Remdesivir. Hydroxychloroquine. Convalescent plasma. Tocilizumab. Three months ago, these names would have been unknown to most people outside of the medical field.
Today they’re discussed on morning talk shows as possible treatments for COVID-19. Despite the reassuring idea of a cure, doctors have nothing that’s been proven to work against the scourge that’s killed more than 57,000 Americans.
All treatments aimed at curbing the virus in humansso far are based on best guesses, extrapolations and hunches.
“We don’t have data to show the benefits outweigh the harms,” said Adarsh Bhimraj, chair for management and treatment guidelines for the Infectious Diseases Society of America.
A perspective story published Tuesday by the New England Journal of Medicine reminded doctors to base their decisions on science and not be distracted by the desire to at least do something to help a patient.
"The 'what do you have to lose?' approach, a common plea of desperate families, must be balanced by the dictum of the Hippocratic Oath: first, do no harm," the authors wrote.
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Fortunately, said Bhimraj, hundreds of clinical trials are underway and real data about which drugs work and which don't should be coming in months, and in some cases, weeks or even days.
Dozens of drugs have been put forward as possible treatments for infection by the SARS-CoV-2 coronavirus that causes COVID-19. They fall into two general groups: antivirals, meant to help stop the virus from reproducing, and immune-based therapies that prevent an infected person's system from going into overdrive and triggering a "cytokine storm," which can lead to organ failure and death.
Here's what's known about the most-discussed treatments.
Hydroxychloroquine and chloroquine
Hydroxychloroquine is an anti-inflammatory drug, and chloroquine is an anti-malaria drug. Both became politicized when they were promoted by President Donald Trump as a possible treatment for COVID-19.
While they've been able to kill viruses in the test tube, there's no solid data to show they are helpful in treating COVID-19. What is known is that the drugs can cause heart rhythm problems in some patients.
Multiple incomplete and anecdotal reports have been published without peer review over the past two months, but none included control groups – where one group of patients receives a drug and a similar group does not – the gold standard for any medical intervention.
“They’ve been given to patients and they got better. But without a control group, you don’t know if they would have gotten better without the drug,” said Bhimraj, an infectious disease physician at Cleveland Clinic in Ohio.
The U.S. Food and Drug Administration on Friday recommended the drugs be given to COVID-19 patients only in the context of a hospital or clinical trial due to possible dangerous side effects.
"Hydroxychloroquine and chloroquine have not been shown to be safe and effective for treating or preventing COVID-19," the FDA warned.
This is an experimental anti-viral drug from the American biotech firm Gilead. It was originally developed to treat Ebola but didn’t work, and it has been re-purposed as a possible COVID-19 treatment.
In cell cultures, remdesivir has been shown to block the ability of the virus to make copies of itself. Multiple large trials to see if it works to block COVID-19 in humans are under way.
A study published April 10 in the New England Journal of Medicine found the majority of people who got the drug improved, but there was no control group.
This month, early and incomplete results from a remdesivir study being conducted in Chicago were leaked to the medical news site STAT. The University of Chicago issued a statement saying that “drawing any conclusions at this point is premature and scientifically unsound.”
Thursday, early data from a Chinese study was prematurely posted then removed from a World Health Organization website. It did not appear to show any difference in outcomes between patients who got the drug and patients who didn’t.
A more complete look at the Chinese study data is expected as soon asthis week. It was not able to enroll as many patients as had been hoped, because case numbers there were beginning to decline just as the study ramped up.
Gilead's chief medical officer, Merdad Parsey, said in a statement that "the safety and efficacy of remdesivir for the treatment of COVID-19 are not yet known," but that multiple studies were ongoing to provide the data needed to determine its potential as a treatment.
A key study, run by the U.S. National Institutes of Health, is expected out in May, said Rajesh Gandhi, an infectious diseases physician at Massachusetts General Hospital and professor at Harvard Medical School.
“That’s a gold-standard, placebo-controlled, randomized study that to my mind will be definitive,” he said.
One of the most puzzling and medically difficult aspects of COVID-19 is that in some very ill patients it sparks what’s known as a cytokine storm. Several drugs are being tested to moderate the sometimes deadly response.
Cytokines are a type of protein released by white blood cells that signal other immune cells to fight an infection. These cytokines trigger inflammation, which allows blood to leak out of blood vessels more easily so immune cells from the blood can go into an infected area.
The novel coronavirus seems to hijack the body's immune response so the initial inflammatory phase is overstimulated. This can damage critical organs.
Several drugs, called Interleukin-6 inhibitors, fight the condition. They inhibit the overactive immune response and are used to treat inflammatory diseases such as rheumatoid arthritis and in some cancers.
Two diametrically opposedearly results came out on Monday about such inhibitors. Results from a study of a drug called sarilumab (brand name Kevsara) from the company Regeneron found a lower dosage in severely ill COVID-19 patients wasn’t promising.
"The trial was stopped for people with severe COVID-19 but who were not critically ill because the results did not look promising in that group. The study is continuing in people who are critically ill with COVID-19," Gandhi said.
The same day, a study in France on tocilizumab (brand name Actemra) from the company Roche found it produced positive results. The company’s news release said that in patients with moderate to severe COVID-19 who were not in the ICU, deaths and the need for ventilators were “significantly reduced.”
The company said it planned to submit the results for publication in a peer-reviewed medical journal.
"Because we don’t yet have information on the results, I wouldn’t bank on it, but I will certainly be looking carefully at the findings when they are released," Gandhi said. .
This treatment dates back to 1891, when a German doctor used the blood plasma from people who survived diphtheria to treat children fighting the disease. Plasma is the almost clear liquid that remains after red and white blood cells and platelets are removed from blood. It contains antibodies that can fight disease.
It is also time-consuming, expensive and difficult to deploy on a large scale and has not been widely used in modern times. Several trials of plasma from people “convalescing,” or recovered, from COVID-19 are under way.
Early data appears to show no major safety problems from the treatment but no solid evidence it works. No definitive studies looking at outcomes in patients who either did or did not get the plasma have been released. A report on a series of cases from China was published on March 27 that seemed to show the possibility of positive outcomes.
“Those are in my mind provocative studies,” Gandhi said. “They raise it to the point that you need to do a comparison study. Without that, you don’t know if people would have gotten better on their own.”
A warning from a previous pandemic
It is easier than might be imagined to get things wrong. During the H1N1 pandemic of 2009, athen-experimental drugcalled peramivir (trade name Rapivab) was initially thought by many doctors to be a panacea.
“We all were trying it. Luckily, the adverse effects were not that severe — but it didn’t work in critically ill or severe patients,” Bhimraj said.
Waiting for solidinformation is difficult in the midst of a pandemic, he said.
“Having clinicians and even patients asking for medication is natural. But it’s unwise to use unproven therapies. We have to pause, reflect and ask ourselves ‘Is there evidence? Could there be potential harm?'”