Abstract
Introduction: The inflammatory mechanisms of COVID-19 suggest that corticosteroids may be beneficial, but their benefits must outweigh their potential risks. The RECOVERY trial results suggest that dexamethasone 6 mg/day (but not other steroids) may confer mortality benefits on ventilated COVID-19 patients. Methods: This is a narrative review of the literature about the use of ciclesonide and dexamethasone for COVID-19 patients. Literature is being created rapidly and 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 reading frames, making its elimination difficult. Coronaviruses have evolved multiple strategies for proteolytic activation of the spike; viral replication occurs entirely in the cytoplasm. In this connection, the RNA-cleaving endoribonuclease (NSP-15 also known as EndoU) may play a key role by facilitating viral double-stranded RNA recognition by the host’s macrophages. Furthermore, the virus is able to undergo RNA recombination rapidly, enabling it to evade host immunity and develop drug resistance. Ciclesonide is an inhaled corticosteroid that reduces lung inflammation and blocks the activity of specific kinases which may explain its anti-inflammatory effect. Dexamethasone is known to reduce mortality in ventilated COVID-19 patients. Discussion: Systemic corticosteroids were used in previous coronavirus epidemics (SARS and MERS) and pulmonary histology of these patients is similar to those in COVID-19 patients. Acute respiratory distress syndrome is the main cause of death in most COVID-19 infections and steroids may be effective in addressing that condition, brought on by cytokine storm. However, it should be noted that inhaled steroids likely have a narrower window for effect than systemic regimens. Conclusion: Dexamethasone has been proven to confer mortality benefits on ventilated COVID-19 patients and may be used with inhaled ciclesonide, which has few side effects and can be locally metabolized. Further study is needed.
Highlights
The inflammatory mechanisms of COVID-19 suggest that corticosteroids may be beneficial, but their benefits must outweigh their potential risks
Measles, Ebola, and flu viruses, the currently pandemic virus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus
The loss of NSP15 activity resulted in greatly attenuated disease in mice and stimulated a protective immune response. These findings demonstrate that coronavirus nonstructural proteins (NSPs) are critical for the evasion of host double-stranded RNA (dsRNA) sensors in macrophages [30]
Summary
The inflammatory mechanisms of COVID-19 suggest that corticosteroids may be beneficial, but their benefits must outweigh their potential risks. The RECOVERY trial results suggest that dexamethasone 6 mg/day (but not other steroids) may confer mortality benefits on ventilated COVID-19 patients. Methods: This is a narrative review of the literature about the use of ciclesonide and dexamethasone for COVID-19 patients. Coronaviruses have evolved multiple strategies for proteolytic activation of the spike; viral replication occurs entirely in the cytoplasm. In this connection, the RNA-cleaving endoribonuclease (NSP-15 known as EndoU) may play a key role by facilitating viral double-stranded RNA recognition by the host’s macrophages. Ciclesonide is an inhaled corticosteroid that reduces lung inflammation and blocks the activity of specific kinases which may explain its anti-inflammatory effect. Dexamethasone is known to reduce mortality in ventilated COVID-19 patients. It should be noted that inhaled steroids likely have a narrower window for effect than
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