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ChemVsCOVID Medicinal Chemistry

#ChemVsCOVID: How were the first treatments for COVID identified?

An infographic titled "Chem vs COVI timeline: 16th June 2020, RECOVERY trial shows dexamethasone as first effective COVID-19 treatment". The structure of dexamethasone is shown at the centre. The left-hand side of the graphic explains how the RECOVERY trial aimed to identify existing treatments that work against COVID-19. 12 treatments were trialled at 181 sites with over 40,000 participants. As of June 2021, 3 treatments have been shown to be effective, and 4 treatments have been shown to be ineffective. The right-hand side of the infographic explains that dexamethasone has antiinflammatory and immunosuppressant effects which may explain the positive results. It's estimated that dexamethasone has saved 22,000 lives in the UK and 1,000,000 lives worldwide. The RECOVERY trial has also shown which treatments are ineffective, including hydroxychloroquine, and set a precedent for how large-scale trials can be carried out during an emergency situation.
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On this day (16 June) a year ago, the first effective treatment for COVID-19 was announced. The corticosteroid drug dexamethasone, already used to treat several inflammatory and autoimmune conditions, was found to be effective for patients in a serious condition in hospital with COVID. This discovery was the product of the RECOVERY trial, a programme started in March 2020 to find COVID treatments.

RECOVERY, as the capitalisation suggests, is an acronym that stands for “Randomised Evaluation of COVID-19 Therapy” (yes, it’s a tenuous acronym). It’s a trial that was set up at the University of Oxford, and has involved over 40,000 hospitalised COVID patients in the UK. The treatments these patients received were randomised from the 12 treatments being trialled, so an individual patient might receive none, one, two or three of the possible treatments.

All of the treatments put to the test in the RECOVERY trial are pre-existing drugs or treatments for other conditions. Repurposing drugs that are already approved for other diseases is a lot less time-consuming than trying to find completely new treatments. The process of approving a new drug for general use in patients can take several years; by contrast, if an already-approved drug is effective, all patients can start using it right away.

Of the treatments tested as part of the RECOVERY trial, three have been found to be effective. Dexamethasone was the first of these, found to be effective in hospitalised patients who require assistance with breathing. Dexamethasone’s structure is similar to that of the stress hormone, cortisol, and it has anti-inflammatory and immunosuppressant effects in the body, which likely explain its effectiveness. One of the other treatments the trial found to be effective, Tocilizumab, has similar effects.

Equally importantly, the RECOVERY trial has shown us which treatments for COVID don’t work. We can all recall the claims made early in the pandemic about hydroxychloroquine, the antimalarial drug that Donal Trump and others touted as the key to curing COVID. The RECOVERY trial has shown that, contrary to these anecdotal claims, the data shows hydroxychloroquine to be ineffective as a COVID treatment. It might not seem that helpful to know which treatments don’t work, but it’s an important step that stops doctors persevering with treatments that don’t work – and allows them to make sure patients get the best treatment possible.

The effects of dexamethasone might sound modest at first. Estimates, when the evidence for dexamethasone’s effectiveness against COVID was first published, suggested that it could prevent one in three deaths in patients on ventilators, and one in five deaths in patients on oxygen. But statistics from March 2021 suggest that dexamethasone treatment has saved 22,000 lives, and over 1,000,000 lives worldwide.

The RECOVERY trial has broader benefits. As well as providing treatments to save lives during the current pandemic, it’s set a precedent for how large-scale, user-friendly treatment trials can be set up and run in an emergency situation, invaluable for when the next pandemic comes along. In the meantime, it’s still providing evidence for treatments that can help us here and now – just today, the trial published news that the injection of intravenous antibodies can help some COVID patients mount an immune response to the disease.

This graphic was developed in partnership with the Royal Society of Chemistry. See the full #ChemVsCOVID series of graphics here.

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