Trump's coronavirus drugs: Regeneron, dexamethasone and more, explained

President Donald Trump returned to the White House on Monday after announcing Thursday he'd tested positive for coronavirus and spending three nights at Walter Reed National Military Medical Center. As he battles COVID-19, Trump has been receiving a handful of different treatments for the disease, including an experimental antibody cocktail produced by biotech company Regeneron. 

As a 74-year-old overweight male, Trump has a heightened risk of experiencing severe complications from COVID-19, according to the CDC. Both age and obesity increase the risk of hospitalization by a factor of three. The White House has maintained a stoic optimism about his condition since diagnosis, and Trump himself has downplayed the seriousness of the novel coronavirus, tweeting Monday "don't be afraid of Covid." 

However, his treatment regime seems to be geared toward addressing a more severe case of disease. So far, the president has received:

• Supplemental oxygen
• An antibody cocktail developed by Regeneron (REGN-COV2)
• Remdesivir, an antiviral manufactured by Gilead
• Dexamethasone, a commonly used corticosteroid

The treatments, outlined by White House physician Dr. Sean Conley over the last several days, could signal worries about Trump's prognosis. It also may just be overly precautionary, because of his multiple risk factors and, of course, his VIP status. In addition, COVID-19 is a complex, multifaceted disease affecting many organs. Though doctors and scientists have dramatically improved our understanding of how it affects the human body, there's no tried and true method to get from sickness to health. Questions remain about the effectiveness of these treatments, and clinical trials are ongoing across the world.

Here's what we know about the drugs Trump has been taking to treat his COVID-19 infection.

Supplemental oxygen

There are two broadly recognized "phases" of COVID-19. The first is during the initial stage of infection, when SARS-CoV-2, the coronavirus that causes COVID-19, replicates exponentially in cells of the lungs. The immune system, noticing the infection, flares up, which can cause the lungs to fill with fluid and prevent adequate oxygen flow. A normal blood oxygen level is at least 95%, but in some COVID-19 patients it drops significantly. The treatment guidelines from the National Institutes of Health suggest severe illness can be defined partly by a blood oxygen concentration below 94%.  

Trump physician Conley had been evasive about whether Trump received supplemental oxygen but confirmed the president received an hour of the treatment on Friday. The president's oxygen level dropped below 95% again Saturday, but it's unclear whether he received oxygen another time. 

"In the president's case, the time from initial diagnosis to the time showing showing serious symptoms, e.g. sudden drops in blood oxygenation and need to administer supplementary oxygen, is exceptionally short," said Jeremy Nicholson, pro vice chancellor of Health Sciences at Murdoch University in Perth, Australia.

Oxygen levels provide an indication of how a patient is faring early in the course of the disease and, along with scans of the lungs, can help determine any internal damage. Lower levels in the initial phase may indicate a poorer prognosis -- and the oxygen levels Trump has experienced likely informed the experimental therapeutics he has received since diagnosis. Current evidence suggests the Regeneron antibody cocktail and remdesivir may work better early on.

When the disease progresses to its second stage, these treatments don't appear to work as well. During the second phase, the virus has caused an extreme reaction from the immune system which can affect many different organ systems. Dexamethasone, for instance, is just one drug aimed at tamping down this response.

Regeneron's cocktail

Regeneron's antibody cocktail is known as REGN-COV2. On Friday, the White House released a memo stating Trump had been given an infusion of the experimental mix. 

REGN-COV2 is a cocktail of neutralizing antibodies, Y-shaped proteins that stick to SARS-CoV-2, preventing it from using its viral machinery to hijack cells. The cocktail was developed in mice that had been genetically modified to have an immune response similar to humans and by identifying antibodies in people who have recovered from COVID-19. The cocktail uses two neutralizing antibodies that attach to the coronavirus spike protein. It takes some time for the immune system to generate these antibodies naturally, so providing a cocktail like this early in the course of disease could benefit patients.

The drug is yet to pass randomized clinical trials, and no data from human trials has been released in a peer-reviewed scientific journal. The cocktail development process was described in an article in the journal Science in August. Preclinical studies in primates and hamsters, posted as a preprint to biorXiv, showed it reduced levels of the virus, providing evidence for its potential.

Regeneron released an investor note on Sept. 29 describing a "descriptive analysis of a seamless Phase 1/2/3 trial" of REGN-COV2, stating it "reduced viral load and the time to alleviate symptoms in non-hospitalized patients." The results are based on the first 275 patients enrolled in Regeneron's trial, but the full published data hasn't been published. 

"We plan rapidly to submit detailed results from this analysis for publication in order to share insights with the public health and medical communities," David Weinreich, Regeneron's head of global clinical development, said in the press release. 

The cocktail is also being studied in three more Phase 3 trials, assessing its utility in various stages of disease.

Trump received a high-dose infusion of the drug after one of his physicians made a request to the FDA and Regeneron for "compassionate use." It isn't in widespread use for patients in the US and wouldn't be made available unless it received an emergency use authorization from the FDA. 

The president has ties to Regeneron CEO Leonard Schleifer, according to a CNN report. On Wednesday, in a video tweeted to his 87 million followers, the president called it "unbelievable" but it's unclear just how successful the cocktail is. Trump said he had "authorized" it on "an emergency basis" which could see it receive an emergency use authorization from the FDA soon.

"It will be a bit of an unknown how he will respond to this therapy," said Elizabeth Hartland, director of the Hudson Institute of Medical Research in Melbourne, Australia.  

Remdesivir

Remdesivir, a drug developed by California's Gilead Sciences, has received the lion's share of the limelight as a COVID-19 therapeutic since March. It was first developed to treat hepatitis C and was also used to combat Ebola.

Remdesivir isn't specifically designed to destroy SARS-CoV-2. Instead, it works by knocking out a specific piece of machinery in the virus, known as "RNA polymerase," which many viruses use to replicate. It has been shown in the past to be effective in human cells and mouse models. During a White House briefing session on April 29, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in the US, touted it as something that could become standard of care. It has received emergency-use authorization from the FDA. 

Trump is receiving five doses of remdesivir, according to his physicians.  

Its modest benefits were reported in the New England Journal of Medicine in July. The drug reduced hospital stays from a median time of 15 days to 11, but it didn't show a significant benefit in reducing the odds of dying from COVID-19.

Dexamethasone

Dexamethasone is a cheap and widely available corticosteroid that has anti-inflammatory activity and can constrict blood vessels. 

"These drugs dampen down the immune system response to COVID," said Greg Kyle, a professor of pharmacy at the Queensland University of Technology. Corticosteroids have been evaluated in patients with respiratory distress for decades, with many clinical trials examining their utility, but only a handful have examined their use in COVID-19 patients.

Dexamethasone rose to prominence as a treatment for COVID-19 after scientists at the University of Oxford in the UK conducted a 6,000-patient trial. The results, published in the New England Journal of Medicine in July, demonstrated dexamethasone could redue the number of deaths in patients on mechanical ventilation by one-third. In patients receiving supplemental oxygen, it reduced deaths by one-fifth. It didn't appear to help patients who weren't receiving respiratory support. Another study, in the Journal of the American Medical Association in September, looked at a group of 299 patients with moderate or severe respiratory distress and suggested it might keep patients off ventilators -- though this wasn't a randomized trial.

However, an observational study in the Journal of Hospital Medicine in July followed the positive NEJM paper, suggesting there may be issues with administering dexamethasone early in the course of disease. 

Some doctors have pointed out the more serious side effects of dexamethasone treatment. "They work on a whole range of different body systems and they work at the level of the nucleus," said Kyle. That means it affects almost every cell in the body -- and so the side effects are rather varied. There are potential negative effects on the brain, influencing aggression, anxiety and mood. Another side effect is "euphoria," according to Nicholson, who says it "might partly explain the president's strong feeling that he is recovering rapidly."

Long-term health effects

Scientists and researchers are still coming to terms with the lasting effects of SARS-CoV-2 infection. While the course of a mild disease may only last for a couple of weeks, those who have experienced severe COVID-19 could have long-term health effects. An Italian team assessed a small group of hospitalized COVID-19 patients in April and May of this year, with almost 90% reporting the persistence of at least one symptom -- most commonly fatigue or labored breathing.

Though Trump is back on his feet and producing videos for Twitter in seemingly good health, his physician, Conley, warns he's "not out of the woods yet." 

While Trump downplayed the severity of his illness and the threat of the coronavirus in briefings from the White House on Monday, science shows that surviving the illness isn't the end of the fight. The effects of COVID-19 may linger for some time. There is still so much we don't know about COVID-19 and the immune response and the factors that can dictate how well a patient responds to complications. 

It has, so far, been difficult to get a clear understanding of just how severe Trump's prognosis is. This makes it hard for outside experts to draw conclusions on what the president is experiencing. Kyle likens it to fighting "with one arm behind your back."

"It becomes very difficult to make a judgment based on the information that's come out," he said. "You need to get the whole picture of the patient."

Progression toward more severe COVID-19 usually occurs about seven to 10 days after returning a positive test. It remains unclear the last time Trump was tested before he returned a positive test last week. "If the COVID-19 trajectory shown by the president is 'typical,' we will not know if he is really recovering for several days yet," Nicholson said.

Updated Oct. 7: Added Trump's comments on Regeneron from Wednesday.