1. Summary of the 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 randomized controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants (e.g. Omicron) and subvariants are also changing the role of therapeutics. In this update, no changes to the strength or direction of recommendations were made. This update concerns the use of nirmatrelvir-ritonavir, now considered to be an option also for pregnant and breastfeeding women with non-severe COVID-19, and includes additional evidence to reinforce the strong recommendations against the use of the neutralizing monoclonal antibodies sotrovimab and casirivimab-imdevimab, given reduction of in vitro neutralization activity.
Prior recommendations, unchanged from previous:
Recommended for patients with severe or critical COVID-19:
• a strong recommendation for systemic corticosteroids;
• a strong recommendation for interleukin-6 (IL-6) receptor blockers (tocilizumab or sarilumab);
• a strong recommendation for the Janus kinase (JAK) inhibitor baricitinib;
• concerning the concomitant use of IL-6 receptor blockers (tocilizumab or sarilumab), and the JAK inhibitor baricitinib; these drugs may now be combined, in addition to corticosteroids in patients with severe or critical COVID-19;
• a conditional recommendation for remdesivir in patients with severe COVID-19.
Recommended for patients with non-severe COVID-19 at highest risk of hospitalization:
• a strong recommendation for nirmatrelvir-ritonavir; also an option for pregnant and breastfeeding women (update January 13 2023 based on new evidence, no change in strength or direction of recommendation);
• a conditional recommendation for molnupiravir;
• a conditional recommendation for remdesivir.
Not recommended for patients with non-severe COVID-19:
• a conditional recommendation against systemic corticosteroids;
• a strong recommendation against convalescent plasma;
• a recommendation against fluvoxamine, except in the context of a clinical trial;
• a strong recommendation against colchicine.
Not recommended for patients with non-severe COVID-19 at low risk of hospitalization:
• a conditional recommendation against nirmatrelvir-ritonavir.
Not recommended for patients with severe and 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;
• a conditional recommendation against remdesivir in patients with critical COVID-19.
Not recommended, regardless of COVID-19 disease severity:
• strong recommendations against the use of sotrovimab and casirivimab-imdevimab
• a strong recommendation against hydroxychloroquine;
• a strong recommendation against lopinavir-ritonavir;
• 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 drug 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. It is supported by living network meta-analyses (LNMAs) (1)(2)(3).
Updates and access: This is the 13th version (12th update) of the living guideline. It replaces earlier versions, latest published 16 September 2022. The current guideline and its earlier versions are available through the WHO website (4), the BMJ (5), and MAGICapp (online and also as PDF outputs for readers with limited internet access). The living guideline is written, disseminated, and updated in an online platform (MAGICapp), with a user-friendly format and easy-to-navigate structure that accommodates dynamically updated evidence and recommendations, focusing on what is new while keeping existing recommendations updated within the guideline. This format should also facilitate adaptation, which is strongly encouraged by WHO to contextualize recommendations in a health care system perspective to maximize country impact.
This living WHO guideline for therapeutics for COVID-19 is related to the larger, more comprehensive guideline for COVID-19 clinical management (6). Guidelines for the use of drugs to prevent (rather than treat) COVID-19 are published separately on the WHO website (7) and by the BMJ (8), supported by a LNMA (9).