A living WHO guideline on drugs for covid-19.

UPDATES: This is the thirteenth version (twelfth 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 under way. Emerging SARS-CoV-2 variants (such as omicron) and subvariants are changing the role of therapeutics. This update does not include any changes to the strength or direction of recommendations, but rather concerns i) the use of nirmatrelvir/ritonavir, now considered to be an option also for pregnant and breastfeeding women with non-severe covid-19, and ii) evidence of reduction of in vitro neutralisation activity supporting the strong recommendations against the use of the neutralising monoclonal antibodies sotrovimab and casirivimab-imdevimab.

RECOMMENDATIONS: • Recommended for patients with severe or critical covid-19—strong recommendations for systemic corticosteroids, IL-6 receptor blockers (tocilizumab or sarilumab) in combination with corticosteroids, and baricitinib as an alternative to IL-6 receptor blockers, in combination with corticosteroids. Concerning the concomitant use of IL-6 receptor blockers (tocilizumab and sarilumab), and the JAK inhibitor baricitinib, these drugs may be combined, in addition to corticosteroids. • Recommended for patients with severe covid-19—a conditional recommendation for remdesivir. • Not recommended for patients with critical covid-19—a conditional recommendation against remdesivir. • Recommended for patients with non-severe covid-19 at highest risk of hospitalisation—a strong recommendation for nirmatrelvir/ritonavir; conditional recommendations for molnupiravir and remdesivir. • Not recommended for patients with non-severe covid-19—a conditional recommendation against systemic corticosteroids and colchicine; a strong recommendation against convalescent plasma; a recommendation against fluvoxamine, except in the context of a clinical trial. • Not recommended for patients with non-severe covid-19 at low risk of hospitalisation—a conditional recommendation against nirmatrelvir/ritonavir. • Not recommended for patients with severe or critical covid-19—a recommendation against convalescent plasma except in the context of a clinical trial; a conditional recommendation against the JAK inhibitors ruxolitinib and tofacitinib. • Not recommended, regardless of covid-19 disease severity—strong recommendations against hydroxychloroquine, lopinavir/ritonavir, sotrovimab, and casirivimab-imdevimab; and a recommendation against ivermectin except in the context of a clinical trial.

ABOUT THIS GUIDELINE: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The Guideline Development Group (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, 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 and updated recommendations on molnupiravir are planned for the next updates to this guideline.