Margaret Novins, 53, received an emerging treatment for COVID-19 at a Freehold, N.J. hospital. “I … [+]
Margaret Novins talked to me on her cellphone from a hospital bed at CentraState Medical Center in Freehold, N.J.
She had been ill since March 8, toughing it out through fatigue, a cough and fevers that brought on vicious chills for five evenings straight.
Finally, on March 15, she went to an urgent care center and, on March 16, to an emergency room. The attending there called it “conversational dyspnea.”
“I couldn’t breathe,” she said.
Novins, who shared her lab tests and medication list, got her diagnosis March 19. Next to the entry for SARS-CoV-2 were the words “Detected Critical.” She had the coronavirus, or COVID-19.
To that point, Novins had been a pneumonia patient for three days, treated mainly with antibiotics. But within an hour, a new drug was added to her med list: hydroxychloroquine, a decades-old malaria-turned-autoimmune drug, also called by its brand name Plaquenil. President Trump is touting the drug, some say overselling it, as the possible answer to the COVID-19 crisis.
Novins’ responded to the treatment. She was better, though surely not well, the next day.
“The fever,” which was still spiking when she was on other meds, “is now gone, which is fantastic,” she said on Saturday March 21, coughing at times but able to speak.
A 53-year-old nurse who described herself as a nonsmoker with no medical issues, Novins spoke to me from the hospital that had cared for some of the seven members of a family ravaged by COVID; two adult brothers, a sister and their mother died from the infection.
“The doctor insisted the pharmacy get it to me the minute we got the positive,” she said of hydroxychloroquine. “It seemed like their go-to right away.”
After three nights in the hospital, Margaret Novins’ COVID test came back positive: “Detected … [+]
Provided by Margaret Novins
There are other anecdotal successes like Novins’, including one in which end-of-life discussions for an older parent had been broached — until Plaquenil apparently kicked in. In that case, the family had to plead for, rather than being offered, the drug.
Anecdotes are surely not science, which for now is limited and new.
Trump is basing his optimism mostly on one small study from Marseilles, France, that, combined with laboratory findings, has prompted ongoing trials in France and the United States. The just-released French study reported that 70 percent of hydroxychloroquine-treated patients, or 14 of 20, were negative for the virus at day 6, as were all six patients who were treated with hydroxychloroquine and the antibiotic azithromycin (which Novins also received). But the study was small – 20 treated patients and 16 controls – and had other serious limitations.
Of concern, six patients dropped out and were not considered in the reported efficacy rates. Three went to intensive care; one died; one left the hospital testing negative, and one opted out due to nausea.
Two scientists at major university centers reviewed the French trial for me. They agreed, separately, that while the study is preliminary, small, and not without flaws, its findings were strong enough, given the drugs’ known safety records, to guide treatment decisions in a crisis.
“Despite the limitations of this study, in the absence of any effective treatment, in this urgent situation, this Plaquenil and Azithromycin combination therapy should be given to patients with COVID-19 as a treatment option,” Ying Zhang, a professor of microbiology at Johns Hopkins Bloomberg School of Public Health, wrote in an email. “For now, there is no time to wait.”
Working against the study, in Zhang’s view: It was not a randomized trial, which would avoid bias; the sample size was small, and the treatment and followup duration was too short. The findings are nonetheless “potentially interesting and justified,” he wrote.
Brian Fallon, a research scientist and clinical trials investigator at the Columbia University Irving Medical Center, agreed on the study’s overall merit despite the patients who dropped out. After analyzing the data and counting all six dropouts as treatment failures, he said the overall rate of improvement was still statistically significant for the entire group, though not for the hydroxychloroquine group alone.
He too had reservations, in particular that the combination therapy group was very small, six patients, and that high doses of the two drugs together carry “serious risk of cardiac arrhythmias.” Physicians must be warned of this, he suggested.
Nonetheless, he wrote in an email, “Given the life and death situation of hospitalized patients with COVID-19 and the possibility that hydroxychloroquine plus azithromycin may be helpful, it was valuable and ethical for the authors to report these promising, preliminary results.”
Others agreed. Lorraine Johnson, who has published on the use of collected data to improve health care outcomes, said, “It is important right now to take the gloves off clinicians and give them access to all available tools; patients are dying and can’t wait for clinical trials.”
At the same time, she and Zhang, who has published on treatments for difficult infections like tuberculosis and Lyme disease, said a database should be set up to track patients, like Margaret Novins, in order to document drug performance. “I would recommend real-time online posting of treatment evaluation results of the Plaquenil+Azithromycin at multi-center sites across the US and the Globe,” Zhang wrote. “Someone has to coordinate this online registry and resources.” He added that other treatments should be included.
Supply issues raised
In a 1982 drug bulletin, the FDA encouraged so-called off-label use of approved drugs: “Valid new uses for drugs already on the market are often first discovered through serendipitous observations and therapeutic innovations, subsequently confirmed by well-planned and executed clinical investigations.”
In the real world, however, a rush to put a relatively safe approved drug to a vastly expanded new use may reduce supplies for others who need it, including lupus, rheumatoid arthritis and Lyme disease sufferers.
Kenneth Farber, president of the Lupus Research Alliance, said there were shortages of Plaquenil throughout the United States and especially in New York and California.
Asked about supplies, a spokesperson for CVS Health, T.J. Crawford, said the drug-store chain has an “adequate supply on-hand” of hydroxychloroquine but supply of a related drug, chloroquine, “is tight across the marketplace.”
Jane Marke, a New York City psychiatrist who takes Plaquenil for Lyme disease, said she had trouble getting her prescription filled at several city chains. After reading the French study, she understands why. “It is really possible that this is a major breakthrough,” she said, envisioning a time when a good test could pick up early infections and the drug would stop the epidemic in its tracks.
In that vein, the University of Minnesota is organizing a trial to treat 1,500 people with hydroxychloroquine who were exposed to the virus from infected family members or as healthcare workers but are not yet ill. The study relied on laboratory experiments in China that found hydroxychloroquine inhibited the infection.
“If effective, this may become a worldwide standard of care for helping prevent disease in other healthcare workers and people exposed,” Dr. David Boulware, a U of M professor of medicine, said in announcing the study.
A key advantage of an off-patent generic drug like hydroxychloroquine: “A five-day treatment course would cost approximately $12,” Boulware said.
Novins, meantime, is expecting to leave the hospital in a day or two. As a nurse for a medical equipment company, she believes she contracted the infection not from a patient but while conducting a day-long training session.
Nonetheless, she said in a text, “I feel fortunate.”
“From my notes it is clear that my fevers and horrible chills I fought hard from 3/8-3/18 turned the corner the day I started Plaquenil 3/19,” she wrote.
While she said COVID is a “violent illness,” Novins never was in intensive care or on a respirator. The French study offers a mere glint of hope for more serious cases too. Of five patients with lower respiratory infection, four turned negative by day 6, three of them on both drugs.
In the meantime, scientists said larger, more rigorous studies must be launched to answer questions of efficacy, dosing, duration, and potential adverse drug interactions — for this and other COVID treatments.