Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Immunology, Tufts University School of Medicine, Boston. MA 02111, USA.
School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.
J Biol Regul Homeost Agents. 2020;34(3):1241-1243. doi: 10.23812/20-EDITORIAL_1-5.
Recent announcements indicated, without sharing any distinct published set of results, that the corticosteroid dexamethasone may reduce mortality of severe COVID-19 patients only. The recent Coronavirus [severe acute respiratory syndrome (SARS)-CoV-2]-associated multiorgan disease, called COVID-19, has high morbidity and mortality due to autoimmune destruction of the lungs stemming from the release of a storm of pro-inflammatory cytokines. Defense against this Corona virus requires activated T cells and specific antibodies. Instead, cytokines are responsible for the serious sequelae of COVID-19 that damage the lungs. Dexamethasone is a synthetic corticosteroid approved by the FDA 1958 as a broad-spectrum immunosuppressor and it is about 30 times as active and with longer duration of action (2-3 days) than cortisone. Dexamethasone would limit the production of and damaging effect of the cytokines, but will also inhibit the protective function of T cells and block B cells from making antibodies, potentially leading to increased plasma viral load that will persist after a patient survives SARS. Moreover, dexamethasone would block macrophages from clearing secondary, nosocomial, infections. Hence, dexamethasone may be useful for the short-term in severe, intubated, COVID-19 patients, but could be outright dangerous during recovery since the virus will not only persist, but the body will be prevented from generating protective antibodies. Instead, a pulse of intravenous dexamethasone may be followed by administration of nebulized triamcinolone (6 times as active as cortisone) to concentrate in the lungs only. These corticosteroids could be given together with the natural flavonoid luteolin because of its antiviral and anti-inflammatory properties, especially its ability to inhibit mast cells, which are the main source of cytokines in the lungs. At the end, we should remember that "The good physician treats the disease; the great physician treats the patient who has the disease" [Sir William Osler's (1849-1919)].
最近的公告表明，在没有分享任何明确公布的结果的情况下，皮质类固醇地塞米松可能仅降低重症 COVID-19 患者的死亡率。最近由冠状病毒[严重急性呼吸系统综合征（SARS）-CoV-2]引起的多器官疾病，称为 COVID-19，由于肺部炎症风暴导致的炎症细胞因子释放，导致高发病率和死亡率。机体防御这种冠状病毒需要激活的 T 细胞和特异性抗体。相反，细胞因子是导致 COVID-19 严重后遗症的原因，会损害肺部。地塞米松是一种 1958 年由美国食品和药物管理局（FDA）批准的合成皮质类固醇，它的活性比可的松高约 30 倍，作用持续时间更长（2-3 天）。地塞米松会限制细胞因子的产生和损伤作用，但也会抑制 T 细胞的保护功能并阻止 B 细胞产生抗体，这可能导致血浆病毒载量增加，在 SARS 患者存活后仍持续存在。此外，地塞米松会阻止巨噬细胞清除继发性、医院获得性感染。因此，地塞米松可能对重症、插管的 COVID-19 患者短期有用，但在康复期间可能会非常危险，因为病毒不仅会持续存在，而且机体将无法产生保护性抗体。相反，静脉注射地塞米松脉冲后，可以给予布地奈德（比可的松活性高 6 倍）雾化吸入，仅在肺部集中。由于其抗病毒和抗炎特性，尤其是其抑制肥大细胞的能力，肥大细胞是肺部细胞因子的主要来源，这些皮质类固醇可以与天然类黄酮芦丁一起使用。最后，我们应该记住，“良医治病，大医医人”[威廉·奥斯勒爵士（1849-1919）]。
