A living WHO guideline on drugs for covid-19
Authors: Agarwal Arnav , Hunt Beverley J , Stegemann Miriam , Rochwerg Bram , Lamontagne François , Siemieniuk Reed AC , Agoritsas Thomas , Askie Lisa , Lytvyn Lyubov , Leo Yee-Sin , Macdonald Helen , Zeng Linan , Alhadyan Ahmed , Muna Al-Maslamani , Amin Wagdy , da Silva André Ricardo Araujo , Aryal Diptesh , Barragan Fabian A Jaimes , Bausch Frederique J , Burhan Erlina , Calfee Carolyn S , Cecconi Maurizio , Chacko Binila , Chanda Duncan , Dat Vu Quoc , De Sutter An , Du Bin , Freedman Stephen , Geduld Heike , Gee Patrick , Haider Muhammad , Gotte Matthias , Harley Nerina , Hashmi Madiha , Hui David , Ismail Mohamed , Jehan Fyezah , Kabra Sushil K , Kanda Seema , Kim Yae-Jean , Kissoo Niranjan , Krishna Sanjeev , Kuppalli Krutika , Kwizera Arthur , Castro-Rial Marta Lado , Lisboa Thiago , Lodha Rakesh , Mahaka Imelda , Manai Hela , Mendelson Marc , Battista Migliori Giovanni , Mino Greta , Nsutebu Emmanuel , Peter Jessica , Preller Jacobus , Pshenichnaya Natalia , Qadir Nida , Ranganathan Shalini S , Relan Pryanka , Rylance Jamie , Sabzwari Saniya , Sarin Rohit , Shankar-Hari Manu , Sharland Michael , Shen Yinzhong , Souza Joao P , Swanstrom Ronald , Tshokey Tshokey , Ugarte Sebastian , Uyeki Timothy , Vazquez Curiel Evangelina , Venkatapuram Sridhar , Vuyiseka Dubula , Wijewickrama Ananda , Tran Lien , Zeraatkar Dena , Bartoszko Jessica J , Ge Long , Brignardello-Petersen Romina , Owen Andrew , Guyatt Gordon , Diaz Janet , Kawano-Dourado Leticia , Jacobs Michael , Vandvik Per Olav 
Published: September 2020

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.