Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis

Ye, Zhikang; Wang, Ying; Colunga‐Lozano, Luis Enrique; Prasad, Manya; Tangamornsuksan, Wimonchat; Rochwerg, Bram; Yao, Liang; Motaghi, Shahrzad; Couban, Rachel; Ghadimi, Maryam; Bała, Małgorzata M; Gomaa, Huda; Fang, Fang; Xiao, Yingqi; Guyatt, Gordon

doi:10.1503/cmaj.200645

Cited by 197 publications

(185 citation statements)

References 84 publications

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“…To create recommendations, the panel relied on evidence synthesised in a living network meta-analysis led by MAGIC,3 on a prospective meta-analysis of RCTs evaluating corticosteroids for critically ill COVID-19 patients commissioned by the WHO,6 as well as systematic reviews of the safety of similar regimens of systemic corticosteroids in distinct but relevant patient populations 78. While the investigators responsible for meta-analyses rate the certainty of the evidence, this is re-assessed independently by the guideline panel.…”

Section: How To Use This Guideline?mentioning

confidence: 99%

A living WHO guideline on drugs for covid-19

Lamontagne

Agarwal

Rochwerg

et al. 2020

BMJ

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708

450

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Clinical questionWhat is the role of drug interventions in the treatment and prevention of covid-19?RecommendationsThe first version on this living guidance focuses on corticosteroids. It contains a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic corticosteroids in patients with non-severe covid-19. Corticosteroids are inexpensive and are on the World Health Organisation list of essential medicines.Howthis guideline was created This guideline reflects an innovative collaboration between the WHO and the MAGIC Evidence Ecosystem Foundation, driven by an urgent need for global collaboration to provide trustworthy and living covid-19 guidance. A standing international panel of content experts, patients, clinicians, and methodologists, free from relevant conflicts of interest, produce recommendations for clinical practice. The panel follows standards, methods, processes, and platforms for trustworthy guideline development using the GRADE approach. We apply an individual patient perspective while considering contextual factors (that is, resources, feasibility, acceptability, equity) for countries and healthcare systems.The evidenceA living systematic review and network meta-analysis, supported by a prospective meta-analysis, with data from eight randomised trials (7184 participants) found that systemic corticosteroids probably reduce 28 day mortality in patients with critical covid-19 (moderate certainty evidence; 87 fewer deaths per 1000 patients (95% confidence interval 124 fewer to 41 fewer)), and also in those with severe disease (moderate certainty evidence; 67 fewer deaths per 1000 patients (100 fewer to 27 fewer)). In contrast, systemic corticosteroids may increase the risk of death in patients without severe covid-19 (low certainty evidence; absolute effect estimate 39 more per 1000 patients, (12 fewer to 107 more)). Systemic corticosteroids probably reduce the need for invasive mechanical ventilation, and harms are likely to be minor (indirect evidence).Understanding the recommendationsThe panel made a strong recommendation for use of corticosteroids in severe and critical covid-19 because there is a lower risk of death among people treated with systemic corticosteroids (moderate certainty evidence), and they believe that all or almost all fully informed patients with severe and critical covid-19 would choose this treatment. In contrast, the panel concluded that patients with non-severe covid-19 would decline this treatment because they would be unlikely to benefit and may be harmed. Moreover, taking both a public health and a patient perspective, the panel warned that indiscriminate use of any therapy for covid-19 would potentially rapidly deplete global resources and deprive patients who may benefit from it most as potentially lifesaving therapy.UpdatesThis is a living guideline. Work is under way to evaluate other interventions. New recommendations will be published as updates to this guideline.Readers noteThis is version 1 of the living guideline, published on 4 September (BMJ 2020;370:m3379) version 1. Updates will be labelled as version 2, 3 etc. When citing this article, please cite the version number.SubmittedAugust 28AcceptedAugust 31

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Section: How To Use This Guideline?mentioning

confidence: 99%

A living WHO guideline on drugs for covid-19

Lamontagne

Agarwal

Rochwerg

et al. 2020

BMJ

Self Cite

708

450

View full text Add to dashboard Cite

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“…Dexamethasone is among the two glucocorticoids (prednisolone being the other) which has the inhibitory action on the NF-κB pathway (Ye et al 2020 ; D’Acquisto et al 2002 )*. Glucocorticoids increase expression of IκB, which helps retain NF-κB within the cellular cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

The Role and Therapeutic Potential of NF-kappa-B Pathway in Severe COVID-19 Patients

et al. 2020

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Coronavirus disease 2019 (COVID-19) pandemic has affected health care systems worldwide. Severe presentations of COVID-19 such as severe pneumonia and acute respiratory distress syndrome (ARDS) have been associated with the post-viral activation and release of cytokine/chemokines which leads to a “cytokine storm” causing inflammatory response and destruction, mainly affecting the lungs. COVID-19 activation of transcription factor, NF-kappa B (NF-κB) in various cells such as macrophages of lung, liver, kidney, central nervous system, gastrointestinal system and cardiovascular system leads to production of IL-1, IL-2, IL-6, IL-12, TNF-α, LT-α, LT-β, GM-CSF, and various chemokines. The sensitised NF-κB in elderly and in patients with metabolic syndrome makes this set of population susceptible to COVID-19 and their worse complications, including higher mortality. Immunomodulation at the level of NF-κB activation and inhibitors of NF-κB (IκB) degradation along with TNF-α inhibition will potentially result in a reduction in the cytokine storm and alleviate the severity of COVID-19. Inhibition of NF-κB pathway has a potential therapeutic role in alleviating the severe form of COVID-19.

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“…Hormone P4 has been shown to weaken sepsis syndrome by suppressing the production of in ammatory cytokines, such as IL-6 and TNFA (14).The effectiveness of corticosteroids, such as DEX, has been reported for the reduction of proin ammatory mediators (16). Corticosteroids may reduce mortality, need for mechanical ventilation, duration of mechanical ventilation, length of ICU stay and length of hospital stay for COVID-19 patients (17). Therefore, these ndings clearly indicate the potential role of steroids in the regulation of COVID -19, in particular in females.…”

Section: Introductionmentioning

confidence: 83%

Computational Modeling Indicates A Decreased Affinity of SARS-CoV-2 to ACE2 by Steroids

Mansouri

Kowsar

Sadeghi

et al. 2020

Preprint

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The novel coronavirus disease (COVID-19) presently poses significant concerns around the world. Latest reports show that the degree of disease and mortality of COVID-19 infected patients may vary from gender to gender with a very high risk of death for seniors. It was hypothesized that sex steroid hormones estradiol (E2), progesterone (P4), testosterone (T), and dexamethasone (DEX) may change the interaction of coronavirus spike protein (CSP) with angiotensin converting enzyme-2 (ACE2). Data showed that E2 was more strongly to interact with the main protease of the coronavirus, while T had the lowest affinity for CSP. The binding energy of the CSP to ACE2 was increased in the presence of steroids; the greatest increase was observed by DEX and E2. The binding free energy of the CSP to ACE2 was the highest in the presence of E2 and DEX. Together, the interaction between CSP and ACE2 can be disrupted by E2 and to a greater extent by DEX, in part explaining the lower incidence of COVID-19 infection in women than men. The potential use of E2 and DEX to reduce coronavirus attachment to ACE2 in the early phase of the coronavirus invasion needs to be clinically investigated.

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Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis

Cited by 197 publications

References 84 publications

A living WHO guideline on drugs for covid-19

A living WHO guideline on drugs for covid-19

The Role and Therapeutic Potential of NF-kappa-B Pathway in Severe COVID-19 Patients

Computational Modeling Indicates A Decreased Affinity of SARS-CoV-2 to ACE2 by Steroids

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