The COVID-19 pandemic caught the world in many ways by surprise. Without a rulebook in hand, front line doctors have been forced to make tough and quick decisions on how to treat their patients. This has led to an unprecedented number of experimental treatments and trials to combat the novel virus. Now, a few months into this ongoing pandemic, some physicians and researchers worry the medical community may be trying too many unproven or experimental treatments as they try to keep COVID-19 patients alive.
A number of letters published in various scientific journals this past month have highlighted this concern. Taken together, they call for reliance on accepted treatments to combat SARS-CoV-2 infection complications, such as acute respiratory distress syndrome (ARDS).
“An extraordinary array of experimental therapies have been given to critically ill patients, often in combination,” write one group of physicians in the American Journal of Respiratory and Critical Care Medicine.
Doctors are people too, says Benjamin Singer, an intensive care doctor at Northwestern University who is the coauthor of a parallel commentary in the American Journal of Respiratory Cell and Molecular Biology. Faced with an onslaught of seriously ill patients, they want to save lives. When those patients have an unknown disease, as in this pandemic, that urge translates into trying countless new therapies to find effective treatments for the complications of this disease.
“It’s kind of a foundational biomedical principle to first do no harm… and then the corollary of not doing harm is to do things we know are beneficial,” says Singer. Without evidence, there’s no way to know if the new therapies will make patients better. That’s why he and his colleagues are calling for doctors to stick with treatments they know will work on the symptoms of COVID-19.
In their article, Singer and his colleagues cite the example of ARDS. This syndrome occurs when fluid in the lungs prevents oxygen from reaching the blood. A number of illnesses can trigger ARDS, including severe pneumonia. When it occurs, it requires swift medical attention: The death rate for patients with ARDS is between 25 and 50 percent, says Singer.
Treatments for ARDS—including the use of ventilators—can help. A number of controlled trials have demonstrated the optimal ways to use ventilators to treat ARDS, including the specific ventilator settings and physical positions of patients that help the most and prevent the greatest number of side effects. However, Singer says, there are numerous examples of doctors trying other approaches to ventilating COVID-19 patients who are displaying ARDS.
According to Singer, although patients with COVID-19 have a new disease, those that go on to develop ARDS should be treated like all other ARDS patients; that is, until proper controlled clinical trials show new treatments are better or more effective, Singer says. “Ventilators, although life-saving, come with a number of potential downsides,” he says.
The same is true of drugs: Used correctly, they can save lives. But there’s no guarantee they’ll work for off-label uses, even if they seem like they will, write another group of scientists in a commentary published in the journal Chest. “Given limitations in resources as well as evidence, we need to tread lightly in the intensive care unit more than ever,” they write.
Numerous drugs are being used off-label to treat individual COVID-19 patients, Singer and his colleagues note in their commentary. At least one—lopinavir-ritonavir, a combination of two antiretroviral drugs used to treat and prevent HIV and AIDS—was the subject of a controlled trial on COVID-19 patients but was found to be ineffective against the virus. Others, like hydroxychloroquine, azithromycin, and remdesivir, have been tried as well and remdesivir was even given a fast-track approval for emergency use from the FDA. There’s still no conclusive evidence, though, that any of these drugs provide a significant improvement in patients with COVID-19.
“We do not suggest that physicians never use unproven medications off-label or off-trial,” Singer and his colleagues write. Intensive care doctors often have to treat the symptoms in front of them even when the causal disease isn’t one for which certain therapies have been approved, they write. But in contrast to those individual emergency situations, “the routine use of the agents listed above for COVID19—outside of controlled trials—strains credulity.”
Faced with the panic of a pandemic, it’s easy to reach for new and untested therapies. “I will acknowledge that it is really hard to wait for the data,” Singer says. But the good news is that a number of clinical trials are taking place on COVID-19, and there’s new knowledge all the time, he says. In the meantime, Singer argues that doctors have a number of tried-and-tested therapies that physicians know help patients with ARDS more often than they hurt.