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Publications

Journal Article Network Meta-Analysis Systematic Review Epublish

PubMed: 40441732 DOI: 10.1136/bmj-2024-081165

Drug treatments for mild or moderate covid-19: systematic review and network meta-analysis.

BMJ 389:e081165

Authors: Sara Ibrahim, Reed A C Siemieniuk, María José Oliveros, Nazmul Islam, Juan Pablo Díaz Martinez, Ariel Izcovich, Anila Qasim, Yunli Zhao, Carlos Zaror, Liang Yao, Ying Wang, Per O Vandvik, Yetiani Roldan, Bram Rochwerg, Gabriel Rada, Manya Prasad, Hector Pardo-Hernandez, Reem A Mustafa, Fatemeh Mirzayeh Fashami, Anna Miroshnychenko, Shelley L McLeod, Cristian Mansilla, Francois Lamontagne, Azin Khosravirad, Kimia Honarmand, Maryam Ghadimi, Ya Gao, Farid Foroutan, Tahira Devji, Rachel Couban, Derek K Chu, Saifur Rahman Chowdhury, Yaping Chang, Gonzalo Bravo-Soto, Claudia Bosio, Diana Biscay, Gurleen Bhogal, Maria Azab, Thomas Agoritsas, Arnav Agarwal, Gordon H Guyatt, Romina Brignardello-Petersen

Affiliations

  • Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
  • Joint first authors.
  • Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
  • Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Universidad de La Frontera, Facultad de Medicina, Departamento de Ciencias de la Rehabilitacion, Temuco, Chile.
  • Universidad Del Salvador, Buenos Aires, Argentina.
  • Center for Research in Epidemiology, Economics and Oral Public Health (CIEESPO), Faculty of Dentistry, Universidad de La Frontera, Temuco, Chile.
  • Department of Medicine, Lovisenberg Diaconal Hospital Trust, Oslo, Norway.
  • MAGIC Evidence Ecosystem Foundation, Oslo, Norway.
  • Epistemonikos Foundation, Santiago, Chile.
  • UC Evidence Center, Cochrane Chile Associated Center, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Department of Clinical Research and Epidemiology, Institute of Liver and Biliary Sciences, New Delhi, India.
  • Iberoamerican Cochrane Centre, Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain.
  • CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
  • Department of Medicine, University of Kansas Medical Center, Kansas City, MO, USA.
  • Schwartz/Reisman Emergency Medicine Institute, Sinai Health, Toronto, ON, Canada.
  • Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
  • Department of Medicine and Centre de recherche du CHU de Sherbrooke, Sherbrooke, Quebec, Canada.
  • Department of Medicine, Western University, London, ON, Canada.
  • Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Ted Rogers Center for Heart Research, Toronto General Hospital, Toronto, ON, Canada.
  • Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
  • Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
  • The Canadian Agency for Drugs and Technologies in Health (CADTH), Toronto, ON, Canada.
  • Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.
  • Division of General Internal Medicine & Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland.

Abstract

OBJECTIVE

To compare the effects of treatments for mild or moderate (that is, non-severe) coronavirus disease 2019 (covid-19).

DESIGN

Systematic review and network meta-analysis.

DATA SOURCES

Covid-19 Living Overview of Evidence Repository (covid-19 L-OVE) by the Epistemonikos Foundation, a public, living repository of covid-19 articles, from 1 January 2023 to 19 May 2024. The search also included the WHO covid-19 database (up to 17 February 2023) and six Chinese databases (up to 20 February 2021). The analysis included studies identified between 1 December 2019 and 28 June 2023.

STUDY SELECTION

Randomised clinical trials in which people with suspected, probable, or confirmed mild or moderate covid-19 were allocated to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.

METHODS

After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias was assessed by use of a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, following GRADE guidance, drug treatments were classified in groups from the most to the least beneficial or harmful.

RESULTS

Of 259 trials enrolling 166 230 patients, 187 (72%) were included in the analysis. Compared with standard care, two drugs probably reduce hospital admission: nirmatrelvir-ritonavir (25 fewer per 1000 (95% confidence interval 28 fewer to 20 fewer), moderate certainty) and remdesivir (21 fewer per 1000 (28 fewer to 7 fewer), moderate certainty). Molnupiravir and systemic corticosteroids may reduce hospital admission (low certainty). Compared with standard care, azithromycin probably reduces time to symptom resolution (mean difference 4 days fewer (5 fewer to 3 fewer), moderate certainty) and systemic corticosteroids, favipiravir, molnupiravir, and umifenovir probably also reduce duration of symptoms (moderate to high certainty). Compared with standard care, only lopinavir-ritonavir increased adverse effects leading to discontinuation.

CONCLUSION

Nirmatrelvir-ritonavir and remdesivir probably reduce admission to hospital, and systemic corticosteroids and molnupiravir may reduce admission to hospital. Several medications including systemic corticosteroids and molnupiravir probably reduce time to symptom resolution.

SYSTEMATIC REVIEW REGISTRATION

This review was not registered. The protocol is publicly available in the supplementary material.

MeSH

Bias, Pharmaceutical Preparations, Adrenal Cortex Hormones, Ritonavir, Covid-19, Network Meta-Analysis, Therapeutics