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. 2025 May 29:389:e081165.
doi: 10.1136/bmj-2024-081165.

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

Sara Ibrahim  1   2 , Reed A C Siemieniuk  3   4   2 , María José Oliveros  1   5   2 , Nazmul Islam  1   2 , Juan Pablo Díaz Martinez  1   2 , Ariel Izcovich  6 , Anila Qasim  1 , Yunli Zhao  1 , Carlos Zaror  1   7 , Liang Yao  1 , Ying Wang  1 , Per O Vandvik  8   9 , Yetiani Roldan  1 , Bram Rochwerg  1   4 , Gabriel Rada  10   11 , Manya Prasad  12 , Hector Pardo-Hernandez  13   14 , Reem A Mustafa  1   15 , Fatemeh Mirzayeh Fashami  1 , Anna Miroshnychenko  1 , Shelley L McLeod  16   17 , Cristian Mansilla  1 , Francois Lamontagne  18 , Azin Khosravirad  1 , Kimia Honarmand  19 , Maryam Ghadimi  1 , Ya Gao  20 , Farid Foroutan  1   21 , Tahira Devji  22 , Rachel Couban  23 , Derek K Chu  1   4 , Saifur Rahman Chowdhury  1 , Yaping Chang  1   24 , Gonzalo Bravo-Soto  1 , Claudia Bosio  10 , Diana Biscay  10 , Gurleen Bhogal  25 , Maria Azab  22 , Thomas Agoritsas  1   26 , Arnav Agarwal  1   4 , Gordon H Guyatt  1   4 , Romina Brignardello-Petersen  1
Affiliations

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

Sara Ibrahim et al. BMJ. .

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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Canadian Institutes of Health Research for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Study selection
Fig 2
Fig 2
Summary of effects of drug treatments compared with standard care for mild and moderate covid-19
See this image and copyright information in PMC

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