Suppressing the immune system could save the lives of patients with severe COVID-19

An Oxford-led trial testing a common immunosuppressive drug used by coVID-19 patients has found that the use of the cheap steroid for seriously ill patients in intensive care can significantly reduce mortality.
This study suggests that providing immunosuppressive drugs at the right time can improve survival in patients with advanced COVID-19.

Dexamethasone was first developed in the 1950s as part of the first anti-inflammatory drugs that revolutionized medicine.
Dexamethasone is an immunosuppressant commonly used to treat acute allergic reactions, skin diseases and asthma.

While it may seem counterintuitive that suppressing the body’s natural defenses can help people survive a deadly viral infection, it’s not unprecedented that this approach has been used to save lives in virus-caused pneumonia.

While this medical use of corticosteroids remains controversial, some data from the H1N1 swine flu outbreak suggest it may help patients with severe viral pneumonia.

Doctors soon began to notice in the early stages of the current pandemic that patients who usually die of COVID-19 have a disease called acute respiratory distress syndrome (ARDS).
When the body’s natural immune defenses overreact, the lungs become inflamed, leading to respiratory failure and death.
David Gaze of the University of Westminster explained that in the case of COVID-19, this may be caused by an immune response called cytokine storm.

In early March, Oxford University launched a series of large randomized controlled trials called RECOVERY (Randomised Evaluation of CoVID-19 thERapY).
The purpose of the trial is to explore whether existing drugs or treatments can be effectively re-used for COVID-19 treatment.
RECOVERY initially explored six different treatments, including azithromycin, a common antibiotic, dexamethasone and hydroxychloroquine.

The hydroxychloroquine trial was recently halted due to a lack of efficacy after the steering committee reviewed the results of an ongoing trial involving more than 1,500 patients on treatment.
Some trials of dexamethasone have also recently been halted for the exact opposite reason – the drug has shown clear clinical success.

The full data for the trial have not yet been published in a peer-reviewed journal, but the researchers have published them in a preprint article.
The results showed that 2,104 patients with severe COVID-19 received a small dose of dexamethasone for 10 days, while 4,321 in the control group received standard treatment.

The results showed that in intensive care patients treated with oxygen, corticosteroids reduced mortality by about 20 percent compared with the control group.
For those on ventilators, the results were even more dramatic, with a 30 per cent reduction in mortality.

More importantly, the study also showed no benefit for patients who did not need breathing support.
This confirms that immunosuppressive therapy should only be used in patients with severe life-threatening stage.

Martin Landray, one of the lead investigators on the trial, said the data were clear and could be immediately used by intensive care doctors around the world.

Simon Maxwell, an independent clinical pharmacologist from the University of Edinburgh, said the RECOVERY trial confirmed the importance of carefully controlled randomized clinical studies that will help doctors from around the world find the best treatment for COVID-19 patients.
“This is the first major breakthrough in the treatment of COVID-19 infection,” said Maxwell.
It demonstrates the efficacy of a simple, inexpensive, familiar and widely successful treatment for those most seriously ill.
Although many units are already being treated with corticosteroids, these results give confidence.”

Tocilizumab, another immunosuppressive therapy used to treat patients with severe COVID-19, has shown beneficial early data.
Tozumab is a very different drug from dexamethasone.
As opposed to the immunosuppressive effects of corticosteroids like dexamethasone, tozumab is a monoclonal antibody designed to block the activity of a cytokine called Interleukin 6 (IL-6) immune cells.

A Yale University study showed that tozumab had a similar overall mortality benefit to dexamethasone in severely ill COVID-19 patients, though unlike the RECOVERY trial, there was no randomized controlled component.

However, these results provide encouraging evidence that the risk of death from COVID-19 can be reduced if immunosuppressive drugs are used when appropriate.
However, this new redesign of existing treatments will only help those with the most severe form of COVID-19.
As Devi Sridhar of Edinburgh University puts it, “the real game changer will be a drug and vaccine that prevents people from going from mild to severe symptoms.”

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