Coronavirus Insights -- Feb. 23, 2021: The Hydroxychloroquine Edition


Dear Nutmeg Aspirin Community, 

If you are reading this newsletter, then it's likely you've had experiences in the modern medical system that have caused you to cast doubt on it and perhaps even lose trust. It's understandable! We are taught to believe doctors, trust experts, and follow the rules. But when neither doctors nor experts can agree, who should we listen to? Which rules do we follow?

Hydroxychloroquine, or HCQ, could be at the center of this idea as a case study. The story of HCQ, an anti-viral drug commonly used to treat malaria and repurposed to treat COVID, goes something like this: During Spring 2020, HCQ was said to be highly effective in treating COVID. Then, a "slam dunk" study published by The Lancet said that it was not only ineffective, but also potentially very dangerous. Next, The Lancet retracted the study after the organization that submitted it would not share its data to participate in the peer-review process. Since then, more studies and retroactive case studies have shown that HCQ is effective when it's used early (and sometimes, in combination with zinc and azithromycin). In Nov. 2020, the American Medical Association (AMA) reversed their position and rescinded that doctors stop prescribing HCQ. Now, in early 2021, the consensus is that more trials are needed, but the benefit of HCQ outweighs the risk.

However, we have not heard that story -- the FULL story -- in mainstream conversations. And so, we are back to our original questions: Who should we listen to? Which rules should we follow?

The following reference list tells the story of HCQ that we summarized above and gives you more information to make the choices you need to make for your own well-being. Reference credit goes to The Highwire, which listed these references (and others that we chose not to include based on our preferred rigor of sources) in their own analysis of HCQ.

We hope it encourages you to continue to think critically and be mindful that choices for effective COVID treatments do exist.



Via National Institute of Health
Chloroquine is a potent inhibitor of SARS coronavirus infection and spread

"Chloroquine is effective in preventing the spread of SARS CoV in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with chloroquine prior to or after SARS CoV infection. In addition, the indirect immunofluorescence assay described herein represents a simple and rapid method for screening SARS-CoV antiviral compounds."


Via Global Research
A Report on Successful Treatment of Coronavirus

Dr. Zelenko shares his successful outpatient regiment that includes hydroxychloroquine (combined with zinc sulfate and azithromycin).


Via Science Direct
COVID-19 outpatients: early risk-stratified treatment with zinc plus low-dose hydroxychloroquine and azithromycin: a retrospective case series study

"Clinical experience from severely ill inpatients with pneumonia who were treated with high-dose HCQ is not readily transferable to the outpatient setting with upper respiratory tract disease only. For outpatients with a median of only 4 days after onset of symptoms, COVID-19 represents a totally different disease and needs to be managed and treated differently [63]. A simple-to-perform outpatient risk stratification, as shown here, allows for rapid treatment decisions and treatment with the triple therapy of zinc, low-dose HCQ and azithromycin and may prevent a large number of hospitalisations and probably deaths during the SARS-CoV-2 pandemic. This might also help to avoid overwhelming of healthcare systems."


Via New York Post
Hydroxychloroquine rated ‘most effective’ coronavirus treatment, poll of doctors finds

"Of the 2,171 doctors asked which drug is most effective, 37 percent said hydroxychloroquine. By contrast, 32 percent answered “nothing.'”


Via The Detroit News
Hydroxychloroquine lowers COVID-19 death rate, study finds

"The study analyzed 2,541 patients hospitalized among the system’s six hospitals between March 10 and May 2 and found 13% of those treated with hydroxychloroquine died while 26% of those who did not receive the drug died."


Via Age of Autism
WHO "Solidarity" and UK "Recovery" Clinical Trials of Hydroxychloroquine using Potentially Fatal Doses

"Last week, I was alerted to the fact that India's ICMR, its official medical research agency, had written to the WHO, telling WHO that the hydroxychloroquine doses being used in the Solidarity trial were 4 times higher than the doses being used in India.  Then I learned that Singapore had been hesitant to participate in the WHO trial due to the hydroxychloroquine dose."


Via The Lancet
RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

The Lancet issued a rare retraction of a May 2020 published study that stated hydroxychloroquine provided little positive impact in fighting Covid and instead, might increase mortality rates. In a statement, the Lancet shared their reason for retracting the study: "Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis as such transfer would violate client agreements and confidentiality requirements. As such, our reviewers were not able to conduct an independent and private peer review and therefore notified us of their withdrawal from the peer-review process."


Via The Guardian
The Lancet has made one of the biggest retractions in modern history. How could this happen?

"Peer review during a pandemic faces a brutal dilemma – the moral importance of releasing important information with planetary consequences quickly, versus the scientific importance of evaluating the presented work fully – while trying to recruit scientists, already busier than usual due to their disrupted lives, to review work for free. And, after this process is complete, publications face immediate scrutiny by a much larger group of engaged scientific readers than usual, who treat publications which affect the health of every living human being with the scrutiny they deserve.

The consequences are extreme. The consequences for any of us, on discovering a persistent cough and respiratory difficulties, are directly determined by this research. Papers like today’s retraction determine how people live or die tomorrow. They affect what drugs are recommended, what treatments are available, and how we get them sooner."


Via ClinCalc
Hydroxychloroquine Drug Usage Statistics, United States, 2008-2018

The data here highlights that hydroxychloroquine (which was approved by the FDA in 1982) was steadily prescribed around the same rate during 2008-2018. This suggests that the drug has been long-established and widely accepted as safe, contrary to some of the criticism surrounding HCQ in the past year (likely related to the prescribed amount for studies being much higher than what is normally given, as shared above!).


Via Sermo
COVID-19 treatment trends over 6 weeks and 33,700 interviews

Global data helps create a wider perspective on how COVID is being treated. For HCQ as of May 2020, this article shared that: "Usage around the world varies widely; in the U.S., 46% of physicians report using it; that is significantly lower than other countries such as Italy (83%), Spain (78%), Mexico (76%), Brazil (85%), and China (62%). Usage in Great Britain is much lower at 19% and Germany at 13%.

Efficacy: Globally 27% of physicians feel that it is highly effective. However, it is felt to be more effective outside of the hospital in mild-symptom patients (32%). This trend follows what we see in usage (higher usage in mild patients)."


Via Fox News
Hydroxychloroquine could save up to 100,000 lives if used for COVID-19: Yale epidemiology professor

"'Our results do differ from some other studies,' Dr. Marcus Zervos, who heads the hospital's infectious diseases unit, said at a news conference. "What we think was important in ours ... is that patients were treated early. For hydroxychloroquine to have a benefit, it needs to begin before the patients begin to suffer some of the severe immune reactions that patients can have with COVID.'"


AMA Handbook Addendum

The American Medical Association quietly reversed their position on Hydroxychloroquine in late October 2020. They rescinded that doctors stop prescribing HCQ and now admit that benefits outweigh the low risk. 


Via National Institute of Health
Efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19

"For this study, we identified a total of 09 published articles: 03 clinical trials with sample size 150; 03 in vitro studies and 03 expert consensus reports. These studies were all suggestive that chloroquine and hydroxychloroquine can successfully treat COVID-19 infections. We found that COVID-19 infections are highly pandemic in countries where malaria is least pandemic and are least pandemic in nations where malaria is highly pandemic.”


Via C19 Study
HCQ for COVID-19 (All studies)

"Database of all HCQ COVID-19 studies. 254 studies, 184 peer reviewed, 208 comparing treatment and control groups. Submit updates/corrections below. HCQ is not effective when used very late with high dosages over a long period (RECOVERY/SOLIDARITY), effectiveness improves with earlier usage and improved dosing. Early treatment consistently shows positive effects. Negative evaluations typically ignore treatment time, often focusing on a subset of late stage studies. In Vitro evidence made some believe that therapeutic levels would not be attained, however that was incorrect, e.g. see [Ruiz]."


Via New England Journal of Medicine
Hydroxychloroquine in Hospitalized Patients with Covid-19

"We were surprised by the hydroxychloroquine dose chosen in the Randomized Evaluation of Covid-19 Therapy (RECOVERY) trial conducted by Horby et al. (Nov. 19 issue).1 In this trial, patients received a higher dose of hydroxychloroquine (4 g cumulated over the first 3 days) than that administered in the trial conducted by Lagier et al.2 (600 mg per day), and it was similar to that in the trial conducted by Borba et al.3

In vitro studies show that the effect of hydroxychloroquine is mainly mediated by alkalinization of the phagolysosomes,4 where it can concentrate about 1500 times more than in plasma. This effect can be obtained with low doses of hydroxychloroquine because of its long elimination half-life. High doses may therefore be useless or even deleterious because of the anti-interferon action of hydroxychloroquine,5 which may result in a more severe form of Covid-19.6 The dose used in the RECOVERY trial, the second highest after that in the trial conducted by Borba et al., arouses concern because it may have been a disease-aggravating factor negating the therapeutic effect."


Via North Jersey News
Hydroxychloroquine may have some use to treat COVID after all, NJ study shows 

"A new Hackensack Meridian Health study shows that people with mild symptoms of COVID-19 may be helped by a controversial drug that had been widely used in the early days of the pandemic before several studies questioned its benefits and safety.

The recently published study looked at a group of people treated as outpatients last year and found that those who received an anti-inflammatory drug, hydroxychloroquine, which is often used for malaria, were significantly less likely to end up in the hospital. Doctors who conducted the study say the findings suggest that it should be tested further."


Via Tablet Magazine
Hydroxychloroquine: A Morality Tale; A startling investigation into how a cheap, well-known drug became a political football in the midst of a pandemic

"This misbegotten episode regarding hydroxychloroquine will be studied by sociologists of medicine as a classic example of how extra-scientific factors overrode clear-cut medical evidence. Please take the time to read this excellent, rigorous assessment of the HCQ science written by Dr. Norman Doidge, the author of The Brain that Changes Itself. The conclusion- HCQ, azithromycin, and zinc given early, work."


Did you know that we've been providing COVID updates like this since Spring 2020? You can review all past newsletters here. If you have any questions or thoughts, please reach out!


What do you think?

This field cannot be blank

Do you have a story to tell?

If you'd like to contribute to Perspectives, please review our submission guidelines.

View The Contributors' Guide