Efficacy and Safety of Corticosteroid Treatment in Patients With COVID-19: A Systematic Review and Meta-Analysis

Cheng, Wenwen; Li, Yufeng; Cui, Liyan; Chen, Ying; Shan, Sharui; Xiao, Duan; Chen, Xiaoyun; Chen, Zhuoming; Xu, Anding

doi:10.3389/fphar.2020.571156

Cited by 44 publications

(26 citation statements)

References 53 publications

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“…Meta-analysis by Pei et al 20 included 5 retrospective studies in 943 patients and concluded that corticosteroids use might increase risk of death (OR: 2.43; 95% CI: 1.44–4.1; P = 0.0001). Similarly, in another meta-analysis based on cohort studies and case series, Cheng et al 21 also concluded that corticosteroids were not effective to decrease mortality, shorten duration of symptoms, or virus clearance time. Of note, both of these two meta-analyses included non-RCTs but observational studies, which had diverse confounding or bias, such as residual confounding, survivor bias, treatment selection bias, collectively decreasing the quality of the conclusion.…”

Section: Discussionmentioning

confidence: 97%

Efficacy and safety of systematic corticosteroids among severe COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

Liu

et al. 2021

Sig Transduct Target Ther

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The benefits and harms of corticosteroids for patients with severe coronavirus disease 2019 (COVID-19) remain unclear. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from December 31, 2019 to October 1, 2020 to identify randomized controlled trials (RCTs) that evaluated corticosteroids in severe COVID-19 patients. The primary outcome was all-cause mortality at the longest follow-up. Secondary outcomes included a composite disease progression (progression to intubation, ventilation, extracorporeal membrane oxygenation, ICU transfer, or death among those not ventilated at enrollment) and incidence of serious adverse events. A random-effects model was applied to calculate risk ratio (RR) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation approach to evaluate the certainty of the evidence. Seven RCTs involving 6250 patients were included, of which the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial comprised nearly 78% of all included subjects. Results showed that corticosteroids were associated with a decreased all-cause mortality (27.3 vs. 31.1%; RR: 0.85; 95% CI: 0.73–0.99; P = 0.04; low-certainty evidence). Trial sequential analysis suggested that more trials were still required to confirm the results. However, such survival benefit was absent if RECOVERY trial was excluded (RR: 0.83; 95% CI: 0.65–1.06; P = 0.13). Furthermore, corticosteroids decreased the occurrence of composite disease progression (30.6 vs. 33.3%; RR: 0.77; 95% CI: 0.64–0.92; P = 0.005), but not increased the incidence of serious adverse events (3.5 vs. 3.4%; RR: 1.16; 95% CI: 0.39–3.43; P = 0.79).

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Section: Discussionmentioning

confidence: 97%

Efficacy and safety of systematic corticosteroids among severe COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

Liu

et al. 2021

Sig Transduct Target Ther

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“…Table 3 summarizes the characteristics and main finding from 13 systematic reviews and meta-analyses published since March 2020 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 . Two of these systematic reviews included only randomized controlled trials 76 , 77 .…”

Section: Summary Of the Clinical Evidence Of Corticosteroids Effects mentioning

confidence: 99%

Corticosteroids for COVID-19

Annane¹

2021

Journal of Intensive Medicine

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COVID-19 is placing a major burden on healthcare, economy and social systems worldwide owing to its fast spread and unacceptably high death toll. The unprecedented research effort has established the role of a deregulated immune response to the severe acute respiratory syndrome coronavirus 2 resulting in systemic inflammation. Thereafter, the immunomodulatory approach has been place in the top list of the research agenda for COVID-19. Corticosteroids have been used for more than 70 years for modulating immune response in a broad variety of disease. These drugs have been shown to prevent and attenuate the inflammation both in tissues and in the circulation via non-genomic and genomic effects. At the bedside, numerous observational cohorts have been published the past months and have been inconclusive. Randomized controlled trials with subsequent high quality meta-analyses have provided moderate to strong certainty for increased chance of survival and relief from life supportive therapy with corticosteroids given at a dose of 6mg per day of dexamethasone or equivalent doses of hydrocortisone or methylprednisolone. The corticotherapy was not associated with increased risk of bacterial infection or of delayed viral clearance. In daily practice, physicians may be encouraged to use to corticosteroids when managing patients with COVID-19 requiring oxygen supplementation.

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“…In the light of these properties, systemic CSs have been empirically used to manage the cytokine storm in COVID-19 patients and mitigate its most severe manifestations such as ARDS, systemic organ failure and death [ 103 , 104 ]. In the early days of this pandemic, guidance regarding CSs was mixed: on the one hand, data collected during previous coronavirus outbreaks that share many clinical characteristics with COVID-19, SARS and MERS, were inconclusive about efficacy and safety of CSs [ 66 , 105 , 106 , 107 ]; on the other hand, the initial clinical experience on adjunctive therapy with CSs, which was essentially documented by case reports, observational and small (and often single-center) studies, similarly emphasized the need for large scale randomized trials to properly assess CSs on outcomes according to severity of COVID-19 disease [ 51 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 ]. On 6 June 2020, breaking news from the RECOVERY ( R andomized E valuation of COV ID-19 th ER ap Y ) trial based in the United Kingdom (NCT04381936) announced that participants who received 6 mg dexamethasone daily for 10 days saw improvements, and in particular the subsets of patients already on ventilators or who required non-invasive oxygen therapy [ 117 ].…”

Section: Css Use During Covid-19 Pandemic: Pros and Consmentioning

confidence: 99%

Challenges and Opportunities from Targeting Inflammatory Responses to SARS-CoV-2 Infection: A Narrative Review

Lariccia

Magi

Serfilippi

et al. 2020

JCM

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The novel coronavirus disease 2019 (COVID-19) is a global pandemic that continues to sweep across the world, posing an urgent need for effective therapies and prevention of the spread of the severe acute respiratory syndrome related to coronavirus-2 (SARS-CoV-2). A major hypothesis that is currently guiding research and clinical care posits that an excessive and uncontrolled surge of pro-inflammatory cytokines (the so-called “cytokine storm”) drives morbidity and mortality in the most severe cases. In the overall efforts made to develop effective and safe therapies (including vaccines) for COVID-19, clinicians are thus repurposing ready-to-use drugs with direct or indirect anti-inflammatory and immunomodulatory activities. Speculatively, there are many opportunities and challenges in targeting immune/inflammatory processes in the evolving settings of COVID-19 disease because of the need to safely balance the fight against virus and aggressive inflammation versus the suppression of host immune defenses and the risk of additional harms in already compromised patients. To this end, many studies are globally underway to weigh the pros and cons of tailoring drugs used for inflammatory-driven conditions to COVID-19 patient care, and the next step will be to summarize the growing clinical trial experience into clean clinical practice. Based on the current evidence, anti-inflammatory drugs should be considered as complementary approaches to anti-viral drugs that need to be timely introduced in the management of COVID-19 according to disease severity. While drugs that target SARS-CoV-2 entry or replication are expected to confer the greatest benefits at the early stage of the infection, anti-inflammatory drugs would be more effective in limiting the inflammatory processes that drive the worsening of the disease.

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Efficacy and Safety of Corticosteroid Treatment in Patients With COVID-19: A Systematic Review and Meta-Analysis

Cited by 44 publications

References 53 publications

Efficacy and safety of systematic corticosteroids among severe COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

Efficacy and safety of systematic corticosteroids among severe COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

Corticosteroids for COVID-19

Challenges and Opportunities from Targeting Inflammatory Responses to SARS-CoV-2 Infection: A Narrative Review

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