Hydroxychloroquine and Azithromycin for COVID-19: Early Evidence

Welcome to another Inside Lyme Podcast. In this episode, I review the early evidence evaluating hydroxychloroquine and azithromycin as potential treatments for COVID-19.

Update: This article was written early in the COVID-19 pandemic when clinicians were urgently evaluating existing medications. Since then, research efforts have focused largely on other antiviral treatments and vaccines rather than hydroxychloroquine and azithromycin.

You may wonder why COVID-19 is being discussed during an Inside Lyme podcast. Like many clinicians, I was concerned for my children, grandchildren, and my patients. I wanted to examine the emerging evidence through the lens of a clinical epidemiologist.

COVID-19 quickly became a global pandemic. At the beginning of the outbreak, clinicians urgently searched for safe and effective medications that could reduce illness severity or shorten the course of infection.

Researchers therefore examined existing medications that might offer antiviral benefits. Two drugs that received early attention were hydroxychloroquine and chloroquine, medications long used to treat malaria and autoimmune diseases.

Hydroxychloroquine and azithromycin have also been prescribed in some Lyme disease treatment protocols. In the United States, hydroxychloroquine is marketed as Plaquenil, while azithromycin is marketed as Zithromax.

Both chloroquine and hydroxychloroquine can cause side effects. The most common side effects of hydroxychloroquine include nausea and diarrhea. In rare cases, hydroxychloroquine can lead to reduced white blood cells, anemia, low platelet counts, and retinal toxicity. Retinal toxicity may cause color vision changes or vision loss.

Both hydroxychloroquine and azithromycin may also prolong the QT interval on an electrocardiogram, which in rare cases can lead to dangerous heart rhythm abnormalities.

Antiviral Effects of Hydroxychloroquine and Chloroquine

Hydroxychloroquine and chloroquine demonstrated antiviral activity in vitro. Wang and colleagues reported laboratory evidence suggesting that these medications might inhibit the novel coronavirus.

These drugs had previously been studied for other coronaviruses, including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).

Early reports from China suggested chloroquine phosphate might improve outcomes in patients with COVID-19 pneumonia. Gao and colleagues described findings suggesting chloroquine reduced pneumonia progression, improved lung imaging findings, and shortened the disease course.

However, many of the early Chinese trials had not yet been fully published, making detailed evaluation difficult.

[bctt tweet=”Hydroxychloroquine and azithromycin were explored early in the COVID-19 pandemic.” username=”DrDanielCameron”]

First French Clinical Trial

Gautret and colleagues published one of the earliest clinical studies evaluating hydroxychloroquine with or without azithromycin for COVID-19.

The investigators treated 26 COVID-19 patients with hydroxychloroquine. Some patients also received azithromycin to prevent bacterial superinfection.

The authors reported a reduction in viral load in nasopharyngeal samples among patients treated with hydroxychloroquine compared with untreated controls.

The reduction appeared greater among the six patients who received both hydroxychloroquine and azithromycin.

Only one patient discontinued treatment because of nausea.

The authors explained that they chose to publish their findings early due to the urgent need for treatment options during the pandemic.

Limitations of the First French Trial

The initial French trial had several limitations. The study was small and lacked well-matched controls. Some control patients were recruited from other medical centers.

The study also did not evaluate major clinical outcomes such as ICU admission or mortality.

Among the patients treated with hydroxychloroquine, four had poor outcomes. Three required transfer to intensive care, and one patient died.

The study also could not determine whether viral clearance in saliva reflected elimination of the virus from other tissues.

Second French Trial

A second study by Gautret and colleagues evaluated 80 hospitalized COVID-19 patients treated with hydroxychloroquine and azithromycin.

The authors reported clinical improvement in most patients, although one 86-year-old patient died and another remained in intensive care.

Planned Clinical Trials

Researchers at the University of Minnesota and other institutions began planning randomized clinical trials to determine whether hydroxychloroquine could prevent or reduce the severity of COVID-19 infection.

Could Reducing Viral Load Help?

Some researchers suggested that lowering viral load could shorten the duration of viral shedding and potentially reduce transmission.

However, it remained uncertain whether reductions in viral load would translate into improved outcomes for patients.

What Happened Next?

At the time this article was written, clinicians and policymakers were divided about whether hydroxychloroquine and azithromycin should be recommended for COVID-19.

As larger randomized clinical trials were conducted, treatment recommendations evolved and other therapies became the focus of treatment strategies.

This episode illustrates how physicians evaluate early clinical evidence during a rapidly evolving public health crisis.

Stay tuned.

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Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

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