President Donald Trump has received a combination of powerful drugs to battle his Covid-19 infection that may never have been prescribed together to an individual patient: the antiviral remdesivir, a coronavirus antibody cocktail and the steroid dexamethasone.
The decision to administer such a drastic combination of treatments might be a sign that Trump is more seriously ill than his personal physician Sean Conley and the White House medical team have admitted. Alternatively, Trump may have demanded to receive as many drugs as possible to speed his recovery. Either way, the use of the experimental treatments will have required a careful weighing of the risks, given the possible side-effects and the chance of adverse interactions between the different chemicals.
Remdesivir
On Friday, Trump started a five-day course of intravenous injections of remdesivir, an antiviral drug produced by the US biotech company Gilead Sciences. It works by blocking an enzyme that some viruses need to replicate.
Remdesivir was originally developed to treat the Ebola virus but clinical trials have shown some effectiveness in Covid-19 patients who are moderately ill, speeding up their recovery.
The US Food and Drug Administration authorised the emergency use of remdesivir for Covid-19 in May for patients with severe coronavirus who need extra oxygen or mechanical ventilation to help them breathe. In August, the FDA extended the emergency use authorisation to anyone in hospital with Covid-19, however severe their disease.
Antibody therapy
Also on Friday, Trump received an 8gm dose of an experimental antibody therapy from Regeneron, another US biotech company. This cocktail, currently known as REGN-CoV-2, contains two antibodies designed to attach themselves to different sites on the "spike protein" that the virus uses to enter and infect human cells.
Several hundred patients with relatively mild disease have received REGN-CoV-2 in phase 2 trials that have shown it does reduce the amount of virus in the body. But the studies have been too small to know whether the drug improves patient outcomes such as reducing the duration of hospital stay, reducing the need for mechanical ventilation, or improving survival.
Larger clinical trials are under way in the US and the UK. The UK Recovery trial, which started last week, will involve up to 4,000 people, with half receiving the antibody drug and half placebo treatment.
Regeneron has not received an emergency use authorisation to supply REGN-CoV-2 outside clinical trials but said it provided the drug to Trump following a “compassionate use” request by his doctors.
Dexamethasone
Finally, on Saturday Trump received dexamethasone – a steroid drug first used 60 years ago – after the oxygen level in his blood dipped. Conley told a media briefing on Sunday: “We decided that in this case the potential benefits early on in the course probably outweighed the risks.”
In June, the UK Recovery trial found that taking dexamethasone for 10 days reduced deaths by a third among patients requiring ventilation in hospital. Last month, the World Health Organisation said doctors should treat severely ill coronavirus patients with dexamethasone or hydrocortisone – another anti-inflammatory steroid that is cheap and widely available.
Steroids help by damping down an excessive immune response to Covid-19 that is causing serious damage to the lungs and other organs throughout the body. But there is no evidence that steroids help patients who are not seriously ill. Indeed there is some concern that they may do more harm than good in people with mild or moderate disease by reducing the immune system’s ability to fight viral infection.
Psychiatrists have also pointed out that dexamethasone can have a powerful effect on mood. Paul Summergrad, chairman of Tufts Psychiatry Centre in Boston and former head of the American Psychiatry Association, wrote on Twitter: "Dexamethasone can cause frank mania or more severe depressive states. Added to the risk of Covid-related neuropsychiatric symptoms/severe delirium, the press ought to be asking the medical team how they are formally monitoring [the president's] mental status." – Copyright The Financial Times Limited 2020