Zhikang Ye1, Ying Wang1, Luis Enrique Colunga-Lozano1, Manya Prasad1, Wimonchat Tangamornsuksan1, Bram Rochwerg1, Liang Yao1, Shahrzad Motaghi1, Rachel J Couban1, Maryam Ghadimi1, Malgorzata M Bala1, Huda Gomaa1, Fang Fang1, Yingqi Xiao1, Gordon H Guyatt2. 1. Department of Health Research Methods, Evidence and Impact (Ye, Tangamornsuksan, Rochwerg, Guyatt, Colunga-Lozano, Yao, Motaghi, Fang, Xiao), McMaster University, Hamilton, Ont.; Department of Pharmacy (Wang), Beijing Chaoyang Hospital, Capital Medical University, Beijing, China; Department of Clinical Medicine (Colunga-Lozano), Health Science Center, Universidad de Guadalajara, Guadalajara, Mexico; Department of Community Medicine (Prasad), North DMC Medical College, New Delhi, India; Faculty of Medicine and Public Health (Tangamornsuksan), HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand; Department of Medicine (Rochwerg); DeGroote Institute for Pain Research and Care (Couban), McMaster University, Hamilton, Ont.; Department of Clinical Pharmacy (Ghadimi), Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Chair of Epidemiology and Preventive Medicine Jagiellonian (Bala), University Medical College, Krakow, Poland; Biostatistics Department (Gomaa), High institute of Public Health, Alexandria University, Alexandria, Egypt; Drug Information Center (Gomaa), Tanta Chest Hospital, Ministry of Health and Population, Egypt; Clinical Medicine College of Acupuncture, Moxibustion and Rehabilitation (Fang), Guangzhou University of Chinese Medicine, Guangdong, China; West China School of Nursing (Xiao), West China Hospital, Sichuan University, China. 2. Department of Health Research Methods, Evidence and Impact (Ye, Tangamornsuksan, Rochwerg, Guyatt, Colunga-Lozano, Yao, Motaghi, Fang, Xiao), McMaster University, Hamilton, Ont.; Department of Pharmacy (Wang), Beijing Chaoyang Hospital, Capital Medical University, Beijing, China; Department of Clinical Medicine (Colunga-Lozano), Health Science Center, Universidad de Guadalajara, Guadalajara, Mexico; Department of Community Medicine (Prasad), North DMC Medical College, New Delhi, India; Faculty of Medicine and Public Health (Tangamornsuksan), HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand; Department of Medicine (Rochwerg); DeGroote Institute for Pain Research and Care (Couban), McMaster University, Hamilton, Ont.; Department of Clinical Pharmacy (Ghadimi), Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Chair of Epidemiology and Preventive Medicine Jagiellonian (Bala), University Medical College, Krakow, Poland; Biostatistics Department (Gomaa), High institute of Public Health, Alexandria University, Alexandria, Egypt; Drug Information Center (Gomaa), Tanta Chest Hospital, Ministry of Health and Population, Egypt; Clinical Medicine College of Acupuncture, Moxibustion and Rehabilitation (Fang), Guangzhou University of Chinese Medicine, Guangdong, China; West China School of Nursing (Xiao), West China Hospital, Sichuan University, China guyatt@mcmaster.ca.
Abstract
BACKGROUND: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. METHODS: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. RESULTS: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. INTERPRETATION: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.
BACKGROUND: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. METHODS: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. RESULTS: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. INTERPRETATION: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.
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