in the May issue of The Federation of American Societies for Experimental Biology (FASEB), researchers from the Harvard Medical School concluded that HCQ was ineffective against Covid-19.

bill-gates-harvard.jpg

US drug regulators on Friday gave emergency-use authorization for COVID-19 treatment to anti-Ebola drug remdesivir, whereas several US hospitals continue to use HCQ to treat coronavirus patients. In India, HCQ remains the first line of therapeutic defence in the battle against Covid-19. India, meantime, raised the production of HCQ tablets to 30 crore in April from 12.23 crore a month before. Several countries including Brazil, Israel, Australia, Canada continue to use HCQ in Covid-19 cases.
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Coronavirus - From North to South 1039 patients treated with hydroxychloroquine at home. The point on experimentation ....

Postby smix » Sun May 17, 2020 4:40 am

Coronavirus - From North to South 1039 patients treated with hydroxychloroquine at home. The point on experimentation: "Collapse of hospitalizations"
il Fatto Quotidiano

URL: https://www.ilfattoquotidiano.it/2020/0 ... i/5783544/
Category: healthNews
Published: April 28, 2020

Description: Translated from Italian
"I am a doctor and, positive for Covid19 , I immediately took hydroxychloroquine : in 3-4 days the fever and other symptoms disappeared ". This is how Paola Varese , head of cancer medicine at the Ovada Hospital in Piedmont , begins . "I applied the same protocol on myself that I planned for 276 patients at home," continues Varese , stressing that "timely intervention by family doctors in patients' homes is essential, with hydroxychloroquine associated with heparin (and if necessary the ' antibiotic ). It is presumable - he says - that the collapse of thehospitalization is due to the immediate use of the drug : we only had 7 hospitalizations: according to the projected expectations of the ISS we should have had 55 ". Hydroxychloroquine is one of the treatments against Coronavirus being tested , and is approved by AIFA (Italian Medicines Agency). The pioneer in this field is the Director of Hematology-Oncology of Piacenza, Luigi Cavanna . It was the first in Italy to use it, an intuition that is proving significant . “Since February 25, I have treated 209 patients and in 90% of cases the response has been positive . Hospitalizations have collapsed: from 30% of hospitalized (serious or moderate cases) it has gone to less than 5% ". The change, according to Cavanna, came with administration of hydroxychloroquine from the early stages of the disease , when patients were at home, and resulted in the hospitalization of very few cases in acute conditions. A treatment that, according to preliminary data collected and systematized by 5 different ASLs on 1,039 patients, is working throughout Italy . However, some of the scientific community remains cautious. According to the director of the infectious diseases department of the "Sacco" of Milan, Massimo Galli , "this drug (hydroxychloroquine) is used as an antimalarial prophylaxis , but it is not useful as a prophylaxis against this virus , and can cause serious damage to those suffering from heart and those with favism ”. In short, this is not an "over the counter" drug : only the doctor can prescribe it and - as with any other drug - the patient's clinical picture must be taken into account . the contraindicationsare known: hydroxychloroquine cannot be taken by those who suffer from favism - who are 0.3% to 3% in Italy - although those who suffer from favism also run serious risks by taking common drugs such as tachipirine and aspirin . Patients with previous heart disease can also experience decompensation. In Italy, before Covid19, each month they bought 134 thousand packs of hydroxychloroquine for about 65 thousand chronic patients with lupus and arthritis rheumatoid . Chloroquine has been used in the clinical setting for more than 70 years , even at high dosages for prolonged periods (for Covid19, the treatment lasts 7 days, on average). After decades of careful studies on its toxicity profile , all these adverse effects have not appeared with enough evidence to propose relevant literature , yet they have emerged in use for Covid19. “Among the 169 patients treated there was no death . 7% of the treaties were hospitalized , but none developed serious complications , nor had any side effects during treatment ". These are the words of Moreno Ferrarese , Pulmonologist of the ASL of Alessandria , who together with the General Director of the ASL, Roberto Stura , have systematized a huge amount of clinical information . “On Excel grids we collected data on all patients treated at home. We followed the clinical evolution day by day - adds Ferrarese - and a clear change in the severity was detected by all colleaguesin the last weeks. The improvement is likely related to the introduction of Plaquenil - hydroxychloroquine - administered within 48 hours of the onset of symptoms . If before the treatment there were changes in temperature for up to 10-12 days, after the systematic introduction of hydroxychloroquine , 75% of the people fever broke by the 4th day and 85% by the 8th day ". To get sideways there is also bureaucracy , which is slowing down an approach in which timeliness is fundamental. To be effective, in fact, the treatment must be started early, better if within 48-72 hours from the appearance of the symptoms in the suspected Covid19 (such as: anosmia, ageusia , fever, cough , diarrhea, intense muscle pain ). Antonio Marfella , oncologist and manager in charge of clinical pharmacology of the Pascale Institute of Naples is very direct: “We need at least 3 days for a swab, if everything goes well. Then other days must be added to have hydroxychloroquine at home from the hospital pharmacy, and thus the treatment is compromised ". "At the imposing organizational machine set in motion in Campania to counter Covid19 - he adds - there are no home therapies , which at this moment are the only ones able to intervene on the disease before it is too late, and avoid hospitalizations and exacerbations and - he concludes - I also want to say that it is a drug that costs, for the entire therapeutic cycle , just over 10 euros ".That it is necessary to intervene from the beginning of the symptomatology , I am also convinced in Imola . "We started administering hydroxychloroquine at home on March 27 and since then 231 patients have been treated promptly." This was reported by Andrea Rossi , Extraordinary Commissioner of the Imola Local Health Authority . The results? "We had a 50% reduction in intensive care and emergency room admissions for hospitalization ." The Director of the Oncology Department, Antonio Maestri , tells us that "two weeks after the start of home treatments we went from 15 to 7 patients in intensive care, and from 70 to 35 patients in non-intensive care beds: a noticeable drop ”. The question at this point is whether the drop in hospitalizations may be due to the lockdown . "It is a hypothesis to be evaluated " Rossi argues, according to which "what I can tell you is that there is growing evidence on the role of early antiviral therapy , which has as its base hydroxychloroquine, associated with antiviral drugs and / or antibiotics, and heparin " . What is certain is that from March 27 to April 12, while the curves of " contagions " and "deaths" of the Emilia Romagna Regionthey grew, the same had a opposite trend to Imola : they decreased. "I repeat, home treatment could have drastically reduced admissions to the emergency room," concludes Rossi, "and we are waiting for further confirmation from a scientific publication ." The protocol applied to Imola was developed by the Extraordinary Commissioner Rossi and Pierluigi Viale , ordinary of the University of Bologna and Director of Infectious Diseases of Sant'Orsola . The region that has the most positive per capita swabs, unexpectedly, is Valle D'Aosta : “We are the region with the most positive per capita patients (in Valle d'Aosta there is one positive patient for every 113 inhabitants, while in Lombardy 1 every 134, editor's note). “In this context - says Luca Montagnani , Director of the USL emergency, anesthesia and resuscitation department and coordinator of the regional Task Force - we started to administer hydroxychloroquine at home . 134 patients were treated, all with positive buffer, and nobody ended up in intensive. Only 13 were hospitalized, with a drop of over 50%, of which 5 immediately discharged and 7 improving. There was only one death : a 95-year-old man with multiple pathologies ”. It is interesting to note that in the subgroup treated with the drug, mortality is 0.6%. In Italy, everything related to regulatory interventions on drugs is up to AIFA . At this point it is necessary to understand the position of the Agency regarding all these data. It must be said, first of all, that the treatment with hydroxychloroquine was approved by the Agency, with a resolution dated March 17th. Since then, the evaluation has always been the same: wait for further confirmation. “Precisely because of a potential efficacy , but in the absence of adequate clinical data, hydroxychloroquine is currently being studied . As soon as the results of the studies launched in Italy, as well as those underway at international level , are available, it will be possible to give a definitive answer to the therapeutic role of hydroxychloroquine in patients with Covid-19 ".The only Italian study , already approved, will start in the Marche region : it is the Hydro-Stop-Covid-19 Trial , on the early administration of hydroxychloroquine . The "principal investigator" is Procolo Marchese , from the cardiology department of the "Mazzoni" hospital in Ascoli Piceno . “It all started with 20 patients (mean age 63 years, 72% male) positive with swab . All were treated with hydroxychloroquine : 400 mg x 2 on the first day and 200 mg x 2 for 5 days, in 40% of cases with the addition of antibiotics . Clinical improvement at first contact after approximately 7 days covered 80% of patients".
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Despite FDA Caution, Trump Says He Is Taking Hydroxychloroquine As A Preventative

Postby smix » Mon May 18, 2020 10:20 pm

Despite FDA Caution, Trump Says He Is Taking Hydroxychloroquine As A Preventative
NPR

URL: https://www.npr.org/sections/coronaviru ... entatively
Category: healthNews
Published: May 18, 2020

Description: President Trump on Monday revealed to reporters that he has been taking hydroxychloroquine and zinc to protect against the coronavirus. Trump has been promoting the drug, used to treat malaria and lupus, in briefings and on Twitter. The impact of the drug on the virus is being studied, but there is not yet evidence from medical trials – and there have been some warnings about side effects from taking the medicine, including from the Food and Drug Administration. Trump volunteered the information at the end of a roundtable with restaurant owners. "I was just waiting to see your eyes light up when I said this," Trump told reporters. He said he had been taking it for a week and a half. He asked his doctor to take it after hearing from people who had done so. "Here's my evidence — I get a lot of positive calls about it," Trump said. "I've taken it for about a week and a half now. And I'm still here," Trump said. Trump said he had asked the White House physician about it, and that he did not start taking it in response to a specific exposure. Medical experts have urged caution around the drug and last month, the FDA strongly warned against using hydroxychloroquine without medical supervision such as in a hospital or as part of a clinical trial.
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Trump says he's been taking hydroxychloroquine despite safety concerns

Postby smix » Tue May 19, 2020 12:17 am

Trump says he's been taking hydroxychloroquine despite safety concerns
The Hill

URL: https://thehill.com/homenews/administra ... hloroquine
Category: Politics
Published: May 18, 2020

Description: President Trump on Monday revealed he's taking hydroxychloroquine, a controversial drug that he's championed as a potential treatment for coronavirus despite limited evidence from the medical community. The president said he consulted with the White House doctor about taking the drug, but it was not explicitly recommended for him since he has not tested positive for the virus. "I asked him what do you think," Trump said. "He said, 'Well if you’d like it.' I said, 'Yeah, I’d like it. I’d like to take it.' " He said he's been taking the drug for about a week-and-a-half along with a zinc supplement, adding he based his decision on positive reviews he's heard from front-line health care workers who have had good results treating patients with it. "Here’s my evidence: I get a lot of positive calls about it," Trump said. "So far, I seem to be OK," he added.



The president's decision to take hydroxychloroquine is controversial and potentially dangerous given that the drug's effectiveness in treating coronavirus remains unproven and there is no evidence that it works as a preventative measure. The pill is typically taken as an anti-malaria drug or to treat lupus. The Food and Drug Administration issued a warning last month that hydroxychloroquine should not be taken outside a hospital or clinical trial because of the risk of severe heart problems. The drug showed no benefit for patients in an analysis of those hospitalized in Veterans Health Administration medical centers. The study, released last month, found the two primary outcomes for COVID-19 patients treated with hydroxychloroquine were death and the need for mechanical ventilation. Medical experts and media figures were quick to raise concerns about Trump's embrace of the drug, expressing alarm that it may encourage others to do the same despite potentially deadly side effects. "If you are in a risky population here and you are taking this as a preventative treatment to ward off the virus ... and you are in this vulnerable population, it will kill you," said Fox News anchor Neil Cavuto. Trump appeared to get a kick out of the media's reaction to his announcement on Monday, which came at a roundtable with restaurant industry executives. "I was just waiting to see your eyes light up when I said this," he said. The White House did not immediately reply to a request for further documentation to show that Trump is taking the drug, or at what dosage. The president spent weeks in March and April touting hydroxychloroquine as a potential panacea to the coronavirus, despite limited evidence to suggest it was effective in a clinical setting. Trump repeatedly argued that patients had “nothing to lose” by taking the drug and even suggested they take it proactively. Fox News hosts and other conservative figures also pushed hydroxychloroquine as a potential treatment, and Laura Ingraham reportedly visited the White House at one point to pitch the president on the drug. The government eventually stockpiled 29 million pills to distribute to hospitals. The president has sparked controversy by suggesting unconventional and in some cases dangerous methods to combatting the coronavirus, which has killed more than 90,000 people in the U.S. Trump in April suggested officials look into injecting disinfectants as a potential treatment, a comment he later claimed was sarcastic.



WH doctor: 'Potential benefit' of Trump taking hydroxychloroquine 'outweighed' risks
The Hill

URL: https://thehill.com/homenews/administra ... ump-taking
Category: Politics
Published: May 18, 2020

Description: President Trump's physician on Monday confirmed that the president is now taking the anti-malaria drug hydroxychloroquine despite not having the coronavirus, saying he and Trump concluded "the potential benefit from treatment outweighed the relative risks." In a 114-word letter released by the White House hours after Trump announced he was taking the medication, presidential physician Sean Conley wrote that he discussed the pros and cons of taking the drug with Trump after one of his personal valets tested positive for the coronavirus. But the letter contained no specifics on when Trump started taking the drug or what his dosage is.

sean-conley-memo.jpg

"In consultation with our inter-agency partners and subject matter experts around the country, I continue to monitor the myriad studies investigating potential COVID-19 therapies, and I anticipate employing the same shared medical decision making based on the evidence at hand in the future," Conley wrote. Trump told reporters earlier Monday he had started taking the controversial drug, which he has championed as a potential treatment for coronavirus despite limited evidence from the medical community. The president said he consulted with the White House doctor about taking hydroxychloroquine, but it was not explicitly recommended for him since he has not tested positive for the virus. "I asked him what do you think," Trump said. "He said, 'Well, if you’d like it.' I said, 'Yeah, I’d like it. I’d like to take it.' " He said he's been taking the drug for about a week-and-a-half along with a zinc supplement, adding he based his decision on positive reviews he's heard from front-line health care workers who have had good results treating patients with it. "Here’s my evidence: I get a lot of positive calls about it," Trump said. "So far, I seem to be OK," he added. The decision drew swift skepticism and some condemnation given the drug remains largely unproven and in some cases dangerous. The pill is typically taken as an anti-malaria drug or to treat lupus, and there is scant evidence it can prevent the onset of coronavirus. The Food and Drug Administration issued a warning last month that hydroxychloroquine should not be taken outside a hospital or clinical trial because of the risk of severe heart problems. The drug showed no benefit for patients in an analysis of those hospitalized in Veterans Health Administration medical centers. The study, released last month, found the two primary outcomes for COVID-19 patients treated with hydroxychloroquine were death and the need for mechanical ventilation. The president spent weeks in March and April touting hydroxychloroquine as a potential panacea to the coronavirus, despite limited evidence to suggest it is effective in a clinical setting. Trump repeatedly argued that patients had “nothing to lose” by taking the drug and even suggested they take it proactively.



Science says Trump was right: Malaria drugs need to be pursued as a coronavirus therapy
The Hill

URL: https://thehill.com/opinion/healthcare/ ... rsued-as-a
Category: Politics
Published: April 14, 2020

Description: When President Donald Trump suggested that an off-labeled repurposing of a pair of old antimalarial drugs might prove to be a “game-changer” coronavirus therapeutic, pundits howled that he was irresponsibly peddling false hope to a weary American public like some late-night snake oil salesman. While predictable, this gut reaction wasn't remotely informed by science, but instead the sort of petty tribalism that makes even pandemics partisan affairs in this country. Set aside whether you support the president or not, because the virus doesn’t care. It's true that the president may not understand the sciences of virology and pharmacology, but I do — and all the available data urgently demand that our government pursue chloroquine and hydroxychloroquine as treatments for the novel coronavirus. But don’t take my word alone. Last week, Jackson & Coker, one of the country’s largest physician staffing agencies, polled more than 1,200 doctors and found that 65 percent would prescribe these drugs to treat COVID-19 in family members. Understand: These drugs are not new, and their nominal side effect profiles are well-known. It wouldn't even be the first time they were repurposed for off-label use. These drugs were first prescribed to treat and prevent malaria. Doctors in World War II found that they had significant therapeutic value in treating the symptoms of lupus. Indeed, many of the reasons the pair proved effective in treating lupus, like its ability to tamp down an over-exuberant immune reaction, explain why scientists are so eager to test it against COVID-19. But there’s even more. In vitro, these drugs prevent a virus from entering a cell and facilitate its elimination once it has breached a cell. A new controlled study released by researchers in China showed that patients with mild to moderate COVID-19 symptoms who were treated with hydroxychloroquine saw faster recovery and were less likely to turn severe compared to patients who did not receive the treatment. But it's not just the Chinese, whose new infections have reportedly fallen to single-digits, who believe the drugs could play an essential role in defeating this virus. Indeed, their data mirror earlier randomized controlled studies in South Korea, Italy and France, which found positive relationships between the two drugs and reductions in fever and improvements in lung function and disease progression. Following the action of other countries’ governments to encourage the drugs’ use, the U.S. Food and Drug Administration on Sunday issued an emergency use authorization for chloroquine and hydroxychloroquine, which allowed private shares of the drugs to be donated to the Strategic National Stockpile and for doctors to begin prescribing them in specific cases. Concurrently, the Department of Health and Human Services said it would fund a $750,000 one-month study on the use of the drugs to treat COVID-19. These new actions are steps in the right direction. But the science says they're not enough — we need to do more to study and use them right now. Rather than merely treating only the sickest patients with these drugs, there's already significant empirical evidence that they have applications in preventing the contagion's spread or mitigating its progression in those infected. Clinical trials always pose some risk to participants, but as the human and economic toll of this virus balloon, there is obvious reward to society, too.
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Trump says he's taking hydroxychloroquine, despite scientists' concerns

Postby smix » Tue May 19, 2020 1:03 am

Trump says he's taking hydroxychloroquine, despite scientists' concerns
Politico

URL: https://www.politico.com/news/2020/05/1 ... rug-265546
Category: Politics
Published: May 18, 2020

Description: President Donald Trump has been taking hydroxychloroquine, the anti-malarial drug he’s touted as a potential cure for Covid-19 despite scientists’ concerns about its effectiveness. “A couple of weeks ago, I started taking it,” Trump told reporters at the White House on Monday, adding that he’d consulted with his presidential physician about the drug. Initial data from observational studies have shown the drug has limited or no proven benefits for coronavirus patients, and may even be harmful when used in certain combinations. The president made the stunning announcement during a roundtable with restaurant executives, dismissing those studies and instead invoking anecdotal evidence that he claimed to have heard from doctors and other front-line medical workers. Trump told reporters that he’d been taking hydroxychloroquine daily for the past week and a half, along with a daily dose of zinc and an initial dose of the antibiotic azithromycin, a combination that has been linked to increased incidences of cardiac arrest. The timing coincides with the first pair of coronavirus cases in the West Wing — on May 7, the president’s personal valet tested positive for coronavirus, and just days later Vice President Mike Pence’s top spokesperson tested positive, as well. Trump emerged as a champion of hydroxychloroquine early on in the pandemic, boosted by his allies in conservative media, and he cited from the White House briefing room podium anecdotal evidence of the drug’s helping coronavirus patients, only to be cautioned by health officials moments later that the drug’s potential benefits remained unproven. Trump’s push for the drug is central to a whistleblower report from a former top vaccine official in the administration who says he was ousted after refusing to back the administration’s push for hydroxychloroquine.

deep-state-war.jpg

The FDA authorized emergency use of the drug against the coronavirus in March, despite sparse evidence that it could work. But it later warned against using the therapy outside of clinical trials, citing potential “life threatening” heart problems. Around the same time, Trump suddenly began to lay off his promotion of the drug, and mentioned it rarely if at all in the weeks before Monday’s revelation. “I take it. I hope to not be able to take it soon because, you know, I hope they come up with some answer,” he told reporters about the drug. He then appeared to rebut his FDA: “But I think people should be allowed to.” While the president denied that his physician at the White House had recommended he take hydroxychloroquine, he indicated that his doctor didn’t object to his request for the drug. “The White House doctor, he didn’t recommend — no, I asked him, ‘What do you think?’ He said, ‘Well if you’d like it.’ I said, ‘Yeah I’d like it. I’d like to take it,’” Trump explained, claiming that “a lot of people are taking — a lot of front-line workers are taking hydroxychloroquine.” He also denied that he was experiencing any adverse effects from taking the drug. “All I can tell you is, so far I seem to be OK,” he said, later adding that after a week and a half of taking it, “I'm still here.” But the president’s disclosure on Monday is sure to revive fears of shortages of the drug, which is already commercially available and most commonly used to treat malaria, lupus and rheumatoid arthritis. Back in the spring when Trump first began to promote hydroxychloroquine, FDA officials allowed the drug to be added to the Strategic National Stockpile “to be distributed and prescribed by doctors to hospitalized teen and adult patients with Covid-19, as appropriate, when a clinical trial is not available or feasible.” A growing number of lupus and arthritis patients had already complained that they‘d been unable to fill their prescriptions amid ongoing shortages, and reports emerged that some physicians began hoarding the drug for themselves. It could also prompt others to begin taking the combination as a preventive measure as well, perhaps exposing them to the same harmful side effects observed in some studies. It wouldn’t be the first time that people desperately hoping to avoid contracting Covid-19, the disease caused by the novel coronavirus, followed the president’s ill-informed medical advice. Last month, Trump was slammed after he offhandedly suggested during a televised news briefing that ingesting disinfectants could treat the virus. Officials in some states reported a spike in calls to their poison control centers and health departments asking about Trump‘s comments. Still, at the White House on Monday, the president told reporters he’d received “many” letters like the one he got last week from a doctor in the New York suburbs who claimed he’d given hydroxychloroquine, azithromycin and zinc to “over 300 patients” and hadn’t lost a single one. The doctor “just wanted me to know the results of what he's doing as a doctor. He was so happy with the fact that I fight for this stuff. And then we have this crazy whistleblower, this fake whistleblower get out and try to knock it,” he said, referring to Rick Bright, the former director of the Biomedical Advanced Research and Development Authority. The president on Monday repeatedly asserted that “many, many” front-line workers and doctors were taking hydroxychloroquine, a claim that appears to misrepresent ongoing studies among health care workers with no definitive results yet.



Trump also fell back on a past defense for touting the drug, that he was willing to take risks to combat the virus that has infected more than 1.5 million Americans and killed more than 90,000. “I get a lot of tremendously positive news on the hydroxy. And I say, hey, do you know the expression I've used, John? What do you have to lose? OK, What do you have to lose?” he professed to reporters. “I want the people of this nation to feel good. I don't want them being sick, And there is a very good chance that this has an impact, especially early on,” he asserted, offering no evidence to back up that claim. “But you look at front-line workers. You look at doctors and nurses. A lot of them are taking it. As a preventative.” Challenged by reporters to divulge his evidence that the drugs can work as a preventative measure — Trump said he continued to test negative in near daily coronavirus tests and has been showing “zero" symptoms” — the president had none. “Here we go. Are you ready? Here’s my evidence. I get a lot of positive calls about it,” he responded, saying the only negatives he’d heard about the drug were the results of a study by the Department of Veterans Affairs, the results of which he appeared to suggest had been politically tainted. While there are studies underway on hydroxychloroquine’s use as a preventative, no results of those studies have been released yet. Of some of the other initial data showing little to no benefits of hydroxychloroquine or even that taking it in certain combinations was harmful, Trump pointed to the fact that many of them were conducted with moderately to severely ill patients — though there’s no evidence hydroxychloroquine is more effective when given to patients who are less ill.

deep-state-swamp.jpg

The theory with zinc is that it has antiviral properties and that certain medicines — like hydroxychloroquine — could boost its ability to get into cells, said Joseph Rahimian, an infectious disease specialist at NYU Langone Health and lead researcher on a study analyzing patients who received zinc along with their hydroxychloroquine and azithromycin regimen. Rahimian said that patients who used zinc along with the other medicines saw improvements in survival from Covid-19, but that in his opinion this was driven by the additive and not hydroxychloroquine. “My clinical experience on the floors was that it did nothing,” he said about the anti-malaria drug. While there are safety concerns around the hydroxychloroquine and azithromycin combination, “zinc is a relatively well-tolerated medicine,” he added. On Monday, the president refused to disclose whether any other administration officials were taking hydroxychloroquine, calling such a disclosure a “personal decision” but saying that he wouldn’t be surprised if he wasn’t alone. “I just want to be open with the American public,” Trump added.
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He Was a Science Star. Then He Promoted a Questionable Cure for Covid-19.

Postby smix » Tue May 19, 2020 3:46 pm

He Was a Science Star. Then He Promoted a Questionable Cure for Covid-19.
New York Times

URL: https://www.nytimes.com/2020/05/12/maga ... quine.html
Category: Politics
Published: May 12, 2020

Description: The man behind Trump’s favorite unproven treatment has made a great career assailing orthodoxy. His claim of a 100 percent cure rate shocked scientists around the world.

didier-raoult.jpg

When diagnosing the ills afflicting modern science, an entertainment that, along with the disparagement of his critics and fellow researchers, he counts among his great delights, the eminent French microbiologist Didier Raoult will lightly stroke his beard, lean back in his seat and, with a thin but unmistakable smile, declare the poor patient to be stricken with pride. Raoult, who has achieved international fame since his proposed treatment for Covid-19 was touted as a miracle cure by President Trump, believes that his colleagues fail to see that their ideas are the products of mere intellectual fashions — that they are hypnotized by methodology into believing that they understand what they do not and that they lack the discipline of mind that would permit them to comprehend their error. “Hubris,” Raoult told me recently, at his institute in Marseille, “is the most common thing in the world.” It is a particularly dangerous malady in doctors like him, whose opinions are freighted with the responsibility of life and death. “Someone who doesn’t know is less stupid than someone who wrongly thinks he does,” he said. “Because it is a terrible thing to be wrong.” Raoult, who founded and directs the research hospital known as the Institut Hospitalo-Universitaire Méditerranée Infection, or IHU, has made a great career assailing orthodoxy, in both word and practice. “There’s nothing I like more than blowing up a theory that’s been so nicely established,” he once said. He has a reputation for bluster but also for a certain creativity. He looks where no one else cares to, with methods no one else is using, and finds things. In just the past 10 years, he has helped identify nearly 500 novel species of human-borne bacteria, about one-fifth of all those named and described. Until recently, he was perhaps best known as the discoverer of the first giant virus, a microbe that, in his opinion, suggests that viruses ought to be considered a fourth and separate domain of living things. The discovery helped win him the Grand Prix Inserm, one of France’s top scientific prizes. It also led him to believe that the tree of life suggested by Darwinian evolution is “entirely false,” he told me, and that Darwin himself “wrote nothing but inanities.” He detests consensus and comity; he believes that science, and life, ought to be a fight. It is in this spirit that, over the objections of his peers, and no doubt because of them, too, he has promoted a combination of hydroxychloroquine, an antimalarial drug, and azithromycin, a common antibiotic, as a remedy for Covid-19. He has taken to declaring, “We know how to cure the disease.” Trump was not the only one eager to embrace this possibility. By the time I arrived in Marseille, some version of Raoult’s treatment regimen had been authorized for testing or use in France, Italy, China, India and numerous other countries. One in every five registered drug trials in the world was testing hydroxychloroquine. In March, Raoult announced that his hospital would test and treat anyone who cared to show up. Crowds gathered at the entrance to the IHU in winding single-file lines, like pilgrims shuffling toward their private audience with the oracle. On March 16, Raoult released the results of a small clinical trial that showed, he said, a 100 percent cure rate. The study has since been widely debated, and Raoult’s boosterism has been lamented by scientists and health officials around the world; in a comment more or less representative of the tenor of the controversy in France, where Raoult’s name and image have now been everywhere for weeks, one detractor, a generally thoughtful politician, suggested that Raoult “shut his face and be a doctor” and that he “stop saying ‘I’m a genius’ all over the place.” His colleagues liken his psychology to that of Napoleon, though he is not physically small. When asked by one journalist about his tendency to “swim against the current” of scientific thought, Raoult responded: “I’m not an ‘outsider.’ I’m the one who’s farthest out in front.” Axel Kahn, a geneticist and physician who has known Raoult for nearly 40 years, told me that he has always been this way. “One of Professor Raoult’s abiding characteristics is that he knows that he’s very good,” Kahn told me. “But he considers everyone else to be worthless. And he always has. It’s not a recent development.” At his home, alongside a collection of Roman busts, he is said to keep a marble statue of himself. Raoult, who is 68, is a sturdily built but fine-featured man, with high cheekbones and a tight, contemptuous mouth. In recent years, he has hidden these behind a straggly white mustache and goatee and has grown his flaxen hair down to his shoulders. On his right pinkie he now wears a silver skull. In internet memes, he has been depicted as the wizard Gandalf and as a druid; except for his white lab coat, he has the general aspect of a fortuneteller who rides a Harley to work. The French journalist Hervé Vaudoit, who has written admiringly about Raoult over the years, once asked him why he’d taken to dressing this way. Raoult replied, “Because it pisses them off.” In the weeks since SARS-CoV-2, the virus that causes Covid-19, spread throughout the world, his disdain for respectable opinion, and for the “Parisian marquesses” who are its representatives, has endeared him to a large segment of the French population. According to one survey, by late March, Raoult had become one of France’s most popular “political personalities,” with particular appeal on the populist extremes. Votives bearing his image were being sold in Marseille, and on some evenings, at 8 p.m., a battalion of municipal garbage trucks assembled on the roadway outside his hospital, where the drivers leaned on their horns in loud and furious tribute. A hundred-foot banner, painted by a club of local soccer fans and strung up near the entrance, read, “Marseille and the world behind Prof. Raoult!!!” Raoult has been collecting the merchandise created by his fans, and he seems to be enjoying his fame, though he claims otherwise. He is certain the drugs will vindicate him in the end; everything else is a matter of appearances. “I really do think we’re in a theater,” he told me. “In my play, the people who judge me as a doctor are my patients. As a scientist, it’s my colleagues. And time.”
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A few weeks ago, I spoke, from the recommended distance, to a man named Jacques Cohen. He was seated on the sidewalk outside the IHU, an angular monument of concrete and glass about a mile and a half from Marseille’s old port. Cohen had his back against a pylon and his wrists on his knees, at the edge of a group of perhaps 60 people. By their unworried proximity to one another — they were standing around in a loose group, as people used to, waiting to enter the hospital through a side door — they were identifiable as the unfortunates who already knew they were positive. I had selected Cohen as my interlocutor under the guidance of a nearby nurse. He was not coughing or sneezing; he wore a mask. “In any case, we’re all going to get it,” the nurse said. I crouched on the pavement and asked Cohen, who is 76, how he was feeling. For the past two days, he had been taking hydroxychloroquine and azithromycin. “It’s getting better,” Cohen said through his mask. He looked ashen but optimistic. His fever had fallen, and he had begun to regain his sense of taste. I noted that there was some debate about the efficacy of the treatment. “There’s no ‘believing’ or ‘not believing,’” Cohen replied. “We know it’s effective!” Hydroxychloroquine and azithromycin are well characterized, well tolerated and widely prescribed medications. Azithromycin was developed 40 years ago in the former Yugoslavia and is today the second-most commonly prescribed antibiotic in the United States. Hydroxychloroquine, along with its more toxic analog chloroquine, was for several decades the most commonly prescribed antimalarial drug in the world. Today it is widely used to treat rheumatoid arthritis and lupus. All three molecules are included on the World Health Organization’s Model List of Essential Medicines, a compilation of “the most efficacious, safe and cost-effective medicines for priority conditions.” Raoult knows the drugs well. From the start of his career, he has experimented extensively with drug repositioning, in which medicines that have been approved for use against one disease are repurposed as treatments for others. Hundreds and hundreds of molecules have already been approved for human use by the Food and Drug Administration. Hidden among these, Raoult contends, are various unanticipated cures. “You test everything,” Raoult told me. “You stop pondering; you just look and see if, by chance, something works. And what you find by chance, it’ll knock you on your derrière.” Antidepressants and antihypertensives have been shown to have antiviral properties; lovastatin, which is prescribed to lower cholesterol levels, has been found to be effective, at least in mice, against plague. In a 2018 paper, Raoult and a team of researchers reported that azithromycin showed strong activity in cells infected with the Zika virus. Raoult spent the first decade of his life in Dakar, in what was then French Senegal, where his father, a military doctor, was posted. To ward off malaria, he was given chloroquine. “I took it all the time when I was a kid,” he told me. In the 1990s, in an early repurposing experiment, he tested the effect of hydroxychloroquine on a frequently fatal condition known as Q fever, which is caused by an intracellular bacterium. Like viruses, intracellular bacteria multiply within the cells of their hosts; Raoult found that hydroxychloroquine, by reducing acidity within the host cells, slowed bacterial growth. He began treating Q fever with a combination of hydroxychloroquine and doxycycline and later used the same drugs for Whipple’s disease, another fatal condition caused by an intracellular bacterium. The combination is now considered to be a standard treatment for both diseases. Given the similarities between intracellular bacteria and viruses, Raoult suspected that chloroquine and hydroxychloroquine might have antiviral effects. Following the SARS outbreak in 2002, researchers found that chloroquine slowed reproduction of the SARS coronavirus in cell cultures. Raoult reviewed that evidence in a 2007 paper, concluding that chloroquine and hydroxychloroquine might be “an interesting weapon to face present and future infectious diseases worldwide.” This winter, as the spread of SARS-CoV-2 began to take on the contours of a pandemic, he surveyed the data that had begun coming out of China. An early report on chloroquine showed good results in vitro. In mid-February, another Chinese team reported that, in more than 100 patients, it had been found to have “potent activity against Covid-19.” Raoult was elated. At the time, health authorities around the world were warning that a viable treatment could be months away. The Chinese reports, however, appeared to confirm Raoult’s longstanding hopes for chloroquine. A deadly virus for which no treatment existed could evidently be stopped by an inexpensive, widely studied, pre-existing molecule, and one that Raoult knew well. A more heedful scientist might have surveyed the Chinese data and begun preparations for tests of his own. Raoult did this, but he also posted a brief, jubilant video on YouTube, under the title “Coronavirus: Game Over!” Chloroquine had produced what he called “spectacular improvements” in the Chinese patients. “It’s excellent news — this is probably the easiest respiratory infection to treat of all,” Raoult said. “The only thing I’ll tell you is, be careful: Soon the pharmacies won’t have any chloroquine left!”
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Raoult has spent nearly his entire life in Marseille, a famously ragged and combative city, which he loves. He named a genus of bacteria, Massilia, for it and has given its name or the names of its neighborhoods to numerous other species of microbe. Marseille has been a major port for more than 2,000 years and has a correspondingly rich history of disease. It was the point of entry into France for all three of the great waves of bubonic plague, beginning in the sixth century. Between 1720 and 1722, the plague killed about half of Marseille’s population; one of its central neighborhoods, on the old port, is today named for the bishop who tended to the ill while the city’s doctors hid in fear. Raoult wrote his first research paper, in 1979, on a tick-borne infection sometimes known as Marseille fever. The disease was also called “benign summer fever,” and more than 50 years of science said it was nonlethal. And yet one of the 41 patients in his data set had died. Before submitting the paper, Raoult, who was then a young resident, gave it to a supervising professor for review. “And he takes it,” Raoult told me, “he doesn’t show it to me again, and he publishes it — and he’d taken out the death. Because he didn’t know how to make sense of the death.” Raoult was disgusted, and the incident shaped his philosophy of scientific inquiry. “I learned that the people who wanted to follow the familiar path were prepared to cheat in order to do it,” he said. In subsequent work, he demonstrated that Marseille fever was indeed fatal in almost precisely one in every 41 cases. “He was a ‘follower,’” Raoult said of the professor. “And these ‘followers’ are all cheaters. That’s what I thought. And it’s still what I think.” He is, fundamentally, a contrarian. In Raoult’s view, little of consequence has been accomplished by researchers who endorse the habitual tools and theories of their age. “I’ve spent my life being ‘against,’” he told me. “I tell young scientists: ‘You know, you don’t need a brain to agree. All you need is a spinal cord.’” He is thrilled by conflict. It is a matter both of philosophy — the influence, no doubt, of the thinker he refers to admiringly as “master Nietzsche” — and of temperament. “He loves to know that things are roiling around him,” one of his lab technicians told me; he sets off storms and admires them as they roll out over the land. His peers shake their heads at this behavior but grant him a grudging respect. “You can’t knock him down,” said Mark Pallen, a professor of microbial genomics at the University of East Anglia. “In terms of his place in the canon, the sainthood of science, he’s pretty secure there.” He is also interested in power and has been attentive to it from the start. In 1985 and 1986, Raoult worked at the Naval Medical Research Institute in Bethesda, Md., where he discovered the Science Citation Index. The index, a tool that can be used to measure a scientist’s influence on the basis of his or her publication history, was relatively unknown in France. Raoult looked up the researchers reputed to be the best in Marseille. “It was really the emperor wears no clothes,” he said. “These people didn’t publish. There was one who hadn’t written a paper in 10 years.” In Raoult’s view, French science was a duchy of appearances, connections and self-reverence. “It was people saying” — he mimed the drone of an aristocrat — “ ‘Oh, him, yes, he’s very good.’ And this reputation, you don’t know what it’s based on, but it’s not the truth.” For decades, Raoult has boasted of his prodigious rates of publication and citation, which, as objective statistics, he considers to be the best measure of his worth as a researcher. Biomedical researchers in France write or contribute to perhaps 10 scientific papers every year and a few hundred in the course of a career. Raoult’s name sits atop several thousand; in each of the past eight years, he has produced more than 100. In 2020, he has already published at least 54. Raoult is reputed to be an indefatigable worker, but he also achieves his extreme rate of publication by attaching his name to nearly every paper that comes out of his institute. Though the practice is not unheard-of, it is unusual. “Even to just read those papers would take up a large percentage of anyone’s time,” Pallen told me. “For someone like me to actually go through them carefully, critique them, make a substantial intellectual contribution — I think that would be practically impossible.” With few exceptions, the department heads at the IHU have worked under Raoult for their entire careers, some for more than 30 years. It is an “ancestral system,” “familial” and “clanlike,” said Michel Drancourt, a clinician who is Raoult’s longest-serving collaborator. Raoult is, without question, the patriarch, and he is in some respects reputed to be benevolent. The IHU spends a great deal of money on scholarships and research grants for students from the developing world, for instance, and Raoult is known to be accessible to young researchers in a way that distinguishes him from other high-powered scientists. He is also known for berating his subordinates. While visiting the IHU, I watched a young researcher emerge from Raoult’s office in tears and rush into the arms of her friends, who were evidently accustomed to this. “When he’s not happy about something, he’ll let you know,” one of them told me. A 2017 employee letter of complaint, which was followed by an investigation of the IHU, described the “screaming,” “insults” and “psychological bullying” of a “leadership of another era.” Along the entryway to Raoult’s institute, there’s a line from Horace: Exegi monumentum aere perennius, “I have crafted a monument more lasting than bronze.” In recent years, Raoult has amused himself, it seems, by staking out tendentious scientific claims, sometimes in territories that are well beyond the scope of his expertise. He is skeptical, for instance, of the utility of mathematical modeling in the realm of epidemiology. The same logic has led him to conclude that climate modelers are no more than “soothsayers” for our “scientistic era” and that their dire predictions are mostly just an attempt to expiate our intense but irrational feelings of guilt. He is also dismissive of the alarmism that is the default position among specialists of infectious disease. He doubted, initially, that SARS-CoV-2 would spread beyond China, or that it might be a terrible problem if it did. On Jan. 20, Chinese scientists confirmed that infections were being transmitted from patient to patient, and President Xi Jinping, in his first public comments about the coronavirus, declared that all possible measures would have to be taken to contain the outbreak. The World Health Organization announced an emergency meeting. The following day, in Marseille, Raoult posted a video to his institute’s YouTube channel. He faced his offscreen interviewer with weary eyes, sighed and said, “You know, the world has gone crazy.” Every year, he said, there are probably 600 or 700 people who die from coronavirus infections in France and thousands more from other respiratory illnesses. “The fact that people have died from a coronavirus in China, I don’t feel like it means much of anything for me,” he said. “I don’t know, maybe people don’t have anything to do, so they’ve gone looking in China for something to be scared about.” Raoult’s most recent book, “Epidemics: Real Dangers and False Alerts,” was published in late March, by which time the W.H.O. had reported more than 330,000 confirmed cases of Covid-19 worldwide and more than 14,500 deaths. “This anguish over epidemics,” he writes, “is completely untethered from the reality of deaths from infectious diseases.”
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By the standards of molecular biology, real-time polymerase chain reaction, the technology most commonly used to test for SARS-CoV-2, is not extravagantly complex. But it depends upon collection swabs, thermocycling machines, chemical reagents and nucleotide probes and primers, and if any one of these components is in insufficient supply, the tests cannot be run. Beginning in January, when the SARS-CoV-2 genome was first published, the IHU bought or borrowed as much of all these as possible, spending a half million euros on new machines alone. Whatever Raoult’s reservations about the virus, he did not intend to miss the opportunity to study it, and perhaps to win the race to find a treatment. His institute receives most of its funding from public sources — Raoult was given 130 million euros to build it — but it effectively controls its own budget, and Raoult, as the founding director, has near-complete control of what goes on inside its walls. “He can essentially say, ‘Hold on, I want to turn the bedroom and the dining room into a kitchen,’” Drancourt said. Nearly 800 people work at the institute. In early March, as coronavirus patients began arriving, almost all the staff members turned their efforts to SARS-CoV-2. Raoult obtained authorization to begin a small clinical trial of hydroxychloroquine. Because viral respiratory infections often lead to secondary bacterial infections, however, Raoult wanted to test a supplementary antibiotic in some patients; he chose azithromycin, which he had previously tested against Zika. “If you’re going to choose one, you might as well choose one that’s been shown to be active against a virus,” said Bernard La Scola, who runs the biosafety lab at the IHU. Hydroxychloroquine is believed to inhibit viral reproduction in infected cells by raising their pH, as in Q fever and Whipple’s disease; the antiviral mechanism of azithromycin has not been explained. But what works works. If we relied only upon medications with precisely established mechanisms, a number of popular drugs — acetaminophen, for instance, the active ingredient in Tylenol — would not be in use. I asked Raoult if the idea to test the drugs together had emerged from discussions with his team. “It was me,” he told me. “Don’t kid yourself.” Testing had been scheduled to run for two weeks per patient, but after only six days, the results were so favorable that Raoult decided to end the trial and publish. “Usually, we’d take time to write, to make corrections, to consider, to go over things 50 times,” said Philippe Gautret, the department head who was the first listed author on the paper. “In this case, we were working with a sense of real urgency. Because we thought we had to get the word out, because, maybe, we’d found a way to make things better.” Others might have proceeded with more caution or perhaps waited to confirm these results with a larger, more rigorous trial. Raoult likes to think of himself as a doctor first, however, with a moral obligation to treat his patients that supersedes any desire to produce reliable data. “We’re not going to tell someone, ‘Listen, today’s not your lucky day, you’re getting the placebo, you’re going to be dying,’” he told me. He believes it to be unnecessary, in addition to being unethical, to run randomized controlled trials, or R.C.T.s, of treatments for deadly infectious diseases. If these have become the accepted standard in biomedical research, Raoult contends, it is only because they appeal to statisticians “who have never seen a patient.” He refers to these scientists disdainfully as “methodologists.” Raoult’s paper included results for 36 patients. Fourteen were treated with hydroxychloroquine sulfate; six were treated with a combination of hydroxychloroquine sulfate and azithromycin; and 16 served as controls. On Day 6 of the trial, 14 of the 16 control patients still tested positive for the virus. Patients receiving hydroxychloroquine fared markedly better, with only six of 14 testing positive on Day 6. Most encouraging, though, all six patients treated with a combination of hydroxychloroquine and azithromycin were found to be rid of the virus. Several prominent French doctors cautioned that the results would have to be confirmed and warned of possible side effects. The French health minister deemed the trial promising but called for more testing. Raoult had already begun assembling data for a larger study, but he dismissed the need for anything particularly vast or lengthy. Like other critics of the R.C.T., he likes to point out that a number of self-evidently useful developments in the realm of human health have never been validated by such rigorous tests. This observation has come to be known as the parachute paradigm: We tend to accept the claim that parachutes reduce injury among people who leap from airplanes, but this effect has never been proved in a randomized study that compares an experimental parachute group to an unlucky parachuteless control. “It’s like Didier says,” Drancourt told me. “If you don’t have something that’s visible in 10 patients, or 30, it’s useless. It’s not of any consequence.” An effective treatment for a potentially lethal infectious disease will be visible to the naked eye.
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On March 16, a Long Island attorney and blockchain enthusiast named Gregory Rigano appeared on Laura Ingraham’s nightly show on Fox News, “The Ingraham Angle.” Ingraham introduced the segment by asking: “What if there’s already a cheap and widely available medication, that’s on the market, to treat the virus? Well, according to a new study, there is such a drug. It’s called chloroquine.” Rigano, who at the time was falsely presenting himself as an adviser to Stanford Medical School, had recently self-published an acclamatory report on the potential of chloroquine, “An Effective Treatment for Coronavirus (Covid-19),” as a Google Doc formatted to resemble a scientific publication. It had begun to circulate in right-wing media and also in Silicon Valley; Elon Musk tweeted a link to it. Raoult saw it and noticed the attention it was receiving online. Another researcher might have found this sort of publication irresponsible and dangerous. Raoult began corresponding with Rigano and his co-author, James Todaro, an ophthalmologist and Bitcoin investor. Raoult authorized them to share his results before they had been published. On air, Rigano announced that a researcher in the south of France, “one of the most eminent infectious-disease specialists in the whole world,” was about to publish the results of a major clinical study. “Within a matter of six days, the patients taking hydroxychloroquine tested negative for coronavirus, for Covid-19,” Rigano said. (He made no mention of azithromycin.) “We have a strong reason to believe that a preventative dose of hydroxychloroquine is going to prevent the virus from attaching to the body, and just get rid of it completely,” he added. “That’s a game changer,” Ingraham said. In the coming days, Ingraham questioned both Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases and a member of President Trump’s pandemic task force, and Alex M. Azar II, the secretary of health and human services, about the drug. Sean Hannity began promoting it as a cure for Covid-19. “Let’s put it this way,” he said on his radio show. “If I had it — personally, I am speaking only for Sean Hannity — I would be all over this.” Rigano appeared on Tucker Carlson’s show and claimed that Raoult’s study had shown hydroxychloroquine to have a “100 percent cure rate against coronavirus.” According to Todaro, Raoult had sent him a copy of his study and allowed him to post it on Twitter that day, two days before the preprint release. “I suspect he gave us permission because he knew it was the fastest way to disseminate the trial results,” Todaro told me. (Rigano did not respond to requests for comment.) Later, Raoult himself appeared on “Dr. Oz,” the talk show hosted by the celebrity doctor Mehmet Oz, a frequent Fox News guest who has promoted hydroxychloroquine. “I believe that ideas and theories are epidemic,” Raoult once wrote. “When they’re good, they take root.” Trump began hyping hydroxychloroquine on March 19, at a White House news conference with his coronavirus task force. “I think it’s going to be very exciting,” Trump said. “I think it could be a game changer and maybe not. And maybe not. But I think it could be, based on what I see, it could be a game changer. Very powerful.” He suggested, inaccurately, that the F.D.A. had approved the drug for use against Covid-19. He made no mention of azithromycin. Commissioner Stephen M. Hahn of the F.D.A. gently corrected him later and said that a large clinical trial would be the appropriate way to evaluate the therapeutic value of the drug. Still, because chloroquine and hydroxychloroquine are available for use in other conditions, doctors were able to provide Covid-19 patients with “off-label” treatment if they believed it would provide a benefit. Shortages of the drugs were reported beginning in mid-March. The F.D.A., under what appears to have been strong pressure from the Trump administration, issued an emergency-use authorization for chloroquine phosphate and hydroxychloroquine sulfate, giving doctors access to tens of millions of doses of the drugs from the Strategic National Stockpile. Unusually, the C.D.C., at what was reportedly Trump’s direct urging, issued Covid-19 prescription guidelines for the drugs based upon unattributed clinical anecdotes. (The guidelines were later withdrawn.) A top government biomedical official was removed from his post, he has claimed, for having resisted political pressure to fund “potentially dangerous drugs,” including hydroxychloroquine. There is much about Raoult that might make him, and by extension his proposed treatment, appealing to a man like Trump. He is an iconoclast with funny hair; he thinks almost everyone else is stupid, especially those who are typically regarded as smart; he is beloved by the angry and conspiracy-minded; his self-congratulation is more or less unceasing. Raoult and I spoke several days after the emergency-use authorization was signed. He said he hadn’t heard about it and seemed surprised, but he also said that Trump had impressed him with his intuition on hydroxychloroquine. “He’s not so dumb,” he said, laughing. Raoult classified Trump’s psychology as that of an “entrepreneur,” by way of contrast with that of a “politician.” “Entrepreneurs are people who know how to decide, who know how to take risks,” he said. “And at a certain point, to decide is to take a risk. Every decision is a risk.” The French waited far too long, in his estimation, to approve the use of hydroxychloroquine in Covid-19 patients. The authorization came only after Raoult announced in the press that he would continue, “in accordance with the Hippocratic oath” and effectively in defiance of the government, to treat patients with his combination therapy. “I’m convinced that in the end, everyone will be using this treatment,” Raoult told Le Parisien. “It’s just a matter of time before people agree to eat their hats.”
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The dynamics of a crisis are not especially conducive to reliable science. In October 1985, in the terrible early years of the AIDS epidemic, a group of French doctors, joined by the French minister of social affairs, held a news conference to announce to the world that they had discovered what looked like a cure. The drug was cyclosporine, an inexpensive immunosuppressant that had until then been used in organ transplants to prevent the rejection of new tissue. In AIDS patients, cyclosporine had the paradoxical effect of increasing white-blood-cell counts; patients underwent a “spectacular improvement,” one researcher said. The announcement was based upon results from only two patients, however, and these patients had begun treatment only one week earlier. The scientists were widely criticized at the time for flouting the norms of biomedical research to report such limited data. “Given the strength of our hypotheses,” they responded, “we believe that, ethically, we could not continue to keep our results a secret just to respect the usual laws of scientific conduct.” “Like Raoult, they felt very strongly about what they said,” said Jean-Michel Molina, who directs the infectious-disease departments at two public hospitals in Paris. “They felt that they had found a cure.” Shortly after the announcement, one of the two patients died, and it was revealed that a third patient had died before the news conference; he had been excluded from the reported results because his case was considered too grave to reverse. Within weeks, the remaining patient’s white-blood-cell count had fallen to its previous level. Experimentation with cyclosporine soon stopped. Like many doctors, Molina viewed Raoult’s study with skepticism, but he was also curious to see if his proposed treatment regimen might in fact work. He tested hydroxychloroquine and azithromycin in 11 of his own patients. “We had severe patients, and we wanted to try something,” Molina told me. Within five days, one had died, and two others had been transferred out of his service to intensive care. In another patient, the treatment was suspended after the onset of cardiac issues, a known side effect of the drugs. Eight of the 10 surviving patients still tested positive for SARS-CoV-2 at the conclusion of the study period. Raoult’s data had come from patients with mild or early cases of the disease, when viral loads are lower, and I asked Molina if his patients had not been too sick to benefit from the treatment. “If there is antiviral activity, you should be able to see it,” he said. “You know, you may say, ‘It’s too late, you’re not going to see the clinical benefit.’ But at least you should see the antiviral activity. If it’s an antiviral.” Raoult’s study had measured only viral load. It offered no data on clinical outcomes, and it was not clear if the patients’ actual symptoms had improved or indeed whether the patients lived or died. At the outset, 26 patients were assigned to receive hydroxychloroquine, six more than the 20 who appeared in the final results. The six additional patients had been “lost in follow-up,” the authors wrote, “because of early cessation of treatment.” The reasons given were concerning. One patient stopped taking the drug after developing nausea. Three patients had to be transferred out of the institute to intensive care. One patient died. (Another patient elected to leave the hospital before the end of the treatment cycle.) “So four of the 26 treated patients were actually not recovering at all,” noted Elisabeth Bik, a scientific consultant who wrote a widely circulated blog post on Raoult’s study. She paraphrased the sarcasm circulating on Twitter: “My results always look amazing if I leave out the patients who died.” The report was also riddled with discrepancies and apparent errors. Its selection criteria called for participants above the age of 12, but three of the control subjects were younger than this. The control patients were drawn not only from the IHU but also from hospitals in two other cities, where the standard of care and the testing protocols may have differed. Fourteen of 16 control patients were reported to have tested positive for the virus at the conclusion of the study on Day 6. In fact, according to the initial report, for five of those 14, no data was collected that day. One of the six patients who received hydroxychloroquine and azithromycin and was recorded as “virologically cured” at Day 6 was found, in the end, to be carrying the virus two days later. This apparent sloppiness was unsurprising to many of those who have tracked Raoult’s work in the past. A prominent French microbiologist told me that, in terms of publication, Raoult’s reputation among scientists has been “long gone” for some time. “In private,” the researcher wrote to me, “everybody agrees on the low reliability/reproducibility of most of the papers coming out of his lab.” (He asked to speak anonymously so as not to anger Raoult, whom he knows.) In 2018, after damning evaluations, Raoult’s principal laboratory groups were stripped of their association with two of France’s top public research institutions. Raoult was found to have produced an extraordinary number of publications but few of great quality. “It’s very easy to publish [expletive] when you know how publishing works,” said Karine Lacombe, a professor of medicine in Paris who has recently been among Raoult’s more outspoken critics. Beyond its apparent errors and omissions, the study’s design — its small size, its flawed control, the unrandomized assignment of patients to the treatment and control groups — was widely viewed to render its results meaningless. Fauci repeatedly called its results “anecdotal”; the biostatistician who analyzed the paper on behalf of the French government’s coronavirus advisory committee wrote that it was “impossible to interpret the effect described therein as being attributable to treatment with hydroxychloroquine.” Large, well-controlled randomized trials are by no means the only way to arrive at useful scientific insights. Their utility is that they enhance statistical signals such that, amid the noise of human variability and random chance, even the faint effect of some new treatment can be detected. The prime statistical hurdle that any proposed treatment for Covid-19 will have to overcome — one that is delicate for even Raoult’s critics to make note of, amid the sorrow and fear of this pandemic — is that the signal is likely to be very faint, because the disease is, in the end, rarely fatal. Nearly everyone survives; an effective treatment will save the life of the one or so patients in every hundred who would not have lived without it. “You know, people sometimes say, ‘If the patient gets better, that’s because of the drug, and if they get worse, it’s because of the virus,’” Molina told me. “And of course that’s not true. And that’s why you need to do a well-conducted, randomized, placebo-controlled study if you want to show anything.” It is possible that hydroxychloroquine and azithromycin are an effective treatment for Covid-19. But Raoult’s study showed, at best, that 20 people who would almost certainly have survived without any treatment at all also survived for six days while taking the drugs Raoult prescribed. “If you haven’t done this stuff, you can look at a report of people responding to such a treatment and figure that the answer is here — right here, and anyone who doesn’t see it must have some ulterior motives,” Derek Lowe, a longtime pharmaceutical researcher, wrote for Science Translational Medicine last month. “But that’s not how it works.” He went on: “Alzheimer’s drugs, obesity drugs, cardiovascular drugs, osteoporosis drugs: Over and over, there have been what looked like positive results that evaporated on closer inspection. After you’ve experienced this a few times, you take the lesson to heart that the only way to be sure about these things is to run sufficiently powered controlled trials. No shortcuts, no gut feelings — just data.”
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“I’ve invented 10 or so treatments in my life,” Raoult told me. “Half of them are prescribed all over the world. I’ve never done a double-blind study in my life, never. Never! Never done anything randomized, either.” He noted, with some satisfaction, that the criticism was more intense than he had anticipated. “Honestly, I couldn’t have imagined that it would set off a frenzy like this,” he said, leaning back in his office chair and gesturing at the storm he had created in the world outside. “When you tell the story, it’s extremely straightforward, no? It’s subject, verb, complement: You detect a disease; there’s a drug that’s cheap, whose safety we know all about because there’s two billion people who take it; we prescribe it, and it changes what it changes. It might not be a miracle product, but it’s better than doing nothing, no?” His subordinates defended the study as the best work they could do under the circumstances and the fastest way to alert the world to the possibility of a treatment. The use of off-site controls was not ideal, for example, but it was the only option if they wanted to move fast. “Of course it’s a methodological weakness,” Gautret, the first author, told me. “But we made do with what we had.” As for the six patients “lost in follow-up,” even if it had been possible to collect data from them, it would have been nonsensical to include most of them in their report. Their aim was “to treat people in the early stages of the disease, when it’s not yet serious,” Gautret said. “We know that in acute viral diseases, the earlier you treat, the better your chances of success. It makes no sense to include people who are at the edge of death in the study. We’re not claiming to be able to treat people who are nearly dead.” Another small study, in 80 patients, likewise showed better results for patients with mild forms of the disease. In Marseille, Raoult told me he would be releasing a third study, this one of 1,000 patients, the following week. Initial results were published in mid-April. Raoult had treated 1,061 patients with a combination of hydroxychloroquine and azithromycin. The study was neither controlled nor randomized; at the time of the preprint release, eight patients had died, and five remained hospitalized, while 46 in total experienced a “poor clinical outcome.” The findings were summarized as “98.7 percent of patients cured so far.” The therapy constituted a “safe and efficient treatment for Covid-19,” the authors wrote. Other scientists disagreed with this characterization of the results. “The cure rate is almost identical to what’s been described about the natural course of the disease,” the virologist Christine Rouzioux told French radio. Lacombe called Raoult’s conclusions “magical thinking,” adding: “I very honestly think he hasn’t shown anything at all.” It was soon discovered, too, that the second and third studies had been conducted without approval from a state ethics board. In an initial version of the third paper, Raoult wrote that he had conducted a “retrospective study on a cohort of patients receiving standard treatment following a research protocol previously registered.” He provided a reference to the protocol that had been approved for the first trial. But that protocol included hydroxychloroquine alone and not azithromycin; Raoult never received approval to systematically test a combination of the drugs. The French medical regulatory agency, the A.N.S.M., sent Raoult a request for evidence of the second study’s “legal status” in mid-April. Later in the month, the French Medical Council issued a statement, widely assumed to be directed at Raoult, reminding its members that “the endangerment of patients” by exposure to “treatments that have not been scientifically validated” could be cause for immediate suspension. Raoult responded on Twitter, where he now has a half million followers, that the council’s threat was “obviously” not applicable to his case. In a statement on the A.N.S.M.’s inquiry, the IHU insisted that the study did not involve experimentation because “no procedure beyond the standard of care” — which, at the IHU, was hydroxychloroquine and azithromycin — had been employed. Raoult had by then begun to lose his composure. He accused Lacombe of being a shill for the pharmaceutical industry; his fans sent her death threats. On Twitter, he called Bik, the consultant who wrote critically about the first study, a “witch hunter” and called a study that she tweeted — one of several published in April and May that seemed to suggest that Raoult’s treatment regimen was ineffectual or even harmful — “fake news.” The authors of another such study were accused of “scientific fraud.” “My detractors are children!” Raoult told an interviewer. The world’s attention has drifted to new studies of other drugs; Raoult has taken to attacking those studies for their methodological weaknesses. The results of his initial trial have yet to be replicated. “I think what he secretly hopes is that no one will ever be able to show anything,” Molina told me. “That all the trials conducted on hydroxychloroquine will not be able to even reach a conclusion of no efficacy.” In recent weeks, Raoult has in fact tempered his claims about the virtues of his treatment regimen. The published, peer-reviewed version of the final study noted that another two patients had died, bringing the total to 10. Where the earlier version called the drugs “safe and efficient,” they were now described merely as “safe.” He has shown flickers of what appears to be doubt. In one interview, Raoult quoted Camus, from the fatalistic coda of “The Stranger,” hoping that “on the day of my execution there should be a huge crowd of spectators, and that they should greet me with howls of hatred.” “I don’t trust popularity,” he told the interviewer. “When too many people think you’re wonderful, you should start to wonder.” His initial YouTube video, “Coronavirus: Game Over!” has also been renamed. The new language is more measured, and in place of the exclamation point there now stands a question mark.



Scientists Question Validity of Major Hydroxychloroquine Study
New York Times

URL: https://www.nytimes.com/2020/05/29/heal ... quine.html
Category: Politics
Published: May 29, 2020

Description: More than 100 scientists and clinicians have questioned the authenticity of a massive hospital database that was the basis for an influential study published last week that concluded that treating people who have Covid-19 with chloroquine and hydroxychloroquine did not help and might have increased the risk of abnormal heart rhythms and death. In an open letter to The Lancet’s editor, Richard Horton, and the paper’s authors, the scientists asked the journal to provide details about the provenance of the data and called for the study to be independently validated by the World Health Organization or another institution. A spokeswoman for Dr. Mandeep R. Mehra, the Harvard professor who was the paper’s lead author, said on Friday that the study’s authors had asked for an independent academic review and audit of their work. Use of the malaria drugs chloroquine and hydroxychloroquine to prevent and treat Covid-19 has been a focus of intense public attention. President Trump has promoted the promise of hydroxychloroquine, despite the absence of gold-standard evidence from randomized clinical trials to prove its effectiveness, and recently said he was taking it himself in hopes of preventing coronavirus infection. The scientists’ challenges to The Lancet paper come at a time of increasing debate about the risks of the rush to publish new medical findings about Covid-19. The paper, published May 22, included data on tens of thousands of patients hospitalized through April 14, meaning that the authors analyzed the trove of data, wrote the paper and went through the journal’s peer review of its findings in just over five weeks, much faster than usual. The experts who wrote The Lancet also criticized the study’s methodology and the authors’ refusal to identify any of the hospitals that contributed patient data, or to name the countries where they were located. The company that owns the database is Surgisphere, based in Chicago.

Bill-Gates-Africa.jpg

“Data from Africa indicate that nearly 25 percent of all Covid-19 cases and 40 percent of all deaths in the continent occurred in Surgisphere-associated hospitals which had sophisticated electronic patient data recording,” the scientists wrote. “Both the numbers of cases and deaths, and the detailed data collection, seem unlikely.” Another of the critics’ concerns was that the data about Covid-19 cases in Australia was incompatible with government reports and included “more in-hospital deaths than had occurred in the entire country during the study period.” A spokeswoman for The Lancet, Emily Head, said in an email that the journal had received numerous inquiries about the paper and had referred the questions to the authors. “We will provide further updates as necessary,” she said. “The Lancet encourages scientific debate and will publish responses to the study, along with a response from the authors, in the journal in due course.” On Saturday, the journal made two corrections to the study but said, “There have been no changes to the findings of the paper.” Dr. Sapan S. Desai, the owner and founder of Surgisphere and one of the paper’s authors, vigorously defended the findings and the authenticity and validity of the company’s database. He said official counts of coronavirus cases and deaths often lagged behind actual cases, which might explain some discrepancies. The paper’s authors said they had analyzed data gathered from 671 hospitals on six continents that shared granular medical information about nearly 15,000 patients who had received the drugs and 81,000 who had not, while shielding their identities. “What the world has to understand is that this is registry-based data,” Dr. Desai said. “We have no control over the source of the information. All we can do is report the data that is given to us.” Another group of researchers from the Barcelona Institute for Global Health also raised questions about the Surgisphere database, both with the authors and editors of The Lancet. Scientists who wrote and signed the letter criticizing the study included clinicians, researchers, statisticians and ethicists from academic medical centers, including Harvard’s T.H. Chan School of Public Health, the University of Pennsylvania, Vanderbilt University and Duke University. One of the signatories, Dr. Adrian Hernandez, who heads the Duke Clinical Research Institute, said the paper contained many troubling anomalies, “but the biggest thing that raised a red flag was that here was such a large database across more than 600 hospitals, and no one had really known about its existence. That was quite remarkable.” Like several other signatories of the letter, Dr. Hernandez is involved in a clinical trial of hydroxychloroquine to see if it can protect health care workers from infection. Allen Cheng, a professor of infectious diseases at Monash University in Melbourne, Australia, who also signed the letter, said in an email that the individual hospitals included in the database should be identified. “Ideally, the database should be made public, but if that isn’t possible, it should at least be independently reviewed and an audit performed,” he said. Surgisphere’s data was also the basis of a study of coronavirus patients published in The New England Journal of Medicine this month by some of the same authors, including Dr. Desai and Harvard’s Dr. Mehra, as well as for two versions of an article on the use of an antimicrobial drug to treat Covid-19 that were not published in an established medical journal. Jennifer Zeis, a spokeswoman for The New England Journal of Medicine, said by email that the journal was aware of the questions that had been raised and was looking into them. Dr. Mehra issued a statement Friday, saying that the paper’s authors “leveraged the data available through Surgisphere to provide observational guidance to inform the care of hospitalized Covid-19 patients” because the results of randomized clinical trials would not be available for some time. Other observational studies had previously reported possible harms associated with the malaria drugs, and the Food and Drug Administration had issued a safety warning about their use. After the Lancet paper was published, the World Health Organization and other organizations suspended clinical trials of the drugs.
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Fauci knew about HCQ in 2005 -- nobody needed to die

Postby smix » Tue May 19, 2020 5:30 pm

Fauci knew about HCQ in 2005 -- nobody needed to die
One News Now

URL: https://onenewsnow.com/perspectives/bry ... ded-to-die
Category: Politics
Published: April 27, 2020

Description: Dr. Anthony Fauci, whose “expert” advice to President Trump has resulted in the complete shutdown of the greatest economic engine in world history, has known since 2005 that chloroquine is an effective inhibitor of coronaviruses. How did he know this? Because of research done by the National Institutes of Health, of which he is the director. In connection with the SARS outbreak - caused by a coronavirus dubbed SARS- CoV - the NIH researched chloroquine and concluded that it was effective at stopping the SARS coronavirus in its tracks. The COVID-19 bug is likewise a coronavirus, labeled SARS-CoV-2. While not exactly the same virus as SARS-CoV-1, it is genetically related to it, and shares 79% of its genome, as the name SARS-CoV-2 implies. They both use the same host cell receptor, which is what viruses use to gain entry to the cell and infect the victim. The Virology Journal - the official publication of Dr. Fauci’s National Institutes of Health - published what is now a blockbuster article on August 22, 2005, under the heading - get ready for this - “Chloroquine is a potent inhibitor of SARS coronavirus infection and spread.” (Emphasis mine throughout.) Write the researchers, “We report...that chloroquine has strong antiviral effects on SARS-CoV infection of primate cells. These inhibitory effects are observed when the cells are treated with the drug either before or after exposure to the virus, suggesting both prophylactic and therapeutic advantage.” This means, of course, that Dr. Fauci has known for 15 years that chloroquine and it’s even milder derivative hydroxychloroquine (HCQ) will not only treat a current case of coronavirus (“therapeutic”) but prevent future cases (“prophylactic”). So HCQ functions as both a cure and a vaccine. In other words, it’s a wonder drug for coronavirus. Said Dr. Fauci’s NIH in 2005, “concentrations of 10 μM completely abolished SARS-CoV infection.” Fauci’s researchers add, “chloroquine can effectively reduce the establishment of infection and spread of SARS-CoV.” Dr. Didier Raoult, the Anthony Fauci of France, had such spectacular success using HCQ to treat victims of SARS-CoV-2 that he said way back on February 25 that “it’s game over” for coronavirus. He and a team of researchers reported that the use of HCQ administered with both azithromycin and zinc cured 79 of 80 patients with only “rare and minor” adverse events. “In conclusion,” these researchers write, “we confirm the efficacy of hydroxychloroquine associated with azithromycin in the treatment of COVID-19 and its potential effectiveness in the early impairment of contagiousness.” The highly-publicized VA study that purported to show HCQ was ineffective showed nothing of the sort. HCQ wasn’t administered until the patients were virtually on their deathbeds when research indicates it should be prescribed as soon as symptoms are apparent. Plus, HCQ was administered without azithromycin and zinc, which form the cocktail that makes it supremely effective. At-risk individuals need to receive the HCQ cocktail at the first sign of symptoms. But Governor Andrew Cuomo banned the use of HCQ in the entire state of New York on March 6, the Democrat governors of Nevada and Michigan soon followed suit, and by March 28 the whole country was under incarceration-in-place fatwas. Nothing happened with regard to the use of HCQ in the U.S. until March 20, when President Trump put his foot down and insisted that the FDA consider authorizing HCQ for off-label use to treat SARS-CoV-2. On March 23, Dr. Vladimir Zelenko reported that he had treated around 500 coronavirus patients with HCQ and had seen an astonishing 100% success rate. That’s not the “anecdotal” evidence Dr. Fauci sneers at, but actual results with real patients in clinical settings. “Since last Thursday, my team has treated approximately 350 patients in Kiryas Joel and another 150 patients in other areas of New York with the above regimen. Of this group and the information provided to me by affiliated medical teams, we have had ZERO deaths, ZERO hospitalizations, and ZERO intubations. In addition, I have not heard of any negative side effects other than approximately 10% of patients with temporary nausea and diarrhea.” Said Dr. Zelenko:
"If you scale this nationally, the economy will rebound much quicker. The country will open again. And let me tell you a very important point. This treatment costs about $20. That’s very important because you can scale that nationally. If every treatment costs $20,000, that’s not so good. All I’m doing is repurposing old, available drugs which we know their safety profiles, and using them in a unique combination in an outpatient setting."

The questions are disturbing to a spectacular degree. If Dr. Fauci has known since 2005 of the effectiveness of HCQ, why hasn’t it been administered immediately after people show symptoms, as Dr. Zelenko has done? Maybe then nobody would have died and nobody would have been incarcerated in place except the sick, which is who a quarantine is for in the first place. To paraphrase Jesus, it’s not the symptom-free who need HCQ but the sick. And they need it at the first sign of symptoms. While the regressive health care establishment wants the HCQ cocktail to only be administered late in the course of the infection, from a medical standpoint, this is stupid. Said one doctor, “As a physician, this baffles me. I can’t think of a single infectious condition — bacterial, fungal, or viral — where the best medical treatment is to delay the use of an anti-bacterial, anti-fungal, or anti-viral until the infection is far advanced.” So why has Dr. Fauci minimized and dismissed HCQ at every turn instead of pushing this thing from jump street? He didn’t even launch clinical trials of HCQ until April 9, by which time 33,000 people had died. This may be why: “Chloroquine, a relatively safe, effective and cheap drug used for treating many human diseases...is effective in inhibiting the infection and spread of SARS CoV.” That’s the problem. It is safe, inexpensive, and it works - in other words, there’s nothing sexy or avant-garde about HCQ. It’s been around since 1934. Given human nature, it’s possible, even likely, that those who are chasing the unicorn of a coronavirus vaccine are doing so for reasons other than human health. I can’t see into anybody’s heart, and can’t presume to know their motives, but on the other hand, human nature recognizes that there’s no glory in pushing HCQ, and nobody is going to get anything named for him in the history books. The polio vaccine was developed by Jonas Salk in 1954, and it is still known as the “Salk vaccine.” There will be no “Fauci vaccine” if HCQ is the answer to the problem. So while Dr. Fauci is tut-tutting and pooh-poohing HCQ, Dr. Raoult and Dr. Zelensky are out there saving lives at $20 a pop. Maybe we should spend more time listening to them than the wizards-of-smart bureaucrats the Talking Snake Media fawns over.

nih-workshop.jpg

Dr. Fauci is regarded by the Talking Snake Media as the Oracle at Delphi. The entire nation hangs on his every word. But if nobody is dying and nobody is locked down, his 15 minutes of fame fades to zero. Very few people are not going to be influenced by that prospect, especially when it’s easy to keep the attention of the public by continuing to feed the panic. It should not be overlooked that there is no money in HCQ for Big Pharma since HCQ is a generic that can be manufactured so cheaply there is little profit margin in it. On the other hand, the payday for a vaccine will literally be off-the-charts. Who knows what kind of behind-the-scenes pressure is being put on Fauci and others in the health care establishment? There is a monstrous reputational risk for those who will be found to have dismissively waved off a treatment that could have been used from the very beginning, even back on February 15 when Dr. Fauci said that the risk from Coronavirus was “minuscule.” How many lives could have been saved if the heads of our multi-billion dollar health care bureaucracy had been advocating for HCQ treatment from day one? We’ll never know. Instead, their advice has been dangerous and deadly in every sense of that word. Someday - maybe even today - we will be able to identify the individuals who had the knowledge and expertise to make a global difference, but turned up their noses at the solution when it could have made all the difference in the world.
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