New reports are full of references to chloroquine and hydroxychloroquine therapy. Such therapy is referred to as "experimental," "unproven," "promising," and so on. Some experts say it should not be used absent scietific data demonstrating its efficacy, others that it makes sense if a patient is in extremis; some suggest that it is a miracle cure, others that it is voodoo.
Hydroxychloroquine was developed as a less toxic version of chloroquine, Both are derivatives of quinine, a substance found in the bark of the cinchona tree. Natives of the Andean forests in which the cinchona trees grow chewed the bark to reduce shivering. When Jesuit missionaries arrived, they reasoned that patients afflicted with malaria shiver, and so perhaps cinchona bark might be used to treat malaria. Whatever the after-the-fact analysis of the underlying reasoning, it turned out to be correct. The active ingredient in cinchona bark was found to be quinine, and British military health authorities developed tonic water for use by British forces in malaria stricken areas. Quinine can have significant aide effects, and so scientists sought ways to modify quinine to make it less toxic. Choloroquine and hydroxychloroquine resulted from these efforts. Clinical observation subsequently found that hydroxychoroquine seemed to be therapeutic in rheumatoid arthritis and lupus. Its efficacy has been proven in these conditions. Chloroquine was also thought to demonstrate some antiviral activity, and even to treat diabetes.
Obviously, cholorquine and hydroxycholorquine seem to be beneficial in a number of disparate conditions, and this implies that they have a number of effects within the body. Their antmalarial effect is thought to be due to alterations in hemoglobin metabolism, allowing toxic heme to accumulate inside the parasites, poisoning them. The benefit in rheumatoid arthritis and lupus is thought to involve downregulation of Toll-like receptors, modifying immune response. The antiviral effects are thought to involve proton trapping within cell lysosomes, altering cell pH. Another theory is that the drugs facilitate entry of zinc into cells, and zinc inhibits viral replication. That is quite an array of effects. They likely share the common factor of altering enzyme function, possibly through affecting intra-celluar acid-base balance.
The suspected activity in coronavirus infection is that they alter acidity within human cells, and many enzymes essential for viral replication are pH dependent. Thus, use of chloroquine and hydroxychloroquine to treat coronavirus infections is rational. That is, there may a reason to think that they will work. Furthermore, there is some evidence, certainly not determinative or scientific enough to establish the efficacy of chlorquine or hydroxychloroquine in treating viral infections, that they are beneficial in treating coronavirus infections. Nonetheless, such evidence supports the empirical use of these medicines in COVID-19 cases.
Both empiric therapy e.g. giving antibiotics to someone with a fever and elevated white blood cell count, but no obvious source of infection, and rational therapy, e.g. treating hepatic encephalopathy with lactulose, are well accepted in modern medicine. Thus, the fact that the benefits of either choloquine or hydroxychloroquine in treatment of COVID-19 have not been proven are not particularly strong arguments against their use. Furhtermore, in severe COVID-19 disease and ARDS, it may be immune-modifying effects that have been demonstrated in rheumatoid arthritis and lupus that is most beneficial. Such effect may mitigate the lung injury caused by the immune response.
Both chloroquine and hydroxychloroquine do have potential adverse effects. The most concerning are provocation of heart arrhythmias and visual impairment. These are the risks that need to be considered in risk/benefit analysis. The fact that neither chloroquine nor hydroxychloroquine have been scientifically proven to benefit COVID patients affects the potential benefits. Nevertheless, a reasonable analysis can occur and a valid decision to use one or the other can be reached. At this point, it would seen that chloroquine and hydroxychloroquine do have a place, although an admittedly uncertain one in patients with COVID-19, especially those with limited options.
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