This page is far from finished. My husband, bless him, insists I publish it now, continuing to add more studies afterwards – since he is sure that this information may save a life and can’t wait. If this information is important to you, please check back every day or so to see what may have been added.
There has been a lot of controversy about the use of Hydroxychloroquine (HCQ) as a treatment of COVID-19. This is an old antiviral medication, in use for more than 60 years, and considered safe for daily use even during pregnancy, yet doctors have risked their careers to use it for patients with COVID-19.
Today, in many parts of the US, pharmacies refuse to fill prescriptions; claims have been made that it is safe, unsafe, deadly, wonderful, terrible, or useless. The reasons for all this go deep into politics and the problem that an emergency vaccine can only be approved if no acceptable treatment or prevention is available.
All this controversy, however, is a topic for another day. Here, we will let the research itself talk a little about the urgent topic of its use for treatment and/or prevention of COVID-19, and — here and there — its use for lupus, malaria, rheumatoid arthritis, and diabetes.
Shah et al (March 2020) full text
A systematic review of the prophylactic role of chloroquine & hydroxychloroquine in coronavirus disease-19 (COVID-19)
This is a review of all the (few) studies on the use of HCQ and the similar CQ for COVID-19 published by March, 2020. They searched a number of databases but only found 45 studies.
Actually, the authors only considered 5 of the studies they found — 3 were in-vitro pre-clinical studies (e.g., not on people) and 2 were opinions. The in-vitro studies showed the drug as having a prophylactic effect against COVID-19 (also known as SARS-CoV-2), and the two opinions recommended the use of HCQ and CQ for prevention of COVID-19. Shah et al acknowledge that HCQ has a better safety profile than CQ, and is even considered safe for use in pregnancy. However, they conclude that the drug should NOT be used against COVID-19, citing unspecified “safety concerns,” “questionable efficacy,” and the “danger” of depriving current users of these drugs. They worry about creating a “false sense of protection among the common masses.”
Singh et al (March 2020) full text
(username/password = private/papers)
Chloroquine & hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search & a narrative review with a special reference to India & other developing countries.
The authors reviewed two studies on humans. concluding that due to the “minimal risk upon use, a long experience of use in other diseases, cost-effectiveness and easy availability across India … these drugs are worthy of fast track clinical trial for treatment.”
They also noted that because HCQ is already approved for diabetes in India, and since diabetics are in the high-risk group for COVID-19 mortality, it should be further researched for use for them.
Here are some studies on the use of HCQ for diabetes:
- Quatraro et al (1990) – Hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus: A new job for an old drug?
- Kang et al (2009) – Hydroxychloroquine: A diabetic drug in disguise?
- Wondafrash et al (2020) – Potential effect of hydroxychloroquine in diabetes mellitus: A systematic review on preclinical & clinical trial studies
Garcia-Cremades et al (August 2020)
Optimizing hydroxychloroquine dosing for patients with COVID-19: An integrative modeling approach for effective drug repurposing
Using pharmacokinetics integrated with in vitro data, the authors are attempting to define the best dose for HCQ both for treatment and for clinical trials, while avoiding the heart QT problem of higher doses.
Notice that in the chart below, the higher dose and the 10-day periods resulted in the lowest viral load compared to the lower dose and shorter treatment period. The addition of azithromycin antibiotic also appeared to be better than the HCQ alone, although since those groups got it three times a day (TID) and not twice a day (BID) it is hard to compare. The amount of zinc consumed doesn’t appear to be included, at least not in this chart.
The least viral load after treatment appears to be 600 mg HCQ twice a day for 10 days, but even 200 mg HCQ twice a day for 5 days is better than nothing (the black column on the left). Keep that in mind when you read other studies.
Marmor (May 2020) – full text
COVID-19 and Chloroquine/Hydroxychloro-quine: Is there ophthalmological concern?
This is an editorial about the concern that while the antivirals HCQ and CQ may be helpful for COVID-19, they can cause retinal damage at high dosage or when used for long periods.
However, he says, while this may occur after 10+ years of use, no vision loss has been reported at “loading” doses up to 1200 mg.
In conclusion, Marmor says, “the evidence to date indicates that extreme doses do accelerate retinal toxicity, but with a probable time course of many months rather than days.” During this time of crisis, he concludes, ophthalmologists should be reassuring physicians and the public that retinopathy is not a serious concern in CQ or HCQ usage for COVID-19.
Should chloroquine & hydroxychloroquine be used to treat COVID-19? A rapid review
This is another review of studies published by March 2020, and only 3 were discussed. They are listed in Table 1.
Of the three studies, the one from China (Gao et al, 2020) was a letter to BioScience Trends, reporting on the treatment of more than 100 patients. They reported that CQ was better than the “control” treatment because it shortened the disease and prevented pneumonia. Based on their findings, regulatory authorities agreed to include it in the treatment of COVID-19 in China.
A study in France (Gautret et al, 2020) of 36 people testing positive, 20 were given 200 mg HCQ 3 times a day (TID) for 10 days, with 6 given azithromycin as well, and 16 were the “controls.” 70% of the treatment group were cured by Day 6, compared to 12% of the controls. All 6 of those given both medications tested negative on Day 6. Unfortunately, the treatment and control groups were not randomly allocated, so the authors suggest there could have been bias.
Another Chinese study (get password for Chen et al, 2020) involved 30 people over 18 who tested positive and were hospitalized. They were given 400 mg/day of HCQ for 5 days. There was almost no difference between the treated and control groups when they were retested on Day 7. (Note: See the chart of Garcia-Cremades et al, 2020, above)
Gbinigie et al complain that none of the studies were done in regular doctor practices but only in hospitals, and that more research is needed since (as of March) there was insufficient evidence to support the use of CQ or HCQ except for research.
Conflict of Interest: This review was funded by the Wellcome Trust, a pharmaceutical company charity.
Giammaria & Pajewski (June 2020) full text
Can early treatment of patients with risk factors contribute to managing the COVID-19 pandemic?
Basically, their answer is YES.
Only about 20% of patients with COVID-19 develop serious symptoms, which seem to take about a week to come on, giving time to identify those at risk and treat them with antiviral medications.
The authors identified two phases, similar to that of SARS and MERS (also coronavirus illnesses). The first is a “viral” phase in which the viral load increases rapidly, infecting cells and triggering an immune response. The second is the “immune” phase which occurs only in some patients – this is when the immune system loses control, causing serious damage to the lungs, kidneys, and heart — also called a cytokine storm.
The authors describe their development of an algorithm using data from Italy and China to identify individuals at risk of developing severe or lethal forms of COVID-19. Risk factors are age (65 years or older), male sex, and at least two of the following: hypertension, diabetes, lung disease, heart disease, or brain/blood vessel disease. Using this algorithm, doctors can decide which of their patients are at risk and also which antiviral medications would be suitable based on possible interactions with other medications the patients are taking.
The authors warn that a delay until hospitalization to begin antiviral treatment could reduce its effectiveness, so those at risk should begin treatment at home as early as possible after symptoms or a positive test is observed — and for those at risk, waiting several days for test results could be a problem, so treatment should begin earlier, and then could be stopped if the test results show it is not needed.
The antiviral drugs known to be effective at the time this paper was published (June 2020) were CQ, HCQ, and a combination of Lopinavir and Ritonavir (which would be the preferred treatment for a patient with a prolonged QT (heart abnormality).
Quote: “Early antiviral treatment of symptomatic patients at risk could result in a reduction in the numbers of hospitalizations and intensive care treatments and, therefore, of the related costs incurred b public health systems.
Mahevas et al (May 2020) full text
Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: Observational comparative study using routing care data
All the patients in this study were in various hospitals. They all needed oxygen and had developed pneumonia. An unknown number of the group given HCQ were not treated for the first two days after admission, and eight were not treated until an unknown number of days after that. The outcome measurement was the percent who survived until the 21st day without going to intensive care. They were about equal — 75% of the control group and 76% of the treatment group. There was a minor difference in that by day 21, 82% of the treatment group no longer needed oxygen, while only 76% of the control (untreated) group were okay without oxygen. 10% of the treatment group were removed from HCQ because they had some kind of heart-related symptom.
The dose of HCQ used was 600 mg per day. They were not given zinc and apparently were not given any sort of antibiotic, either. The authors concluded that for patients in a hospital and needing oxygen, HCQ doesn’t do much to improve their condition. They admitted they did not know if giving it earlier would be more effective.
Note: Take a look at Garcia-Cremades et al, 2020 above for more on the QT with high dose HCQ. Since Garcie-Cremades et al were considering HCQ use early in the illness, it can make one wonder if the patient is more vulnerable to this side effect as he gets sicker.
Conflict of interest: In the original publication, they claimed to have no conflicts. Someone wrote to the British Medical Journal complaining, and they investigated. The authors had to include their relationship to various pharmaceutical companies, and this was published as a correction. Although none of the companies directly funded this paper, they were apparently very generous in other funding and “non-financial support.” There were SO MANY that I got tired of highlighting them. You can see the list on Page 8.
To be continued …