COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Treatment Agarwal A, Hunt B, Stegemann M, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. doi: 10.1136/bmj.m3379.
Abstract

UPDATES: This is the fourteenth version (thirteenth update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline.

CLINICAL QUESTION: What is the role of drugs in the treatment of patients with covid-19?

CONTEXT: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants and subvariants are changing the role of therapeutics.

WHAT IS NEW?: The guideline development group (GDG) defined 1.5% as a new threshold for an important reduction in risk of hospitalisation in patients with non-severe covid-19. Combined with updated baseline risk estimates, this resulted in stratification into patients at low, moderate, and high risk for hospitalisation. New recommendations were added for moderate risk of hospitalisation for nirmatrelvir/ritonavir, and for moderate and low risk of hospitalisation for molnupiravir and remdesivir. New pharmacokinetic evidence was included for nirmatrelvir/ritonavir and molnupiravir, supporting existing recommendations for patients at high risk of hospitalisation. The recommendation for ivermectin in patients with non-severe illness was updated in light of additional trial evidence which reduced the high degree of uncertainty informing previous guidance. A new recommendation was made against the antiviral agent VV116 for patients with non-severe and with severe or critical illness outside of randomised clinical trials based on one RCT comparing the drug with nirmatrelvir/ritonavir. The structure of the guideline publication has also been changed; recommendations are now ordered by severity of covid-19.

ABOUT THIS GUIDELINE: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF on the WHO website, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact.

FUTURE RECOMMENDATIONS: Recommendations on anticoagulation are planned for the next update to this guideline. Updated data regarding systemic corticosteroids, azithromycin, favipiravir and umefenovir for non-severe illness, and convalescent plasma and statin therapy for severe or critical illness, are planned for review in upcoming guideline iterations.

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.