About the existing drugs being tested to fight Covid-19.
An update from doctor heading up trials.
Physicians are using two drugs in combination— hydroxychloroquine and azithromycin,
which I’ll abbreviate HC and AZ—to treat patients with advanced Covid-19 symptoms. We use a regimen reported in a recent open-label trial in Marseille, France, which was updated March 26, and which doctors may modify in any given case.
For HC, two bodies of evidence support its potential in treating Covid-19: in vitro (test tube) studies and initial clinical reports from the field. After the 2002-03 global outbreak of SARS, a coronavirus related to the one that causes Covid-19, an in vitro study conducted by doctors from the Centers for Disease Control and Prevention identified chloroquine (a relative of HC) as an attractive option for prevention and treatment. If added before the virus was introduced, the drug was highly effective in preventing cellular infection. Even later application markedly inhibited infection. Another contemporaneous study showed similar results. As for Covid, a Chinese study published March 9 showed HC has excellent in vitro effects. Other recent information suggests potential antiviral mechanisms of HC and chloroquine.
The bedrock of all infectious medicine, from developing treatments for specific infections to treating individual patients, is in vitro laboratory testing and patient trials. Covid-19 is no exception. Current laboratory data suggest that HC should work.
Clinical information has also emerged from Covid treatment. During the initial Chinese outbreak, Wuhan doctors observed that patients with lupus—a disease for which HC is a common treatment—did not seem to develop Covid-19. Of 178 hospital patients who tested positive, none had lupus and none were on HC. None of this Wuhan hospital’s dermatology department’s 80 lupus patients were infected with the novel coronavirus. The Wuhan doctors hypothesized that this may be due to long-term use of HC. They treated 20 Covid-19 patients with HC. Their result: “Clinical symptoms improve significantly in 1 to 2 days. After five days of chest CT examination, 19 cases showed significant absorption improvement.”
Second, consider AZ—the antibiotic marketed as Z-Pak—combined with HC. The French study showed that 57% of 14 Covid-19 patients receiving HC without AZ tested negative for the virus on a nasal swab on day six. But 100% of the six patients who received both HC and AZ tested negative on day six. Compare that with 16 infected patients at another hospital who didn’t receive either treatment: only 12% tested negative on day six. These are small samples, but significant.
The authors of the French study last week published the results of an additional 80 hospitalized patients receiving a combination of HC and AZ. By day eight of treatment, 93% showed a negative nasopharyngeal swab for the virus. “This allowed patients to rapidly be discharged from highly contagious wards with a mean length of stay of five days,” the authors write. “Other teams should urgently evaluate this cost-effective therapeutic strategy, to both avoid the spread of the disease and treat patients as soon as possible before severe respiratory irreversible complications take hold.” I agree.
What are the risks?
The World Health Organization lists both HC and AZ as essential medicines, “considered to be the most effective and safe to meet the most important needs in a health system.” These drugs have been in use for many years—HC since 1955 and AZ since 1988. Only the combination is new. For now it isn’t well understood why the mix is so effective.
The clinical information service Lexicomp lists the interaction between HC and AZ as Category B, which means the majority of patients require no special caution. Long-term HC use can have adverse effects. Chronic use can cause eye problems, Heartbeat arrhythmia is occasionally observed. Increased electrocardiogram tracking may be appropriate for patients at risk of the latter effect. Potential mental-health effects should be closely observed.
All drugs have side effects, and HC’s overall record is safe. Yes, this is an “off label” use. But that isn’t unusual, either. One study showed 21% of U.S. prescriptions were for off-label use.
These drugs are still needed to treat malaria, lupus and other diseases, which makes it important not to exhaust supplies treating Covid-19 patients. Yet this is a historic pandemic, and treatment with HC and AZ shows considerable promise. That is reason to increase supplies quickly.
What are the next steps?
New York state has started a large controlled clinical trial, and there are reports of others. Many believe that patients who can’t be in a trial should be allowed to decide, in consultation with a physician, whether to use this treatment. This is happening in some U.S. practices.
In a perfect world with unlimited supplies, any infected patient could receive treatment. With limited supplies, we should treat the sickest first and be strategic about it. We should consider this regimen for highly exposed people such as health-care workers and first responders. These heroes in the war against Covid-19 deserve protection.
Early treatment is always better, whether for cancer, diabetes or infection. The in vitro results, field experience and French trial suggest Covid-19 is no different. If this regimen’s promise is borne out by more data, and if supply is ramped up, then we can expand treatment.
For my entire career, I have taken a conservative approach to medicine. I don’t want to give false or premature hope. All of this is subject to further refinement as more information arrives. But likewise I can’t ignore the available evidence. This appears to be the best widely available option for treating Covid-19 and not merely easing the suffering from the disease. It would be irresponsible not to pursue this option aggressively.
Dr. Jeff Colyer is a practicing physician. He served as governor of Kansas, 2018-19.
His article appears in the Monday edition of the Wall Street Journal.
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