A living WHO guideline on drugs for covid-19 (2020-2023)
Agarwal A., Hunt BJ., Stegemann M., Rochwerg B., Lamontagne F., Siemieniuk RAC., Agoritsas T., Askie L., Lytvyn L., Leo Y-S., Macdonald H., Zeng L., Alhadyan A., Muna A-M., Amin W., da Silva ARA., Aryal D., Barragan FAJ., Bausch FJ., Burhan E., Calfee CS., Cecconi M., Chacko B., Chanda D., Dat VQ., De Sutter A., Du B., Freedman S., Geduld H., Gee P., Haider M., Gotte M., Harley N., Hashmi M., Hui D., Ismail M., Jehan F., Kabra SK., Kanda S., Kim Y-J., Kissoo N., Krishna S., Kuppalli K., Kwizera A., Castro-Rial ML., Lisboa T., Lodha R., Mahaka I., Manai H., Mendelson M., Battista Migliori G., Mino G., Nsutebu E., Peter J., Preller J., Pshenichnaya N., Qadir N., Ranganathan SS., Relan P., Rylance J., Sabzwari S., Sarin R., Shankar-Hari M., Sharland M., Shen Y., Souza JP., Swanstrom R., Tshokey T., Ugarte S., Uyeki T., Vazquez Curiel E., Venkatapuram S., Vuyiseka D., Wijewickrama A., Tran L., Zeraatkar D., Bartoszko JJ., Ge L., Brignardello-Petersen R., Owen A., Guyatt G., Diaz J., Kawano-Dourado L., Jacobs M., Vandvik PO.
Abstract Updates This is the fourteenth and final version of this living guideline published in The BMJ . It replaces earlier versions, available as data supplements. The WHO continues to update the guideline, and readers should refer to their website and the MAGICapp version of the guideline for the latest version. 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 has evolved with numerous randomised controlled trials (RCTs) completed since the inception of the pandemic. Emerging SARS-CoV-2 variants and subvariants are changing the role of therapeutics. What is new? The fourteenth and final BMJ version of the guideline was published on November 10 2023. At that time, 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 was also changed; recommendations were 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. This version and previous versions were published in The BMJ . Updates after 2023 will continue to be available on the WHO website and via MAGICapp. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact.