M. Tagliati, Marianna Leopoulou, J. LeQuang, Charles Wollmuth, J. Pergolizzi, Kailyn Mitchell, P. Magnusson
{"title":"在COVID-19中的使用:并非所有类固醇都是相同的","authors":"M. Tagliati, Marianna Leopoulou, J. LeQuang, Charles Wollmuth, J. Pergolizzi, Kailyn Mitchell, P. Magnusson","doi":"10.4236/PP.2021.121002","DOIUrl":null,"url":null,"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.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":"13 1","pages":"10-24"},"PeriodicalIF":0.0000,"publicationDate":"2021-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Ciclesonide Use in COVID-19: Not All Steroids Are the Same\",\"authors\":\"M. Tagliati, Marianna Leopoulou, J. LeQuang, Charles Wollmuth, J. Pergolizzi, Kailyn Mitchell, P. Magnusson\",\"doi\":\"10.4236/PP.2021.121002\",\"DOIUrl\":null,\"url\":null,\"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.\",\"PeriodicalId\":19875,\"journal\":{\"name\":\"Pharmacology & Pharmacy\",\"volume\":\"13 1\",\"pages\":\"10-24\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2021-01-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacology & Pharmacy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4236/PP.2021.121002\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology & Pharmacy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4236/PP.2021.121002","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Ciclesonide Use in COVID-19: Not All Steroids Are the Same
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.