Chloroquine and hydroxychloroquine in COVID-19 Disease

Chloroquine and hydroxychloroquine in COVID-19 Disease

The press has given much attention to the treatment of COVID-19 with antimalarials. President Trump has touted this therapy and Dr./Governor Jeff Colyer recently supported treatment of COVID with hydroxychloroquine and/or chloroquine in some instances. Whereas these therapeutics may provide some hope for treatment of this disease, Dr. Anthony Fauci is correct to state that the benefit has only been shown to be beneficial in anecdotal reports and is devoid of any scientific certainty.

Antimalarials have been shown to be modestly effective in-vitro (meaning in a test tube or lab, not in a living person) against several viruses, including other coronaviruses, influenza, zika, chikunguya, and ebola. In-vivo studies, however, have been repeatedly disappointing.

More recently, some studies have demonstrated the benefit of antimalarials in vitro against COVID-19. Gautret et al ( studied 26 patients and showed significant reduction in nasal carriage of the virus on day 6. There was no initial randomization and the clinical significance and outcomes are unclear. Gao et al (Biosci Trends (2020), 10.5582) claim that chloroquine is effective in COVID-19 pneumonia in a multicenter trial in China, although data from the trial registries has been noted to be difficult to obtain and verify (Cortegiani et a/j.jcrc.2020.03.005). I could not identify any other outcome, in vivo studies at this time.

Given the serious nature of the COVID-19 pandemic, expert consensus from the Department of Science and Technology from Guangdong Province and Health Commission recommends chloroquine phosphate at a dose of 500mg twice daily for 10 days for COVID-19 pneumonia, while also recommending careful assessment for toxicity with laboratory tests and QT measurements with electrocardiograms. Dutch and Italian societies have also suggested antimalarials may be beneficial in some settings
The World Health Organization, FDA, and CDC view antimalarial treatment as experimental, based on the lack of clinical benefit in any transparently reviewable studies. Given malaria resistance and very few other indications, chloroquine has been sparsely prescribed in the US over the past several years. The major side effects include arrhtyhmias , QT prolongation, retinopathy, nausea, diarrhea, hypoglycemia, and hemolytic anemia. Hydroxychloroquine, in contrast, is very commonly used in lupus, rheumatoid arthritis, and other rheumatic diseases. Side effects are uncommon and include nausea, diarrhea, and retinopathy.

The present pandemic has caused shortages and possible hoarding of this medication, leading to increasing health challenges for those needing this medication for noninfectious reasons.

I agree with WHO, Dr. Fauci, and CDC that treatment of COVID-19 infections with antimalarials should be considered experimental. The Chinese outcome studies are seemingly difficult or impossible to review and verify. The French studies shows decrease duration to the elimination of nasal carriage, but no clear benefit in clinical outcomes. Although several studies demonstrate in vitro benefit, we need to be mindful that the great majority of all medical studies showing in vitro benefit for other diseases eventually show no clinical benefit clinically and in vivo.

Recognizing the severity of the present pandemic, the above evidence, and the current shortage of antimalarials, I will recommend limiting treatment to those patients who are severely ill and jeopardized by an acute COVID-19 infection. This includes immunocompramised patients and those with moderate to severe pneumonia. In vitro studies inconclusively suggest hydroxychloroquine may be more effective and less toxic than chloroquine, at a dose of 400mg twice a day on day one, then 200mg once or twice a day for four days.

Considering the shortage of antimalarials, use of this medication for routine prophylaxis in the Kansas City area and treatment of mild disease threatens the lives and health of those that need this medication for noninfectious purposes and others with severe disease with no access to antimalarials.

The upcoming weeks should provide more conclusive studies on the risks and benefits of antimalarials in acute COVID-19 disease and COVID-19 prophylaxis.

Hopefully our supply will be replenished soon.
Jonathan Jacobs MD FACP FAAP 25 March 2020
Direct Primary Care and Concierge Care
Internal Medicine, Overland Park, Kansas