NEW YORK (VINnews) — When Margaret Novins of Freehold, N.J. fell ill on March 8, it started with fatigue, a cough and fevers that brought on vicious chills for five evenings straight. A week later she went to an urgent care center and on March 16th to an emergency room, where she complained of difficulty breathing.
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 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 told Forbes Magazine 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 said that “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.”
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.
However 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, which is cosigned by the number one world expert on infectious diseases, Professor Didier Raoult, 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).
Professor Raoult , the head of the IHU Méditerranée Infection, has been tasked by – and consulted by – the French government to research possible treatments of Covid-19.
He reported that the first Covid-19 patients he had treated with the drug chloroquine had seen a rapid and effective speeding up of their healing process, and a sharp decrease in the amount of time they remained contagious.
Chloroquine – which is normally used mainly to prevent and treat malaria – was administered via the named drug, Plaquenil.
The treatment was offered to 24 patients, who were among the first to become infected in the south east of France, and who had voluntarily admitted themselves to hospital for the process.
Patients were given 600mcg per day for 10 days. They were closely monitored, as the drug can interact with other medication, and cause severe side effects in some cases.
Professor Raoult said: “We included everyone who was in agreement [to be treated], which was almost everyone. Two towns in the protocol, Nice and Avignon, gave us [infected] patients who had not yet received treatment.
“We were able to ascertain that patients who had not received Plaquenil (the drug containing hydroxychloroquine) were still contagious after six days, but of those that had received Plaquenil, after six days, only 25% were still contagious.”
But the study was small and had other serious limitations.
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 Forbes writer Mary Beth Pfeiffer. 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 could 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 also be included.
The FDA has in the past encouraged so-called off-label use of approved drugs, stating that “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.”
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.
The drug is cheap- just 12$ for a five-day course of treatment, but massive use for the tens of thousands of coronavirus patients in the US could create shortages for other patients.
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 University of Minnesota professor of medicine, said in announcing the study.
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 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.