A living WHO guideline on drugs for covid-19 (2020-2023)
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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.
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These living SRNMAs informed linked guidelines for covid-19 treatments and prophylaxis.
“These living SRNMAs informed linked guidelines for covid-19 treatments and prophylaxis.20”
From Consistency of covid-19 trial preprints with published reports and impact for decision making: retrospective review (2022) · cites this paper as [20]
The choice of timepoints was informed by timeframes within which guideline developers needed to issue recommendations.
“The choice of timepoints was informed by timeframes within which guideline developers needed to issue recommendations.20”
From Consistency of covid-19 trial preprints with published reports and impact for decision making: retrospective review (2022) · cites this paper as [20]
For interleukin 6 receptor blockers, consideration of evidence from preprints could have importantly accelerated the time to incorporation of this treatment as part of standard care.
“For interleukin 6 receptor blockers, consideration of evidence from preprints could have importantly accelerated the time to incorporation of this treatment as part of standard care.”
From Consistency of covid-19 trial preprints with published reports and impact for decision making: retrospective review (2022) · cites this paper as [20]
The assessment of the contribution of trial preprint reports to meta-analytic estimates and their effect on the certainty of evidence was undertaken in the context of pairwise meta-analysis and the minimally contextualised approach for assessing the certainty of evidence, whereas parallel guideline recommendations have been based on network meta-analyses and the fully contextualised approach.
“Our assessment of the contribution of trial preprint reports to meta-analytic estimates and their effect on the certainty of evidence was undertaken in the context of pairwise meta-analysis and the minimally contextualised approach for assessing the certainty of evidence, whereas parallel guideline recommendations have been based on network meta-analyses and the fully contextualised approach.”
From Consistency of covid-19 trial preprints with published reports and impact for decision making: retrospective review (2022) · cites this paper as [20]
The assessment of the impact of meta-analyses including versus excluding preprint reports on meta-analytic estimates was limited to only interventions that have been addressed by the WHO living guideline at the time of analysis.
“We limited our assessment of the impact of meta-analyses including versus excluding preprint reports on meta-analytic estimates to only interventions that have been addressed by the WHO living guideline at the time of analysis.”
From Consistency of covid-19 trial preprints with published reports and impact for decision making: retrospective review (2022) · cites this paper as [20]
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- Authors
- Agarwal, A., Hunt, B. J., Stegemann, M., Rochwerg, B., Lamontagne, F., Siemieniuk, R. A., Agoritsas, T., Askie, L., Lytvyn, L., Leo, Y.-S., Macdonald, H., Zeng, L., Alhadyan, A., Muna, A.-M., Amin, W., da Silva, A. R. A., Aryal, D., Barragan, F. A. J., Bausch, F. J., Burhan, E., Calfee, C. S., Cecconi, M., Chacko, B., Chanda, D., Dat, V. Q., 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, S. K., Kanda, S., Kim, Y.-J., Kissoo, N., Krishna, S., Kuppalli, K., Kwizera, A., Castro-Rial, M. L., 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, S. S., Relan, P., Rylance, J., Sabzwari, S., Sarin, R., Shankar-Hari, M., Sharland, M., Shen, Y., Souza, J. P., Swanstrom, R., Tshokey, T., Ugarte, S., Uyeki, T., Vazquez Curiel, E., Venkatapuram, S., Vuyiseka, D., Wijewickrama, A., Tran, L., Zeraatkar, D., Bartoszko, J. J., Ge, L., Brignardello-Petersen, R., Owen, A., Guyatt, G., Diaz, J., Kawano-Dourado, L., Jacobs, M., & Vandvik, P. O.
- Affiliations
- University of Alberta (CA)
- St Thomas' Hospital (GB)
- LRS Institute of Tuberculosis and Respiratory Diseases (IN)
- Université de Sherbrooke (CA)
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- University Hospital of Geneva (CH)
- World Health Organization (CH)
- McMaster University (CA)
- National Centre for Infectious Diseases (SG)
- BMJ Group (United Kingdom) (GB)
- Saudi Arabia
- Communicable Disease Center, Qatar
- Ministry of Health and Population (EG)
- Fluminense Federal University, Brazil
- Nepal Mediciti Hospital (NP)
- Antioquia University Medellin, Colombia
- Geneva University Hospital, Switzerland
- University of Indonesia (ID)
- University of California, San Francisco (US)
- Department of Anesthesia and Intensive Care Medicine, Humanitas Clinical and Research Center, Italy
- Christian Medical College, Vellore, India
- University Teaching Hospital (ZM)
- Hanoi Medical University (VN)
- University of Gent, Belgium
- Peking Union Medical College Hospital (CN)
- University of Calgary (CA)
- Stellenbosch University (ZA)
- United States
- Ministry of Public Health (AF)
- University of Alberta, Canada
- The Royal Melbourne Hospital (AU)
- Ziauddin University (PK)
- Chinese University of Hong Kong (HK)
- Indira Gandhi Memorial Hospital (MV)
- Aga Khan University (PK)
- All India Institute of Medical Sciences (IN)
- Samsung Medical Center (KR)
- University of British Columbia (CA)
- St George's, University of London (GB)
- World Health Organization, Geneva, Switzerland
- Makerere University (UG)
- Hospital do Coração (BR)
- Zimbabwe
- Tunis University (TN)
- Groote Schuur Hospital, University of Cape Town, South Africa
- Clinical Scientific Institutes Maugeri, Italy
- Hospital Alcívar (EC)
- Sheikh Shakhbout Medical City (AE)
- Malaysia
- Central Research Institute of Epidemiology (RU)
- Fudan University (CN)
- University of California, Los Angeles (US)
- National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India
- Guy’s and St Thomas’ NHS Foundation Trust, London, UK
- St George's Hospital (GB)
- University of Colombo, Sri Lanka
- Universidade de São Paulo (BR)
- Charité – Universitätsmedizin Berlin (DE)
- University of North Carolina, USA
- JDW National Referral Hospital, Bhutan
- Faculty of Medicine Andres Bello University, Indisa Clinic, Santiago, Chile
- Centers for Disease Control and Prevention (US)
- King's College London (GB)
- Lovisenberg Diakonale Sykehus (NO)
- Universidad Andrés Bello (CL)
- Corresponding author
- Hunt, Beverley J
- Stegemann, Miriam
- Rochwerg, Bram
- Guyatt, Gordon
- ORCID
- Agarwal, Arnav
- Hunt, Beverley J
- Stegemann, Miriam
- Rochwerg, Bram
- Lamontagne, François
- Agoritsas, Thomas
- Askie, Lisa
- Lytvyn, Lyubov
- Leo, Yee-Sin
- Macdonald, Helen
- Zeng, Linan
- Amin, Wagdy
- Aryal, Diptesh
- Burhan, Erlina
- Calfee, Carolyn S
- Cecconi, Maurizio
- Chanda, Duncan
- Dat, Vu Quoc
- Du, Bin
- Freedman, Stephen
- Geduld, Heike
- Gee, Patrick
- Hashmi, Madiha
- Hui, David
- Jehan, Fyezah
- Kabra, Sushil K
- Kim, Yae-Jean
- Krishna, Sanjeev
- Kuppalli, Krutika
- Kwizera, Arthur
- Lisboa, Thiago
- Lodha, Rakesh
- Mahaka, Imelda
- Mendelson, Marc
- Nsutebu, Emmanuel
- Preller, Jacobus
- Qadir, Nida
- Ranganathan, Shalini S
- Relan, Pryanka
- Rylance, Jamie
- Sabzwari, Saniya
- Shen, Yinzhong
- Swanstrom, Ronald
- Tshokey, Tshokey
- Uyeki, Timothy
- Venkatapuram, Sridhar
- Wijewickrama, Ananda
- Tran, Lien
- Zeraatkar, Dena
- Bartoszko, Jessica J
- Ge, Long
- Owen, Andrew
- Diaz, Janet
- Kawano-Dourado, Leticia
- Jacobs, Michael
- Vandvik, Per Olav
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2020-09-04
- Volume
- 370
- Pages
- m3379
- ISSN
- 1756-1833 (ISSN-L)
- OpenAlex
- W3081745349
- Cited by
- 1,041
- References
- 35
- Citations by year
- 2026: 40 · 2025: 82 · 2024: 126 · 2023: 195 · 2022: 287 · 2021: 262 · 2020: 48
- FWCI
- 25.94
- Type
- journal article
- Language
- en
- Update notices
- correction (2022-04-25)
- Open access
- Licence
- Locations
- BMJ (publishedVersion)
- PubMed (publishedVersion)
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- Funders
- Bill and Melinda Gates Foundation
- World Health Organization
- National Institute for Health and Care Research (RP-2016-07-012)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- COVID-19 pandemic, SARS-CoV-2, antiviral therapy, nirmatrelvir/ritonavir, molnupiravir, remdesivir, ivermectin, non-severe COVID-19, SARS-CoV-2 variants
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Adrenal Cortex Hormones, Humans, Pneumonia, Viral, World Health Organization, Coronavirus Infections, Pandemics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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