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  • Dexamethasone, Potential Treatment on Covid-19

    Structure of Dexamethasone


    IUPAC Name:- (8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one

    It is natural corticosteroids, which are hormones secreted by the adrenal glands situated right above the kidneys. They are required for sustaining many vital functions of the body. Dexamethasone is a long-acting potent synthetic steroid available in oral (tablet), topical (ointment), and intravenous (injection) forms. It has been around for decades. Low-dose Dexamethasone widely available, generally safe, and well-known drug. It presents a favorable benefit-risk profile, particularly in patients with severe forms of pneumonia.

    Dexamethasone is a synthetic adrenal corticosteroid with potent anti-inflammatory properties or immunosuppressive properties and the ability to penetrate the CNS.

    It has been proposed that the potent anti-inflammatory effects of corticosteroids might prevent or mitigate these harmful effects.

    Patients with severe COVID-19 develop a systemic inflammatory response that can lead to lung injury and multisystem organ dysfunction. It appears there are two phases of the disease. The first phase is where the virus grows rapidly in the body and then there is a second phase when your immune system reacts to that virus and reacts very aggressively. Dexamethasone helps tone down this “immune response gone bad stage”. It is at best an adjunct to a proper antiviral drug against Covid-19.

    Many studies have been done on dexamethasone’s role in acute respiratory distress syndrome with mixed results. ARDS is a type of severe lung injury that is treated primarily with mechanical ventilation. It is a complication of many illnesses like toxins, drowning, and bacterial and viral pneumonia (including Covid-19).

    Dexamethasone is seen and if given very early in the disease onset phase, it proves to be actually harmful. It could worsen the case because, at the beginning of the disease, a person actually needs his immune system to work well,” Dexamethasone is useful for those who have to deal with the disease in its later phase within the body.

    Dexamethasone is the first medicine to be shown to result in a “significant reduction in mortality” in those with COVID-19 requiring oxygen or ventilation, researchers have said. Chris Whitty, chief medical officer for England, described the development as “the most important trial result for COVID-19 so far”, and the government’s chief scientific advisor, Sir Patrick Vallance, described the trial results as “ground-breaking”.

    Peter Horby, professor of emerging infectious diseases in the Nuffield Department of Medicine, University of Oxford, and one of the chief investigators for the trial, described the outcome of the trial as “an extremely welcome result”.

    As per Bram Rochwerg, Mcmaster University, It makes sense that steroids should work. They help dampen the host response. They help knock down those inflammatory cytokines and all those white blood cells going to the lungs.

    According to preliminary findings shared with WHO (and now available as a preprint), for patients on ventilators, the treatment was shown to reduce mortality by about one-third, and for patients requiring only oxygen, mortality was cut by about one-fifth. Dexamethasone has been on the WHO Model List of Essential Medicines (EML) since 1977 for several indications in multiple formulations. Since 2013, dexamethasone (Injectable formulation) has been indicated for respiratory distress syndrome in newborns.

    The only other thing to get protected from COVID-19 is to wear a mask that can help. It is cheap and relatively easy to have and we should ensure to wear a mask when interacting with other people. Another strategy is to increase testing, tracing, isolation, and also focus on social distancing.

    References:

    1. Randomized Evaluation of COVID-19 Therapy (RECOVERY). Low-cost dexamethasone reduces death by up to one-third in hospitalized patients with severe respiratory complications of COVID-19. 2020. Available at: 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. Accessed June 23, 2020.
    2. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32167524.
    3. Yang Z, Liu J, Zhou Y, Zhao X, Zhao Q, Liu J. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis. J Infect. 2020;81(1):e13-e20. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32283144.
    4. Kolilekas L, Loverdos K, Giannakaki S, et al. Can steroids reverse the severe COVID-19 induced ‘cytokine storm’? J Med Virol. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32530507.
    5. Fadel R, Morrison AR, Vahia A, et al. Early short course corticosteroids in hospitalized patients with COVID-19. Clin Infect Dis. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32427279.
    6. C, Ro S, Murakami M, Imai R, Jinta T. High-dose, short-term corticosteroids for ARDS caused by COVID-19: a case series. Respir Case Rep. 2020;8(6):e00596. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32514354.