Two weeks ago, I interviewed outspoken French infectious disease specialist Dr. Didier Raoult, who had just released hastily gathered data on a small group of patients treated for COVID-19 in his Marseille hospital. He believed that a combination of the Malaria drug hydroxychloroquine and azithromycin (often sold as Z-Pak) could meaningfully reduce the amount of virus released by patients and make them less infectious. A week later, he released data on 80 sequential patients on this protocol, which revealed few side effects and better results than experts would expect, but drawing conclusions without a randomized control group is difficult. The American medical community and the Food and Drug Administration appropriately expect large, randomized trials before supporting widespread use of drugs. Thus, despite the embrace of countries such as China and Turkey, which include hydroxychloroquine in their official protocols for managing COVID-19, we awaited more data.
During my interviews with Dr. Raoult, he shared that Chinese researchers had already embarked on randomized trials based on a simple observation. Physicians at the Renmin Hospital of Wuhan University noted that of 178 novel coronavirus patients admitted by the hospital since December 2019, none of them were systemic lupus erythematosus patients taking hydroxychloroquine. Meanwhile, none of 80 patients with lupus treated with this medication were infected with novel coronavirus pneumonia. This raises the tantalizing possibility that hydroxychloroquine may prevent infection, a hypothesis currently being studied in a clinical trial at my institution, NewYork-Presbyterian/Columbia University.
In the middle of a devastating pandemic, this clue also catalyzed efforts to treat patients with infections. Dr. Zhan Zhang and her respected team initiated a randomized trial, the results of which they just released to the world this week, even prior to peer review and publication because of the urgent demands of the coronavirus pandemic. The small study looked at 62 total patients diagnosed with early COVID-19 disease. Thirty-one were randomly assigned to either a control or an experimental group. The control group received standard treatment of oxygen therapy, antivirals, antibiotics, and immunomodulators. The experimental group received the standard treatment plus 400 mg of hydroxychloroquine per day for five days.
The researchers found that patients who took hydroxychloroquine had, on average, one day less of both fever and cough compared to controls. More impressively, they saw that 81% of the patients taking hydroxychloroquine had improvement in pneumonia on CT scan compared to 55% of those in the control group. All of this data was statistically significant, meaning that the findings are unlikely to be due to coincidence.
Four patients in the control group progressed to severe disease, and zero patients taking hydroxychloroquine progressed to severe disease, but this was not statistically significant. Two patients in the hydroxychloroquine group had side effects: One developed a rash, and one complained of a headache, a safety record on par with Dr. Raoult’s data. Both groups were cautious in screening patients for potential complications from the drug, and U.S. physicians would want to practice similar protocols to ensure safety.
Does this settle the hydroxychloroquine efficacy issue? No.
I hosted famed virus hunter Dr. Ian Lipkin on The Dr. Oz Show this week to break the news of this study and highlight the opportunities and limitations of our current knowledge. He highlighted that another recent study from China found no difference in outcomes between the hydroxychloroquine-treated patients and the control group, but that study was even smaller, and the results of both groups were excellent, so proving a benefit is harder. We still need a larger, randomized trial to clarify which patients, if any, will benefit from these drugs.
But we march into battle with the army we have, and doctors around the world are choosing hydroxychloroquine more than any other solution.
The new emergency authorization from the FDA will free physicians to discuss the options with their patients as we seek ways to tame the COVID-19 virus. Each recommendation will be made in the trenches, as evidenced by world expert Dr. Lipkin’s decision when he contracted COVID-19 last week. Wisely hoping to avoid being his own physician, he contacted several other world experts who concluded that he would be well served to start hydroxychloroquine. Dr. Lipkin complied and is doing well.
Dr. Mehmet Oz (@DrOz) is host of The Dr. Oz Show and an attending surgeon at NewYork-Presbyterian/Columbia University. Akshay Syal (@AkshaySyal) is a member of The Dr. Oz Show’s medical unit.
