Chloroquine flatlines?

• Chloroquine is a drug that has a poorly defined mechanism of antiviral action
• It also has significant toxicity
• It is unlikely to be a therapeutic option for COVID-19.

Given the good news about remdesivir, I thought it would be an appropriate time to review the status of chloroquine, the other drug that initially was reported to show antiviral activity. 

Chloroquine is a drug used in treating malaria. That treatment involves altering the malaria parasite’s metabolism of hemoglobin protein in red blood cells. This protein then becomes toxic to the growing malaria parasite and kills it. COVID-19 does not infect red blood cells; this could not be a mechanism of action against the virus. Chloroquine has some reported antiviral actions, but none specific for COVID-19. Treatment of other viral infections with chloroquine has not been tested in humans.

Chloroquine is an inexpensive drug and has been used in mass treatments of populations with malaria. However, chloroquine is very toxic. This is a partial list of side effects from Wikipedia.

•         blurred vision, nausea, vomiting, abdominal cramps, headache, diarrhea, swelling legs/ankles, shortness of breath, pale lips/nails/skin, muscle weakness, easy bruising/bleeding, hearing and mental problems. 

•         Unwanted/uncontrolled movements (including tongue and face twitching) 

•         Deafness or ringing of the ears. 

•         Mental/mood changes (such as confusion, personality changes, unusual thoughts/behavior, depression, feeling being watched, hallucinating) 

•         Skin itchiness, skin color changes, hair loss, and skin rashes. 

•         Unpleasant metallic taste

•         Chloroquine retinopathy

•         Electrocardiographic changes

•         Pancytopenia, aplastic anemia, reversible agranulocytosis, low blood platelets, neutropenia.

Originally chloroquine came to the forefront because of a report from Dr. Didier Raoult of Marseilles and his co-workers on clinical treatment of very ill COVID-19 patients with chloroquine and the antibiotic azithromycin (Z pack). The study concluded that the combination could markedly improve patients with serious pneumonia. A second publication followed with more patients and reported no side effects from the drugs in these very sick patients.

These publications have come into question because they lacked a non-treatment control group, involved a small number of patients and the dosing of the drug was not clearly defined. It also appeared that patients were included in the trial without specific criteria on the character/severity of their COVID-19 illness.

The drug became a media “cause celebre”with celebrities and politicians endorsing its use. Enthusiasm outweighs data supporting its use. A number of clinical trials to treat COVID-19 with chloroquine were started in the United States and in other areas. 

The chloroquine trials in the United States are large and will take many months to complete. One trial in Brazil, however, had to be stopped because of cardiac toxicity (heart problems) that could have stopped the hearts of patients (flatline) with higher doses of chloroquine. This previously known toxicity has raised cautions when using the drug.

Chloroquine has been approved by the FDA; any physician theoretically could prescribe it to treat any disease including COVID-19. Most physicians outside of experimental, clinical trials are not prescribing chloroquine for COVID-19. At my own institution, the University of Michigan, the risk-benefit ratio of using this drug in severely ill COVID-19 patients did not appear to warrant its use.

In summary, chloroquine is a drug that has a poorly defined mechanism of antiviral action and significant toxicity. Unless fairly impressive data comes from the current clinical trials, it will likely not be a therapeutic option for COVID-19.