As I wrote before, it is unfortunate that the president of the United States has endorsed the use of hydroxychloroquine against COVID-19, because this has politicized everything having to do with the perception of this drug by the public. When scientists or non-scientists think about hydroxychloroquine, they should be thinking about it as “a drug” that we are researching to find out whether it’s beneficial against COVID-19. Unfortunately, as I warned before, this is becoming more and more difficult. Now hydroxychloroquine is “the president’s drug”. In the current social mindset if you think hydroxychloroquine works, then some people believe you are for the president and for promoting and using a worthless drug, and if you think hydroxychloroquine doesn’t work, some people believe you are against the president and against saving thousands of lives using a drug that has been proven to work. Any statement about the drug is viewed through these warped lenses.
In my exchanges on Twitter, I often encounter individuals who promote many erroneous or ambiguous claims about hydroxychloroquine. I have stated, for example, that we can’t rely on the opinions and experiences of doctors and patients to establish whether the drug works. We need clinical trials. I try to explain that doctors, patients, and all human beings in general including scientists are prone to biases that arise through no fault of their own, and that is why we have procedures such as blind protocols and placebos to guard against these biases. However, my comment is invariably interpreted to mean that I am questioning the qualifications of hundreds of doctors, and the trustworthiness of thousands of patients, because I want to discredit positive results for hydroxychloroquine.
I have also tried to explain that not all clinical trials are well-designed. Just because some trials found that hydroxychloroquine works, that doesn’t mean it works. Just because some trials found that hydroxychloroquine doesn’t work, that doesn’t mean it doesn’t. Scientists have to evaluate the quality of the trials. All clinical trials have limitations, which we have to take into account before we make a decision. The results of one well-designed clinical trial can trump hundreds of poorly designed trials. However, my comments regarding the hydroxychloroquine clinical trials are invariably interpreted to mean that I am trying to discredit the studies that favor the drug because of ulterior motives.
As I have stated before, I am a hydroxychloroquine skeptic, but my skepticism towards the drug is not rooted in a desire to shoot it down just because the president promoted it. My skepticism is based on well-designed published studies, soon to be published studies, and reviews that indicate that hydroxychloroquine as a single agent or combined with antibiotics is not effective to treat patients sick with COVID-19 or as a prophylactic to prevent patients from being infected with COVID-19 or at least ameliorating their disease. Below are some of these studies:
Efficacy of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-Analysis
Update I. A systematic review on the efficacy and safety of chloroquine/hydroxychloroquine for COVID-19
A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19
Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial
A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease
Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19
Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial
Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial
In addition to the above, the hydroxychloroquine trials at the World Health Organization (Solidarity trial) and the NIH (Orchid trial) were halted when independent reviewers of the data concluded that hydroxychloroquine offered no benefits (these trials have not yet been published)..
Early on in the pandemic, the narrative was put forward that patients with Lupus who were taking hydroxychloroquine were less affected, or did not develop COVID-19 with the same severity. But this is not true. Lupus patients on hydroxychloroquine get COVID-19 at rates and severity comparable to Lupus patients not taking hydroxychloroquine.
Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19
Finally, there are also studies with animals that have shown no effects of hydroxychloroquine.
Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2
Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates
Back in 2005, some observations on the effectiveness of chloroquine were made in an experiment performed in culture on a cell line derived from the kidneys of an African Green Monkey (Vero E6 cells). The results of this experiment have been used nowadays to try to discredit Dr. Fauci. In the article that I quoted above on testing hydroxychloroquine on non-human primates, the authors tested hydroxychloroquine on Vero E6 cells and found that it has an antiviral effect. Then they tried the drug on a model of reconstituted human airway epithelium developed from primary nasal or bronchial cells (a more relevant model) and they found that hydroxychloroquine has no antiviral effect, whereas previously the authors had found that remdesivir did have an antiviral effect in this model.
Based on some of the above evidence the FDA revoked its emergency use authorization of hydroxychloroquine.
Like I have said many times, all studies have limitations, and it’s healthy to discuss the strengths and weaknesses of studies. But in their comments, many of the apologists of hydroxychloroquine go beyond this, as they infer a nefarious intent behind the limitations of the studies, which they assume to have been introduced into the study protocol on purpose to make hydroxychloroquine (and the president) look bad. If these people have very good evidence that this is the case, then they should present it, otherwise engaging in this innuendo is unwarranted, disrespectful, and unacceptable.
Even though I am skeptical of hydroxychloroquine, I don’t want to be right, I want to save lives. If well-designed clinical trials prove that hydroxychloroquine works, then it works, and we HAVE to accept it works; no excuses. However, if well-designed clinical trials prove that hydroxychloroquine doesn’t work, then it doesn’t work, and we HAVE to accept it doesn’t work; no excuses. Whether the president promoted the drug or whether the results of the studies agree with your politics is irrelevant. This is what science is, or at least should be about. Hydroxychloroquine should just be “another drug” being evaluated for COVID-19 by scientists having the best interests of the patients in mind. Hydroxychloroquine should not be “the president’s drug”. Making it the president’s drug fans the biases and prevents a rational appraisal of whether it works or not.
Note: after I published this, it was pointed out to me that hydroxychloroquine may work when combined with zinc. I have acknowledged that to establish this we need to wait for the results of several clinical trials that are ongoing. However, the subject of this post is the original claim that was made for hydroxychloroquine: that it works as a single agent or combined with antibiotics. Sure, we will move on to zinc, but first can we agree that the evidence from the best studies indicates that hydroxychloroquine as a single agent or combined with antibiotics DOES NOT work against COVID-19?
The photo of President Trump from Whitehouse.gov is in the public domain. This photo was merged with an image of hydroxychloroquine by Fvasconcellos also in the public domain.