COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Treatment Siemieniuk R, Rochwerg B, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. doi: 10.1136/bmj.m3379.
Abstract

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

NEW RECOMMENDATION: The latest version of this WHO living guidance provides strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir in patients with covid-19 regardless of disease severity. These recommendations follow the publication of results from the WHO SOLIDARITY trial

RECOMMENDATIONS: This guidance adds to recommendations for corticosteroids and remdesivir published in the previous versions, with no changes made in this update: (a) a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, (b) a conditional recommendation against systemic corticosteroids in patients with non-severe covid-19, (c) a conditional recommendation against remdesivir in hospitalised patients with covid-19.

HOW THIS GUIDELINE WAS CREATED: WHO has partnered with the non-profit Magic Evidence Ecosystem Foundation (MAGIC) for methodologic support, to develop and disseminate living guidance for covid-19 drug treatments, based on a living systematic review and network analysis. An international standing Guideline Development Group (GDG) of content experts, clinicians, patients, and methodologists produced recommendations following standards for trustworthy guideline development using the GRADE approach. No competing interests were identified for any panel member.

UNDERSTANDING THE NEW RECOMMENDATION: When moving from the to the strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir in patients with covid-19, the panel was informed by a living systematic review and network meta-analysis of 30 trials with 10 921 participants for hydroxychloroquine and seven trials with 7429 participants for lopinavir-ritonavir. The trials for both drugs included inpatients and outpatients. Moderate certainty evidence for both drugs demonstrated no reduction in mortality or need for mechanical ventilation. There was also low certainty of evidence for harm with both drugs, including diarrhoea and nausea/vomiting. The panel did not anticipate important variability when it comes to patient values and preferences. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and health care systems did not alter the recommendation.

UPDATES: This is a living guideline. It replaces earlier versions (4 September and 20 November 2020) and supersedes the BMJ Rapid Recommendations on remdesivir published on 2 July 2020. The previous versions can be found as data supplements. New recommendations will be published as updates to this guideline.

READERS' NOTE: This is the third version (update 2) of the living guideline (BMJ 2020;370:m3379). When citing this article, please consider adding the update number and date of access for clarity.

Ratings
Discipline / Specialty Area Score
Family Medicine (FM)/General Practice (GP)
Emergency Medicine
General Internal Medicine-Primary Care(US)
Hospital Doctor/Hospitalists
Internal Medicine
Infectious Disease
Respirology/Pulmonology
Intensivist/Critical Care
Comments from MORE raters

Emergency Medicine rater

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

Emergency Medicine rater

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 rater

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 rater

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 rater

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

Intensivist/Critical Care rater

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 rater

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 rater

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 rater

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 rater

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.