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Clinician Article

A living WHO guideline on drugs for covid-19.



  • Lamontagne F
  • Agoritsas T
  • Macdonald H
  • Leo YS
  • Diaz J
  • Agarwal A, et al.
BMJ. 2020 Sep 4;370:m3379. doi: 10.1136/bmj.m3379. (Review)
PMID: 32887691
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Disciplines
  • Emergency Medicine
    Relevance - 7/7
    Newsworthiness - 6/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 7/7
    Newsworthiness - 6/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 7/7
    Newsworthiness - 6/7
  • Hospital Doctor/Hospitalists
    Relevance - 7/7
    Newsworthiness - 5/7
  • Internal Medicine
    Relevance - 7/7
    Newsworthiness - 5/7
  • Infectious Disease
    Relevance - 6/7
    Newsworthiness - 5/7
  • Respirology/Pulmonology
    Relevance - 6/7
    Newsworthiness - 5/7
  • Intensivist/Critical Care
    Relevance - 6/7
    Newsworthiness - 4/7

Abstract

CLINICAL QUESTION: What is the role of drug interventions in the treatment and prevention of covid-19?

RECOMMENDATIONS: The 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. HOW: this 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 EVIDENCE: A 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 RECOMMENDATIONS: The 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.

UPDATES: This is a living guideline. Work is under way to evaluate other interventions. New recommendations will be published as updates to this guideline.

READERS NOTE: This 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.

SUBMITTED: August 28 ACCEPTED: August 31.


Clinical Comments

Emergency Medicine

This is a nice review with visualization of the benefits of giving steroids for severe and critical COVID-infected patients.

Emergency Medicine

This living meta-analysis and guideline published in the BMJ evaluates treatments for COVID-19. This document is a tremendous resource for clinicians. It will undergo repeated updates to ensure the information is current. The recommendations are based on 8 randomized trials with 7184 patients. This version states systemic steroids are recommended in those with severe and critical COVID-19, but contains a weak/conditional recommendation against steroids for those with non-severe illness. In those with severe or critical illness and COVID-19, steroids reduce 28-day mortality in critically ill (87 fewer deaths per 1000 patients) and severely ill (67 fewer deaths per 1000 patients) patients.

Emergency Medicine

This is a "living" guideline for drug treatment of COVID-19. The term "living" refers to the fact that periodic updates are planned for and will be incorporated into the guideline. The guideline is based on evidence from a meta-analysis of 8 randomized controlled trials. There are two recommendations: 1. Seriously or critically ill patients should be given steroids; and 2. Others should not. There were a number of steroids and different routes of administration studied, and no restrictions on choosing among these were found.

Infectious Disease

WHO Guidelines recommend PO or IV steroids for patients with severe or critical COVID-19, oxygen saturation <90% on room air, respiratory rate >30, or clinical signs of respiratory distress. There should be caution with resultant hyperglycemia and opportunistic infections. Watch for Strongyloides Hyperinfection. Avoid early use of steroids for non-severe COVID-19, but do not stop chronic steroid use for underlying diseases.

Intensivist/Critical Care

Excellent presentation regarding all the data on corticosteroids in COVID-19.

Intensivist/Critical Care

This is an example of knowledge translation done well with real-time trustworthy evidence synthesis in the middle of a pandemic. Of essential importance for those of us struggling to keep up with the rush of information.

Internal Medicine

There is so little quality evidence but so much low-quality evidence that the whole area is confusing. I don`t think this guideline will be news for anyone with critical appraisal skills who is keeping track of the literature.

Respirology/Pulmonology

This living evidence-based guideline makes a strong recommendation for the use of corticosteroids in severe or critical COVID-19, and a weak recommendation against their use in non-severe COVID-19. Most clinicians likely already know the evidence underlying this guideline from the high-profile publication of a systematic review of observational studies on this topic and from the RECOVERY trial, which provided most of the studied patients.

Respirology/Pulmonology

This manuscript is a summary of the WHO assessment of drug therapy for COVID-19 patients that particularly focuses on the role of corticosteroids. Presumably, future "living documents" will address other drug therapies more completely, such as remdesivir, convalescent plasma, etc.

Respirology/Pulmonology

Evidence-based document on the use of medications for COVID-19 infection including mild-moderate and severe infections. Would help the general practitioner decide when to use steroids vs not.

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