Over the weekend, President Donald Trump was reportedly treated for the coronavirus with a combination of antibodies geared to stop the virus from entering cells and replicating. It’s a promising but unproven therapy that, for virtually anyone else, would be impossible to access without entering a clinical trial.
In a trial, there’s always a chance a patient will get a placebo — though volunteers still receive what’s considered the best proven standard of care. Trials like these help scientists learn something important that could benefit many others. It might be unrealistic to expect the president of the United States to enter a clinical trial, but it wouldn't necessarily have been more dangerous than taking an untested treatment, and it would have been a great counter-argument to accusations that he's anti-science.
As it is, the headlines are playing up the elitist nature of Trump's treatment.
“This sends a signal to the American public that clinical trials are for chumps,” says Jonathan Kimmelman, a medical ethicist at McGill University in Canada.
It also sends a confusing signal about the severity of Trump’s illness. The antibodies, made by Regeneron Pharmaceuticals, appear to be part of what experts are calling a “kitchen sink” approach to treating the president. Trump reportedly also received the antiviral Remdesivir and a steroid called dexamethasone. Experts were somewhat baffled at the combination, since the antibody treatment has shown signs of promise for those in an early stage of the disease. Dexamethasone, on the other hand, has been shown to help only those at an advanced, severe stage.
Regardless, the doctors in charge of his medical care were savvy to obtain the antibodies.
“It’s a reasonable thing to try because there are preliminary data to support it,” says David Ho of Columbia University, a prominent AIDS researcher who has been developing a different version of the therapy Trump received.
The principle is based on the body’s natural defense against viruses. Once the immune system recognizes an invader, it produces antibodies to attack it. This natural defense is a shotgun approach — the body releases lots of different antibodies, only a few of which actually disable the virus.
But building those antibodies takes a few days, and the system works better in some people than others. Early in the pandemic, scientists were boosting immunity by giving people so-called convalescent plasma — essentially transfusing antibodies from people whose bodies had successfully killed off the virus. This kind of treatment goes back a century and earned its discoverers the very first Nobel Prize in medicine.
But when used for Covid-19, convalescent plasma became mired in controversy. In August, the FDA granted it emergency use authorization, after which researchers at the National Institutes of Health tried to stop the approval, arguing there weren’t yet enough data.
One problem with convalescent plasma is that each donor produces a very different mixture of antibodies to SARS-CoV-2, and in very different quantities, says Ho. So he and other researchers have isolated several specific antibodies that attack the so-called spike protein, which the virus employs to enter human cells. It’s a pretty big protein, says Ho, and a number of different antibodies will disable it. In animal studies, some spike-directed antibodies are much more effective than others at stopping or preventing infection.
Over the summer, Ho and colleagues discovered an antibody which has a particularly powerful effect on the virus, and he expects his work to lead to a more advanced antibody treatment down the road.
Ho says that in the meantime, both Regeneron and Eli Lilly are testing products that, at least in animals, look much more powerful than the currently approved drug Remdesivir. A few days before Trump’s illness, Regeneron sent out a press release touting early human data indicating that the antibodies appear to prevent severe illness in those not sick enough to be hospitalized.
(These antibodies are often referred to as monoclonal because scientists create uniform batches of them through a cloning process. Though some reports said the Regeneron drug was a polyclonal antibody, Science Magazine reported it’s a “cocktail” made from two different monoclonal antibodies.)
While the Washington Post reports that these antibody treatments will be hard to scale up enough to give to every Covid-19 patient, Ho is optimistic that they could make a big difference for certain vulnerable populations, such as nursing home residents.
The antibodies could also potentially be used to protect such people from getting infected at all, at least for a few months. That might be necessary even after a vaccine is approved, he says, because vaccines often don’t work well in elderly people or those who have immune-compromising health conditions. That’s still a ways off, though — for now, the antibodies’ preventive power remains untested except in animals.
Right now, antibody therapy is given through an IV, but it could potentially be done with an injection. Before there was a hepatitis A vaccine, people who wanted to travel to certain countries would get a shot of gamma globulin, which is a prophylactic antibody therapy.
What’s needed now is more clinical trial data, and Lilly and Regeneron both desperately need volunteers. According to a recent article in the medical website STATnews, the multiple days most people have to wait for test results make it hard to locate people in the early stages of the disease, when they appear most likely to benefit.
Trump, on the other hand, was tested often, so his infection was caught much earlier than most. There may have been technical reasons why he wouldn’t qualify for a trial, but from all appearances, he would have made an ideal volunteer — as would others in the White House and Senate who’ve seemingly been diagnosed early.
The fact that Trump left the hospital Monday proves nothing about the efficacy of any parts of the kitchen sink regimen. Without a scientific study, it’s impossible to know how his disease would have progressed had he received no treatment, or something different. We also don’t know the truth about how his body is faring — there have been conflicting reports about his blood oxygen levels and the severity of his symptoms, and his doctors have declined to provide information about his lung scans or the date of his last negative test.
Trump’s return to the White House tells us nothing about treating SARS-CoV-2. For that, we have to thank the researchers and patients willing to embrace the hard, slow work of science.
Bloomberg
