How to save lives by suppressing the immune system in severe cases of COVID-19

Oxford University-led trials testing commonly available immunosuppressive drugs in COVID-19 patients found that cheap steroids significantly reduced deaths when given to critically ill patients in intensive care. Called the “first major breakthrough in the treatment of COVID-19 infections,” this treatment suggests that timely delivery of immunosuppressive drugs to late-stage patients can improve survival outcomes.

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

It may seem a little counterintuitive to suggest that blocking the body’s natural defenses may help survive a life-threatening viral infection, but this method does Being used to save lives in the face of is not unprecedented.

Although this medical use of cortocosteriod is controversial, some data from the H1N1 swine flu outbreak suggest that it may be helpful in patients with severe viral pneumonia. However, Large-scale meta-review published last year A study of the effects of cortocosteriodos in adults with influenza-induced pneumonia concluded that treatment was associated with higher mortality.

During the early stages of the current pandemic, doctors say that the most common cause of death from COVID-19 is acute respiratory distress syndrome (ARDS). It occurs when the body’s natural immune defenses overreact and cause respiratory failure due to excessive inflammation of the lungs. In the case of COVID-19, this condition can be triggered by an immune response known as the cytokine storm, as explained by David Gaze of the University of Westminster.

“In severe cases, the body’s immune system overreacts to the virus, attacking cells that contain the virus.” Draw a line of sight.. “This is known as the cytokine storm, and chemicals called cytokines are released by cells of the immune system, causing excessive inflammation.”

At the beginning of March, Oxford University recovery (Randomized evaluation of COVid-19 th ERapY). RECOVERY was designed to examine whether existing drugs and treatments could be effectively transferred to COVID-19. First, six different treatments, including azithromycin (common antibiotics, dexamethasone, hydroxychloroquine), were considered by the RECOVERY program.

The hydroxychloroquine group of trials was recently discontinued due to lack of efficacy after Steering Committee Evaluated ongoing results From over 1,500 treated patients. Dexamethasone group of trial Recently stopped, But for the exact opposite reason. The drug showed clear clinical success.

The full data set for the trial has not yet been published in a peer-reviewed journal, but researchers have Preprint articles.. The results show that 2,104 severe COVID-19 patients received daily low doses of dexamethasone for 10 days compared to 4321 controls receiving standard care.

The findings suggest that corticosteroids reduced mortality in intensive care patients receiving oxygen by approximately 20% compared to controls. The results were even more pronounced in those on ventilators, where treatment reduced mortality by 30%.

Importantly, this study also showed that treatment does not benefit patients who do not require respiratory support. This asserts that immunosuppressive therapy is only useful for patients in the critical, life-threatening stages of the disease.

Martin Randley, one of the principal investigators in the trial, suggests that the data is incredibly clear and could be immediately applied by intensive care physicians around the world.

“The preliminary results of these RECOVERY trials are very clear. Dexamethasone reduces the risk of death in patients with severe respiratory complications. COVID-19 is a global illness. It’s great that the first treatment that has been proven is a readily available and affordable treatment around the world.” Randley’s comment..

Simon Maxwell, an independent clinical pharmacologist at the University of Edinburgh, said in the RECOVERY trial, a carefully controlled, randomized clinical trial to help doctors around the world determine the best treatment for COVID-19 patients. He said that he would confirm the importance of research.

“This is the first major breakthrough in the treatment of COVID-19 infections.” Maxwell says.. “This shows the effectiveness of simple, inexpensive, friendly, and widely successful treatments in the people most affected. Many departments are already using corticosteroid therapy. But these results provide the conviction that this treatment will do better for many patients.”

Tocilizumab is another immunosuppressive treatment that has been diverted for severely ill patients with COVID-19 and has shown useful initial data. Tocilizumab is a very different drug than dexamethasone. Unlike the widespread immunosuppressive effects of cortocostellides such as dexamethasone, tocilizumab is a monoclonal antibody designed to block the activity of one type of cytokine immune cell called interleukin 6 (IL-6).

Ah Yale University Research A study of tocilizumab in severe COVID-19 patients suggests a similar overall mortality benefit to dexamethasone, but unlike the RECOVERY trial, the study does not have a randomized control component. Recovery is also investigating the efficacy of tocilizumab, but no data is available at this time.

These results provide a very promising indication that immunosuppressive drugs could reduce the risk of death from COVID-19 if given at the appropriate time. But this new diversion of existing therapies only helps patients suffering from the worst COVID-19. As Devi Sridhar of the University of Edinburgh, Point out ScienceMag, We still need therapies to prevent the virus from becoming established first and prevent mild cases from progressing to life-threatening situations.

“The real transformers are the drugs and vaccines that prevent people from getting mild to serious conditions,” Sridhar said.

Recovery dexamethasone preprint research published MedRxiv..