How will Trump’s COVID-19 treatments work together?

In the four days since revealing he had COVID-19, President Donald Trump has been treated with three experimental drugs to bring the infection under control: monoclonal antibodies, the antiviral remdesivir and the steroid dexamethasone.

Individually, all three treatments have shown promising results in clinical trials. The U.S. Food and Drug Administration has issued emergency use authorization to give remdesivir to patients ill enough to require hospitalization. Several large studies have shown steroids can reduce the risk of death in critically ill patients. And biotechnology company Regeneron Pharmaceuticals just released preliminary antibody results on September 29 from an early-stage clinical trial with 275 COVID-19 patients suggesting a high-dose cocktail of lab-made immune proteins can help speed recovery.

But it’s unclear how the drugs might work when used together to treat patients, says Rajesh Gandhi, an infectious diseases physician at Massachusetts General Hospital and Harvard Medical School in Boston.

Here’s what we know so far about the treatments used to treat the president.

How do the treatments work?

In a news release on October 2, the White House announced that Trump had received a single dose of Regeneron’s antibody cocktail shortly after his diagnosis. (Regeneron, in Tarrytown, N.Y, is a major financial supporter of Society for Science & the Public, which publishes Science News.)

That cocktail includes a pair of monoclonal antibodies that each target a different part of the coronavirus’s spike protein. The virus uses the spike protein to pick a cellular lock, called ACE2, to break into cells and begin replicating. By binding to the spike, antibodies can neutralize the virus and curb the infection. Such monoclonal antibodies have been tested early in infection, in people who are not severely ill with COVID-19.

Later that day, physicians moved Trump to Walter Reed National Military Medical Center in Bethesda, Md., where he began a five-day course of remdesivir, a drug developed by biopharmaceutical company Gilead Sciences, which is based in Foster City, Calif. Remdesivir, which is given intravenously, mimics a building block of the coronavirus’s genetic material. It tricks the virus into incorporating the faux compound into the virus’s genetic blueprint, instead of incorporating a real building block, bringing viral replication to a halt.

Then, on October 3, the president also received dexamethasone, his medical team said in a news conference on October 4. The steroid, administered through a muscle injection or intravenously, is typically reserved for patients who require supplemental oxygen or are on a ventilator. The drug suppresses inflammation, an immune response that is behind some severe COVID-19 cases.

What do the data say so far about these drugs?

Some monoclonal antibodies, such as those from Indianapolis-based pharmaceutical company Eli Lilly and Regeneron have shown early hints of success, although the results are still preliminary (SN 9/22/20). The treatments appear to reduce levels of the virus in the body.

Such antibodies are likely best used early on, while the virus is still replicating in a patient’s body, Gandhi says.

Later during disease, viral replication wanes but severely ill patients may have massive amounts of inflammation from an overactive immune response. Without lots of virus circulating in the body, antibodies that dampen viral growth are less effective at making patients better.

So far, studies suggest that remdesivir and dexamethasone can help people who end up in the hospital, Gandhi says. Remdesivir may be best used early, before patients require hospital care, but it hasn’t yet been tested in mildly ill patients. The company is working on developing an inhaled version that could be administered earlier in an infection outside of a hospital setting.

Remdesivir was the first drug shown to curb viral replication and potentially speed recovery in hospitalized COVID-19 patients (SN: 4/29/20). Dexamethasone has been used for decades to treat a variety of ailments and was the first drug shown to reduce COVID-19 deaths among people who need supplemental oxygen (SN: 6/16/20). In September, the World Health Organization confirmed that steroids are beneficial for COVID-19 patients — specifically those who were severely or critically ill (SN: 9/2/20).

The WHO and U.S. National Institutes of Health do not recommend steroid use in people who are less sick, as the drugs can suppress their immune system’s response to the coronavirus and might make the disease worse, says Gandhi, who has helped write COVID-19 treatment guidelines for NIH as well as the Infectious Diseases Society of America. 

Trump received remdesivir and dexamethasone within a day or two, respectively, of his diagnosis. Such treatment may be a sign that Trump’s condition is more severe than reported, or it could be a preemptive measure to ensure his symptoms don’t become severe. Initially, his symptoms were described as mild, but his physicians have said that since his diagnosis, Trump had a fever and has received supplemental oxygen when his blood oxygen level dipped.

What we know about how the drugs might work when combined?

“We don’t yet know how they work together,” Gandhi says.

Researchers have made strides in uncovering potential treatments, and trials for a wide variety of drugs are ongoing. But, so far, the use of remdesivir, monoclonal antibodies and dexamethasone in combination hasn’t been studied. Some efforts are under way to find answers. Participants in the treatment arm of one clinical trial for a monoclonal antibody, for instance, are receiving both the antibody and remdesivir to compare their use together with remdesivir alone.

“There are theoretical reasons to think that it would make sense to combine them,” Gandhi says. For instance, an antiviral drug like remdesivir should “shut down virus replication and then dexamethasone would mop up the inflammation.”

Inflammation is part of the body’s natural response to viral infection and normal levels help clear the virus from the body. If a patient is suffering from high amounts of inflammation and requires steroid treatments to suppress the response, it might be beneficial to have an antiviral on hand to help snuff out the infection.  

Because antivirals target the virus while the steroids dampen a potentially harmful immune response, such combination therapies shouldn’t overstimulate a patient’s immune system, he says. It’s unknown whether using the drugs together might help or hinder their effectiveness.  

“Sometimes we in medicine end up making decisions without perfect data,” Gandhi says. “Unfortunately, that’s the situation [in a pandemic], and then we use our best judgment.”

That judgment is under a bright spotlight thanks to Trump’s high profile. Saying that Trump “may not be entirely out of the woods yet,” White House physician Sean Conley on October 5 reported in a news conference that the president’s condition had improved enough that he was cleared to leave the hospital and return to the White House.  “If we can get through [another week] to Monday with him remaining the same — or improving, better yet — then we will all take the final deep sigh of relief.”