After just two days in hospital with Covid-19, Donald Trump is back at the White House and, according to his doctor, symptom free. His speedy recovery is credited to an experimental antibody treatment. So what do we know about this treatment?
- The treatment is a neutralizing antibody cocktail called REGN-COV2. The combination of two synthetic human antibodies (REGN10933 and REGN10987) binds to spike proteins on the surface of corona virus particles. Once bound by antibody the virus can no longer bind and infect cells – therefore virus spread and replication is halted. Neutralizing antibodies also mark the virus for degradation by immune cells such as macrophages. Using two antibodies that bind non-competitively different parts of the spike protein reduces the likelihood of mutated virus forms to escape this route of treatment.
- Regeneron are not the only ones developing such a treatment – Eli Lilly for example is also working in this direction. Both companies have tested their antibody cocktail in patients and in late september/early october reported that the treatment can reduce viral load, symptoms and shorten hospital stays. Both companies tested their antibody treatment in outpatients, so in early stages of the infection or mild cases that did not require hospital care. Still, receiving the antibodies decreased the likelihood of a hospital stay and shorted the time of disease, which is a good indication for a treatment. So far both studies have not been published in peer-reviewed journals, but only as press releases.
- Trump only received a single dose, every early on. Only 1-2 days after testing positive for the virus. Timing seems crucial, as Regeneron states it sees best results with the treatment in patients before they mount their own immune response. The CEO of Regeneron said that the cocktail can “provide a therapeutic substitute for the naturally-occurring immune response.” Immune response, in this case, refers to adaptive immune response. Regeneron found that people lacking SARS-CoV-2 antibodies in their blood – people that are „seronegative“ – had greater gains from the treatment. Hence, the cocktails would be particularly helpful in people early on, before the adaptive immune response, which takes 7-10 days to establish, kicks in. Like in Trumps case. The cocktail would also particularly help people who can’t mount an efficient response for some reason and therefore need help clearing the virus.
- The treatment is not (yet) approved to use by the FDA or any other regulatory body. Less than 300 people have received the treatment – less than 10 outside the double-blind clinical trial. Without approval, experimental treatments can only be used if all other options have failed and the patient is likely to die without the experimental treatment. This process is called compassionate use. While Trump was not dying, his doctors were able to ask for use and got permission by the FDA. While a privilege due to his job, the possible benefit and low risk – as seen in the ongoing clinical trials – made this safe and logical decision. Still everyone, who is not president, will have to wait for official approval (and longer..). There are simply not enough resources to grant everyone testing positive and showing mild symptoms – which is still the official word on Trump’s health last week – a compassionate use claim.
- Regeneron has since applied for Emergency Use Authorization (EUA). If granted they have an agreement with the US government to supply them with 300.000 doses of the cocktail. The government is then in charge of distributing them. Currently 50.000 dosis are available. Regeneron has announced a collaboration with Roche to meet global production. A timeline of when and how many doses will be available are uncertain as making of monoclonal antibodies is both expansive and time consuming.
Finally, I want to note that alongside the antibodies Trump also received antiviral medication called remdesivir and the steroid dexamethasone. Dexamethasone has been shown to decrease mortality in hospitalised Covid-19 cases, but due to its severe side effects is not recommended for mild cases. Remdesivir is an antiviral component used for Ebola, which has emergency use clearance from the FDA for Covid-19 patients. Both drugs will also have affected Trump’s recovery, so the claim the antibody therapy saved him is bold. Like so many of his statements. It may have helped, but only complete evaluation of the finished double-blind placebo-controlled clinical trial will tell us the potential of this medication- not one case. Especially not, if the patient has ulterior motives. Not only is Trump friends with the company CEO- the stocks of which company saw a massive increase – but by claiming to have personally found and tested a treatment in this pandemic and promising it for free to everyone, he eyes an advantage in the upcoming election.