Key Words: hydroxychloroquine, azithromycin, antiviral, evidence
Abstract
During the current COVID-19 epidemic, most of the evidence is collected by treating physicians, most of whom do not report their results in peer reviewed journals. Hence, there appears to be an especially broad gap between field experience and academic coverage of hydroxychloroquine-based COVID-19 treatments. The objective of this study is to bring field evidence into the academic literature.
Four relevant, non-academic surveys of physicians, in the US and globally, have been identified and checked for quality, statistical significance, coverage, and conflicts of interest. To avoid uninformed and unduly influenced opinions, only surveys conducted from April 4 to April 19 have been considered. These surveys were answered by thousands of physicians, who treated tens of thousands of COVID-19 patients.
The results: 85% of doctors said that hydroxychloroquine is at least somewhat effective for COVID-19. Hydroxychloroquine was the most utilized treatment for COVID-19 patients. 35%-40% of the doctors using the drug called it very effective or extremely effective against COVID-19. 65% of doctors said they would prescribe hydroxychloroquine for COVID-19 to their family members.
The author declares no competing interest.
No funding was provided for this work.
All relevant ethical guidelines have been followed.
Introduction
The largest body of knowledge of COVID-19 treatments is collected by practicing physicians, outside of research settings, and not reported in peer reviewed publications. The objective of this systematic review is to capture some of this clinical experience and bring it into the academic literature. The scope is limited to hydroxychloroquine-based treatments, administered in the early (viral) stages of COVID-19.
The most effective and popular COVID-19 treatment regimen, combining hydroxychloroquine with azithromycin, was introduced by Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, directed by Didier Raoult. The HCQ based treatment was presented at a March 16, 2020 conference (Raoult, 2020), and published a few days later as (Gautret, et al., 2020). It became instantly popular among physicians on March 20-21.
Many doctors and hospitals used this treatment from March 20 to March 27. The treatment’s effects were observed and discussed with colleagues, from March 27 to April 4. Thus, starting around April 4, doctors who used or observed the use of any HCQ-based treatment were able to provide eyewitness testimonies. Many other doctors were able to give their expert opinions, based on the experiences of their colleagues and their professional knowledge. On April 20, the NIH COVID-19 Panel published guidelines that were adverse to HCQ treatment (The National Institutes of Health COVID-19 Treatment Guidelines Panel , 2020). On April 24, the FDA issued a warning (The FDA, 2020) concerning the drug’s safety. These events might have prejudiced some doctors against HCQ. The time frame chosen for this systematic review, April 4 to April 19, is selected to ensure that physicians had sufficient experience with HCQ but had not yet been prejudiced by external events.
Explanation of Methods
A physician’s answers to questions regarding the treatment s/he has used can be considered direct evidence. Corresponding statistics computed from the responses of N physicians, treating on average M patients, should have equal power and higher resilience than results of a randomized clinical trial conducted on N*M patients, in the absence of a systematic bias.
A physician’s choice of a certain treatment over another, indicates that the chosen treatment is considered more effective. A physician’s decision to implement a certain treatment rather than no treatment proves that the treatment’s effectiveness/risk profile is considered high enough. This can be considered indirect evidence.
A physician’s opinion about a treatment which he or she did not directly use in practice, but learned about from other physicians, can be considered an expert opinion.
Well implemented surveys can capture much of this evidence and expert opinions.
Methods
Surveys or polls of physicians were sought, using multiple search engines (DuckDuckGo, Bing, Google, Yandex), searching for ‘physician survey hydroxychloroquine’, ‘doctors survey hydroxychloroquine’, and similar combinations of keywords; no quotes; not limited by dates. The search was repeated many times, excluding previously found items.
Surveys or polls from three companies were found. Each of the three survey companies were researched and confirmed as reputable. A list of all relevant surveys and polls, done by these three companies, in the selected time frame, was compiled. This yielded four surveys from three different companies: Sermo (two surveys), InCrowd, and Jackson Coker. Sermo’s surveys appeared to be most professional and informative. No strong competing interests, that may have any bearing on the surveys, were found in any of the three companies.
Drugs used for other effects, other than antiviral, have been excluded from this review for the following reasons. High dose steroids are used during a cytokine storm. Acetaminophen, Ibuprofen, and Herbal remedies are used as symptomatic treatment. Vitamin D is not considered an antiviral treatment or an essential part of one. Bronchodilators are bronchodilators.
Results
Although the surveys posed different questions to different audiences, the results were congruent. Because CQ is hardly used in practice, CQ and HCQ are both referred to as HCQ.
Table 1. Summary of results
| J C | Sermo W3 | Sermo W4 | InCrowd | |
| Polling Date | April 4-7 | April 6-9 | April 13-15 | April 14-15 |
| Publication Date | April 8 | April 15 | April 23 | April 21 |
| Location | USA | Global | Global | USA |
| # doctors | 1271 | 4016 | 5500 | 203 |
| Recommended HCQ | 65% (1) | n/a | n/a | n/a |
| # COVID-19 treaters | n/a | 1337 | 1376 (3) | 203 |
| Used HCQ / HCQ+AZ | n/a | 50% | 53% | n/a |
| % HCQ users rating VEE (4) | n/a | 40% | 35% | n/a |
| Reported HCQ effective | n/a | 85% (5) | n/a | n/a |
| Would give to patients’ % | n/a | n/a | n/a | 30% (2) |
| Remarks | HCQ shortages |
- Would give HCQ to their family
- Would prescribe HCQ / HCQ+AZ to this percentage of their COVID-19 patients, on average. 30% is quite a high number, because most COVID-19 patients probably need no treatment, especially the patients of the surveyed physicians, about a third of whom are pediatricians. The numbers for plasma and Remdesivir are 21% and 16%, respectively.
- This number includes physicians who used HCQ in outpatient and hospital ex/ICU settings.
- VEE = Very or Extremely Effective (4 or 5 on the scale 0 – 5)
- 2 or higher on the scale 0 – 5
Notice that except for Jackson Coker, surveys’ results were published about a week after they had been conducted, so their results could not influence each other.
Sermo Week 3
(Sermo W3, 2020)
Survey Period: April 6-9
Published on April 15
Country: Global
N = 4016 – the total number of physicians surveyed, including those who have not treated COVID-19
Effectiveness:
The top treatments used or seen to be used by physicians and reported as very or extremely effective among COVID-19 treaters include:
Table 2. VEE Treatments
Hydroxychloroquine n=875 (40%)
Plasma from recovered patients n=363 (46%)
Percentage of physicians to report that HCQ/CQ is at least partially effective (scoring 2 or higher on the scale 0 – 5) against COVID-19:
Table 3. Physicians rating HCQ/CQ at least partially effective
Global: 85%
US: 81%
Italy: 94%
Spain: 91%
China: 88%
This data suggests that physicians in countries with more than average COVID-19 experience appreciate HCQ more than physicians in countries with less than average experience.
Usage
N = 1337 (the number of COVID-19 treaters out of the 4016 physicians surveyed)
SCREENING: COVID-19 treaters
Table 4. Medications physicians have used to treat COVID-19 patients
| Drug | % |
| Azithromycin or similar antibiotics | 58% |
| Hydroxychloroquine or Chloroquine | 50% |
| Anti-HIV drugs (e.g. Lopinavir plus Ritonavir) | 23% |
| Drugs used to treat flu (e.g., Oseltamivir) | 22% |
| None | 16% |
Treatments used by less than 10% COVID-19 treaters are excluded here.
The survey did not include inquiries about drug combinations. However, these numbers and well-known information from other sources suggest that in most cases when HCQ or CQ was prescribed, it was in combination with Azithromycin (AZ).
There were important differences in the perceived effectiveness of HCQ in the US as compared to the rest of the world. In the US, HCQ/CQ was used by 39% of COVID-19 treaters, compared to 75% and 83% of practitioners in Spain and Italy, respectively. Of note, Spain and Italy broke the rapid rise and started a rapid decrease in death rates around April 2-3 (Our World in Data, 2020).
Sermo Week 4
(Sermo W4, 2020)
Survey Period: April 13-15
Published on April 23
Country: Global
N = 1376 (after screening; 5,500 doctors were surveyed)
SCREENING: COVID-19 treaters
Effectiveness
N = 1376 (636 Non-Hospital physicians / 1045 Hospital physicians; except ICU only)
Q11. Effectiveness on patients outside hospital setting (Mild/Moderate): For patients you treat outside the hospital (mild/moderate in community setting), rate the efficacy of medications you have used to treat COVID-19.
NET: Very/Extremely Effective (Don’t Know Excluded)
Table 5. VEE Treatments
| Non-Hospital | Hospital ex/ICU | |
| n=636 (Q8) | n=1,045 (Q9) | |
| Hydroxychloroquine | 88 (38%) | 196 (31%) |
| Azithromycin | 79 (23%) | 126 (19%) |
| Vitamin C | 39 (26%) | 36 (19%) |
| Drugs to treat flu | 31 (24%) | 66 (26%) |
| Plasma | 23 (68%) | 63 (61%) |
| Zinc | 20 (25%) | 19 (20%) |
| Anti-HIV drugs | 19 (27%) | 71 (22%) |
| Remdesivir | 10 (27%) | 50 (34%) |
Results ordered by the number of physicians who rated the drug Very/Extremely Effective in the more relevant, non-hospital group. (Results are listed only for drugs in Table 6 in the next section) Notice that percentages in parentheses exclude treaters who did not answer the question about each drug’s effectiveness. Effectiveness of HCQ was rated differently in different countries. In the US, it was rated below its rating in the rest of the world.
HCQ / HCQ+AZ is clearly in the league of its own, per number of physicians rating it as “Very or Extremely Effective”.
Usage
N = 1376 (636 / 1045 for Non-Hospital physicians / Hospital physicians, except ICU only)
SCREENING: COVID-19 treaters
Table 6. Share of COVID-19 Treating Physicians Who’ve Used Medication Within Setting
| Non-Hospital | Hospital ex/ICU | Computed Average | |
| n=636 (Q8) | n=1,045 (Q9) | ||
| Azithromycin | 60% | 70% | 65% |
| Hydroxychloroquine | 40% | 66% | 53% |
| Drugs to treat flu | 22% | 25% | 23.5% |
| Anti-HIV drugs | 12% | 32% | 22% |
| Vitamin C | 28% | 21% | 24.5% |
| Zinc | 17% | 11% | 14% |
| Remdesivir | 6% | 16% | 11% |
| Plasma | 6% | 10% | 8% |
Simple averages have been computed to reflect the higher probability that HCQ-based treatment was started early in non-hospital settings compared with hospital settings.
Given the low standalone effectiveness and broad use of AZ, it is likely that in most cases HCQ was used in combination with AZ. The relatively large percentage for physicians using and highly rating Zinc suggests that HCQ+AZ+Zn was used extensively.
Note 1
33% of treaters complained about HCQ shortages. For comparison, only 27% of the treaters complained about ventilator shortages. The number was 48% for Super Treaters (doctors who treated >20 COVID-19 patients) outside of hospital settings. It is reasonable to conclude that HCQ treatment results would have been even better if not for HCQ shortages, causing treatment delays.
Note 2
This survey captures the relevant results of treating about 25,000 – 30,000 COVID-19 patients (Q7).
InCrowd
(InCrowd, 2020)
Survey Period: April 14-15
Published on April 21
N = 203
Country: USA
Specialties: US Primary Care Physicians (61), Pediatricians (59), and Emergency Medicine or Critical Care Physicians (83)
SCREENING: Physicians who have or are currently treating 20 or more patients with flu like symptoms
Q11: For what percentage of your COVID-19 patient population would you prescribe each of the following treatments? If other, please specify.
The offered options are: Acetaminophen, Antibiotics (e.g. azithromycin, etc.), Bronchodilators, Hydroxychloroquine, Plasma (from recovered patients), Ibuprofen, Remdesivir, Antivirals, Chloroquine, Steroids (High Dose), Flu treatments (e.g. Tamiflu, Xofluza), Herbal remedies, Anti-HIV Drugs, Interferon-Beta, Other.
Table 7. Surveyed physicians would prescribe to this % of their COVID-19 patients
| Drug | % |
| “Azithromycin etc.” | 41% |
| Hydroxychloroquine or Chloroquine | 30% |
| Plasma | 21% |
| Remdesivir | 16% |
| Antivirals (non-specific) | 10% |
Flu treatments (e.g. Tamiflu, Xofluza), Anti-HIV Drugs, Interferon-Beta, and Other scored 2%-7% each.
No answers were reported about the combination of drugs, but the numbers suggest that non-pediatric doctors would prescribe HCQ+AZ to ~40% of their COVID-19 patients. Many physicians using HCQ prescribe it only to those deemed at risk, so 30-40% is impressive.
Jackson Coker
(Jackson-Coker, 2020)
Survey Period: April 4-7
Published on April 8
N= 1,271
Country: USA, all 50 states
Reported margin of error is 3% with a 95% confidence level.
SCREENING: None. All physicians who elected to answer the survey, about 1% of the firm’s database of physicians. It was not established whether they treated or did not treat COVID-19 patients. It is likely that there was positive self-selection by doctors who treated COVID-19.
65% said they would prescribe drugs chloroquine or hydroxychloroquine to treat or prevent COVID-19 in a family member. 54% said they would prescribe it early, while another 11% said they would prescribe it if the disease becomes serious. 30% said they would prescribe chloroquine or hydroxychloroquine to a family member prior to the onset of symptoms if they had been exposed to the coronavirus. 11% said they would not use the drug.
73% of physicians practicing solo or with ownership stake in a practice, said they would prescribe HCQ/CQ to a family member. That means that more experienced physicians are more likely to prescribe HCQ. The share drops among critical care, emergency medicine, and hospitalists to 43%, 55%, 54%, respectively.
The lower usage of HCQ by critical care and emergency physicians can be explained by the fact that they are dealing with patients in a later stage of COVID-19, which might be characterized as a different illness, dominated by ADRS and multiple organs damage, rather than by viral infection.
Discussion
Only a small fraction of physicians use plasma, but they highly rate it.
Doctors’ wide-spread use and high recognition of HCQ+AZ treatment against COVID-19 is strong evidence, and, possibly, conclusive proof of the treatment’s safety and effectiveness.
Later Surveys
Sermo’s weekly COVID-19 surveys break the results down by regions, countries, and other useful categories. Sermo continued publishing surveys about doctors’ choices of COVID-19 treatments even after April 19. In May, they reported a decline in the use of CQ/HCQ and a rise in the use of Remdesivir.
InCrowd conducted a similar survey on May 29-31. It also reported a decline in the use of CQ/HCQ and a rise of Remdesivir, possibly for external reasons.
Jackson Coker has conducted no other related surveys.
Remarks
Some doctors started adding Zinc to the HCQ+AZ cocktail, as reported in (Risch, 2020). It is expected that additional experience in treating COVID-19, since the surveyed period, has increased the safety and effectiveness of multiple treatments, including HCQ-based ones.
Conclusions
85% of the globally surveyed physicians recognized HCQ as at least partially effective in treating COVID-19, according to Sermo W3. More than half of the surveyed US physicians would take the drug or give it to family members early or even before onset of symptoms, according to JC.
Aside from the rarely used plasma, HCQ / HCQ+AZ based treatments are preferred by physicians by wide margin over other drugs. HCQ / HCQ+AZ based treatments are the most used, most recommended, and most highly rated by physicians treating COVID-19 at an early stage.
Personal Note
Except for this paragraph, this paper appears here exactly as it was submitted to medrxiv.org on June 30 (MEDRXIV/2020/143800). It was rejected today, on July 4: “We regret to inform you that your manuscript will not be posted. A small number of papers are deemed during screening to be more appropriate for dissemination after peer review at a journal rather than as preprints.“
I felt this might happen when I saw medrxiv’s home page “Supported by Chan Zuckerberg Initiative“. Now, I submit it to an open peer review.
On a side note, speaking of New Paper Demonstrates Strong Efficacy of Hydroxychloroquine. Mortality rate cut in half!
there is an earlier peer-reviewed paper, confirming HCQ+AZ effectiveness:
Jean-Christophe Lagierab, Matthieu Million, Philippe Gautret, Raoult, Didier et al., Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis, June 25, Travel Medicine and Infectious Disease https://www.sciencedirect.com/science/article/pii/S1477893920302817
References
FDA. 2020. FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems. fda.gov. April 24, 2020. [Cited: April 24, 2020.] http://archive.is/xwOAc.
Gautret, Philippe , Lagier, Jean-Christophe and Raoult, Didier et al. 2020. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents. March 20, 2020. https://www.sciencedirect.com/science/article/pii/S0924857920300996.
InCrowd. 2020. Novel Coronavirus COVID-19 Physician Tracking Report. InCrowdNow.com. April 21, 2020. https://incrowdnow.com/wp-content/uploads/2020/04/InCrowd-Novel-Coronavirus-COVID-19-Physician-Tracking-Report-Wave-4.pdf.
Jackson-Coker. 2020. Physicians Poll on COVID-19 Medications. JacksonCoker.com. April 8, 2020. includes https://jacksoncoker.com/about/in-the-news/physician-poll-on-covid-19-chloroquine-and-hydroxychloroquine/. https://jacksoncoker.com/landing-pages/physicians-poll-on-covid-19_medications/.
Our World in Data. 2020. Daily new confirmed COVID-19 deaths per million people, rolling 7d average, Spain & Italy. ourworldindata.com. 2020. [Cited: June 29, 2020.] https://ourworldindata.org/coronavirus-data-explorer?zoomToSelection=true&time=2020-03-09..2020-05-15&deathsMetric=true&dailyFreq=true&perCapita=true&smoothing=7&country=ESP~ITA&pickerMetric=location&pickerSort=asc.
Raoult, Didier. 2020. COVID-19, presentation at GENERAL ASSEMBLY AP-HM CARE AND DIAGNOSIS. mediterranee-infection.com. March 16, 2020. https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-19.pdf.
Risch, A Harvey. 2020. Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis. American Journal of Epidemiology. May 27, 2020. https://doi.org/10.1093/aje/kwaa093.
Sermo W3. 2020. Sermo’s COVID-19 Real Time Barometer Study, Wave 3. Sermo.com. April 15, 2020. includes https://app.sermo.com/covid19-barometer, https://www.sermo.com/press-releases/sermo-reports-week-3-results-globally-17-point-increase-in-covid-treaters-who-have-used-hydroxychloroquine-33-50-and-azithromycin-41-58/. https://public-cdn.sermo.com/covid19/dd/c7f7/f7344a/344a00427889ec27e2b8df1c15/w3-sermo-covid-19-barometer.pdf.
Sermo W4. 2020. Sermo’s COVID-19 Real Time Barometer Study, Wave 4. Sermo.com. April 23, 2020. includes https://www.sermo.com/press-releases/sermo-reports-jury-is-still-out-on-remdesivir-31-of-physicians-who-have-used-remdesivir-rate-it-as-highly-effective-31-rate-it-with-low-effectiveness-38-rate-it-as-somewhere-in-the-middle/. https://public-cdn.sermo.com/covid19/c2/3aba/ba8889/88898d406a8a84a60947e34a56/sermo-barometer-banner-tables-wave-4.xlsx.
The National Institutes of Health COVID-19 Treatment Guidelines Panel . 2020. Coronavirus Disease 2019 (COVID-19). covid19treatmentguidelines.nih.gov. April 20, 2020. [Cited: May 1, 2020.] http://archive.is/gk3xt.
Can’t believe WUWT either. Do your own research.
+42^42, Bluecat, regarding any topic. One finds nonsense on WUWT, like anyplace else.
Breaking news: Trump has notified Congress that the US has withdrawn from the WHO.
Great and this!!! https://www.theepochtimes.com/trump-urges-fda-to-act-now-on-hydroxychloroquine-after-new-study-shows-positive-effect_3414918.html
Trump is doing the right thing, especially because Nicholas McGinley disagrees!
Brilliant. The man who think we can inject disinfectant knows best. During a pandemic he fires the group who are working to overcome this problem. I wonder why? Maybe he wants to distract from his olympic level poor decisions. And I see Trumps “best fwend” Jair Bolsonaro has tested positive for the coronavirus. What an irony that the man who called it a hoax now has it. He will be fine though he has taken Dr Trumps advice and started on hydroxychloroquine.
So, you support the following:
* WHO lied about where it found out about coronavirus
* The health organization took China’s word for it that the virus appeared in late December, when it started earlier.
* The health organization chastised Trump for instituting a travel embargo on China early in the pandemic
* WHO took China’s word for it when it claimed that the virus did not travel from person to person
* The health organization lavished praise on China for reacting quickly to the virus when it had not
* WHO praised China for releasing the genome sequence for the virus, though it took a crucial 17 days to do so and under much pressure
* WHO is so cozy with China that it removed Taiwan from a map and included it as part of China
Good news as that your ilk are being exposed and erased, largely through the efforts and leadership of one strong man with the help of a wonderful team of patriots. America is watching, and your team is being exposed. You are a stain. I know, I could not resist the ad hominem metaphor…
“Good news as that your ilk are being exposed and erased, largely through the efforts and leadership of one strong man”
Yes well that “strong” man has to lift his popularity somewhat (https://projects.fivethirtyeight.com/trump-approval-ratings(https://projects.fivethirtyeight.com/trump-approval-ratings/) before he can erase me.
And by the way the WHO were not the only ones praising China. I seem to recall Twumpy saying how great they were at the start of the pandemic.
Simon, you are the perfect self eraser. You’re in a class by yourself… a perfect barometer. If you occasionally said something reasonable, you’d be less reliable a measuring device.
Only until President Trump learned the facts about ChiCom and WHO duplicity, Simon. Your TDS is tedious.
“Only until President Trump learned the facts about ChiCom and WHO duplicity…”
It’s true he did change his tune on China, but that was because he made maybe the single most damaging call in US history…. to minimise the threat of the pandemic. Now we are at 133,000 deaths (and counting). So Trump is doing what Trump does… blaming someone else. His behaviour now is so predictable, you don’t have to be Einstein to see this coming.
First rule of the Trump playbook. When things are going well, it is all his doing. When things go wrong… it is someone else’s fault.
TDS BS from Simon.
Yes Trump is deranged for sure.
Simon, as I have proven before, is an inverse barometer for truth. So he is batting 1000.
Translation from Simon: “I know you are but what am I?” I was guilty of similar behavior at 6 years old, until I learned more words for which to argue my side of the story.
You are a known liar. Shame on you.
Trump’s next move needs to be to fire Fauci. That guy is diametrically opposed to the well-being of America.
Fauci Downplays Lower Coronavirus Death Rate as ‘False Narrative’
https://www.breitbart.com/politics/2020/07/07/fauci-downplays-low-coronavirus-death-rate-as-false-narrative/‘
Yes he should fire Fauci, but it’s a chess game. Trump’s using his power effectively… and balancing where he gets the attacks to come from. First show Trump Right Fauci Wrong…
“Trump’s next move needs to be to fire Fauci. That guy is diametrically opposed to the well-being of America.”
Let me change that for you ….Trump’s next move needs to be to fire Fauci. That guy is diametrically opposed to Trump. He tells the truth.
I mean he did say don’t open too early. Florida and Texas wouldn’t listen. Now look what has happened. But Trump will fire him, because that’s what Trump does when someone is being too honest. Although having said that, that is not always true. Didn’t he fire Flynn?
TDSx42^42, Simon.
Trump can’t fire his niece Mary.
What’s happening in FL and TX is that deaths are plummeting and “cases” are increasing. I put cases in quotes because it’s a meaningless number when positive antibody tests and prospective covid cases (no PCR) are included in the case count. Plus testing has ramped up exponentially, so of course positive test results are increasing, but that’s entirely meaningless because those people are not progressing to serious illness. That’s why Fauci needs to be fired – he’s trying to equate positive test results, and other meaningless data, with illness.
a link to what Dr. Ron Paul has to say about the Texas spike:
https://www.lewrockwell.com/2020/07/ron-paul/is-the-texas-covid-spike-fake-news/
numbers games being played once again. Seems to me that the only way to determine what is actually going on is to stay far away from the msm.
There’s a reason there’s a lack of quality randomised controlled trials in this area.
HCQ works in early treatment. In London where I practice, the epidemic raged during March and early April and tailed off thereafter. The peak of transmission was week 3 in March. The PRINCIPLE trial is the only one in the UK looking at early treatment with HCQ. My GP Surgery is enrolled in this trial, but it did not start recruiting GPs let alone patients until the first week of April. By the time they were ready to recruit patients (close to the end of April), we weren’t seeing any patients in general practice with new Covid-19 illness. We have had zero recruits to date from our patient population.
The care pathway for the UK NHS was essentially:
i) stay at home if you’re sick
ii) if you have to call someone, call 111
iii) 111 says stay at home unless you’re acutely breathless or chest pain in which case we’ll arrange a 999 ambulance to take you to A&E
iv) A&E admits you if O2 <92%. Otherwise they send you home without testing
So one of the reasons the UK was abysmal and a dead loss for research into early-stage treatment for Covid-19 was that the NHS care pathway prevented Covid-19 patients from seeking medical advice during the early stage of illness. This is the main reason why my GP Surgery saw so few patients in March. It was only once they'd developed ARDS and later stage viral pneumonia that they were deemed 'worthy' of hospital admission. Clap that, NHS!!
The Principle Trial is well designed but got going too late. No country has yet managed to complete such a trial in sufficient numbers. This is partly due to local factors (like the UK's godawful NHS) but also because the epidemic moved through populations so rapidly.
So faced with a fat-tailed event with high risk of harm, high uncertainty on efficacy of treatments and no RCTs, what should one use. Nassim Taleb 'analysed' the Raoult series back in mid-March and compared it to neighbouring Marseilles hospitals under the following assumptions:
– the hospitals are under identical conditions
– the non-Raoult hospitals are the representative benchmark
Using a probabilistic approach that is completely alien to innumerate medics, his Monte Carlo and binomial distribution approaches determined that Raoult's results were significantly different from the rest of Marseilles. That approach operating under that uncertainty has now been vindicated by:
– Raoult's ever-growing series, including outcomes when adjusted for age and other risk factors. compared to the rest of France
– countries using HCQ early (much lower death rates, much fewer cases)
– countries/ states that switched to HCQ after poorer outcomes prior (e.g. Turkey)
There's no uncertainty now that HCQ works during the early stages of the illness.
On a personal note, I prescribed it off label for a few patients back in March including two who had had previous respiratory ITU admissions. Their SaO2 and general condition improved within 16 hours. It was a more dramatic turnaround then I've seen with antibiotic treatment in general practice.
I’m curious… before covid, what would have been your diagnosis in those few patients with low SaO2? Or is this the first time you have ever seen that?
Thank you for that MDMan. Finally some sense from a UK medic.
How can the UK justify ‘protecting the NHS’, when noone is protecting the patients.
The UK approach to just leave the disease alone until you need hospital is quite simply staggering.
Yes, it ‘protects’ the NHS from 80-90% of people who dont need anything, but it is a virtual death sentence for the people who effectively end up going to hospital far too late.
So, hypothetially, if i had symptoms this afternoon, my approach would be to ring my GP and demand HCG plus antibiotics.
What do you think would happen? Lets hope i dont find out ever.
Why did the epidemic tail off in April? It is unlikely that “herd immunity” developed, at least by seroprevalence.
One way or another herd immunity always eventually develops. The percent of the public that need to be immune for herd immunity to exist depends on the population density and the extent of precautions taken. If precautions slacken, cases will increase according to the R value (number of persons an infected person infects) with the slackened precautions. Case rate will increase until R again becomes less than 1.
Unfortunately, the science is being fogged by the profoundly biased msm and extant TDS.
Want to take out the TDS element out of this thread and inject a bit of real new science.
I noted in a guest post some months ago on Wuhan virus that U Mn and McGill were starting a well designed classic rdb clinical trial of HQC as prophylaxis post severe known exposure. Those results were just published in NEJM. All here can read the the trial design and results as a pdf at NEJMao2016638. Clear Answer: HQC did NOT work. Explains why all the symptomatic HQC stuff —except the newish Michigan Ford hospital system retrospective—did not work either.
Now the potential flaw is that zinc was not part of the protocol, same flaw as the many other HQC alone doesn’t work reports. So we still dunno about HQC or other ionophores (like the flavenoid quercetin) plus zinc as prophylactic and/or therapy.
As for these opinion surveys. Largely worthless. Here is why. We know most recover by themselves with or without HQC. Per CDC, US CFR is 0.4% ofsymptomatics, and 0.26% after adding estimated asymptomatics. About twice a normal flu and a bit worse than a typical severe flu season with mismatched vaccine. Those that do not recover (fatalities) are overwhelmingly over 65 and/or with comorbidities: obesity, diabetes, hypertension. Unless the opinion surveys also controlled for these factors —and this guest post proves they did not—they provide no meaningful information and are therefore essentially worthless.
Rud: Did you mean to write this? [I refer to the brackets in your quote below]
“I noted in a guest post some months ago on Wuhan virus that U Mn and McGill were starting a well designed classic rdb clinical trial of HQC as prophylaxis [post severe known exposure]”
My response would be, what do you mean by post severe exposure? How long after? And does that mean after the patient was severely ill, and how long after that?
Mario, its in the referenced paper. Criterion was >10 minutes to a (later) confirmed symptomatic case with no PPE. Enrolled within 1 day of exposure. Primarily immediate family or care providers. Presumably all indoors. N>800.
Thank you Rud!
Rud
Hopefully, you have enough credibility here that you won’t be attacked as ruthlessly as McGinley.
Thanks for the thought. I care only about truth, so do not care about WUWT popularity. Doubt CtM would ban me for posting a new peer reviewed paper saying Leo is probably just wrong—no different than his last HQC post. See my comment to it there.
At this point Mario is trying to dox me, asking around for personal info about where I live and work.
I am reviewing the law now.
He seems to have cross the line.
McGinley: You wrote: “At this point Mario is trying to dox me, asking around for personal info about where I live and work.”
That’s another bald faced lie! It’s now about the 10th time you claimed I wrote something that is 100% a lie.
You’re the one that brought up doxxing, and I referenced you saying that just like I am responding now.
Everyone here knows you have made up fake names and I had asked about what you do, because you seemed to act like a doctor. I got the answer, you are a teacher… of what I don’t know.
Your dishonest blasphemy should get you put into a corner somewhere for a time out.
Guys, can we all just stop it?
Disagree, but stop the bitch slapping.
Thank I agree. The seriousness is that person is literally writing that I posting things I did not post. That is defamatory and untrue. I will not respond to that person any further.
I can’t believe I have to say this.
I don’t care who started it.
Just stop.
I will keep the promise made previously. I promise.
Charles, although it may appear I responded after I promised to stop, that post to which you asked me to just stop, happened before I got the message and promised to stop. So I have stopped, previously.
[snip. I said stop it~cr]
Here is the link to when you started getting really obnoxious and passing along clearly false info about availability of medicines that can save someone life:
https://wattsupwiththat.com/2020/07/05/hypothesis-restrictions-on-hydroxychloroquine-contribute-to-the-covid-19-cases-surge/#comment-3029760
Alright Charles, he says he did not say these things, I post his quotes and links, and you snip it?
I am done here.
That is so wrong!
Adios muchachos.
Charles the moderator,
Mario says,
“Thank I agree. The seriousness is that person is literally writing that I posting things I did not post. That is defamatory and untrue. I will not respond to that person any further.”
And then I posted the quotes and the links to where he said those things.
You snip mine, and leave his up?
Just.
Stop.
Everyone else has.
HCQ+AZ have antiviral effect against Wuhan coronavirus. Given early (in the viral stage of the disease) they prevent coronavirus’ replication.
We need to stop treating patients! The virus just kills those who have genes inherited from neanderthals:
https://www.biorxiv.org/content/10.1101/2020.07.03.186296v1
/sarcasm off
I have an auto immune disorder, related to ankylosing spondylitis and lupus and have been taking all sorts of meds for 26 years, including a moderate dose of steroids daily that entire time.
It was interesting to find out in June that patients receiving steroids fared much better than those who did not receive steroids.
This is thought to be from the reduction in inflammation(in the lungs) and also the suppressing/modulating of the immune system which steroids cause. In COVID patients the immune system can go berserk, setting off a cytokine storm.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2767939
There are several things that we know about HCQ with certainty. One of them is that its been given to hundreds of millions of people world wide, mostly for malaria with very few side effects. So it’s proven to be safe if used properly.
Another thing is that it reduces inflammation. This is why its also given to patients with lupus and other forms of arthritis, with significant benefits and improvements in health/inflammation.
https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-019-2040-6
So in using it with COVID patients, we already know that its safe and that it WILL reduce inflammation in at least some patients……….that’s what the drug does.
With that being the case, one assumes that if inflammation in the lungs from COVID is adversely affecting patients and outcomes, then HCQ, with its anti inflammatory PROVEN benefits should help at least some patients by reducing inflammation.
You can find results in recent studies that are all over the place about this drug. Which ones to believe and which ones not to believe? Some completely contradict each other.
However, medical doctors should/do understand how HCQ works and the clear anti inflammatory properties and the long proven safety. This is why they are prescribing it to so many patients.
Their patients would/will be dead or recovered if they wait around for the wishy washy, incompetent, corrupt and political FDA to decide on a final position with regards to HCQ.
Yeah, HCQ has anti-inflammatory properties.
So how should it help patients with that in the early phase of a viral infection exactly? Wouldn’t it be a bad idea to give it too early then cause it would suppress the immune response upon infection making things worse? Wouldn’t same apply to a prophylactic use? Making people more vulnerable? Aren’t people with lupus not more prone to get infections cause the drugs are suppressing the immune system?
Like steroids do and are therefore contraindicated in the early phase of infection, doctors have been hesitant to use them in the early pandemic because of that and they seem to have no benefit in people with mild symptoms. As one would expect with their mode of action.
Ron I explained this mechanism of action in an earlier quest post months ago.
HQC itself in RA/lupus acts by raising cytosol Ph. This causes lysosomes to ‘leak’ their enzymes. Those enzymes in turn reduce the cellular signals beaconing autoimmune response proven in vivo.
In Wuhan, this same Ph lysosome leakage changes the shape of the cell wall ACE2 receptor the virus uses to lock on. Change the lock, the viral key works less well. Unfortunately, not Less well’ enough to matter for prophylaxis.
The second mechanism is quite different. HQC is a zinc ionophore. Helps zinc enter the cell, where it is well established zinc will then inhibit viral replication. (Not the only zinc ionophore—quercetin flavenoid is perhaps better ignoring bioavailability issues solved by formulation or dosing). So HQC plus Supplemental zinc is a potential double whammy. Unfortunately NOT properly tested to my knowledge.
This part has me more excited.
The second mechanism is quite different. HQC is a zinc ionophore. Helps zinc enter the cell, where it is well established zinc will then inhibit viral replication. (Not the only zinc ionophore—quercetin flavenoid is perhaps better ignoring bioavailability issues solved by formulation or dosing). So HQC plus Supplemental zinc is a potential double whammy. Unfortunately NOT properly tested to my knowledge.
Nothing I disagree with here either. It should be more tested, but in the meanwhile, there are loads of benefits with quercetin that I have experienced in general since taking it now for 3 months. Never in my life have my sinuses been open without need for 12-hr nasal spray 4 times times per day…
It might be the NAC doing that. I take it almost every day and my lungs and sinuses feel so much less clogged. Less boogers too. NAC does thin out mucus.
Thank you! I did a non scientific thing and took a combo supplement with Stinging Nettles, NAC and quercetin. Not a lot of quercetin in that so I take two 500mg doses of quercetin single sup’ on top of that. what’s a little money when I have my large nose clear and lungs clear.?.?
Rud,
I have repeatedly explained why those two statements are false:
HCQ is not a Zn ionophore. It simply cannot be a Zn ionophore cause it lacks the chemical properties to be one in the first place. The one and only PLOS One study about that does a misinterpretation of their results. HCQ traps Zn in lysosomes which was taken up via endocytosis. Bafilomycin A and knockdown of ZnT2 and ZnT4 show the same trapping effect in another study but the authors are smarter and are not claiming bafilomycin A would be a Zn ionophore.
The inhibitory effect of Zn on viral RDRP was only shown with unphysiological concentrations on purified protein in a test tube. There is no direct evidence of intracellular elevated Zn concentrations having an effect on SARS-CoV RDRP and viral replication in cells.
This is pure speculation on your part, I guess? Haven’t seen any study proving that.
What most people don’t know: the applied concentrations of HCQ in viral in vitro studies are 1) very toxic to non-transformed primary cells and 2) pharmacological not possible to achieve in blood plasma at all by at least the factor 50.
Well, then you have apparently not researched the Medical literature as I did before my first of several guest posts on this topic.
You want to disagree with me, then counter with betters the references I previously provided.
Ron, Rud,
I am agnostic about the lysosome/pH issue.
But I have to say, just to be clear…I have looked very carefully for the source of the assertion that HCQ is a ZI.
I started off, three months ago, asking questions about the evidence that taking zinc and an ionophore was a antiviral.
I found many references to “HCQ” is a zinc ionophore (ZI) assertion.
It was only when I traced the references for that assertion back to the source material, that I saw something very peculiar.
One person after another had given a reference to chloroquine(CQ) research which appeared to demonstrate that CQ is a ZI, as a source for the assertion that HCQ is a ZI.
And this was from some seemingly authoritative people.
No one wants to look at it carefully, though.
I am glad Ron has, because this is important.
I am not getting very close to sure no one has any evidence that HCQ is a ZI.
I have looked at lists of all known ZIs, and even all ionophores.
I have read the chemistry of what makes a molecule a ZI, or a ionophore in general.
Wikipedia has an article on them.
A search engine query gives plenty of material to read, and many examples of ionophores and which cations that they can transport.
They are important molecules so a lot of very careful and obviously costly research has gone into the subject.
Many new antibiotics have been found by first screening large numbers of known molecules for ionophoric activity.
The other day I read carefully the newish paper by Zelenko, et al.
I am not in the habit of opening and looking at every reference and footnote.
It is the only way to catch it when someone is making unsupported references and then having them published.
And it is getting through a lot.
Anyhow, in Zelenko’s report, it is acknowledged that HCQ being a ZI is only a supposition. No basis for believing it is likely to be a valid supposition is given.
Many people are basing a lot of what they believe on the proposition that HCQ is a zinc ionophore.
Can be and Ron be the only two people who think this is important, given that it seems to be a substantial portion of the rationale being offered for a whole lot of research and a whole lot of oftentimes people getting a certain medical treatment rather than another.
I want nothing more than the people here and elsewhere who are serious scientists to make sure they are not basing a whole structure on a bad foundation.
And I think all serious scientists want that as well.
The question of zinc ionophores being a proven mode of action for an effective antiviral therapy is an important one.
Just imagine what it means if this has gone on for this long and with this many people around the world doing all this work, with all those lives in the balance, and the underlying basic premise is a false inference based on pretty much nothing?
Typo in this sentence:
“I am not getting very close to sure no one has any evidence that HCQ is a ZI.”
Should be:
“I am now getting very close to sure no one has any evidence that HCQ is a ZI.”
Source
Also a worth reading
Rud,
please be so kind and show me another study than this one from Xue at al. showing that HCQ is a zinc ionophore:
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109180
Is there anywhere another? This is exactly the one I criticized above.
Are there more than those three in vitro studies from China, two from the same group from Wuhan, that describe an effect on viral replication in Vero6 cells?
https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa237/5801998
https://www.nature.com/articles/s41421-020-0156-0
https://www.nature.com/articles/s41422-020-0282-0
Is there any paper that shows efficacy of HCQ in other cell types?
I would also very much appreciate if you could name a real data study about ACE2 and hydroxychloroquine. I know there is this study:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128678/
but that is only in silico modelling.
And btw, does anybody else see the irony that data from China, Wuhan, is basically the foundation of the HCQ hype?
In epidemiology there are two similar yet argot. Efficacy. Effectiveness.
Effectiveness: It appears to work in a clinical setting.
Efficacy: We know why and how this compound is effective.
Perhaps it is acting as a ZI, maybe not.
However, it shows high effectiveness *even though we don’t know why.* So we have no proof of efficacy.
Effectiveness: Doctors report dose, side effects and results.
Efficacy: The chemistry is known and proven with clinical trials.
When a drug appears to work ethical physicians do not do trials. Withholding a medication which can lead to death is not wise. Even when its efficacy is unproven.
“Additionally, chloroquine (and by extension, hydroxychloroquine) has been shown to increase cellular intake of zinc, …”
And that is all there is.
Chloroquine has been shown to.
HCQ is “by extension” assumed to be so.
By people who have offered no rationale or chemistry based reason for that assumption.
HCQ is in all probability not a zinc ionophore.
There is no valid reason to think it is.
No one who has said it is, has posted any evidence to back up what is a empty assertion.
Rud, thank you for all of the fine work you have provided WUWT over time, as well as this latest work on the ChiCom virus and its resultant WuFlu.
Given your information on the studies and your clarifications, I am not dissuaded from taking HCQ+ given my recent diagnosis of WuFlu. The addition of Zinc to the mix seems to be the wild card in the studies. Also, with Mario’s and your additional information, I will be investigating the addition of Quercetin to my regimine.
Thanks to all of you who have provided useful information here on WUWT. Given all that, I am no longer going to argue about my taking HCQ+ on this Thread. And all you TDS Trolls can screw off.
Finally, does anyone have additional information about the possible benefits of EGCG?
EGCG has been said to be a stronger Zn ionophore than quercetin. I have been taking it for the general benefits of it. But after I started taking quercetin with NAC, my sinuses have cleared for the first time in my memory… and my bronchitis seems to have vanished. Quercetin is great for inflammation. This post by Medcram shows quercetin. The video gets going at 1:30 into it. It’s short.
I should add that at: 7:50 in the video, you see a chart showing EGCG but I do not know why he did not mention it’s use. And I correct it’s underneath Quercetin in the graph. Maybe it has fewer studies… also, it appears that CoQ10 is also on that graph, which I take too but just for it’s wide antioxidant properties and claims it helps with enabling the heart to better use energy from glucose.
My hope is that when I am your age, I function well enough to tag a dog back… 🙂
Thanks again, Mario. I’ll be in touch by email pretty soon. I’m done with this WUWT Thread.
🙂
Something to look out for:
@Nicholas
agreed, see it.
java is a bit problematic on my PC,
So, the differences are even more tiny.
😀
I have been combing through info about known ionophores, and what structural properties make a molecule able to shuttle metal ions through a cell wall.
They are related to chelating agents, and there are a few types.
Many antibiotics are ionophores…they open up pores in the membrane of bacteria as a mechanism of action.
I have found exactly two quinolones that are ionophores.
The subject is research extensively.
The research that showed CQ is one was rather recent, around 2009-2009.
I have found exactly zero references to HCQ as an ionophore.
I do not think any such finding exists.
And since it is a far safer and more commonly available alternative to CQ, I am sure it has been screened for activity as an ionophore.
Ions can only be shuttled by an ionophore that has a very specific set of properties, and most of the ionophores are very specific to one or a few cations of a certain size.
It does not follow from any principle of chemistry that similar molecules will have the same properties in the world of biochemistry.
The opposite is true.
Tiny changes have huge effects on the shape and stereoisomeric shape of a molecule.
Adding the OH group to chloroquine alters it’s shape and properties dramatically.
Look at the safety profile, elimination half life, and melting point differences for the two.
They are starkly different.
I am not ready to say HCQ is categorically not a ZI, but every reference to that being the case is recent, and makes references that trace back to research on a different molecule…CQ, not HCQ.
I have been going over the history and especially the recent evolution of this set of what can only be called “beliefs”.
And the more I look, the more I see conflation of disparate bits of information, shifting goalposts and storylines, a hodge-podge of reasons for justifying one poorly outlined hypothesis, and what looks more and more like an idea springing fully formed out of nowhere but whisper down the lane internet confabulation.
Over 30 years I watched warmistas behave badly, like bad people, act in bad faith, exaggerate, etc, and all the while they constantly had to change the logic, change the justification, change the underpinnings, come up with new explanations, use every disingenuous way they could think of to avoid any actual look at the complete set of relevant facts…
Everything changed, constantly, and seamlessly, except for the conclusion.
The conclusion had to stay the same, because that was the only thing being defended.
I see a fast motion microcosm of the same sort of thing here.
First it was chloroquine, because it had antiviral properties, had to do with lysosomes, cell wall config, ACE2 receptors, intracellular pH, etc.
A lot of mechanisms, each with a faction.
For quite a while no one had mentioned HCQ.
But anyone questioning whether CQ was the cure was attacked viciously.
I was just looking at a thread from March…dozens of people were saying it was over, done deal, the cure, government has to buy chloroquine for everyone in the country, pronto.
But then the story began to morph. Zinc ionophore, have to add Zpak…no, it could be any antibiotic…no, only zpak…then people started to conflate any quinine derivative, they were all the same metabolically after all (eye roller), then HCQ popped up, and CQ was okay too.
They are the same was how it was explained.
Or close enough.
The some big name advocates got a lot of press and attention with big hand wavy pronouncements. That Rigano guy…the doctor from Sanford. Oh, wait, he is a lawyer who peddles bit coin, Sanford disavows him and his supposed research. Now we know he was a total fraud. Didier Raoult went from ridiculing concern about the virus to having the cure and hard data to prove it, in a matter of day! Wow!
Good thing, cause that Rigano thing was about to get the big spotlight.
Raoult had The Cure…we swear, and everyone needs to jump on board.
But the paper he put out in record time was a fraud…he had one patient die and three go to ICU, and he wrote them out of his study, never mentioned them, and said in plain language he had 100% success.
Around when his fraud came to light, and was hand waved away but not very convincingly, here comes Zelenko!
Same story…was ridiculing concern on early March, had invented the cure by mid March, and had treated, personally, 669 people by himself and cured them all in the space of ten days.
Trust him, would he lie? He no need no stinking documentation.
Good thing, because he had none, and has produced none.
Around the time he was being investigated by the Justice department and on the way to being disowned by his close knit community, the panic was in full bloom, and the whole shebang had taken on a life of it’s own.
No more talk about CQ, or ACE2, or pH … Now it was HCQ (oh, okay, maybe a little CQ maybe, meh!). Now it was HCQ, it was Zn++, it was ionophore, zinc kills virus, malaria drugs are antivirals (huh?), and so is Zpak! huh?
Then why does doxycycline work better in the previous 15 years of clinical trials? Okay, works better is a little strong. Failed to work, but less dangerously.
15 plus years? Wait, what?
Yes, there are 15 years of clinical trials using CQ and/or Zpak against everything one can think of. Cancer. Lot’s of separate viruses. At least one trial compared CQ and Zpak to CQ and doxycycline.
It never had any success against anything. But it was not for lack of trying.
Why?
I did not hear one single reason for why those drugs work against COVID that did not imply that they would work against viruses in general.
By now, we have people all over the map, but as long as they agree HCQ is the cure, none of the advocates seems concerned that the various regimens, and why this trial and then that trial got the results they did, had the same people arguing, depending on which “fact” they were defending, that you needed to have the zinc. Trial failed because no zinc.
You needed to have all three…trial failed because all three.
You need to treat early, trial failed because they were already sick.
It is an antiviral.
No, it cures cytokine storm.
No, antiviral…that is why it will not work late and you need the zinc.
If it was cytokine storm and anti-inflammatory that did the track, you do not need zinc.
Bacterial secondary infection comes late in disease progression, weeks after the person has mild symptoms in most cases…but it cured people by giving 5 days of antibiotics, either before or just after any serious symptoms developed.
A 100% novel theory of how an antibiotic can “cure” viral pneumonia…give it before it happens, and only for 5 days! No one bats an eyelash or misses a beat.
From the beginning, the people and the specific protocol and even the exact drug used have been sequentially discredited and then replaced with another rationale or another advocate.
Raoult flat out lied, committed research fraud, or at the very least he was shockingly disingenuous to claim what he claimed.
Zelenko turns out to have worked at his computer, and did telehealth…he had cancer and a lung removed recently, and is high risk, and could not see anyone…but he said he SAW 669 people in ten days.
The drug was almost impossible to get, and some states had banned prescriptions outside of a hospital or for people who had been getting it. But Zelenko says he treated 669 people by himself, and they were all cured. What that could mean after first five days and then 10 days was not anything his fawning faithful cared about.
He has never given any further info on those 669, or produced documentation, or explained how he could have known the subsequent history of 669 people after they logged off his computer screen?
He was investigated and kicked out of his community.
Chloroquine was shown to be too toxic and not effective at the highest level that could be induced in a persons bloodstream. The in vitro result was from a amount that would be toxic in a person.
HCQ is called an ionophore. Maybe it is, but if so, where is a shred of evidence?
Where is the research on antiviral effect of ionophores?
That ionophore research was regarding chloroquine and zinc for inducing apoptosis to treat cancer!
There was other research that showed chloroquine could kill SARS1 in vitro, but that drug failed in vivo in animal models.
But there was never any research that combined these two research dead ends (dead ends because no one has treated a single cancer patient successfully with CQ or HCQ, or showed zinc and either one of them killed virus in vivo.
100% unjustified conflation of two disparate lines of inquiry.
Now this retrospective from Henry Ford health in Michigan.
It is a dead cat bounce, or at least I hope so.
Dozens of hospitals, the CDC, the NIH, WHO, France, Sweden, the USA, hundreds of separate doctors, the VA, the US Army…all have announced bans, said they have given up after trying and trying to have success with them.
Even Henry Ford Health put out a study last month showing the opposite of the one from this past week.
Those same hospitals used remdesivir, plasma, and also IL-6 blocker, and steroids, to treat patients and had a drastic improvement between the March 10-20th group, and the March 21-29th group.
This latest study never mentioned those hospitals had used plasma or remdesivir during that interval. But they said the patients were a sequential cohort of everyone admitted between March 10 and May 2!
The ER doctors in Wuhan were interviewed as soon as that city opened back up, and asked about their treatments. They said very emphatically they had abandoned the malaria drugs because they did not help and were dangerous for some people.
As of May 2, the US standard of care for COVID-19 is remdesivir.
A large randomized and blinded clinical trial showed a 33% reduction in fatalities in patients getting steroid drugs.
Large studies and a long list of patients and doctors have reported the IL-6 blocker to be the superior was to treat cytokine storm.
Large reductions in mortality have attended usage of ECMO machines, being less quick to use mechanical ventilation and the required induced coma.
Death rates are down every where we look, concurrent with discontinuation of HCQ and CQ.
As surely as large increases in deaths were precisely concurrent with widespread adoption of malaria drugs in Belgium, France, Germany, Switzerland, the USA, Sweden, and many more places.
The early rationales evaporated.
The early advocates discredited.
The best studies have showed a contrary result.
And yet the advocates are now frothing at the mouth with rage at any suggestion that they were ever wrong.
They do not acknowledge any result or fact point that casts a dim light on the malaria drugs, and act like there have not been several large trials that used the gold standard and showed no benefit.
Now they see themselves fighting evil.
Conservative stalwarts are called left wing murdering trolls for disagreeing with a hypothesis that has failed to be validated.
And meanwhile, these same people have nothing to say for the obvious successes.
Are they talking about ECMO?
Are they acknowledging the great results seen from IL-6 blockers, or steroids, or the more modest but clearly positive news about remdesivir?
Oh, hell no!
And that is where we are.
There is a mountain of data in the pipeline, and more new possible drugs and vaccines being trialed every day.
Successful antiviral therapies in the past have started with one drug that had some effect, usually modest. The finding another drug with another mode of action and testing them in combination.
In reply to:
Nicholas McGinley’s comment:
“Now this retrospective from Henry Ford health in Michigan. It is a dead cat bounce, or at least I hope so.
Dozens of hospitals, the CDC, the NIH, WHO, France, Sweden, the USA, hundreds of separate doctors, the VA, the US Army…all have announced bans, said they have given up after trying and trying to have success with them.”
‘Nicholas’,
Six different Michigan hospitals treated 2541 patients and their evidence based results are….
Early treatment of Covid patients (the earlier the better) with Hydroxychloroquine and Azithromycin plus zinc reduced the covid death rate as compared to untreated patients by 71%.
I do not understand why this great, good news, Covid treatment breakthrough is a ‘dead cat’ bounce.
Why has the Lancet study that ‘alleged’ negative Covid results, withdrawn and the data from that fake study has disappeared and the ‘company’ that provided the fake data is not returning phone calls?
Science cannot work if people lie and have an agendas.
https://www.ijidonline.com/article/S1201-9712(20)30534-8/fulltext
Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19
Results
Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4-10 days), median age was 64 years (IQR:53-76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3-53)
Science Research: On People’s Side
HCQ with azithromycin reduced deaths by 71% compared to no treatment. 2500 patients, no heart attacks. 6 Michigan hospitals.
Fake Research: Fake Research should result in criminal charges.
Lancet HCQ ‘study’ had 25% heart attacks and worse outcomes. Logical Reason: Lancet patients were near dead when they were given HCQ to start the study. HCQ treatment cannot reverse damage.
Second possible explanation, Key Lancet negative Covid study database has disappeared and Lancet has removed the study and apologized. ‘Company’ that had database not responding to calls.
The great HCQ/AZ plus Zinc results makes sense as HCQ is a zinc ionophore and zinc stops the virus from replicating.
Our body’s have a natural means to get the zinc into our cells to stop the class of viruses that must connect to the ACE-2 connector to replicate.
Vitamin D deficient people have a 19 times greater chance of dying from covid than Vitamin D normal people, regardless of sex or age. Vitamin D is a proto hormone that modifies our cells.
Nicholas,
I know you are interesting in ways to reduce the Covid death rate in the US.
Did you know that?
82% of the US black population, 69% of the US Hispanic, and 42% of the US general population is Vitamin D deficient (25 (OH)D less than 20 mg/ml)
Prevalence and correlates of vitamin D deficiency in US adults.
https://tahomaclinic.com/Private/Articles4/WellMan/Forrest%202011%20-%20Prevalence%20and%20correlates%20of%20vitamin%20D%20deficiency%20in%20US%20adults.pdf
Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D concentrations ≤20 ng/mL (50 nmol/L). The overall prevalence rate of vitamin D deficiency was 41.6%, with the highest rate seen in blacks (82.1%), followed by Hispanics (69.2%).
4000 UI/day per person of Vitamin D supplements is required to raise the blood serum 25(OH)D of the entire US general population above 30 ng/ml.
Did you know that regardless of sex or age that Vitamin D people deficient people 25(OH)D less than 20 ng/ml are 19 times more like to die from Covid than Vitamin D normal people?
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3585561
Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study
Vitamin D Insufficient Patients 12.55 times more likely to die
Vitamin D Deficient Patients 19.12 times more likely to die
William: I love how clearly you summarize good information. It’s astounding how much energy there is put towards torturing the science to disclaim good news for society. The bold mischaracterization of the “dangers” of HCQ is deeply concerning.
I have sat in court rooms where opposing sides have a vested interest in the outcome, so the motivation drives the reasoning. Reframe the facts into strawman arguments to obfuscate and confuse. A foundation of facts be damned. What happens is the storyline gets so complicated that people will end up choosing a side and appeal to the authority of their choice. “I trust the scientists”… which one?
I have not seen anyone talking about HCQ being dangerous.
Recently.
It is a very useful medication.
It has a well know safety profile.
But we must know, how useful is it for this purpose?
I think someone who was upset about straw man arguments is now bringing up an objection that was not made, and refuting it.
As for the Henry Ford Health System study, it is known to be the case that they treated patients during the interval of the retrospective study using treatments and drugs which are not revealed in the study.
Among them are powerfully effective ones.
The study purports to be all of the patients admitted from March 10th to May 2nd.
During that time, they used many drugs this study chose make no mention of.
You do not have to like it.
But by their own published and publicly documented records, including a study of a subset of these same patients prove it to be the case.
Refusal to acknowledge this information will not make it go away, but it is transparently obvious that ignoring it is a deliberate refusal to look at the facts.
Facts.
Not from me.
From Henry Ford Health System.
Here is what doctors there say about their use of HCQ:
“Henry Ford Health System has continued its multiple clinical trials of hydroxychloroquine, including one that is testing whether the drug can prevent COVID-19 infections in first responders who work with coronavirus patients. The first responder clinical trial was trumpeted by Trump administration officials early in the pandemic.
But the top infectious disease doctor at Henry Ford Macomb Hospital said he only treats COVID-19 patients with hydroxychloroquine if families insist. ”
https://www.detroitnews.com/story/news/local/michigan/2020/06/10/health-systems-mixed-use-hydroxychloroquine-covid-19/5328358002/
They only use it if the patient insists.
And the other hospitals in that state have stopped using it.
But wait, there is more, and this speaks directly to concerns about safety.
Not from me.
This is the director of infection prevention at Henry Ford Macomb.
“There’s no good study to support benefit (of hydroxychloroquine), but certainly serious concerns about side effects,” said Dr. Nasir Husain, director of the Infection Prevention Program at Henry Ford Macomb. “
William,
You asked:
“Nicholas,
I know you are interesting in ways to reduce the Covid death rate in the US.
Did you know that?
82% of the US black population, 69% of the US Hispanic, and 42% of the US general population is Vitamin D deficient (25 (OH)D less than 20 mg/ml)”
Yes, I do know this.
I took an active and vocal part in discussions about vitamin D many many months ago, on many article here on WUWT.
I have repeatedly stated my astonishment at the lack of concern from many quarters about vitamin and mineral deficiencies.
I have used supplements myself since the 1960’s, when my mom was a vocal advocate of the work of Adel Davis.
I have expounded on the details of that vitamin at length, many times.
You may be right, but after reading a lot I dare to say you are wrong.
I will not dig 48 years back, telling that I learned a lot of chemics and med.-science, parts in French, most in German, but never in English, so my vocabulary may not be accurat.
First of all, you can’t simply add OH, if there is no free connection.
In HCQ, there was an exchange of one of CH3 groups with OH.
There are several studies about CQ fighting against cancer, in one, they looked for Zn and realised an accumulation of Zn without understanding themechanism behind, but declared CQ as ionophore.
There are studies about HCQ fighting against cancer, and there is a study comparing CQ and HCQ fighting against cancer.
If you compare these different papers you may realise not very strong differences in the working mechanism to act, to say it realistic, the differences are negligeable.
To say is too, they all wrote about different cancers.
But if CQ is an ionophore, there is no reason, viewing the minor differences in working, that HCQ isn’t.
As nevertheless layman my estimate, not guess, of the probability to be an ionophore is about at least 95%.
As somebody with organic chemistry and biochemistry as majors in his masters degree my estimate it is not an ionophore would be at least 99.9%. So what?
Personally, I don’t think the difference in the one hydroxy group between CQ and HCQ makes any difference there because ionophores need a steric proximity of two negatively polar prosthetic groups to work for positively charged divalent cations and the hydroxy group doesn’t fulfil this criteria anyway. The rest of the molecule doesn’t do this either. Hence my opinion.
Krishna, you said:
“First of all, you can’t simply add OH, if there is no free connection.
In HCQ, there was an exchange of one of CH3 groups with OH.”
You are wrong.
Look again.
If you still do not see, I can tell you in detail.
But it is obvious for anyone who knows how to interpret a diagram of a molecule.
Here it is again:
Reference 3d interactive diagrams of the two:
HCQ
https://chem.nlm.nih.gov/chemidplus/structure3D/viewer/118-42-3
CQ
https://chem.nlm.nih.gov/chemidplus/structure3D/viewer/54-05-7
@Nicholas
I compared these 2 pictures:
CQ
HCQ
See 3 x CH3 (CQ) and 2 CH3 +OH (HCQ)
Yes, although it is easier to see the distinction when one uses diagrams with the same orientation.
You do know how to read such a diagram, no?
The lines are the carbon backbone of the molecule.
Any of the bends in the line is the location of a carbon atom.
Also, it is not shown but understood that every carbon has for covalent bonds.
Any carbon atom represented, which is not bound to four other atoms, is understood to have hydrogen atoms bound to those carbons.
Oxygen is understood to be divalent.
If it is attached to a carbon by itself, as in a ketone, an aldehyde, an ester, or a carboxylic acid, is joined via a double bond, occupying two of the carbon atoms’ four bonds (not relevant here).
It may be helpful to look at a diagram which shows the entire molecule including the hydrogens to make it more clear that the difference between HCQ and CQ is a SUBSTITUTION of a H for an OH.
It is easier to see in a ball and stick that shows the hydrogens, such as the 3 d version I posted a link to, or this one:
HCQ
https://pubchem.ncbi.nlm.nih.gov/compound/3652#section=3D-Conformer
CQ
https://pubchem.ncbi.nlm.nih.gov/compound/2719#section=3D-Conformer
If you do not see it is a substitution of an H for an OH…
“See 3 x CH3 (CQ) and 2 CH3 +OH (HCQ)”
No.
CQ is C18 H26 Cl N3
HCQ is C18 H26 Cl N3 O
Same number of everything, except one oxygen atom.
Because the only difference is a substitution of an H for an OH
@Nicholas – PS
btw, thanks to add “bonds ” and “divalent” to my voc. book.
Should be better to dig a bit deeper in my memory instead of only scratching the surface.
@Nicholas
That comment belongs to that place here
The PS is the follow up.
Williams asks:
“Nicholas,
I know you are interesting in ways to reduce the Covid death rate in the US.
Did you know that?
82% of the US black population, 69% of the US Hispanic, and 42% of the US general population is Vitamin D deficient (25 (OH)D less than 20 mg/ml)”
Good for you to be looking at this issue.
Few have spoken about it.
But one company has been studying this data and working to help treat all patients achieve the same level of survival.
Today they presented some findings, showing evidence that their treatment ensures equality of outcome across disparate racial and ethnic groups.
This is the first such finding I have seen of this nature.
They also presented stats on the dose dependent interference of CQ and HCQ with their drug:
“Additional new data on the safety and efficacy of remdesivir presented at the Virtual COVID-19 Conference feature subgroup analyses, including race and ethnicity of patients treated in the United States, and global baseline characteristics associated with improved clinical status, and concomitant use of hydroxychloroquine.
In this study, 229 patients were enrolled at trial sites in the United States; clinical improvement was defined as a ≥ 2-point improvement on a 7-point ordinal scale. Among these patients, rates of clinical improvement at Day 14 were 84 percent in African American patients (n=43), 76 percent in Hispanic white (HW) patients (n=17), 67 percent in Asian patients (n=18), 67 percent in non-Hispanic white (NHW) patients (n=119) and 63 percent in patients who did not identify with any of these groups (n=32). Key efficacy and safety results with remdesivir treatment across race and ethnicity in the United States are included in the following table.
NHW
n=119
Black
n=43
HW
n=17
Asian
n=18
Other
n=32
Mortality, Clinical Improvement and Discharge by Race – U.S. Patients Only at Day 14
≥ 2-point clinical improvement
80 (67%)
36 (84%)
13 (76%)
12 (67%)
20 (63%)
Discharge
80 (67%)
32 (74%)
13 (76%)
12 (67%)
20 (63%)
Death
13 (11%)
3 (7%)
1 (6%)
2 (11%)
3 (9%)
Among the 397 patients who received remdesivir treatment globally, Black race, age under 65 years, treatment outside of Italy and requirement of only low-flow oxygen support or room air at baseline were factors significantly associated with clinical improvement of at least two points at Day 14.
Following the availability of in vitro data demonstrating chloroquine inhibits the antiviral activity of remdesivir in a dose-dependent manner, Gilead conducted an analysis of clinical outcomes with patients who were treated with both remdesivir and hydroxychloroquine concomitantly, versus patients who were treated with remdesivir and who did not receive concomitant hydroxychloroquine. Through a median follow-up of 14 days, the rates and likelihood of recovery were lower in patients who received concomitant hydroxychloroquine compared with patients treated with remdesivir who did not receive hydroxychloroquine (57 percent vs. 69 percent, covariate-adjusted HR [95% CI] 0.61 [0.45, 0.83], p=0.002). Concomitant hydroxychloroquine use was not associated with increased mortality in the 14-day analysis window. The analysis also showed that patients in the concomitant hydroxychloroquine group experienced overall higher rates of adverse events. After adjusting for baseline variables, this difference was significant for Grade 3-4 adverse events.”
This announcement moved world markets significantly this morning.
https://www.gilead.com/news-and-press/press-room/press-releases/2020/7/gilead-presents-additional-data-on-investigational-antiviral-remdesivir-for-the-treatment-of-covid-19
Study to HCQ, lupus and COVID-19:
https://ard.bmj.com/content/early/2020/05/20/annrheumdis-2020-217690
I know, I know, no Zn…
Thank you for picking that up, Ron.
They searched globally, and found 17 immuno-suppressed lupus patients on HCQ, who developed C19. The study does not compare chances of lupus patients on HCQ to get C19.
@Leopold Danze Goldstein
I suggest you should take the trouble and read a tiny abstract completely and carefully.
The number 17 is from another study they were citing. There own data is this:
They had 80 patients with SLE and 121 of 573 COVID-19 positive patients with rheumatic disease who took antimalarial prior to their infection. Yet, 60 (49.6%) required hospitalisation.
Leo,
It has been two days since I showed you data on these patients.
For one thing, it was not a search, it was a voluntary registry.
https://www.youtube.com/watch?v=1plkwhi5KUE
Title: Vindication! HCQ + Ivermectin work!
The MSM deceives by reporting covid cases, which is meaningless partly because that includes those who don’t even have symptoms, and cumulative deaths which is misleading. The decline of hospitalizations and deaths tells the real story:
US hospitalizations per week
https://drive.google.com/file/d/1dggXGX9KPtbhgSOWQqeJ9Jk9fRANIT3l/view?usp=sharing
US deaths per week: https://drive.google.com/file/d/1AJ-9WxOHlTUFm8T_sOSosoCMDdeVrDaH/view?usp=sharing
That’s great… but what confuses me is the death counts appear to be around 300 per week by June 20. Where is this from? We are at about 500/day in US now?
mar,
The source is the US government, CDC. Where did 500/day come from?
Link address is provided with each graph. Here are hot links:
Deaths: https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm
Hospitalizations: https://gis.cdc.gov/grasp/COVIDNet/COVID19_5.html
If you want to see evidence about the causes of climate change, click my name.
Hi Dan. The daily deaths in US, from World-O-Meter.
https://www.worldometers.info/coronavirus/country/us/
I think they are the standard for what’s happening. I could be wrong.
Scroll down to the charts and you can see the daily deaths chart.
That’s interesting. The US CDC weekly “provisional deaths”shows an order of magnitude fewer deaths than World-O-Meter daily death count in the US. Is http://www.worldometers.info/coronavirus
using a model? Their sources vary using local health departments and some other sources.
So, now what to believe?
“So, now what to believe?”
You could try reading what CDC actually says about their data. Above the graph they have a para highlighted in blue, with a bit (i) marker. It says:
”
Note: Provisional death counts are based on death certificate data received and coded by the National Center for Health Statistics as of July 8, 2020. Death counts are delayed and may differ from other published sources (see Technical Notes). Counts will be updated every Wednesday by 5pm. Additional information will be added to this site as available.”
In the caption to the graph is says that the data “do not represent all the data that occurs in that period.”
In the notes, there is a section which says:
“Why These Numbers are Different
Provisional death counts may not match counts from other sources, such as media reports or numbers from county health departments. Counts by NCHS often track 1–2 weeks behind other data.”
and then
“Provisional counts are not final and are subject to change. Counts from previous weeks are continually revised as more records are received and processed.
Provisional data are not yet complete. Counts will not include all deaths that occurred during a given time period, especially for more recent periods. However, we can estimate how complete our numbers are by looking at the average number of deaths reported in previous years.”
The point is that data for any given week will continue to rise as more data comes in. Worldometer just gives the increment in total reported deaths, without reassigning to date of death. So each days figure is not subject to increasing as later data comes in.
Nick: Thank you for your detailed explanation. I did see that… and over the long term, there is time to catch up. It seems that they don’t catch up or a quite significant thing is happening with World O Meter… which makes me thing if the sources reporting to them have much higher numbers, this begs the question, how to US local sources give higher numbers… are they an estimate, do they use a model to calculate? Thank you for looking into this.
I am asking the question because I have not put in the time and figured someone else may have. If I get too frustrated I will have to put in an effort myself, but do not want to duplicate the effort if someone knows.
@mario lento
worldometers does not use a model for their updates. They have models for predictions available but their daily updates are not modelled. If you look at the country data for the U.S. here
https://www.worldometers.info/coronavirus/country/us/
you can see the column “source”. There is a link listed where their data comes from. That can be one or multiple sources.
Hi Ron: I do understand that they use predictive models for future outcomes. I am wondering how they have been able to show an order of magnitude more deaths than the CDC… given that the CDC has had time over the past to update for latency of reporting of deaths. At some lag, the counts should be updated to reflect all deaths reported and they seem not to be.
It is accepted by nearly everyone in numerous fields, economics, criminology, epidemiology…that accurate statistics from a given interval of time, are only going to be available after a considerable period of time.
All such numbers are always revised for many months after the initial readings are given.
It does not matter if it is employment data, economic activity, GDP growth, crime, flu deaths…none of it is considered usable for an absolute value in real time.
Many of us have known this for years and years, because it has always been true, even when populations were smaller, economies were smaller, etc.
Real time numbers are always taken to be preliminary estimates at best.
@mario lento
One order of magnitude would be 1.3 million vs. 130k. I think you meant something different.
I don’t know how worldometers averages the data when there are different sources for one state but for Arizona e.g. they just take the official number from this website:
https://www.azdhs.gov/preparedness/epidemiology-disease-control/infectious-disease-epidemiology/covid-19/dashboards/index.php
Nothing else. This is just faster than the CDC. Probably weeks faster.
Ron: CDC are showing about 150 to 200 deaths per week now (note weekly not daily).
So, Worldometer is showing about an order of magnitude deaths if you multiply the daily count to get weeks. Seems they get a complete count whereas the CDC does not get a complete count until some lag in time.
This is the CDC data. https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm
Scroll down to the graph of deaths. It’s stunning in the decline, which is artificial.
But I did notice something… the older data on CDC site seems to have been updated to show the lagged data got back filled. The more recent data is not up-to-date yet, showing less deaths. That explains the steep slope of the downtrend to recent times.
In summary:
The more recent data is not complete, where as the older data has been updated to reflect all death’s reported.
So this begs the question, how does Worldometer get the data immediately?
Taking all the available up-to-date state data and just summing them up?
Doesn’t seem too complicated.
Ron: We’re going around in circles.
Although I do wish for the declining trend in deaths to be steep… I question the CDC’s trend graph as misleading.
The CDC’s trend graph shows the trend being steeper than reality. It’s because there is a lag in summing up the deaths, such that the date on deaths at time = to present are lower than they will be over time. The function is that yesterday’s deaths will increase from where they were and so forth for some period of time!
They do not “directly” make this obvious, so I sought out to find an explanation. I figured it out, and think it’s useful information.
The CDC is not in the business of maintaining up to date stats on a website.
That is not their job or mandate.
They have had disclaimers since March saying that for up to dat info, check with states one by one.
It’s appalling that this survey arbitrarily chooses to disregard the supplement with perhaps the strongest correlation to COVID-19. Vitamin D deficiency is a common link between cohorts with severe COVID-19 cases (elderly, Mediterraneans, African Americans), whereas high levels of vitamin D (Norway, Sweden, and Finland) have far less prevalence/severity. Multiple studies are showing this correlation. I don’t understand the unwillingness of medical experts to even consider vitamin D as a possible preventive and early stage therapeutic. I take vitamin D3 every and urge everyone I meet to do so.
It seems that the medical profession is averse to discussing nutrition in the context of infectious diseases.
It is not one nutrient. It is all of them, in general.
I am not so sure anyone who checks into a hospital is even tested for serum concertation of vitamins and minerals.
They are not part of any routine blood work panel.
I have not seen anyone talking about HCQ being dangerous.
Recently.
It is a very useful medication.
It has a well know safety profile.
But we must know, how useful is it for this purpose?
I think someone who was upset about straw man arguments is now bringing up an objection that was not made, and refuting it.
As for the Henry Ford Health System study, it is known to be the case that they treated patients during the interval of the retrospective study using treatments and drugs which are not revealed in the study.
Among them are powerfully effective ones.
The study purports to be all of the patients admitted from March 10th to May 2nd.
During that time, they used many drugs this study chose make no mention of.
You do not have to like it.
But by their own published and publicly documented records, including a study of a subset of these same patients prove it to be the case.
Refusal to acknowledge this information will not make it go away, but it is transparently obvious that ignoring it is a deliberate refusal to look at the facts.
Facts.
Not from me.
From Henry Ford Health System.
Here is what doctors there say about their use of HCQ:
“Henry Ford Health System has continued its multiple clinical trials of hydroxychloroquine, including one that is testing whether the drug can prevent COVID-19 infections in first responders who work with coronavirus patients. The first responder clinical trial was trumpeted by Trump administration officials early in the pandemic.
But the top infectious disease doctor at Henry Ford Macomb Hospital said he only treats COVID-19 patients with hydroxychloroquine if families insist. ”
https://www.detroitnews.com/story/news/local/michigan/2020/06/10/health-systems-mixed-use-hydroxychloroquine-covid-19/5328358002/
They only use it if the patient insists.
And the other hospitals in that state have stopped using it.
But wait, there is more, and this speaks directly to concerns about safety.
Not from me.
This is the director of infection prevention at Henry Ford Macomb.
“There’s no good study to support benefit (of hydroxychloroquine), but certainly serious concerns about side effects,” said Dr. Nasir Husain, director of the Infection Prevention Program at Henry Ford Macomb. “
Hey Nicholas…
You have Linked to Propaganda article … Absolutely no data… Just quoting people who say they would not use HCQ….
Which is odd as the Michigan study 2541 patients found that HCQ/AZ plus zinc reduced the covid death rate by more than 50% and the covid organ damage by more than 70%.
Anyway why ‘argue’ when you are absolutely incorrect. ‘Arguments’ just noise does not change the truth.
The game is afoot!
These macho type Presidents, may have exactly what is needed to defeat the SWAMP.
Brazil could change the Covid picture if HCQ plus AZ works as expected to stop the spread of Covid.
Brazil going to use HCQ/AZ in a big way to both treat covid patients and as covid prophylactic.
https://www.reuters.com/article/us-health-coronavirus-brazil-hydroxychlo/special-report-bolsonaro-bets-miraculous-cure-for-covid-19-can-save-brazil-and-his-life-idUSKBN249396
RIO DE JANEIRO/BRASILIA (Reuters) – Brazilian President Jair Bolsonaro has gone all in on hydroxychloroquine to help his coronavirus-ravaged country beat COVID-19. He has pushed his government to make the malaria drug widely available and encouraged Brazilians to take it, both to prevent the disease and to treat it.
Now the far-right populist is putting his convictions to the ultimate test: Bolsonaro on Tuesday announced that he had tested positive for the disease and was taking hydroxychloroquine.
Bolsonaro said in a televised interview that he had taken an initial two doses, in conjunction with the antibiotic azithromycin, and felt better almost immediately. His only regret, he said, was not using it sooner.
“If I had taken hydroxychloroquine preventively, I would still be working” instead of heading into quarantine, Bolsonaro said.
Later, in a separate video, he gulped down a third pill. He said he was aware of other treatments, but noted none of them had been proven to work.
“I trust in hydroxychloroquine,” he said. “And you?”
Brazil could change the Covid picture if HCQ plus AZ works as expected to stop the spread of Covid.
Brazil going to use HCQ to both treat covid patients and a covid prophylactic.
https://www.reuters.com/article/us-health-coronavirus-brazil-hydroxychlo/special-report-bolsonaro-bets-miraculous-cure-for-covid-19-can-save-brazil-and-his-life-idUSKBN249396
RIO DE JANEIRO/BRASILIA (Reuters) – Brazilian President Jair Bolsonaro has gone all in on hydroxychloroquine to help his coronavirus-ravaged country beat COVID-19. He has pushed his government to make the malaria drug widely available and encouraged Brazilians to take it, both to prevent the disease and to treat it.
Now the far-right populist is putting his convictions to the ultimate test: Bolsonaro on Tuesday announced that he had tested positive for the disease and was taking hydroxychloroquine.
Bolsonaro said in a televised interview that he had taken an initial two doses, in conjunction with the antibiotic azithromycin, and felt better almost immediately. His only regret, he said, was not using it sooner.
“If I had taken hydroxychloroquine preventively, I would still be working” instead of heading into quarantine, Bolsonaro said.
Later, in a separate video, he gulped down a third pill. He said he was aware of other treatments, but noted none of them had been proven to work.
“I trust in hydroxychloroquine,” he said. “And you?”
To William, if you’re not claiming to be a scientist, that does not make what you understand incorrect! Thank you for the information… sincerely, Mario. There is a lot that can be learned from you… and some others.
Look past the messenger to the message.
I am not arguing, I am explicating.
But when you say we need to believe something because our President needs to defeat the swamp, I agree about the swamp, I agree we have the right president.
I completely disagree we need to decide what to believe regarding a medical treatment, based on any of that.
It is ludicrous.
Beyond that William, you have studiously ignored every single bit of information I have presented.
You do not refute it by logic, or by evidence, or even address it at all.
You dismiss it without a word about the information.
You can tell it is meaningless with a glance…it comes from a source you do not trust.
But the source is the same hospitals and doctors you accept as the last word.
We know for a 100% for sure and true fact that those hospitals used therapies that the recent paper chose to pretend do not exist.
Nicholas McGinley,
Perhaps that is the problem Nicholas. I do not see a ‘point’ in your comments. You do not have a hypothesis that explains the observations.
I do not ‘listen’ to you, because you do not have a hypothesis that explains the observations.
There is sufficient observations to differentiate between hypotheses.
We have peer reviewed observations that HCQ/AZ plus zinc when it is given to the covid patient as early as possible reduces the death rate by stopping the virus from replicating by working as a zinc ionophore.
The Zinc ionophore hypothesis explains why Vitamin D deficient people are 19 times more likely to die from Covid, and Vitamin D insufficient people are 12 times more likely to die from covid.
Vitamin D is also stopping the virus from replicating by creating a zinc ionophore which gets the Z+2 into our negative charged cells.
2541 patients covid patients, six different Michigan hospitals were treated with HCQ/AZ plus zinc …
That HCQ/AZ plus zinc treatment reduced the covid death rate by more than 50% and follow up scans showed a 70% reduction in lung damage…..
And there was not one heart attack in the 2541 treated people.
Kind of a good thing reduces the death rate by more than 50% and reduce lung damage. Great.
This study found HCQ/AZ plus zinc worked if the treatment was started early, as the treatment works by stopping the virus from replicating.
This is a quote from the Michigan study that states exactly what I summarized above to explains why the Michigan study of HCQ work while others did not.
The difference has the HCQ can only work is it is used before the Covid virus has replicated.
“Among a number of limitations, this study included patients who were initiated on hydroxychloroquine therapy at any time during their hospitalization.
In contrast, in our patient population, 82% received hydroxychloroquine within the first 24 hours of admission, and 91% within 48 hours of admission.
Because treatment 13 regimens likely varied substantially (including delayed initiation) across the 25 hospitals that contributed patients to the study, it is not surprising that the case-fatality rate among the New York patients was significantly higher than in our study.”
Some HCQ studies gave HCQ to near dead people. HCQ stops covid by stopping the virus from replicating. It cannot repair covid virus damaged people. When people are near death HCQ can cause heart attacks.
We also know that regardless of sex or age Vitamin D deficient (blood serum 25(OH)D 30 ng/ml.
Vitamin D supplements 4000 UI/day is required to raise the US population blood serum level above 30ng/ml.
Vitamin D is a proto hormone that adds functionality to our cells. In this case is appears Vitamin D creates a Zinc ionophore which enables a tiny amount of Zn +2 into our negative charged cells.
I has been shown in vitro that zinc stops the virus from replicating in our cells.
This above explanation explains why the covid death rate correlates directly with how Vitamin D deficient the person is before getting covid.
Vitamin D deficient people had a 19 times greater chance of dying and Vitamin D insufficient people who were less Vitamin D deficient had a 12 times less chance of dying than…
… than Vitamin D normal people.
That is an amazing range of death rates.
Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3585561
Vitamin D Insufficient Patients 12.55 times more likely to die
Vitamin D Deficient Patients 19.12 times more likely to die
Based on the observations, as Trump says, What have you got to lose?
No evidence that treatment will cause nasty problems. There were spurious indications, but they have been debunked. There is significant evidence HCQ and Zn reduces death. There are way more factors too, and you listed many of them William.
I say, do the inexpensive safe treatment and do a proper placebo double blind study with the proper implementation of HCQ and Zn.
By all means, the precautionary principal should be do what has been shown to work and gather more information. Even the Do No Harm doctrine has been tortured to incorrectly mean, “don’t treat unless you can prove it works…” while knowing that people will die before the proof is agreed upon.
The rest of the scientific debate is healthy, and we will all learn from each other. But first PREVENT the death with what works while mitigating risks as best possible.
I am disgusted with the torturous reasoning behind driving policy that prevents treatment.
Hcq interfere with Remdesivir.
Remdesivir lowers mortality by at least 62%.
Other data shows shorter time to recovery across all patients populations.
HOW is abandoned.
Deaths rates are down
Almost everyone gets it in the hospital.t
And you will never understand this.
https://www.gilead.com/news-and-press/press-room/press-releases/2020/7/gilead-presents-additional-data-on-investigational-antiviral-remdesivir-for-the-treatment-of-covid-19
Mountains of data in the pipe.
The blind focus on irrelevant specks.
The world moves on.
I am going to repost a comment I made back in April.
Anyone can read it and see I have been very consistent.
I have continuously gone back and reread what I am others were thinking and talking about since this started:
“Nicholas McGinley April 24, 2020 at 12:39 pm
“Then add a zinc ionophore plus zinc to one.”
Whoa, wait a second.
If you add two things to one dish, you only know that either one, or the other, or both, had an effect.
You need to do a lot more than two dishes to narrow down if it is zinc, or the ionophore, or both, that had the effect.
And even then you only know there was an effect…it does not prove any single hypothesis regarding the cause for the effect seen (or not seen).
Confirmation bias can be hard to spot in our own thinking, so we have to be careful not to fool ourselves, as I know we are all abundantly aware.
Besides for that, I have asked elsewhere and gotten zero response so far that I have seen, that the many assertions regarding HCQ being a zinc ionophore, have apparently all assumed this to be the case since CQ is one.
Many articles with the assertion in many print and online media have even linked to the source for the assertion, and posted a link to CQ research, not HCQ, and nothing about why it should be assumed let alone proven that HCQ is, as well.
Also, that research was not looking for antiviral effects, it was looking for anti cancer activity, or more precisely evidence for a reason to investigate such activity.
What the research showed was, that zinc was introduced into lysosomes, which are not how this virus enters a cell.
And the net outcome being researched was that this combination of zinc and CQ reduced autophagy, and stimulated apoptosis.
IOW…it killed the cell, by inducing them to undergo programmed cell death.
Adding zinc this way caused the cells to die, an important thing if you want to kill cancer cells.
The research was done, BTW, on cancer cells.
I can think of a lot of reasons not to assume a general systemic effect in a normal person who has a viral illness due to a finding in cancer cells in vitro.
Here is a link to it:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/
There is other research on chloroquine and on zinc ionophores, but none, as far as I have seen, showing the same for HCQ.
Although they are not vastly different in terms of their diagrammed structure, they are very different in when one examines the three dimensional shape.
It may well be an ionophore, but just because the molecules are similar and both work as an antimalarial is very weak evidence for such. Nonexistent really. It is cause to suspect it might be, but we should keep in mind that experts in the relevant fields do not assert that the zinc ionophore effect is a fact, or even a leading theory of why and how these drugs work.
Small changes in structure can completely alter how molecules behave in the body or within a cell.
I have seen where many commenters on WUWT that asserted without evidence that the two drugs are equivalent, and that one is transformed into the other inside the body, or than one is the metabolite of the other.
These are both false.
How different can a molecule be just by substituting a OH for one of the H’s?
How different are methane and methanol?
For anyone who thinks that is an exaggeration, when one substitutes an OH for an H in the chloroquine molecule to make hydroxychloroquine, the melting point of the molecule goes from ~289°C to ~90°C!
And the toxicity data alone demonstrates they are nothing at all like metabolically the same.
The lethal dose for both compounds varies depending on whether man, woman, or an animal, as well as mode of administration (and it varies hugely) but for example in a child the oral LDsubL0 (lethal dose low, the smallest amount that can cause death under controlled conditions) is just ~38mg/kg for chloroquine, but 600mg/kg for hydroxychloroquine.
That is a huge difference.
There are other thresholds listed separately for mental effect, cardiac one, etc.
There is far more toxicity data for chloroquine than HCQ, and it varies hugely for a given affect and a given animal, but in no creature are the number similar.
Pharmacology reference texts say zip about zinc ionophore as a mode of action for any therapeutic effect.
And in fact more and more data is showing these drugs do not kill this virus in a person.
As one might well have surmised (and some of us have) if this result is confirmed, it will match data for in vivo activity vs all the other viruses they two have been tested on.
Any therapeutic value most probably is limited to immunomodulatory and anti-inflammatory effects.
References include 3d interactive diagrams of the two:
HCQ
https://chem.nlm.nih.gov/chemidplus/structure3D/viewer/118-42-3
CQ
https://chem.nlm.nih.gov/chemidplus/structure3D/viewer/54-05-7
And toxicological data here:
HCQ
https://chem.nlm.nih.gov/chemidplus/rn/118-42-3
CQ
https://chem.nlm.nih.gov/chemidplus/rn/54-05-7
Physical properties here:
HCQ
https://chem.nlm.nih.gov/chemidplus/rn/118-42-3
CQ
https://chem.nlm.nih.gov/chemidplus/rn/54-05-7
And detailed human health related data:
HCQ
https://pubchem.ncbi.nlm.nih.gov/compound/3652
CQ
https://pubchem.ncbi.nlm.nih.gov/compound/2719
Finally, I want to point out that anyone who goes back and reads the many lengthy discussions about these drugs here over the past many weeks, will find that the original reports and rave reviews and assurances that this was the cure, the whole debacle would evaporate in a few weeks, CQ cured 100%, back slapping etc.
Only later did the focus widen to include HCQ.
And only gradually did speculations and assertions regarding zinc become part of the story.
There was nothing about using it only at the early stages, or using it with an antibiotic or forget it, or using it with zinc or it is a bullshit study, and especially not that HCQ was THE drug, not that crap chloroquine.
And yet reading now we have people saying all sorts of such things, and acting as if this is common knowledge and anyone who does not know it is a dope.
I have ben reading over threads on the virus from the past two months, and the comments from people then and now are in very few instances and for very few people even slightly reconcilable.
I am not gonna name any names (yet), but few of the most prolific commenters here have stuck to the same story or beliefs, and at no time was there any declarations that new knowledge has caused a rethink.
Instead, glib assurances have morphed into other glib assurances.
Again, I am not gonna start calling specific people out (right now), but it sure would be nice for some of the people to please tell those they are berating when between then and now they acquired such knowledge and such surety.
I have seen some of the people here on other blogs and sites sneering at medical doctors about how stupid they are, given that this commenter has astutely and through pharmacological acumen and encyclopedic knowledge of biochemistry and microbiology, handily cured themselves of COVID 19…but this person can be found a about 5 weeks ago saying that MAYBE they perhaps might have had the virus back in early December, and that one possible reason for a mild case may have been green powders from Costco and some extra vitamin D, with no mention of ionophore or zinc at the time, or even more than a hint of a possibility that the illness might possibly have been COVID.
A similar evolution has occurred in numerous individuals, such that the conversations we are finding now are a case study in moving goalposts, confirmation bias, and non-evidenced certitude that would make a Warmista High Priest blush with shame.
On the other hand, some have shown and yet retain what IMO is a highly evidenced degree of scientific thinking and willingness to abide by new information and to stick to the evidence.”
And here is a reply from Mr Steven Mosher to my comment.
I hope he does not mind my reposting it here.
(please tell me if you do, Steven)
He restates what was on my mind and completes the thought very effectively:
“Steven Mosher April 24, 2020 at 4:47 pm
“Only later did the focus widen to include HCQ.
And only gradually did speculations and assertions regarding zinc become part of the story.”
yep.
it is predictable. Once people decided, ahead of the evidence, that Chloriqine was a cure
then they must defend it to the end.
and every bit of data that falsifies their belief, must be bad.
or they change their hypothesis.
its HCQ
wait
with zithromician
wait
with Zinc
wait
only given early
wait
only given to those with no comorbidity
wait
only for men
wait
only given in dose x
wait
only given on a tuesday
There is no bottom to the number of ways that data can be rejected and hypotheses can be amended to preserve a belief.”
https://wattsupwiththat.com/2020/04/24/coronavirus-covid-19-and-rumination-6/#comment-2976711
“History repeats the old conceits
The glib replies the same defeats
Keep your finger on important issues
With crocodile tears and a pocketful of tissues
I’m just the oily slick
On the windup world of the nervous tick
In a very fashionable hovel
I hang around dying to be tortured
You’ll never be alone in the bone orchard”
-E. Costello
That is a misinterpretation from the presented 3D pictures.
What the 3D picture does not tell is the story about flexibility of conformation or degrees of freedom. Chloroquine and hydroxychloroquine are the same when it comes to that. They might differ in the most likely confirmation though cause of steric differences. I did not check this. Maybe they don’t even do this.
The 3 D structure is typically taken to indicate the conformation with the lowest energy state.
Of course all of the usual rules of degrees of freedom apply.
Consider how a single substitution on a single amino acid can alter the folding of an entire protein.
The 3 D structure is typically taken to indicate the conformation with the lowest energy state.
Of course all of the usual rules of degrees of freedom apply.
Consider how a single substitution on a single amino acid can alter the folding of an entire protein.
There are probably people who will take your remarks to be a dismissal of my comment.
The particulars of the structure are not the point I was trying to make.
I am not sure if you mean to dispute whether CQ is an ionophore.
Certainly on research paper finding it to be so hardly proves it beyond doubt.
This is, IMO, an unnecessary distraction, even if it is a valid argument.
The people that did the research on CQ in 2009 no doubt knew that HCQ was a similar and far less toxic molecule.
They were looking for molecules to test for anticancer activity.
As such, it would behoove them to look for the least toxic version of whatever they wanted to look at more closely.
The fact that no research has been offered to show that HCQ might be an ionophore is significant.
At this point, I am moving on.
No one has shown what has been asserted re HCQ, but no one who has made the assertion wants to even concede they are operating on a supposition.
Not that it matters.
What matters is what happens when people get a medicine.
Lots of molecules have activity in vitro that does not translate into similar activity in vivo, and even fewer of the ones that do, translate into clinical efficacy in curing diseases.
Antiviral activity is not enough to eliminate an infection.
No one has even demonstrated in vivo activity, let alone viral elimination.
Tens of thousands have gotten these drugs.
Millions maybe.
It is not clear any fewer have died as a result.
It is clear that people getting them still die.
It is clear that these drugs have been given to far more people than was warranted by evidence.
I am pretty much done weighing in on this subject for now.
I expect the people who are ardent in their beliefs for the value of this treatment will be the last people to move on.
Many never will.
We can see it very plainly and hear it in what they say.
Reality does not enter into the equation.
They know it, now they just have to convince everyone else.
Proving it was never a requirement for them.
Brad Keyes, where are you?
As it was me who first brought up the fundamental chemical structure problems for HCQ to even be considered an ionophore… probably not? : )
Your argument was just not scientifically valid. Any binding to another molecule, even water’s pH, could change the preferred conformation. And except of the -H location of the OH there is not a difference in the possible conformations and this is neglectible for the overall similarity.
But in the general, I have to repeat something which did not get sufficient attention:
Does anybody else see the irony that data from China, Wuhan, is basically the foundation of the HCQ hype?
I have said it several times.
Chinese doctors in Wuhan are on record as dismissing CQ and HCQ beneficial treatments.
They were the first to do so with finality.
I was talking about the pre-print about the Vero6 cell assay, later published on Feb 4th in Cell Research. That is where it started and it was a group from Wuhan.
President Trump mentioned it at a press conference on March 18th.
I was talking about treating patients with the virus.
A factor in all this:
I helped a nephew do a remodel on a 4 story building, each floor had 4~6 doctors, on the first floor was the doctor cafeteria and the second floor cafeteria for general employees. Every day a sales rep would arrive along with a catered lunch, a different manufacture each day. The food was unbelievable, like first class on a cruise liner, deserts alone were $10 worth of pasties a serving, main course and drinks another $15~$30. Every spare inch had cases of sample drugs… I didn’t notice any Hydroxychioroquine
FYI: Everyone I was with in Vietnam took the dam pills, nobody died from the pills.
Looking at the data from Louisiana vs. Orleans Parish
https://experience.arcgis.com/experience/746f03e88d204a2b82a7b958ea744bba/?data_id=dataSource_3-LDH_Data_1126_386%3Anull%2CdataSource_3-Overall_2016_Tracts_5791%3Anull%2CdataSource_3-LDH_Data_1126%3Anull%2CdataSource_3-LDH_Data_1126_5410%3Anull
I have a provocative claim to make:
Drinking outside will saves lives!
The numbers of new cases per day in Louisiana is going up very steep but not in Orleans Parish where it is allowed to drink outside from an open container.
It’s time to change this legislation now everywhere!
Thank you Mr. Goldstein!
You hard work producing this piece, and all previous articles, is very much appreciated. Someday, hopefully someday soon, the truth will come out about HCQs early use in helping people LIVE though this disaster.
As a health care professional and reader/critical appraiser of medical literature I was intrigued by this contribution to the literature – not because of the idea that HCQ may help Covid 19 but at the reported gullibility of the medical fraternity to quackery and non-evidence based medicine.
Plus the author promoting opinion surveys as evidence or even a systematic review? Errr….no. It’s absolutely not evidence. It may be a form of consensus though…..
I’m afraid Mr Goldsteins statement physicians choice is comparable to a RCT is absolutely wrong. There are many hierarchies for evidence in medicine which are based on one of the original and enduring which was proposed by Guyatt and Sackett way back in 1996 and can be summarised thusly (after Greenhalgh):
1 Systematic reviews and meta-analyses of “RCTs with definitive results”.
2 RCTs with definitive results (confidence intervals that do not overlap the threshold clinically significant effect)
3 RCTs with non-definitive results (a point estimate that suggests a clinically significant effect but with confidence intervals overlapping the threshold for this effect)
4 Cohort studies
5 Case-control studies
6 Cross sectional surveys
7 Case reports
You can see where this survey rates,
A good study on a medicine is prospective, with randomised study groups, double-blind and contains a controlled group, with and active comparetor or a placebo. It contains sufficient numbers to provide sufficient power statistically. Diagnosis, outcome and measurements are standardised and assessors are blinded to randomisation.
There is no convincing study in the world which has reported positively on hydroxychloroquine (with or without concomitant treatments). There is no favourable risk/benefit known.
It’s true we are being let down by people rushing in to print or pre-print with poor studies (I found this summary clear – https://www.statnews.com/2020/07/06/data-show-panic-and-disorganization-dominate-the-study-of-covid-19-drugs/) and the WHO have discontinued studies in to this agent https://www.who.int/news-room/detail/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19
Everyone in the health field around the world would be very, very grateful for any crumbs of comfort against the Covid-19 virus, (while dexamethasone is probably useful in the ventilated patient, it’s not a prophylactic agent or treatment agent for those with less severe disease states) but there is little comfort out there.
A review of surveys of opinion has no scientific validity in medicine – and it will certainly not inform my practice, or of any health care practitioners I know across the world, especially if New Zealand ever becomes significantly exposed to the virus in the future.
Kia kaha
(stay strong)