Tailoring glucocorticoids in patients with severe COVID-19: a narrative review

Abstract

To discuss the pathogenesis of severe coronavirus disease 2019 (COVID-19) infection and the pharmacological effects of glucocorticoids (GCs) toward this infection. To review randomized controlled trials (RCTs) using GCs to treat patients with severe COVID-19, and investigate whether GC timing, dosage, or duration affect clinical outcomes. Finally. to discuss the use of biological markers, respiratory parameters, and radiological evidence to select patients for improved GC therapeutic precision.Background: COVID-19 has become an unprecedented global challenge. As GCs have been used as key immunomodulators to treat inflammation-related diseases, they may play key roles in limiting disease progression by modulating immune responses, cytokine production, and endothelial function in patients with severe COVID-19, who often experience excessive cytokine production and endothelial and reninangiotensin system (RAS) dysfunction. Current clinical trials have partially proven this efficacy, but GC timing, dosage, and duration vary greatly, with no unifying consensus, thereby creating confusion.Methods: Publications through March 2021 were retrieved from the Web of Science and PubMed. Results from cited references in published articles were also included.Conclusions: GCs play key roles in treating severe COVID-19 infections. Pharmacologically, GCs could modulate immune cells, reduce cytokine and chemokine, and improve endothelial functions in patients with severe COVID-19. Benefits of GCs have been observed in multiple clinical trials, but the timing, dosage and duration vary across studies. Tapering as an option is not widely accepted. However, early initiation of treatment, a tailored dosage with appropriate tapering may be of particular importance, but evidence is inconclusive and more investigations are needed. Biological markers, respiratory parameters, and radiological evidence could also help select patients for specific tailored treatments.

Postoperative glucocorticoids in patients with acute type A aortic dissection (GLAD): study protocol for a prospective, single-center, randomized controlled trial

“…1 g MP) when given prophylactically before the initiation of CPB. However, benefits of GC to regulate dysregulated inflammation have mostly been observed in critical care studies adopting a mild-to-moderate dose of GC, as we have seen in inflammation-mediated conditions, such as acute respiratory distress syndrome [ 21 – 23 ]. In our study, we will implement an initial dosage of 4 mg/kg/d MP on POD 1 and taper it to 1 mg/kg/d on POD 3.…”

The Relationship between COVID-19 and Hypothalamic–Pituitary–Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess—The CAPISCO International Expert Panel

“…Mechanistically methylprednisolone achieves higher lung-to-plasma ratios in animal models than dexamethasone, and smaller trials have demonstrated its superiority to dexamethasone; however, the therapeutic dosing was not equivalent between groups [21,22]. Regarding the best possible initiation time for the treatment, the current evidence suggests their usage in the second week of infection, when inflammatory instead of infectious mechanisms predominate [8,23,24]. In trials so far, different dosage regimes have been reported in patients with severe COVID-19, from consistent doses throughout the treatment course, to the administration of a tapering dose, or the administration of pulse doses for a short period [8].…”

“…Glucocorticoids have been widely used in the previous severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) epidemics and ARDS in general; however, the data regarding their efficacy were contradictory and generally of low quality [6]. They exert potent antiinflammatory effects across both innate and adaptive immune systems through the DNA-dependent regulation of antiinflammatory proteins, non-genomic modulation of inflammation, and direct protein interference of transcription factors such as nuclear factor kappa B [7][8][9]. In early 2020, a retrospective study of 201 patients admitted with confirmed COVID-19 pneumonia in Wuhan, China, provided the first evidence supporting their usage by demonstrating that treatment with methylprednisolone was associated with a reduced risk of death among patients with ARDS [10].…”

“…Despite considerable efforts, it is challenging to derive definitive conclusions on an optimal glucocorticoid agent, or its timing, dose, and duration from the current literature [8]. Mechanistically methylprednisolone achieves higher lung-to-plasma ratios in animal models than dexamethasone, and smaller trials have demonstrated its superiority to dexamethasone; however, the therapeutic dosing was not equivalent between groups [21,22].…”

“…Regarding the best possible initiation time for the treatment, the current evidence suggests their usage in the second week of infection, when inflammatory instead of infectious mechanisms predominate [8,23,24]. In trials so far, different dosage regimes have been reported in patients with severe COVID-19, from consistent doses throughout the treatment course, to the administration of a tapering dose, or the administration of pulse doses for a short period [8].…”