As I posted last week (god, it seems like so much longer ago), there is some interest in studying Chloroquine and its close chemical relative, Hydroxychloroquine. Just as a refresher, these drugs were developed in the middle of the 20th century as a treatment for malaria. As you may know, malaria is a disease caused by a parasite, transferred by mosquitos to humans. A parasite is basically a very little single celled animal, sort of like the animal equivalent to a bacterium. The malaria parasite infects red blood cells and causes disease. Chloroquine was shown to be effective in treating malaria, but remember malaria is a parasitic disease not a viral disease.
So why is there interest in chloroquine now? The answer is that at the time of the original SARS outbreak, virologists tested thousands of drugs and chemical compounds in the lab to see if one of them could prevent tissue cells grown in flasks (tissue culture) from a challenge with the SARS virus. Chloroquine and Hydroxychloroquine both showed a statistically significant affect. BUT that affect was not strong enough to merit trials in human subjects. With the novel COVID-19 (originally called SARS-2, to distinguish it from the original SARS virus, now called SARS-1) interest in these effects was rekindled.
A single study from some French researchers, published a in the last few weeks looked at less than 50 total COVID-19 patients and whether there was any effect of chloroquine treatment on their condition. The results were equivocal. Four of those patients were treated with both hydroxychloroquine and azithromycin, and the four all recovered.
So, what do we conclude from that study? Very little can actually be taken. Particularly the 4 patients who received the two drugs. The media and rumors on the web have jumped on that result to claim that the combination of the two drugs may be the “miracle cure”. PLEASE, WAIT! The fact that those 4 individuals recovered MAY have been related to the drugs, but there are many, many other factors that may have been responsible. For example, were they all recovering anyway; were they taking any other medications at the same time that others weren’t, maybe for blood pressure, liver disease, etc.? Did they all have strawberry yogurt for breakfast? (that last one is intended to show that if THAT had been the case would we all be rushing out now to buy strawberry yogurt? Which brand? Regular, Greek, French, or non-fat?)
However, a second study was published last week from Shanghai University in China. In this study, 30 patients that had been hospitalized for COVID-19 received EITHER hydroxychloroquine, or a placebo (a similar looking medication, dispensed and taken the same way as the first, indistinguishable to the patient or the doctor, but with no active drug in it).
The results: Whether the patients received hydroxychloroquine or the placebo, their body temperature returned to normal a day after hospitalization, and the time it took for levels of the virus to become undetectable was comparable.
Unlike the study from France, these were randomly assigned to either the hydroxychloroquine group or the placebo-controlled group.
So, what conclusions should we take from this? Again, a little bit better than the French study, but still a very small sample of patients, and a set of patients with a specific presentation of symptoms. The results seem to point to the fact that hydroxychloroquine may not be effective in treating patients whose disease has progressed to the point of hospitalization. This is consistent with the discussion in my previous post, in which I pointed out that the mechanism of action of these drugs is to interfere with the way the receptor is presented on the cell surface and would therefore suggest minimal value in treating a disease in which the cells have already been widely infected.
It will be very important to study patients who are either asymptomatic, but who test positive for the presence of virus, or who have initial mild symptoms and to determine whether, again in a controlled study, if the treatment is therapeutic, lessening the infection or the accompanying disease severity. For example, you would try to get a group of patients, all approximately the same age and health profile, all of whom are asymptomatic, but have been screened because they were exposed to people who had been infected, and all of whom have tested positive for the virus. You would then treat half with hydroxychloroquine and half with a placebo. Following their progress forward you would study whether there was any difference in the progression of disease in the two groups; did one group become ill at a higher frequency, or a shorter time, or with more or less severe symptoms, and which recovered more quickly. That study would give better answers.
One final thought: This is the way that pharmaceutical companies move forward. If there is a clue that one of these drugs can affect the disease process, severity or recovery, then there would be a great push to try “analogs” in tissue culture. “Analogs” are chemicals that are identical to the original chemical (in this case hydroxychloroquine), but with one small change made to them. Maybe the chemist adds an extra oxygen atom, a chlorine atom, some other change like removing a hydrogen atom to create a double bond in place of a single bond between two carbon molecules. They would try again and again in tissue culture to see if they could come up with a variation on the hydroxychloroquine molecule that worked even better. Those new chemicals would then have to be tested for safety and efficacy but could provide eventual therapeutics for treating the disease. That is science, but it, unfortunately takes time.