President Donald Trump has maintained a steady schedule of campaign rallies, which may have exposed him to SARS-CoV-2.

By Jon CohenOct. 5, 2020 , 12:20 PM

Sciences COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

On 2 October, the White House announced President Donald Trump received an experimental antibody treatment after a test revealed hesinfected with SARS-CoV-2. At the time, he reportedly hadmild COVID-19 symptoms, including fever and congestion, and he was transferred to Walter Reed National Military Medical Center. Later, the presidents medical team confirmed he had started a course of remdesivir, an antiviral drug shown to modestly help hospitalized COVID-19 patients. Two days later, on 4 October, the team revealed Trump had been given a steroid normally reserved for severe COVID-19 cases, although his physician offered optimism about a quick recovery, even suggesting he might soon be discharged from Walter Reed.

Its a combination of two antibodies directed against a key protein of the virus that causes COVID-19, SARS-CoV-2. They bind to a region on the main surface spike protein that helps the virus attach to a receptor on human cells calledangiotensin-converting enzyme 2. The targeted region is dubbed the receptor binding domain. One antibody comes from a human who had recovered from a SARS-CoV-2 infection; a B cell that makes the antibody was harvested from the persons blood and the genes for the immune protein isolated and copied. The other antibody is from a mouse, which was engineered to have a human immune system, that had the spike protein injected into it.

Experiments in bothgolden hamsters and rhesus macaquesthat were intentionally infected with SARS-CoV-2 showed the cocktail could reduce viral levels and disease pathology.

Regeneron, the maker of the cocktail, earlier last week presented preliminary data from its ongoing clinical trial in people who tested positive for SARS-CoV-2 but were asymptomatic or, in the most extreme cases, had moderate diseasea group that would appear to mirror Trumps current condition. No serious safety concerns surfaced, andthe treatment reduced viral loadand shortened symptomatic disease in patients who did not have SARS-CoV-2 antibodies at the trials start. Its unclear whether the treatment can prevent severe disease, but there were hints that it might: Participants who received a placebo had more medical visits.

A separate trial is assessing the impact of the treatment on hospitalized COVID-19 patients, but Regeneron has yet to report any results from that study.

Not exactly. Trump received an 8-gram infusion of the treatment. Regenerons data showed a 2.4-gram infusion worked as well as the higher dose at reducing SARS-CoV-2 levels in people. This was widely seen as good news because monoclonals are difficult and expensive to produce, and a lower dose means more people can ultimately receive it.(On7 October, Trumps personal physician said the president was negativefor SARS-CoV-2 antibodies when he received the cocktail.)

Likely out of an abundance of caution by the presidents medical team, says George Yancopoulos, co-founder and chief scientific officer of Regeneron. Yancopoulos does not directly know why Trumpsphysicians chose to use 8 grams, but says the companys data indicate theres very, very limited risk that the antibodies will cause harm at either dose. The higher dose might last longer, he said, and at some time points in the companys study, Regeneron did see trends suggesting the higher dose more powerfully beats back the virusthe company used the amount of viral genetic material found with nose swabs as a proxy for SARS-CoV-2 levels in the entire body.

If I had to treat one patient, Id give the high dose, Yancopoulos says. From a societal point of view and the need to treat as many people as possible, Id give the lower dose.

The Regeneron study found the treatment only worked in people who did not have SARS-CoV-2 antibodies at the start of the study. It also worked best in people who had higher levels of the virus. Whether the president had those antibodies and a high viral load has not been made public. I couldnt speculate because it has to do with an individual patient, Yancopoulos says.

No. The treatment consisted of two monoclonal antibodiesmeaning each was produced by making identical copies, or clones, of an antibody gene in a single B cell. Polyclonal antibody cocktails refer to antibodies made by mixtures of B cells.

The antibodies are typically only available to people who participate in clinical trials. Trump theoretically could have enrolled in the ongoing treatment study that reported preliminary data last week, but that trial randomly assigns half the participants to receive the antibodies; the other half serves as a control group and receives infusions of an inactive placebo. A U.S. Food and Drug Administration (FDA) regulation called expanded accesstechnically known as21 CFR 312.310allows physicians to request compassionate use of experimental treatments through an investigational new drug pathway used for individual patients or for emergencies. These are designed to be used in these rare and special circumstances, Yancopoulos says. This is not the first time weve done compassionate use for these monoclonal antibodies. This is not a mechanism for widespread distribution.

Yes. Both Regeneron and Eli Lilly, which similarly reported encouraging preliminary clinical trial data last month from a single SARS-CoV-2 monoclonal antibody, are discussing the possibility of an EUA with FDA. Lilly reported signs that its antibody reduced the need for hospitalization, but as with Regeneron, too few participants have so far become seriously ill to reach a convincing conclusion to this critical question.

No. Although the monoclonal antibodies infused into Trump were not made from or in fetal cells, Regeneron did develop that treatment with the help of a long-lived line of cells established from the kidneys of a fetus electively aborted in the Netherlands around 1972. The company relied on those widely used cells, known HEK-293 cells, to make mimics of the coronavirus spike protein. Researchers used these proteins to test the potency of antibodies found in COVID-19 patients or made inmice with a humanlikeimmune system (see initial question).The antibodies selected for the companys cocktail, however, were thenmass produced in nonfetal cells.The creation of the humanized mice also did not rely on HEK-293 cells or other cells from aborted fetuses or human embryos.Regeneron scientists detail their methods inthe supplementary materialtothis paperpublished inSciencein August.

Remdesivir is an antiviral drug developed by Gilead Sciences, originally to treat the hepatitis C virus. It did not perform well against that pathogen but has been tried against Ebola and other viruses, after showing some activity in cells and animal models. The drug inhibits a viral enzyme used for replication of the pathogen. Earlier this year, it demonstrateda modest clinical benefit in a trial with hospitalized COVID-19 patients, leading FDA to grant Gilead an EUA for the drug. That EUA has since been expanded for use in patients with mild disease although its benefit in them is not clear. The drug has become widely used for COVID-19 patients despitecontinuing skepticism that it has a major clinical benefit. Because it and the monoclonal antibodies target different parts of the virus, administering them together may have a synergistic effect. One COVID-19 clinical trial is testing remdesivir and Lillys antibody, for example.

On 4 October, Sean Conley, the White House physician, said in a press conference that Trump had also been started on the steroid dexamethasone. The drug dampens the bodys immune response and can keep it from wreaking havoc in the late stages of COVID-19. It is the onlytreatment so far that has been shown to reduce the mortality in patients with severe COVID-19, but there are some indications that it may actually be harmful if given too early in the disease course. In the United Kingdoms Recovery trial there was a clear benefit for patients requiring oxygen or ventilation but not for other patients. Conley said Trump had experienced two episodes of transient drops in his oxygen saturation. Independent doctors were quick to point out that dexamethasone can have serious side effects including agitation, paranoia, and even psychosis.

The statement released on 2 October by the presidents physician said that in addition to the antibodies, Trump has been taking zinc, vitamin D, famotidine, melatonin and a daily aspirin. That wording leaves unclear whether he was taking those substances before his diagnosed infection. Notably, the statement does not indicate whetherTrump was or is taking hydroxychloroquine, the antimalarial he controversially pushed as a COVID-19 treatment.

Famotidinehas been suggested to be a treatment for COVID-19, but its also a popular heartburn remedy, sold widely under the name Pepcid. A clinical trial testing it in hospitalized COVID-19 patients in New York was not able to recruit enough patients to properly evaluate its impact. The Feinstein Institutes for Medical Research, which initiated that trial, released a statement on 2 October citing evidence it was helpful for COVID-19 but also saying, We have yet to prove [famotidines] efficacy. The institute says its eagerly awaiting FDA approval of a trial that will evaluate whether famotidine can help people who are not hospitalized.

This story was originally published on 2 October at 9:25 p.m.

*Update, 3 October, 1:20 p.m.:Information about Trumps use of remdesivir was added to the story.

*Update, 5 October, 9:15 a.m.:Information about Trumps use of dexamethasone was added to the story.

*Update, 7 October, 3:55 p.m.:Information about the Regeneron treatment was added to this story.

Read this article:

Update: Here's what is known about Trump's COVID-19 treatment - Science Magazine