Ciclesonide Use in COVID-19: Not All Steroids Are the Same

Abstract

Introduction: The inflammatory mechanisms of COVID-19 suggest that corticosteroids may \nbe beneficial, but their benefits must outweigh their potential risks. The \nRECOVERY trial results suggest that dexamethasone 6 mg/day (but not other steroids) may confer mortality \nbenefits on ventilated COVID-19 patients. Methods: This is a narrative review of the literature about the use of ciclesonide \nand dexamethasone for COVID-19 patients. Literature is being created rapidly \nand this review is offered as a state-of-the-science narration. Results: The SARS-CoV-2 virus is an RNA virus whose RNA is transcribed via open \nreading frames, making its elimination difficult. Coronaviruses have evolved \nmultiple strategies for proteolytic activation of the spike; viral replication \noccurs entirely in the cytoplasm. In this connection, the RNA-cleaving \nendoribonuclease (NSP-15 also known as EndoU) may play a key role by facilitating \nviral double-stranded RNA recognition by the host’s macrophages. Furthermore, the virus is able to undergo RNA \nrecombination rapidly, enabling it to evade host immunity and develop \ndrug resistance. Ciclesonide is an inhaled corticosteroid that reduces lung \ninflammation and blocks the activity of specific kinases which may explain its \nanti-inflammatory effect. Dexamethasone is known to reduce mortality in \nventilated COVID-19 patients. Discussion: Systemic corticosteroids were used in previous coronavirus epidemics \n(SARS and MERS) and pulmonary histology of these patients is similar to those \nin COVID-19 patients. Acute respiratory distress syndrome is the main cause of \ndeath in most COVID-19 infections and steroids may be effective in addressing \nthat condition, brought on by cytokine storm. However, it should be noted that \ninhaled steroids likely have a narrower window for effect than systemic \nregimens. Conclusion: Dexamethasone has been proven to confer mortality benefits on ventilated \nCOVID-19 patients and may be used with inhaled ciclesonide, which has few side \neffects and can be locally metabolized. Further study is needed.