What President Trump’s emergency COVID-19 therapies say about his condition

The president’s medications suggest that he has at least a moderate case of COVID-19—and even as he returns to the White House, details on his condition are still missing.

President Donald Trump’s diagnosis of COVID-19 is the most significant threat to presidential health in decades—and another case among the millions in the United States so far.

On Monday, the president confirmed his intentions to return to the White House, just a day after his physicians disclosed that he has needed supplemental oxygen twice so far—once on Friday morning and again on Saturday—in response to periods when his blood oxygen saturation levels had dipped below 94 percent. Blood oxygen saturation is an indicator of lung function and thus of the severity of a COVID-19 case.

The White House’s physicians are treating the president with a mixture of medications—including an experimental drug known as a monoclonal antibody cocktail, a treatment that has raised questions because its safety and efficacy aren’t fully proven.

“We’re witnessing in real time the intersection between a national crisis and one person’s life-threatening medical emergency,” says emergency medicine doctor Jeremy Faust, an attending physician at Brigham and Women’s Hospital in Boston.

Monoclonal antibodies are expected to help the immune system mount an early response to COVID-19. The concept is similar to convalescent plasma—but instead of being a crude extract yanked from blood, monoclonal antibodies are a bioengineered scalpel that carefully establishes an immunity shield. But the drug in question—REGN-COV2, supplied by the American biotechnology firm Regeneron—doesn’t yet have full results from ongoing clinical trials.

Regeneron said in a statement to National Geographic that the president isn’t the only person to have received REGN-COV2 under what’s called “compassionate use.” Alexandra Bowie, a Regeneron spokesperson, said that fewer than 10 other people had received the treatment in “rare and exceptional circumstances.”

Bowie declined to say whether First Lady Melania Trump or other COVID-positive senior government officials had received a dose, citing medical privacy. “We will continue to evaluate each request on an individual basis, on its own merits,” Bowie said.

What is President Trump’s condition?

The commander-in-chief undergoes an annual physical, and information released from those examinations offers a mixed picture of his risk to coronavirus.

The 74-year-old president is in an age bracket in which about one in 500 COVID-19 cases results in disease severe enough to require hospitalization. His height and weight—reported this summer as six feet three inches and 244 pounds—also mean he could be considered slightly overweight or obese, another risk factor for complications with the virus. Physicians to the president—including the current appointee, Navy Commander Sean Conley—have described Trump’s heart health as normal. In his favor, the president does not use alcohol or tobacco, and has reduced his cholesterol and maintained a borderline-normal blood pressure over the last three years.

“People who have those demographics are precisely the ones we needed to protect the most in this crisis,” Faust says.

Sunday’s disclosure about blood oxygen dips was an about-face from earlier in the weekend, when Conley dodged repeated questions on Trump’s oxygen therapy during press conferences at Walter Reed National Military Medical Center in Maryland.

“I was trying to reflect the upbeat attitude that the team [and] his course of illness has had,” Conley said during a press briefing on Sunday. “I didn’t want to give any information that might steer the course of illness in another direction.”

In more severe cases of COVID-19, blood oxygen levels can drop below 94 percent—putting patients at risk of damaging hypoxia, even if they can still move and breathe normally at first. As a result, Trump’s physicians administered a treatment of the steroid dexamethasone. In June, the U.K.’s RECOVERY trial announced evidence that this immune-modifying drug boosted the survival odds in severe COVID-19 cases, where patients needed supplemental oxygen or more intensive ventilation.

(Related: They don’t struggle to breathe—but COVID-19 is starving them of oxygen.)

The prescription of dexamethasone may signal that Trump has had more than the mild case initially reported by his physicians and White House staff on Friday. Guidelines from the U.S. National Institutes of Health recommend giving dexamethasone only if a patient requires supplemental oxygen or mechanical ventilation. Likewise, the World Health Organization recommends dexamethasone only for “severe” or “critical” COVID-19 cases where, at a minimum, blood oxygen saturation levels have dropped abnormally below 90 percent.

The question of whether the president has needed consistent supplemental oxygen is crucial: Requiring such treatment is seen as a fork in the road between a mild infection and a more severe one.

In the late stages of severe COVID-19 cases, most damage to the body isn’t from the virus itself, but rather from an overzealous immune response called a cytokine storm. It’s thought that dexamethasone helps quell this storm, lowering the injury from inflammation.

Giving dexamethasone in too mild a case could risk weakening a patient’s ability to fight the virus. In the U.K.’s RECOVERY trial, COVID-19 patients who didn’t need supplemental oxygen died more often with dexamethasone than without it. Doctors started giving Trump dexamethasone on Saturday morning, two days after the president reportedly started showing symptoms.

(Related: These promising coronavirus treatments are saving lives.)

Based on this time course, Trump is receiving dexamethasone on the early side: In the RECOVERY trial, patients who received dexamethasone within seven days of first showing symptoms didn’t see much benefit to using the drug. “We looked at the data and decided that we’d rather push ahead on it than hold and risk the opposite,” Conley said in a Monday briefing.

The president’s physicians added that Trump would be continuing his treatment at the White House, which has its own medical unit. Conley also continued to deflect two questions: the details of Trump’s lung scans, which could show signs of damage or pneumonia even when symptoms are mild, and the date of his last negative test, which could suggest how long the president might have been infectious.

"We all remain cautiously optimistic and on guard. We're in a bit of uncharted territory when it comes to a patient that received the therapies he has so early in the course," Conley said Monday. "We're looking to this weekend. If we can get through to Monday with him remaining the same or improving better yet, then we can all take that final deep sigh of relief."

What are monoclonal antibodies, and how are they made?

Antibodies are Y-shaped proteins that the immune system makes in response to a foreign pathogen. They serve two vital roles: If enough glom onto a virus, then the invader can’t penetrate cells and multiply. Antibodies also can tag the germ for destruction by other parts of the immune system.

Vaccines work, in part, by coaxing the body to make its own antibodies. Treatments such as monoclonal antibodies and convalescent plasma introduce antibodies to a patient’s body. The goal: to give the body’s immune system a leg up in its effort to identify and fight the infection.

Trump is in a race where his immune system is racing against the virus, and if the virus wins, you can have dire consequences,” Regeneron CEO Len Schleifer told CNN late Friday. “What our antibodies do, is make it a fairer fight.”

Unlike convalescent plasma—an extract from the blood of recovered COVID-19 patients that may contain a blend of many antibodies—monoclonal antibodies are engineered much more finely. The drugs are designed to prevent the SARS-CoV-2 virus from thriving in the nose and mouth, before the virus settles into the lungs and brings on a more severe case.

“The theoretical idea is, ‘Hey, there’s no virus to find its way into the lungs,’ ” says Myron Cohen, an infectious disease doctor at the University of North Carolina-Chapel Hill and co-leader of the COVID-19 Prevention Trials Network (CoVPN). “You’re not worried about a nasal infection, you’re worried about the lower respiratory infection.”

Many companies, such as Eli Lilly, develop antibody candidates by analyzing the blood of recovered COVID-19 patients. In Regeneron’s case, the company used lab mice that are engineered to have a human-like immune system. This tweak let researchers infect the mice with SARS-CoV-2 and then extract human immune cells that made antibodies to the virus.

Scientists then assess which of these cells can make a single type of antibody that binds best to the virus’s spike proteins, its lockpick for entering human cells.

This screening process is what makes the antibodies “monoclonal.” The goal is to establish distinct breeding lines—made of cloned cells—that each crank out a single, specific type of antibody.

As the Washington Post’s Carolyn Johnson reported recently, Regeneron bioengineers use cells from hamster ovaries to mass-produce the antibodies, brewing them in large tanks and then extracting the antibodies for medicine.

The final concoction, REGN-COV2, contains two monoclonal antibodies, each of which binds to the virus in a slightly different way. In much the same way that an antiviral “cocktail” effectively treats HIV, the antibody duo is thought to have a better shot of binding to the SARS-CoV-2 virus.

Does this experimental treatment work? Is it safe? How was it administered?

REGN-COV2 is classified as an experimental therapy because the jury’s still out on whether it can safely waylay COVID-19. The U.S. Food and Drug Administration hasn’t issued an emergency use authorization for the treatment, as it has for convalescent plasma or remdesivir.

The gold standard for vetting any medical treatment is a clinical trial in which patients are randomly assigned a treatment or an ostensibly ineffective placebo. Regeneron is running the early stages of those trials for REGN-COV2. However, full results haven’t been published—leaving some medical experts leery of using it on anyone, let alone a world leader.

Trump’s doctors are “just so worried about him, that even if it’s really harmful or even if it does nothing, they might as well do it,” Faust adds. “It doesn’t project anything positive at all.”

During a September 29 briefing to investors and the media, Regeneron announced preliminary results from the first 275 patients in an ongoing clinical trial. In people who hadn’t yet made many of their own antibodies, an eight-gram dose of REGN-COV2 (infused into the veins) reduced the amount of virus in patients’ noses. The company reported a trend in improvement with symptoms, though those results were not statistically significant yet. Regeneron said it would formally publish its results as quickly as possible.

Cohen, who is partnering with Regeneron to test REGN-COV2 as a preventative treatment, says the monoclonal antibodies look safe so far, “and there’s no reason that they wouldn’t be,” he says. “This is attacking a virus spike protein, so there’s every reason to believe that it wouldn’t interact with human tissues.”

But one potential concern with antibody treatments is that in certain situations, they can inadvertently increase a virus’s ability to bind to human cells, making an infection more severe.

So far for REGN-COV2, this paradoxical effect—called antibody-dependent enhancement (ADE)—hasn’t appeared in animal tests, though these results have not been peer-reviewed.

In a statement, Bowie said that more than 2,000 people have participated in the trials so far, and an independent board monitoring the data hasn’t raised any safety concerns. “Safety is of paramount concern, and we are always watching carefully, but so far things seem good,” she stated.

Questions linger with the president’s use of the therapy. For one, Regeneron’s early trial results involved patients who were 44 years old, on average—three decades younger than Trump. Regeneron says that it doesn’t yet have enough data to tell whether the drug causes different responses in different age groups. But Cohen posits that older adults may benefit more often from the medication because immune systems slow down and weaken as we age.

What else is President Trump taking?

In a Friday memo, Conley, the president’s physician, said that besides REGN-COV2, Trump is taking an assortment of supplements and other medications.

Vitamin D and zinc are general boosters for the immune system, though zinc also has ties to the debunked COVID-19 treatment hydroxychloroquine. Trump also is taking a daily low dose of aspirin, a routine remedy for older men to ward off heart disease, a pre-existing condition that can worsen COVID-19 outcomes. Trump has been on this regimen since at least his first presidential physical exam in 2018.

Beyond REGN-COV2, Trump’s emergency regimen so far includes three other drugs currently in trials but not fully approved for use with COVID-19. Two of them—the sleep aid melatonin and the over-the-counter heartburn drug Pepcid—remain in early stages of investigation but are considered to reduce inflammation, a frequent complication with the infectious disease.

Trump also is taking remdesivir, a repurposed antiviral that has received emergency use authorization from the FDA. So far, clinical data show that remdesivir can slightly shorten recovery time.

In a Monday briefing, medical team member Brian Garibaldi said that President Trump would be receiving his fifth and final dose of remdesivir at the White House on Tuesday evening.

Editor’s note: This story will be updated as the president’s situation changes. It was originally published October 3.

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