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Those of us following #RECOVERYtrial know it’s one of the most important clinical trials for COVID-19, not just for its potential to identify new therapeutic options but also to temper the excitement over unproven therapies. 1/ https://twitter.com/swapneilparikh/status/1264810177913651201
My thoughts on the RECOVERY trial PRESS release on mortality benefit for COVID-19 with dexamethasone.
RECOVERY trial is a large randomized controlled trial with multiple arms. 11k+ patients and multiple treatments being evaluated. See image for therapeutics under evaluation. 2/
RECOVERY trial is a large randomized controlled trial with multiple arms. 11k+ patients and multiple treatments being evaluated. See image for therapeutics under evaluation. 2/
First, what is dexamethasone?
Dexamethasone is a corticosteroid, commonly called a steroid (not the anabolic kind). In addition to many other effects, it can reduce the inflammatory resonse caused by an out of control immune system. 3/
Dexamethasone is a corticosteroid, commonly called a steroid (not the anabolic kind). In addition to many other effects, it can reduce the inflammatory resonse caused by an out of control immune system. 3/
#TheCoronavirusBook - During an infection (like COVID-19) the immune system releases small proteins called cytokines. Cytokines are like a trumpet rallying the immune system to battle. In severe COVID-19 there is a massive and excessive cytokine release called cytokine storm 4/
While dexamethasone can calm the cytokine storm, it can make infections worse. Early in the infection, the virus is massively replicating and the immune system needs to control it. If dexamethasone is given, infection could worsen or the person could stay infectious for longer.5/
Later in the infection (in some people) the immune system is out of control and starts attacking the body. At this point dampening the immune system may help. This process is called immunomodulation and IL-6 antagonists (an other drugs) are already being used for this purpose. 6/
From #TheCoronavirusBook:
“Calming the Storm: Immunomodulators.
Perhaps, the key to treating the cytokine storm lies in finding the right balance between an immune response strong enough to fight the virus but not so strong that it damages the body’s tissues...” 7/
“Calming the Storm: Immunomodulators.
Perhaps, the key to treating the cytokine storm lies in finding the right balance between an immune response strong enough to fight the virus but not so strong that it damages the body’s tissues...” 7/
#TheCoronavirusBook
“....The immune response needed when the virus is multiplying rapidly differs greatly from what is appropriate a few hours later when the viral infection is slowing down due to a counterattack....” 8/
“....The immune response needed when the virus is multiplying rapidly differs greatly from what is appropriate a few hours later when the viral infection is slowing down due to a counterattack....” 8/
#TheCoronavirusBook
“....Treating patients with the right immunomodulating drug at the wrong time could worsen the disease. Attempting to modulate the immune response may reduce the severity of the infection or could lead to a fatal outcome...” 9/
“....Treating patients with the right immunomodulating drug at the wrong time could worsen the disease. Attempting to modulate the immune response may reduce the severity of the infection or could lead to a fatal outcome...” 9/
Apologies for the detour from #RECOVERYtrial press release. I wanted to explain dexamethasone and immunomudlation before sharing my thoughts on the PRESS release. 10/ https://www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratory-complications-of-covid-19
In #RECOVERYTrial 2,104 patients received dexamethsone (6mg/day x 10 days) vs 4,321 patients who received usual care without dexamethasone. Per the press release, dexamethasone reduced deaths by a third in patients on a ventilator and by a fifth in patients on oxygen. 11/
There was no benefit in mild patients who did not need oxygen. These results (in the press release) sound encouraging but we need far more information to make clinical decisions on the use of dexamethasone. I’m sure those details will be forthcoming. 12/
We need to see actual data to understand the results (from the PRESS release) better and help us decide which patients will benefit the most from dexamethasone and which patients might be harmed by it. Very important - dexamethasone is not a miraculous silver bullet! 13/
Dexamethasone is easily available, easy to make, easy to scale and cheap. This amakes it easy to use and misuse. DISCLAIMER: Dexamethasone can suppress a healthy immune system. It may harm those with mild or early infections. DO NOT TAKE THIS UNLESS PRESCRIBED BY YOUR DOCTOR. 14/
