Big news yesterday was the announcement by UK scientists that the steroid dexamethasone reduced deaths in ventilated #covid19 patients by a third. It was the kind of good news we all sorely needed. A little thread after a night‘s rest (and story is here https://www.sciencemag.org/news/2020/06/cheap-steroid-first-drug-shown-reduce-death-covid-19-patients)

First of all: Everyone wants to see full results. Announcing top-line results with no data, no publication to back it up is a huge problem and obviously not normal. Practically everyone I talked to pointed this out, @BhadeliaMD and @ashishkjha to name just two here.

I asked the investigators, of course. „There is this tension between having the final details and the final decimal points nailed down, and having what is actually a clear-cut and practical message in the public domain“, @MartinLandray told me.

There is an important debate here on how science (and journalism) should work normally and in this pandemic. I‘ll try to start a debate thread about this later and I‘m sure we‘ll be discussing this at #wcsj and elsewhere a lot. But for now I want to concentrate on the therapy:

Where did dexamethasone come from? There is a long debate about using steroids like it in viral pneumonias. Steroids were used (in huge doses soemtimes) to treat SARS patients in 2003 for instance and also in the 2009 H1N1 pandemic.

Logic is clear: At least some of the damage in severe cases of viral pneumonia comes from immune system fighting the virus. So from the beginning drugs that lessen this immune response were seen as one option in #covid19 next to drugs like remdesivir that attack the virus.

But there is a risk too: Dampening the immune system could make it easier for the virus to spread through the body and also hamper the body in fighting off other infections that might come on top of the virus.

The trade-off between the two likely shifts as disease progresses. So the benefit (stopping immune system damaging the lung) could outweigh risk (hampering fight against virus) mostly in patients in late stage of the disease. That‘s what the Recovery trial investigators found.

According to the press release, deaths were reduced by a third in ventilated patients, by one fifth in patients receiving oxygen only and there was no benefit in patients that did not need help breathing. https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_final.pdf

The important point: Before #covid19 it was unclear whether risks outweigh benefits. A Cochrane Review first published in 2016 found that treating H1N1 patients with corticosteroids was associated with a higher risk of dying. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010406.pub3/full

But that result may well have been due to the fact that sicker patients were more likely to receive the drugs. Wei Shen Lim, one of the authors, told me that the data just wasn‘t clear: „Before the Recovery trial, I was neither an advocate for or an opponent of steroids.“

Lim wanted to be sure and so he prepared a study protocol ready to go for the next time a viral pneumonia came around. That protocol ended up one arm of the UK’s Recovery Trial. It is just one little example in the many ways that some scientists were prepared for this pandemic.