Coronavirus Antiviral Treatments

[4/1/20 update]

HCQ

The first RCT of HCQ as a treatment for coronavirus came out today. It was a small but positive step. 62 patients with pneumonia that was described as “mild” were randomized to receive standard care alone or standard care with a daily dose of HCQ for five days. The patients who got HCQ got over their cough and fever about one day faster on average. CT scans showed somewhat larger improvement in their pneumonia as well. Four patients in the control group advanced to “severe illness” versus none in the group who received HCQ. This study was too small and too short to tell us if HCQ decreases the infection fatality rate. It also doesn’t tell us if people who take HCQ are less likely to contract coronavirus.

The French study that kicked off the excitement measured viral load, which this study did not. The mechanism could be that HCQ acts as an antiviral, but apparently it also modulates the immune system, so it might just help our bodies not overreact to the virus.  Larger, longer studies in people at various stages of the disease should be forthcoming.

[3/29/20 updates]

HCQ

The French scientists who released an early paper with promising initial results for HCQ have released a new paper. The new paper is…not what I expected. The first one had a small treatment group and a small control group, but the group assignments weren’t random or blinded. We should cut them a lot of slack for throwing together a preliminary study as fast as possible. The logical next step would be a proper randomized controlled trial. Instead, they’ve gone in the opposite direction. The new paper had more patients, but didn’t have any control group at all. Out of 80 patients, 1 died. That’s right on the nose of the infection fatality rate of 1%. On the other hand patients were selected after they were hospitalized, so that result might be better than typical. Still, without a control group, this tells us almost nothing.

Still waiting on a number of larger, higher quality RCTs.

FPV

I can’t find any new published research.

Remdesivir

“Two trials in China are scheduled to end as soon as next month.”

Convalescent Plasma

I’ll add convalescent plasma – blood from people who have recovered from COVID – to the list of treatments I check up on regularly. Five critically ill patients were treated with convalescent plasma in an uncontrolled trial in China (published here). Randomized controlled trials should start treatments this week (see here).

[original post from 3/21/20]

I’m going to starting attempting to keep track of research into antiviral treatments for coronavirus. Unlike a vaccine, these could help if given to people who are already sick, meaning we wouldn’t need to produce nearly as much to make a difference. It’s possible but not certain they could also be used prophylactically.

I’ll ignore in vitro (petri dish) research because there is so much of it and so little of it translates to effective and practical treatments in humans. I’ll also ignore human anecdotes for the same reasons and because they’re often just not true.

Hydroxychloroquine (HCQ)

HCQ looks like one of the more promising treatments in the short-term. It’s been used for malaria for a long time and seems to be pretty safe when given to otherwhile healthy people. It’s possible it’s not as safe when given to people with COVID-19 and there’s a good chance it just doesn’t help them.

This half-decent French study published on March 17 suggests it probably does help clear the virus more quickly from people with moderate symptoms (hospitalized, but not in the ICU). The sample size was small and the control group wasn’t randomized or blinded. The researchers followed-up with the treatment group every day whereas they only got medical records from the control group. We can see that the treatment group was tested for the virus daily, whereas the control group was tested more sporadically. It’s possible there are other differences between the two control groups that we don’t know about. Still, patients in the treatment group appear to have been cleared of the virus much faster. The plot below shows the fraction of patients who tested positive for the virus by day  since the beginning of treatment.

Screen Shot 2020-03-21 at 2.15.26 PM

In this small trial, treatment started an average of 4 days after the onset of symptoms. The benefit could be greater if the treatment were given earlier (but that has to wait until there’s a positive test result). The authors propose that if further trials verify effectiveness of the treatment, the drug could be given as prevention. Without knowing how long it would take to scale up production, starting by giving this to healthcare workers could make a big difference, if it works.

This isn’t enough evidence to start a massive treatment program. It is enough to justify quickly running larger, higher quality clinical trials, which is exactly what’s happening.

Favipiravir (FPV)

Similar to HCQ, there is already an early trial of FPV, previously approved to treat flu. Like the other one, this trial was relatively small and non-randomized, but did include a group of people with different treatment as a control.

The lines in the plot below show what fraction of the patients test positive for the virus by day. ‘LPV’ is another drug used as control. As you can see, the treatment group seemed to clear out the virus faster. Separate results showed their lung function also improved faster.

Screen Shot 2020-03-21 at 3.37.09 PM

Further clinical trials are underway and apparently if everything goes very well FPV could be approved in May (in Britain, but presumably a similar timeline elsewhere).

Remdesivir

This drug has never been approved for anything, as far as I can tell, but has been tried as an antiviral several times in the past. Three of the first nine US COVID-19 patients were given remdesivir. They all recovered, but so do 99% of people, so that doesn’t mean anything. Several clinical trials are already underway, but there’s no strong indication one way or the other yet.

 

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