A living WHO guideline on drugs to prevent covid-19
Authors: Lamontagne François , Stegemann Miriam , Agarwal Arnav , Agoritsas Thomas , Siemieniuk Reed , Rochwerg Bram , Bartoszko Jessica , Askie Lisa , Macdonald Helen , Al-Maslamani Muna , Amin Wagdy , Araujo Da Silva Andre Ricardo , Barragan Fabian Alberto Jaimes , Bausch Frederique Jacquerioz , Burhan Erlina , Cecconi Maurizio , Chacko Binila , Chanda Duncan , Dat Vu Quoc , Du Bin , Geduld Heike , Gee Patrick , Haider Muhammad , Harley Nerina , Hashimi Madiha , Jehan Fyezah , Hui David , Hunt Beverley J , Ismail Mohamed , Kabra Sushil , Kanda Seema , Kawano-Dourado Leticia , Kim Yae-Jean , Kissoon Niranjan , Krishna Sanjeev , Kwizera Arthur , Lisboa Thiago , Leo Yee-Sin , Mahaka Imelda , Hela Manai , Battista Migliori Giovanni , Mino Greta , Nsutebu Emmanuel , Pshenichnaya Natalia , Qadir Nida , Ranganathan Shalini Sri , Sabzwari Saniya , Sarin Rohit , Shankar-Hari Manu , Sharland Michael , Shen Yinzhong , Souza Joao Paulo , Tshokey Tshokey , Ugarte Sebastian , Uyeki Tim , Venkatapuram Sridhar , Wachinou Ablo Prudence , Wijewickrama Ananda , Vuyiseka Dubula , Preller Jacobus , Brignardello-Petersen Romina , Kum Elena , Qasim Anila , Zeraatkar Dena , Owen Andrew , Guyatt Gordon , Lytvyn Lyubov , Jacobs Michael , Vandvik Per Olav , Diaz Janet 
Published: March 2021

Abstract

Clinical question
What is the role of drugs in preventing covid-19?

Why does this matter?
There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective.

Recommendations
The second version of this living guideline reiterates the previous strong recommendation against the use of hydroxychloroquine and includes a new conditional recommendation against the use of tixagevimab-cilgavimab in individuals who do not have covid-19.

How this guideline was created
This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provides methodological support. A living systematic review with network analysis informs the recommendations. An international guideline development group (GDG) of content experts, clinicians, patients, an ethicist and methodologists produces recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Understanding the recommendations
The living network meta-analysis informing this guideline included 12 trials (8379 participants) comparing hydroxychloroquine to standard care/placebo, and one trial (5197 participants) comparing tixagevimab-cilgavimab to standard care/placebo. When moving from evidence to the continued strong recommendation against the use of hydroxychloroquine, the GDG emphasised additional evidence suggesting no or little effect on mortality and hospital admission, and an increased risk of adverse effects. For the new conditional recommendation against the use of tixagevimab-cilgavimab, the GDG emphasised in vitro evidence reducing the applicability of available trial data. While trial results demonstrated modest reduction in the occurrence of laboratory confirmed symptomatic covid-19, lack of in vitro neutralisation of new SARS-CoV-2 sub-lineages was considered to have rendered these results obsolete.

Updates
This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline.

Readers note
This is the second version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19 and living guidance regarding covid-19 related clinical management. When citing this article, please consider adding the update number and date of access for clarity.