Intended for healthcare professionals

Practice Rapid Recommendations

A living WHO guideline on drugs for covid-19

BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3379 (Published 04 September 2020) Cite this as: BMJ 2020;370:m3379

Visual summary of recommendation

Population Disease severity Non-severe Severe Critical SpO 2 <90% on room air Respiratory rate >30 in adults Raised respiratory rate in children Signs of severe respiratory distress Requires life sustaining treatment Acute respiratory distress syndrome Sepsis Septic shock Absence of signs of severe or critical disease This recommendation applies only to people with these characteristics: Patients with confirmed covid-19 Recommendation 1 Recommendation 2 ≥60 in children <2 months≥50 in children 2-11 months≥40 in children 1-5 years
Interventions compared Nocorticosteroids Usualsupportive care Corticosteroids Suggested regimen Acceptable alternative regimens Dexamethasone 6 mg Oral or intravenous Hydrocortisone 50 mg Intravenous Every 8 hours for 7-10 days Daily for7-10 days Every 6 hours for 7-10 days Methylprednisolone 10 mg Intravenous Daily for7-10 days Prednisone 40 mg Oral
Recommendation 1 We recommend corticosteroids Usual supportive care Corticosteroids or Patients with severe and critical covid-19 Strong All or nearly all informed people would likely want usual supportive care without corticosteroids. Benefits would outweigh harms for almost everyone Weak Most people would likely want usual supportive care without corticosteroids. Benefits would outweigh harms for the majority, but not for everyone Weak Most people would likely want corticosteroids. Benefits would outweigh harms for the majority, but not for everyone Strong All or nearly all informed people would likely want corticosteroids. Benefits would outweigh harms for almost everyone
Recommendation 2 We suggest no corticosteroids Usual supportive care Corticosteroids or Patients with non-severe covid-19 Strong All or nearly all informed people would likely want usual supportive care without corticosteroids. Benefits would outweigh harms for almost everyone Weak Most people would likely want usual supportive care without corticosteroids. Benefits would outweigh harms for the majority, but not for everyone Weak Most people would likely want corticosteroids. Benefits would outweigh harms for the majority, but not for everyone Strong All or nearly all informed people would likely want corticosteroids. Benefits would outweigh harms for almost everyone

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Find recommendations, evidence summaries and consultation decision aids for use in your practice
  1. François Lamontagne, methods chair, critical care physician1 2,
  2. Thomas Agoritsas, methodologist, internist3 4 5,
  3. Helen Macdonald, UK research editor6 *,
  4. Yee-Sin Leo, clinical chair, infectious disease specialist7,
  5. Janet Diaz, lead, clinical team for covid-19 response8 *,
  6. Arnav Agarwal, methodologist, internist3 5 9 *,
  7. John Adabie Appiah, paediatric critical care physician10,
  8. Yaseen Arabi, intensive care physician11,
  9. Lucille Blumberg, infectious disease physician12,
  10. Carolyn S Calfee, intensive care physician13,
  11. Bin Cao, chest physician14,
  12. Maurizio Cecconi, critical care physician15 16,
  13. Graham Cooke, infectious disease physician17,
  14. Jake Dunning, infectious disease physician18,
  15. Heike Geduld, emergency physician19,
  16. Patrick Gee, patient panel member20,
  17. Hela Manai, emergency physician21,
  18. David S Hui, chest physician22,
  19. Seema Kanda, patient partner23,
  20. Leticia Kawano-Dourado, respiratory medicine physician24 25,
  21. Yae-Jean Kim, paediatric infectious disease physician26,
  22. Niranjan Kissoon, paediatric intensive care physician27,
  23. Arthur Kwizera, critical care physician28,
  24. Jon Henrik Laake, intensive care physician29,
  25. Flavia R Machado, intensive care physician30,
  26. Nida Qadir, critical care physician31,
  27. Rohit Sarin, chest physician32,
  28. Yinzhong Shen, infectious disease physician33,
  29. Linan Zeng, methodologist3 5 34 *,
  30. Romina Brignardello-Petersen, methodologist3 5 *,
  31. Lyubov Lytvyn, methodologist3 5 *,
  32. Reed Siemieniuk, methodologist, internist3 5 *,
  33. Dena Zeraatkar, methodologist3 *,
  34. Jessica Bartoszko, methodologist3 *,
  35. Long Ge, methodologist3 35 36 *,
  36. Brittany Maguire, methodologist37,
  37. Bram Rochwerg, critical care physician3 38 *,
  38. Gordon Guyatt, methodologist, internist3 5 39 *,
  39. Per Olav Vandvik, methodologist, internist5 40 *
  1. 1Université de Sherbrooke, Sherbrooke, Quebec, Canada
  2. 2Centre de recherche du CHU de Sherbrooke, Sherbrooke, Quebec, Canada
  3. 3Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
  4. 4Division of General Internal Medicine & Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland
  5. 5MAGIC Evidence Ecosystem Foundation, Oslo, Norway
  6. 6The BMJ, London, UK
  7. 7National Center for Infectious Diseases, Singapore
  8. 8World Health Organization, Geneva, Switzerland
  9. 9Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  10. 10Kwame Nkrumah University of Science & Technology, Kumasi, Ghana
  11. 11King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
  12. 12National Institute for Communicable Diseases, South Africa
  13. 13University of California, San Francisco, USA
  14. 14China-Japan Friendship Hospital, Beijing, China
  15. 15Department of Anesthesia and Intensive Care Medicine, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089 Rozzano (MI), Italy
  16. 16Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele – Milan, Italy
  17. 17Imperial College London, London, UK
  18. 18Public Health England, UK
  19. 19Division of Emergency Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
  20. 20USA
  21. 21Emergency Medical Services, Faculty of Medicine, Tunis, Tunisia
  22. 22Stanley Ho Centre for Emerging Infectious Diseases, Chinese University of Hong Kong, China
  23. 23McMaster University (alumnus)
  24. 24Pulmonary Division, Heart Institute (InCor)- HCFMUSP, Medical School, University of Sao Paulo, São Paulo, Brazil
  25. 25Research Institute, Hospital do Coração (HCor), São Paulo, Brazil
  26. 26Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea
  27. 27Department of Paediatrics and Emergency Medicine, University of British Columbia, Vancouver, Canada
  28. 28Department of Anaesthesia and Critical Care, College of Health Sciences, Makerere University, Kampala, Uganda
  29. 29Critical Care and Emergencies, Rikshospitalet Medical Centre, Oslo, Norway
  30. 30Anesthesiology, Pain and Intensive Care, Federal University of São Paulo, Brazil
  31. 31Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
  32. 32National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India
  33. 33Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
  34. 34Pharmacy Department-Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
  35. 35Evidence Based Social Science Research Centre, School of Public Health, Lanzhou University, Lanzhou, China
  36. 36Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China
  37. 37Infectious Diseases Data Observatory (IDDO), Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
  38. 38Department of Medicine, McMaster University, Hamilton, Ontario Canada
  39. 39Division of Pulmonary, Critical Care and Sleep Medicine, Miller School of Medicine, University of Miami, Miami, Florida, USA
  40. 40Department of Health Economics and Health Management, Institute for Health and Society, University of Oslo, Oslo, Norway
  41. *Not panel member; resource for methodology, systematic review, and content support
  1. Correspondence to: Francois Lamontagne, Université de Sherbrooke, 3001 12e avenue N, Sherbrooke, QC, Canada J1H 5N4 Francois.Lamontagne{at}usherbrooke.ca

Abstract

Clinical question What is the role of drug interventions in the treatment and prevention of covid-19?

Recommendations The first version on this living guidance focuses on corticosteroids. It contains a 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. Corticosteroids are inexpensive and are on the World Health Organisation list of essential medicines.

How this guideline was created This guideline reflects an innovative collaboration between the WHO and the MAGIC Evidence Ecosystem Foundation, driven by an urgent need for global collaboration to provide trustworthy and living covid-19 guidance. A standing international panel of content experts, patients, clinicians, and methodologists, free from relevant conflicts of interest, produce recommendations for clinical practice. The panel follows standards, methods, processes, and platforms for trustworthy guideline development using the GRADE approach. We apply an individual patient perspective while considering contextual factors (that is, resources, feasibility, acceptability, equity) for countries and healthcare systems.

The evidence A living systematic review and network meta-analysis, supported by a prospective meta-analysis, with data from eight randomised trials (7184 participants) found that systemic corticosteroids probably reduce 28 day mortality in patients with critical covid-19 (moderate certainty evidence; 87 fewer deaths per 1000 patients (95% confidence interval 124 fewer to 41 fewer)), and also in those with severe disease (moderate certainty evidence; 67 fewer deaths per 1000 patients (100 fewer to 27 fewer)). In contrast, systemic corticosteroids may increase the risk of death in patients without severe covid-19 (low certainty evidence; absolute effect estimate 39 more per 1000 patients, (12 fewer to 107 more)). Systemic corticosteroids probably reduce the need for invasive mechanical ventilation, and harms are likely to be minor (indirect evidence).

Understanding the recommendations The panel made a strong recommendation for use of corticosteroids in severe and critical covid-19 because there is a lower risk of death among people treated with systemic corticosteroids (moderate certainty evidence), and they believe that all or almost all fully informed patients with severe and critical covid-19 would choose this treatment. In contrast, the panel concluded that patients with non-severe covid-19 would decline this treatment because they would be unlikely to benefit and may be harmed. Moreover, taking both a public health and a patient perspective, the panel warned that indiscriminate use of any therapy for covid-19 would potentially rapidly deplete global resources and deprive patients who may benefit from it most as potentially lifesaving therapy.

Updates This is a living guideline. Work is under way to evaluate other interventions. New recommendations will be published as updates to this guideline.

Readers note This is version 1 of the living guideline, published on 4 September (BMJ 2020;370:m3379) version 1. Updates will be labelled as version 2, 3 etc. When citing this article, please cite the version number.

Submitted August 28

Accepted August 31

Footnotes

  • Competing interests: All guideline panel members have completed the WHO interest disclosure form. All authors have completed the BMJ Rapid Recommendations interest of disclosure form. The WHO, MAGIC and The BMJ judged that no panel member had any financial conflict of interest. Professional and academic interests are minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions. MAGIC and BMJ assessed declared interests from other co-authors of this publication and found no conflicts of interests.

  • Provenance and peer review: This publication was commissioned by The BMJ in partnership with WHO and the MAGIC Evidence Ecosystem Foundation, in the context of the BMJ Rapid Recommendations. Pre-publication internal and external peer-review managed by WHO, and internal review at The BMJ. Post-publication review on bmj.com on rapid responses and through MAGICapp.

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