All The President’s Medicine

(Posted on Monday, October 5, 2020)

The article originally appeared in Forbes on October 5, 2020. 

No one receives worse medicine, an old saying goes, than the poor and the powerful. The poor because they face so many barriers to medical care and supports, and the powerful because they face no barriers at all.

The latest updates on President Trump’s Covid-19 treatment suggest he is very much of the latter ilk. The day after his positive diagnosis, he received two experimental therapies, the antiviral drug remdesivir and Regeneron’s anti-SARs-CoV-2 monoclonal antibodies, in combination with vitamin D, famotidine (pepcid), zinc, and melatonin. It was announced Sunday afternoon that dexamethasone, a steroid, was thrown into the mix on Saturday. Neither hydroxychloroquine nor convalescent sera, the two treatments touted by Trump so ardently and for so long, were included.

This cocktail is not just highly unusual. The president is likely the first human being on the face of the earth to receive the triple whammy of remdesivir, monoclonal antibody drugs, and dexamethasone almost all at once. While the pronouncements of White House physician Sean Conley and his medical team would lead us to believe that the combination is a matter of necessity and sound clinical judgment, we cannot forget that this is no ordinary doctor-patient relationship. Trump is Conley’s ultimate superior, not to mention commander-in-chief to the doctors attending to him at Walter Reed National Military Medical Center.

Reports from White House physician Sean Conley on Trump’s condition have been heavy on reassurances but light on clinical details, making it difficult to determine whether these therapies are intended to improve worsening symptoms or placate a panicked president. We may never know the true motivation, but we can at least use science to predict the outcome.

Let’s begin with REGN-COV2, the monoclonal antibody drug developed by Regeneron Pharmaceuticals. Monoclonal antibody drugs are engineered using a single cell that produces a single, highly neutralizing antibody, one that is replicated over and over again at a large scale. Hundreds of groups around the world, some of which I know well, are currently developing such antibodies against the SARS-CoV-2 spike protein, one of the key mechanisms the virus uses to replicate itself. The Regneron drug is what you might call an antibody cocktail—two neutralizing antibodies paired up to reduce the potential for immune escape.

Trump was able to receive an 8-gram infusion of Regeneron’s monoclonal antibodies on Friday due to the FDA’s compassionate use program, which permits case-by-case use of as yet unapproved experimental therapies. The only data we have on the safety and efficacy of REGN-COV2 was released not even a week ago—in a company press release, rather than a peer-reviewed journal. While researchers conducting clinical trials for the drug claim it helped reduce viral load in Covid-19 patients with mild symptoms, it also appeared to have no effect on patients who had already developed anti-SARS-CoV-2 antibodies. Moreover, the study was unable to show any effect on prevention of serious disease or death. Two patients experienced adverse side effects, though the reasons why weren’t disclosed.

The other experimental drug on the docket is remdesivir, an antiviral drug that has undergone more extensive evaluation than REGN-COV2. Though authorized in May by the FDA for emergency use, in clinical trials and patient population studies remdesivir has yielded only modest and rather disappointing results. The lack of notable therapeutic effects may be attributed to the fact that viral load peaks sooner rather than later in the progression of this disease, spiking shortly after symptom onset and dwindling within days. Antivirals can only provide so much relief when any active virus is already on the ebb—at that point, the damage is done and any treatment must palliate ensuing complications, rather than target the virus itself.

Trump’s treatment course for remdesivir will take a total of five days and require several hospital-based infusions. Before today, there was still a decent possibility that Trump’s first infusion, also given on Friday, may have been administered just in time to help alleviate his symptoms. It has been speculated that Trump contracted the virus the day of or shortly after September 26, when an outdoor ceremony celebrating his Supreme Court nominee, Judge Amy Coney Barrett, was held in the White House Garden. Seven attendees, the president included, have since tested positive for Covid-19.

But now that Trump’s doctors have confirmed, a day after the fact, that he has in addition to REGN-COV2 and remdesivir received a dosage of dexamethasone, the alternative suddenly seems more likely: that the initial therapies failed to turn the tide on his illness and consequently desperate measures might be in order. Since steroids can harm, not help, the body’s innate immune response to Covid-19 if taken prematurely, they’re typically reserved for those in critical condition, deployed as a last resort to help mitigate the hyperinflammation seen in severe cases of the disease.

According to a large study of the drug published in July, dexamethasone had the biggest and most beneficial impact on patients who had been critically ill and hospitalized for over a week. Given that Trump checked into Walter Reed just three days ago, the outlook—at least from the outside looking in—doesn’t seem particularly promising. If Trump is experiencing hyperinflammatory symptoms, he may be at risk for hypercoagulation, too, which in some Covid-19 patients causes heart attacks, lung emboli, and strokes major and minor. Prescribing anticoagulants (also known as blood thinners) to prevent clotting might help, but that would mean adding yet another medication to an already sizable list.

Not for nothing must we note that large doses of dexamethasone can have potent, destabilizing effects on mood, temper, and reasoning, akin to mania. It is not advisable to entrust individuals being treated with the drug with making difficult judgment calls in a timely fashion, especially when they’re the leader of the United States. We may never know if the peculiar combination of remdesivir, REGN-COV2, and dexamethsome is what the doctor ordered or what Trump demanded. Either way, it will sadly fall to the American people to deal with what could be disastrous consequences.