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Dr. David Borenstein M.D. 3/2020

Hydroxychloroquine is a close relative of chloroquine, a drug that was used during WWII for preventing malaria. Hydroxychloroquine has been mentioned increasingly as a possible treatment for the coronavirus infection. During the 1940’s, soldiers who received chloroquine had a decrease in their arthritis. Hydroxychloroquine (HCQ) was developed to be more easily tolerated.

HCQ was first used in 1951for the treatment of rheumatoid arthritis (RA). HCQ remains an important component of disease modifying therapy for RA. This drug is also frequently prescribed for the treatment of systematic lupus erythematosus (SLE). HCQ is particularly helpful for the skin and joint problems associated with SLE.

Viruses are replicating machines. Their existence is based upon reproducing themselves, using a host’s cells to be the manufacturing plants. The virus attaches to the cell membrane at different specific receptors related to the type of virus. The virus invades the cell where it forms an endosome or lysosome. In the endosome, the virus will use the energy of the cell to replicate itself multiple times. Importantly, the ideal function of the lysosome occurs in an acidic environment. If the lysosome or endosome becomes more basic, the function of this structure is impaired. When the lysosome works appropriately, the process of reproducing the virus kills the host cell.

HCQ has a wide variety of actions, a number of which affect the immune system. An important mechanism that appears to interfere with normal physiologic function in structures like the endosome depends on the acidic environment. HCQ is a weak base that is able to enter this acidic space and make it more basic. The rise in ph results in a disorganization of the lysosome making it unable to reproduce proteins and viral particles.

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The exact dose of HCQ that is required in this acute circumstance to halt replication is not determined. The usual dose is 400 mg of hydroxychloroquine at night. For the Covid-19 infection 600 mg has been used for a 2 week period to suppress the infection. Clinical trials have been started to determine the duration and dose necessary to control the infection.

Pharmacies have already reported shortages of chloroquine and hydroxychloroquine as individuals obtain these drugs in anticipation of their beneficial efficacy. India, a prime supplier of the drug, has suspended export of the drug to other countries. Other manufactures of hydroxychloroquine like Novartis and Teva, have announced increased production of the drug in anticipation of demand.

Although, on a mechanistic basis, hydroxychloroquine could have a beneficial effect in slowing the replication of the Covid-19 virus, the parameters that tell us who is the appropriate recipient of the drug and the potential side effects they may experience remain to be determined. Further data from the ongoing clinical trials will answer these questions. Until the results of those trials are available, the use of hydroxychloroquine for Covid-19 infection is experimental.