Although hydyroxchloroquine received FDA marketing approval about 65 years ago, until recently it generated little interest.  Primarily indicated as therapy for systemic lupus erythematosus and rheumatoid arthritis, hydroxychloroquine remains among the top 150 prescription drugs in America.  In some circumstances hydroxychloroquine may also find use in treating or preventing malaria.  Hydroxychloroquine is a close relative of the slightly more toxic chloroquine.

Laboratory Studies

During the mid-1990s studies in the laboratory, not in humans, demonstrated hydroxychloroquine could inhibit growth of a wide array of RNA viruses including the causative agents of rabies, influenza, Dengue fever and some forms of hepatitis.  Other experiments suggested similar actions against bacteria and fungi. 

In 2009 scientists observed an otherwise lethal exposure of newborn mice to coronavirus OC43 could be transformed into a survivable condition when the mice received milk containing chloroquine.


During the outbreak of SARS in 2002-2003, hydroxychloroquine inhibited growth of the virus – SARS-CoV – in laboratory investigations.  That SARS epidemic spontaneously disappeared before hydroxychloroquine was tested in humans.  During the MERS outbreak, caused by a different but related coronavirus, a tantalizing observation hinted hydroxychloroquine might exhibit anti-MERS-CoV properties.

More recently both laboratory and human testing of hydroxychloroquine against SARS-CoV-19, the causative agent of COVID-19, hinted that the drug might inactivate the virus.  Initial modeling studies estimated blood levels necessary in humans would be easily achieved at a dose of 400 mg two times of day 1 followed by 200 mg twice daily for 4 more days.

Preliminary use in Chinese patients suffering from COVID-19 indicated a favorable response at similar doses with duration of therapy at times extending to 10 days.  French studies published in mid-March demonstrated a positive response to hydroxychloroquine at a daily dose of 600 mg for 10 days either alone or with an antibiotic – Azithromycin.

A larger trial examined patients with mild-moderate illness hospitalized at Renmin Hospital – Wuhan University.  Patients receiving hydroxychloroquine at a dose of 200 mg twice daily for 5 days clearly demonstrated major improvement compared to a group treated with routine care.  The condition in four patients deteriorated; none of these were in the hydroxychloroquine group.   

FDA Emergency Use Authorization

With the coronavirus pandemic sweeping the world, other countries are adding hydroxychloroquine to the therapeutic armamentarium.  In the United States, on March 28, 2020 the FDA issued an Emergency Use Authorization  allowing hydroxychloroquine to be prescribed for patients hospitalized with COVID-19 and weighing at least 110 pounds.  The approval letter noted: “Based on the totality of scientific evidence available to FDA, it is reasonable to believe that chloroquine phosphate and hydroxychloroquine sulfate may be effective in treating COVID-19, and that…the known and potential benefits…outweigh the known and potential risks of such products.”

Lack of Thorough Investigation

While hopes for hydroxychloroquine remain high, the drug lacks formal randomized clinical testing.  In short, the small laboratory and human trials lack the scientific rigor necessary to confirm the actual clinical utility of the drug.  While it may fulfill expectations, other similarly small studies fail to confirm any benefit of hydroxychloroquine in therapy of COVID-19.

Potential Harm

Hydroxychloroquine appears well tolerated and tends to cause typically mild to no side effects at least for its original indications.  Adverse reactions include nausea, vomiting, mild diarrhea, abdominal cramps and headache in small numbers of patients.  Some experience hives, dizziness, fatigue, ringing in the ears or a decrease in hearing.  Rarely hydroxychloroquine leads to tremor, seizures and thoughts of suicide. 

Other complications of hydroxychloroquine tend to be associated with genetic deficiency of an enzyme G-6-PD in which case severe blood abnormalities may occur.  Damage to the eye , at times leading to irreversible vision loss, occurs but usually after several years of continuous treatment.  Hydroxychloroquine predisposes to potentially life threatening and fatal heart disease especially in those with abnormalities of the electrical conducting system that transmits impulses from the upper chambers to the ventricles.  Muscle weakness and severe skin abnormalities comprise additional but uncommon issues with hydroxychloroquine. 

In spite of the long list of potential adverse consequences associated with hydroxychloroquine, the drug appears well tolerated by the vast majority of patients.  However alcohol abuse, impairment of liver or kidney function and simultaneous administration of an array of different drugs elevate the likelihood of toxicity.

Interference with the Virus

Hydroxychloroquine appears capable of interfering with the ability of SARS-CoV-2 to bind to its receptor in the lungs and gastrointestinal tract.  In order to gain entrance the spike protein on the surface of the virus must interact with its receptor ACE2 on the host cell.  Hydroxychloroquine prevents maturation of the ACE2 receptor. 

The drug also appears to alter the pH of the compartment where the virus resides after entering the cell.  Hydroxychloroquine creates an alkaline environment which inactivates another key pathway necessary for viral replication.  At the same time it appears to inhibit the toll like receptors critical in the immune reaction to the virus and in the process decreases the inflammatory reaction associated with the body’s response to the virus.


Unlike so many of the recently marketed drug therapies, hydroxychloroquine is available as a generic drug.  Until the recent uptick in interest in hydroxychloroquine, with a coupon from GoodRx 60 of the 200 mg pills could cost as little as $20.  Interestingly the price for the brand name drug Plaquenil would be more than $650 with a coupon.


So whether hydroxychloroquine proves itself as a bridge until a vaccine becomes available remains uncertain at this time.  Very preliminary evidence exists that supports the drug as a major breakthrough in treatment of COVID-19.  Alternatively other small inadequate studies cast doubt on the drug’s effectiveness.  Which side will prevail awaits more thorough controlled studies.  But in the meantime as my father used to say: “any port in a storm.”

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