The Role of Inhaled Corticosteroids (ICS) in Critically Ill Patients With COVID-19: A Multicenter, Cohort Study
Khalid Al Sulaiman, PharmD, BCCCP Ohoud Aljuhani, PharmD Kholoud Al Aamer, PharmD Omar Al Shaya, PharmD, BCCCP Abdulrahman Al Shaya, MD Alawi S Alsaeedi, PharmD Alaa Alhubaishi, PharmD, BCPS Ali F Altebainawi, PharmD Alaa Al Harthi, PharmD Shorouq Albelwi, PharmD Rahaf Almutairi, PharmD Norah Alsubaie, PharmD Alanoud Alsallum, PharmD Ghazwa B Korayem, PharmD Amjaad Alfahed, PharmD Raed Kensara, MD Elaf F Altebainawi, PharmD Raghdah S Alenezi, MD Thamer Alsulaiman, PharmD Huda Al Enazi, PhD Statistics Ramesh Vishwakarma, MD Tarek Al Dabbagh, MD Umar Bakhsh, MD Ghassan Al Ghamdi
Journal of Intensive Care Medicine, doi:10.1177/08850666211053548
Background: Severe coronavirus disease 2019 (COVID-19) can boost the systematic inflammatory response in critically ill patients, causing a systemic hyperinflammatory state leading to multiple complications. In COVID-19 patients, the use of inhaled corticosteroids (ICS) is surrounded by controversy regarding their impacts on viral infections. This study aims to evaluate the safety and efficacy of ICS in critically ill patients with COVID-19 and its clinical outcomes. Method: A multicenter, noninterventional, cohort study for critically ill patients with COVID-19 who received ICS. All patients aged ≥ 18 years old with confirmed COVID-19 and admitted to intensive care units (ICUs) between March 1, 2020 and March 31, 2021 were screened. Eligible patients were classified into two groups based on the use of ICS ± long-acting beta-agonists (LABA) during ICU stay. Propensity score (PS)-matched was used based on patient's Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, systemic corticosteroids use, and acute kidney injury (AKI) within 24 h of ICU admission. We considered a P-value of < 0.05 statistically significant. Results: A total of 954 patients were eligible; 130 patients were included after PS matching (1:1 ratio). The 30-day mortality (hazard ratio [HR] [95% confidence interval [CI]]: 0.53 [0.31, 0.93], P-value = 0.03) was statistically significant lower in patients who received ICS. Conversely, the in-hospital mortality, ventilator-free days (VFDs), ICU length of stay (LOS), and hospital LOS were not statistically significant between the two
Author's Contribution Khalid Al Sulaiman: conceptualization, methodology, software, data curation, writing -0riginal draft preparation, coordination, and management, visualization, investigation. Ohoud Aljuhani: conceptualization, literature review, methodology, investigation, data acquisition and processing, supervision, research coordination, and management, revising and editing the manuscript. Kholoud Al Aamer: data acquisition, data analysis, data processing, data preparation, and original draft writing. Omar Al Shaya: data acquisition, data analysis, data processing, data preparation, interpretation of the data and original draft writing. Abdulrahman Al Shaya: data acquisition, data analysis, data processing, data preparation, interpretation of the data and original draft writing. Alawi S. Alsaeedi: data acquisition, data analysis, data processing, data preparation, interpretation of the data and original draft writing. Alaa Alhubaishi: data curation, writing-original draft, revising and editing the manuscript, visualization, investigation and data interpretation. Ali F. Altebainawi: methodology, software, data curation, revising and editing the manuscript, supervision, visualization, investigation. Alaa Al Harthi: data acquisition, data analysis, data processing, data preparation, and original draft writing. Shorouq Albelwi: data acquisition, data analysis, data processing, data preparation, and original draft writing. Rahaf Almutairi: data acquisition, data analysis,..
References
Ahmad, Rathore, Neurological manifestations and complications of COVID-19: a literature review, J Clin Neurosci Off J Neurosurg Soc Australas,
doi:10.1016/j.jocn.2020.05.017Aleidan, Alkhelaifi, Alsenaid, Incidence and risk factors of carbapenem-resistant enterobacteriaceae infection in intensive care units: a matched case-control study, Expert Rev Anti Infect Ther,
doi:10.1080/14787210.2020.1822736Arentz, Yim, Klaff, Characteristics and outcomes of 21 critically Ill patients With COVID-19 in Washington state, JAMA,
doi:10.1001/jama.2020.4326Azkur, Akdis, Azkur, Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19, Allergy,
doi:10.1111/all.14364Burn, You, Sena, Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study, Nat Commun,
doi:10.1038/s41467-020-18849-zCdc) C For, Dc, People with Certain Medical Conditions
Checchi, Bellini, Bencivenni, Consolo, COVID-19 Dentistry-Related aspects: a literature overview, Int Dent J,
doi:10.1111/idj.12601Choi, Jung, Yoon, Inhaled corticosteroids and COVID-19 risk and mortality: a nationwide cohort study, J Clin Med,
doi:10.3390/jcm9113406Contoli, Pauletti, Rossi, Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD, Eur Respir J,
doi:10.1183/13993003.00451-2017Finney, Glanville, Farne, Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon, J Allergy Clin Immunol,
doi:10.1016/j.jaci.2020.09.034For, Global Strategy for Asthma Management and Prevention
Gold) Gi For, Global Strategy for Prevention, Diagnosis and Management of COPD
Grasselli, Zangrillo, Zanella, Baseline characteristics and outcomes of 1591 patients infected With SARS-CoV-2 admitted to ICUs of the lombardy region, Italy, JAMA,
doi:10.1001/jama.2020.5394Guan, Liang, Zhao, Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis, Eur Respir J,
doi:10.1183/13993003.00547-2020Halpin, Faner, Sibila, Badia, Agusti, Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection?, Lancet Respir Med,
doi:10.1016/S2213-2600(20)30167-3Jeon, Ko, Lee, Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs, Antimicrob Agents Chemother,
doi:10.1128/AAC.00819-20Koenig, Truwit, Ventilator-associated pneumonia: diagnosis, treatment, and prevention, Clin Microbiol Rev,
doi:10.1128/CMR.00051-05Lin, Chen, Acute kidney injury classification: aKIN and RIFLE criteria in critical patients, World J Crit Care Med,
doi:10.5492/wjccm.v1.i2.40Matsuyama, Kawase, Nao, The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting the viral replication-transcription complex in cultured cells, J Virol,
doi:10.1128/JVI.01648-20Milne, Li, Yang, Inhaled corticosteroids downregulate SARS-CoV-2-related genes in COPD: results from a randomised controlled trial, Eur Respir J,
doi:10.1183/13993003.00130-2021O'byrne, Pedersen, Carlsson, Risks of pneumonia in patients with asthma taking inhaled corticosteroids, Am J Respir Crit Care Med,
doi:10.1164/rccm.201005-0694OCPinna, Scabini, Corcione, Lupia, Rosa, COVID-19 pneumonia: do not leave the corticosteroids behind!, Future Microbiol,
doi:10.2217/fmb-2020-0199Ramakrishnan, Nicolau, Langford, Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial, Lancet Respir Med,
doi:10.1016/S2213-2600(21)00160-0Rodriguez-Roisin, Pulmonary gas exchange in acute respiratory failure, Eur J Anaesthesiol
Schultze, Walker, Mackenna, Risk of COVID-19-related death among patients with chronic obstructive pulmonary disease or asthma prescribed inhaled corticosteroids: an observational cohort study using the OpenSAFELY platform, Lancet Respir Med,
doi:10.1016/S2213-2600(20)30415-XSen, Majumdar, Zein, Hatipoğlu, Attaway, Inhaled corticosteroids do not adversely impact outcomes in COVID-19 positive patients with COPD: an analysis of Cleveland clinic'S COVID-19 registry, PLoS One,
doi:10.1371/journal.pone.0252576Sheffer, Silverman, Woolcock, Díaz, Lindberg et al., Long-term safety of once-daily budesonide in patients with early-onset mild persistent asthma: results of the inhaled steroid treatment as regular therapy in early asthma (START) study. Ann Allergy, Asthma Immunol Off Publ Am Coll Allergy, Asthma, Immunol,
doi:10.1016/S1081-1206(10)61285-9Sulaiman, Aljuhani, Eljaaly, Clinical features and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19): a multicenter cohort study, Int J Infect Dis IJID Off Publ Int Soc Infect Dis,
doi:10.1016/j.ijid.2021.02.037Wang, Liou, Lin, Association of cardiovascular risk With inhaled long-acting bronchodilators in patients With chronic obstructive pulmonary disease: a nested case-control study, JAMA Intern Med,
doi:10.1001/jamainternmed.2017.7720Xie, Wu, Li, Clinical characteristics and outcomes of critically ill patients with novel coronavirus infectious disease (COVID-19) in China: a retrospective multicenter study, Intensive Care Med,
doi:10.1007/s00134-020-06211-2Yamaya, Nishimura, Deng, Inhibitory effects of glycopyrronium, formoterol, and budesonide on coronavirus HCoV-229E replication and cytokine production by primary cultures of human nasal and tracheal epithelial cells, Respir Investig,
doi:10.1016/j.resinv.2019.12.005Yang, Chen, Zhang, Long-term use of inhaled corticosteroids and risk of upper respiratory tract infection in chronic obstructive pulmonary disease: a meta-analysis, Inhal Toxicol,
doi:10.1080/08958378.2017.1346006Yang, Li, Zhang, Sun, Chen, Prevalence and impact of acute renal impairment on COVID-19: a systematic review and meta-analysis, Crit Care,
doi:10.1186/s13054-020-03065-4Yu, Bafadhel, Dorward, Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial, Lancet,
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'abstract': '<jats:p> Background: Severe coronavirus disease 2019 (COVID-19) can boost the systematic '
'inflammatory response in critically ill patients, causing a systemic hyperinflammatory state '
'leading to multiple complications. In COVID-19 patients, the use of inhaled corticosteroids '
'(ICS) is surrounded by controversy regarding their impacts on viral infections. This study '
'aims to evaluate the safety and efficacy of ICS in critically ill patients with COVID-19 and '
'its clinical outcomes. Method: A multicenter, noninterventional, cohort study for critically '
'ill patients with COVID-19 who received ICS. All patients aged ≥ 18 years old with confirmed '
'COVID-19 and admitted to intensive care units (ICUs) between March 1, 2020 and March 31, 2021 '
'were screened. Eligible patients were classified into two groups based on the use of ICS\u2009'
'±\u2009long-acting beta-agonists (LABA) during ICU stay. Propensity score (PS)-matched was '
'used based on patient’s Acute Physiology and Chronic Health Evaluation II (APACHE II) score, '
'Sequential Organ Failure Assessment (SOFA) score, systemic corticosteroids use, and acute '
'kidney injury (AKI) within 24\u2005h of ICU admission. We considered a P-value of < 0.05 '
'statistically significant. Results: A total of 954 patients were eligible; 130 patients were '
'included after PS matching (1:1 ratio). The 30-day mortality (hazard ratio [HR] [95% '
'confidence interval [CI]]: 0.53 [0.31, 0.93], P-value\u2009=\u20090.03) was statistically '
'significant lower in patients who received ICS. Conversely, the in-hospital mortality, '
'ventilator-free days (VFDs), ICU length of stay (LOS), and hospital LOS were not '
'statistically significant between the two groups. Conclusion: The use of ICS\u2009±\u2009LABA '
'in COVID-19 patients may have survival benefits at 30 days. However, it was not associated '
'with in-hospital mortality benefits nor VFDs. </jats:p>',
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