A living WHO guideline on drugs for covid-19

Abstract

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.

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Affiliated Institutions

• Hanoi Medical University VN
• Central Research Institute of Epidemiology RU
• Christian Medical College, Vellore IN
• University of California, Los Angeles US
• Sheikh Shakhbout Medical City AE
• Humanitas University IT
• King's College London GB
• University of Indonesia ID
• Epworth Hospital AU
• St George's, University of London GB
• Charité - Universitätsmedizin Berlin DE
• St Thomas' Hospital GB
• Universidade de São Paulo BR
• Samsung Medical Center KR
• Shanghai Public Health Clinical Center CN
• Peking Union Medical College Hospital CN
• Stellenbosch University ZA
• Western Cape Department of Health ZA
• University of Cape Town ZA
• Makerere University UG
• LRS Institute of Tuberculosis and Respiratory Diseases IN
• Ministry of Health and Population EG
• Centers for Disease Control and Prevention US
• Istituti Clinici Scientifici Maugeri IT
• Sungkyunkwan University KR
• Guy's and St Thomas' NHS Foundation Trust GB
• Impact CA
• Nepal Medical College Teaching Hospital NP
• Groote Schuur Hospital ZA
• Lovisenberg Diakonale Høgskole
• Universidade Federal Fluminense BR
• The Royal Melbourne Hospital AU
• Ziauddin University PK
• Ministry of Public Health AF
• University of British Columbia CA
• University Teaching Hospital ZM
• Centre for Bhutan Studies and GNH Research BT
• All India Institute of Medical Sciences IN
• Ghent University BE
• Hospital do Coração BR
• Aga Khan University PK
• Universidad Andrés Bello CL
• University Hospital of Geneva CH
• Chinese University of Hong Kong HK
• University of Calgary CA
• McMaster University CA
• University of California, San Francisco US
• Indira Gandhi Memorial Hospital MV
• National Centre for Infectious Diseases SG
• University of Colombo LK
• World Health Organization CH
• Université de Sherbrooke CA
• Chinese Academy of Medical Sciences & Peking Union Medical College CN
• University of Alberta CA

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