Hydroxychloroquine for the Prevention or Treatment of COVID-19
Prior to the pandemic, hydroxychloroquine was used for a wide variety of ailments due to a broad array of benefial effects.
Rationale
There are numerous rationale for using HCQ as prophylaxis to prevent SARS-CoV-2 infection and as treatment for COVID-19 patients including immuno-modulatory, immuno-suppression, anti-thrombotic, and in particular antiviral properties.1) In particular, antivirals are effective only when used early during infection, so the best uses of HCQ would likely be as prophylaxis or as early ambulatory (outpatient) treatment. Since HCQ is relatively inexpensive, and with a good safety history, it need only demonstrate modest efficacy to have a positive risk-benefit as a prophylactic or treatment.2)
Additional Research:
See also zinc ionophores
Prior Research
Since shortly after the first SARS-CoV outbreak, researchers compiled evidence that chloroquine and hydroxychloroquine would likely help fight another deadly coronavirus outbreak.3)
- In 2005, researcher Martin Vincent and colleagues noted that chloroquine is a potent inhibitor of SARS coronavirus infection and spread.4)
Antiviral Properties Research (Mechanisms)
- Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture5)
Evidence for Prophylaxis
Prophylaxis Meta-Analysis
- A meta-analysis of 11 studies on Pre-exposure prophylaxis, all performed in India, and with highly similar protocols, showed statistically significant protective effects by those taking hydroxychloroquine. All six of the studies with information to determine dose dependence showed additional prophylactic effects for those taking hydroxychloroquine for at least six weeks, consistent with the hypothesis that hydroxychloroquine shows antiviral action.6) 7)
- Mathew Crawford points out that among 56 studies examining the efficacy of hydroxychloroquine in the prevention of COVID-19, most published with a few in preprint, that 42 (75%) of them measured positive effects (the control arm suffered more COVID-19 than those given hydroxychloroquine prophylactically). Just 12 of the 14 negative studies examined effects on auto-immune patients. The large prophylaxis trials that were to be conducted in the U.S. were either canceled or positive, but stopped mid-trial prior to reaching statistical significance.8)
- The HERO Trial (RCT) measured a 29.3% risk reduction, which was not quite statistically significant. The trial followed healthcare workers for only 30 days, which is less time than the studies out of India that found greater effect sizes. The HERO Trial intended to study 15,000 healthcare workers, but claimed recruiting difficulties, so only reported on 1,360. Authors reported conflicts of interest with numerous pharmaceutical corporations and biotechnology firms.
- The Crown Coronation Trial, which was funded by the Bill and Melinda Gates Foundation and run out of Washingtin University in St. Louis, was to study pre-exposure prophylaxis effects of hydroxychloroquine on 30,000 participants, but was changed to exclude hydroxychloroquine from its protocols.
Evidence Supporting HCQ Use in Treatment
Evidence supporting HCQ's substantial evidence as an early therapeutic is quite strong, both in published literature, and in statements made by physicians successfully caring for large numbers of COVID-19 patients.
Meta-Analysis of HCQ Studies
A substantial majority of published randomized control trials (RCTs) examining HCQ efficacy showed patients in the treatment arm performing better by numerous metrics than those who did not receive HCQ.9)
Controversy
From early on in the COVID-19 pandemic, a large and often vicious propaganda campaign was waged against HCQ's use in the prevention or treatment of SARS-CoV-2 and COVID-19. This started with what appears to have been an orchestrated conspiracy of silence over expectations by infectious disease and coronavirus researchers that HCQ would be the most likely drug to help in the event of another deadly coronavirus outbreak.10)
Media Blitz
Throughout the pandemic, the media parroted incorrect statements suggesting the both chloroquine (CQ) and HCQ were dangerous drugs, which is not generally true. More damaging was the logically incorrect interpretation of research at multiple levels. Dr. Anthony Fauci and numerous other physicians were often interviewed sharing the plainly illogical11) interpretation that one or a small number of studies could demonstrate the inefficacy of HCQ.
Tainted Research
Surgisphere: https://www.the-scientist.com/features/the-surgisphere-scandal-what-went-wrong--67955
Simpsons paradox Suboptimal trial protocols
Links to be Sorted
A paper from July 28, 2020, by Jeffrey Aronson and Robin Ferner on behalf of the Oxford COVID-19 Evidence Service Team which concludes that;
“The hypothesis that the 4-aminoquinolines chloroquine and hydroxychloroquine may be beneficial in the treatment of COVID-19 is a weak one, based on poor mechanistic reasoning and inconsistent results of studies in vitro, in laboratory animals, and in humans.”