Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints

Abstract

Prolonged, low-dose glucocorticoids (GCs) have shown the highest efficacy among pharmacological and non-pharmacological treatments for COVID-19. Despite the World Health Organization’s recommendation against their use at the beginning of the pandemic, GCs at a dose equivalent to dexamethasone 6 mg/day for 10 days are now indicated in all COVID-19 cases who require respiratory support. However, the efficacy of the intervention depends on the timing of initiation, the dose, and other individual factors. Indeed, patients treated with similar GC protocols often experience different outcomes, which do not always correlate with the presence of comorbidities or with the severity of respiratory involvement at baseline. This prompted us to critically review the literature on the rationale, pharmacological principles, and clinical evidence that should guide GC treatment. Based on these data, the best treatment protocol probably involves an initial bolus dose to saturate the glucocorticoid receptors, followed by a continuous infusion to maintain constant plasma levels, and eventually a slow tapering to interruption. Methylprednisolone has shown the highest efficacy among different GC molecules, most likely thanks to its higher ability to penetrate the lung. Decreased tissue sensitivity to glucocorticoids is thought to be the main mechanism accounting for the lower response to the treatment in some individuals. We do not have a readily available test to identify GC resistance; therefore, to address inter-individual variability, future research should aim at investigating clinical, physiological, and laboratory markers to guide a personalized GC treatment approach.

Effect of pinocembrin on thymocyte proliferation and death

“…In the present study, we used a synthetic glucocorticoid, DX, known for inducing the death of immunocompetent cells. Actually, it is widely used as an effective medication for the treatment of inflammatory and autoimmune disorders, being recommended for the treatment of patients with coronavirus disease 2019 (COVID-19) (38). Here we showed that 1 μM DX caused a dramatic increase in the fraction of necrotic PI-positive cells in the total population up to 50.8 ± 7.2 % and increased the proportion of AnnVpositive (apoptotic) cells up to 16.7 ± 1.3 % (Figure 3).…”

Oscillometry Longitudinal Data on COVID-19 Acute Respiratory Distress Syndrome Treated with Non-Invasive Respiratory Support

“…The first study included hospitalized patients in their last days before RICU discharge, the second study reported weekly changes in oscillometry parameters in a patient before, during, and after a severe COVID-19 infection, and the third one reported oscillometry data 3 and 5 months after COVID-19 infections. While all the studies reported lung mechanics improvements over time, differences in the study designs, timing of the measurements, and the use of steroids, which may impact lung mechanics [39,40], prevent a direct comparison of these results.…”