A living WHO guideline on drugs for covid-19

Bram Rochwerg, Thomas Agoritsas, François Lamontagne, Yee-Sin Leo, Helen Macdonald, Arnav Agarwal, Linan Zeng, Lyubov Lytvyn, John Adabie Appiah, Wagdy Amin, Yaseen Arabi, Lucille Blumberg, Erlina Burhan, Frederique Bausch, Carolyn S Calfee, Bin Cao, Maurizio Cecconi, Duncan Chanda, Graham Cooke, Bin Du, Jake Dunning, Heike Geduld, Patrick Gee, Madiha Hashimi, David S Hui, Sushil Kabra, Seema Kanda, Leticia Kawano-Dourado, Yae-Jean Kim, Niranjan Kissoon, Arthur Kwizera, Jon Henrik Laake, Flavia R Machado, Imelda Mahaka, Hela Manai, Greta Mino, Emmanuel Nsutebu, Natalia Pshenichnaya, Nida Qadir, Saniya Sabzwari, Rohit Sarin, Michael Sharland, Yinzhong Shen, Shalini Sri Ranganathan, Joao Souza, Sebastian Ugarte, Sridhar Venkatapuam, Vu Quoc Dat, Dubula Vuyiseka, Ananda Wuewickrama, Brittany Maguire, Dena Zeraatkar, Jessica Bartoszko, Long Ge, Romina Brignardello-Peterson, Reed Siemieniuk, Gordon Guyatt, Janet Diaz, Michael Jacobs, Per Olav Vandvik

Abstract

CLINICAL QUESTION
What is the role of drug interventions in the treatment of patients with covid-19?

 NEW RECOMMENDATION 
The latest version of this WHO living guidance focuses on remdesivir, following the 15 October 2020 preprint publication of results from the WHO SOLIDARITY trial. It contains a weak or conditional recommendation against the use of remdesivir in hospitalised patients with covid-19

RECOMMENDATIONS
The first version on this living guidance focused on corticosteroids. The strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic corticosteroids in patients with non-severe covid-19 are unchanged.

HOW THIS GUIDELINE WAS CREATED
WHO has partnered with the non-profit Magic Evidence Ecosystem Foundation (MAGIC) for methodologic support, to develop and disseminate living guidance for covid-19 drug treatments, based on a living systematic review and network analysis. An international standing Guideline Development Group (GDG) of content experts, clinicians, patients, and methodologists produced recommendations following standards for trustworthy guideline development using the GRADE approach. No competing interests were identified for any panel member.

UNDERSTANDING THE NEW RECOMMENDATION
When moving from evidence to the conditional recommendation against the use of remdesivir in patients with covid-19, the panel emphasised the evidence suggesting no important effect on mortality, need for mechanical ventilation, time to clinical improvement, and other patient-important outcomes. Considering the low or very low certainty evidence for all outcomes, the panel interpreted the evidence as not proving that remdesivir is ineffective; rather, there is no evidence based on currently available data that it does improve patient-important outcomes. The panel placed low value on small and uncertain benefits in the presence of the remaining possibility of important harms. In addition, the panel considered contextual factors such as resources, feasibility, acceptability, and equity for countries and health care systems.

UPDATES
This is a living guideline. It replaces an earlier version published on 4 September 2020 and the BMJ Rapid Recommendations on remdesivir published on 2 July 2020, and the previous version can be found as a data supplement. Future updates are planned to cover hydroxychloroquine and lopinavir-rotinavir. New recommendations will be published as updates to this guideline.

READERS NOTE
This is the third version (update 2) of the living guideline (BMJ 2020;370:m3379). When citing this article, please consider adding the update number and date of access for clarity.

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