Dexamethasone to Reduce Mortality in Serious Covid 19 Patients
Author: Dr. Guneet J Mann, MD
Low-dose steroid treatment with dexamethasone is a major breakthrough in the fight against SARS-CoV-2 virus. Dexamethasone has been used since the early 1960s to treat a wide range of conditions, such as rheumatoid arthritis and asthma
The drug is part of the world’s biggest trial that is testing existing treatments to see if they also work for coronavirus. The RECOVERY trial, launched in March, is one of the world’s biggest randomized, controlled trials for coronavirus treatments; it is testing a range of potential therapies. The trial was led by a team from Oxford University. The study enrolled 2,100 participants who received dexamethasone at a low or moderate dose of six milligrams per day for ten days, and compared how they fared against about 4,300 people who received standard care for coronavirus infection.
For patients on ventilators, it cut the risk of death from 40% to 28%. For patients needing oxygen, it cut the risk of death from 25% to 20%. These findings suggested that one life could be saved for every eight patients on a ventilator and every 20-25 patients treated with oxygen. The steroid had no effect on people with mild cases of COVID-19 — those not receiving oxygen or ventilation.
About 19 out of 20 patients with coronavirus recover without being admitted to hospital. Of those who are admitted, most recover, but some may need oxygen or mechanical ventilation. These are the high-risk patients dexamethasone appears to help. Dexamethasone is a corticosteroid. Steroids have a significant effect, in vitro, on T-cell proliferation, blocking interleukin-2 production. A variety of other actions may augment their immunosuppressive activity (e.g., preventing the induction of interleukin-1 and interleukin-6 genes in macrophages). Their anti-inflammatory activity is perhaps mediated by the inhibition of migration of monocytes to areas of inflammation. This same anti-inflammatory activity has a deleterious effect on wound healing. Dexamethasone is used in the treatment of many conditions, including rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, and along with antibiotics in tuberculosis. In preterm labor, it is used to improve outcomes in the baby. It can be taken orally, intramuscularly, or intravenously. The effects of dexamethasone are frequently seen within a day and last for about three days.
The anti-inflammatory and immunosuppressive properties of dexamethasone appear to help stop some of the damage that happens when the body’s immune system goes into overdrive as it tries to fight off coronavirus. This over-reaction of the immune system called the cytokine storm, can be deadly.
The drug is given intravenously in intensive care and in tablet form for less seriously ill patients. So far, the only other drug proven to benefit Covid patients is remdesivir, which has been used for Ebola. Remdesivir has been shown to reduce the duration of coronavirus symptoms from 15 days to 11. There was not enough evidence to show that it reduced mortality.
Use of steroids to treat viral respiratory infections such as COVID-19 has been controversial. Data from steroid trials during outbreaks of SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome), caused by related coronaviruses, were inconclusive. Nevertheless, given the widespread availability of dexamethasone, and some promising results from steroid studies in previous outbreaks, the investigators of RECOVERY trial feel that it is important to test the treatment in a rigorous clinical trial.
Treatment guidelines from the World Health Organization and many countries have cautioned against treating people with coronavirus with steroids. There have been concerns about anecdotal reports of widespread steroid treatment. Though steroids suppress the immune system and provide some relief to patients whose lungs are ravaged by an over-active immune response, as seen in severe cases of COVID-19, such patients still need a fully functioning immune system to fend off the virus itself.
The RECOVERY trial suggests that at the doses tested, the benefits of steroid treatment may outweigh the potential harm. The study found no outstanding adverse events from the treatment.
The pattern of response with dexamethasone is such that there is greater impact on severe COVID-19 and no effect on mild infections. This supports the notion that a hyperactive immune response is more likely to be harmful in long-term, serious infections, says Anthony Fauci, head of the US National Institute of Allergy and Infectious Disease. When a patient has COVID-19, that is severe enough for the patient to be put on a ventilator, it usually means that the immune system has become aberrant or there is a hyperactive inflammatory response that contributes as much to the morbidity and mortality as any direct viral effect.
The above findings could also have implications for other severe respiratory illnesses like Acute Respiratory Distress Syndrome (ARDS) where steroid treatment is controversial. This suggests that a closer look needs to be taken at some of the severe respiratory conditions, since the mortality benefit of using steroids in these conditions could be quite large. The medical fraternity feels that this will affect patients well beyond COVID-19.
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