tetano
Editor, Senior Moderator
BMJ
. 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[SUP] 1 2 [/SUP], Reed A C Siemieniuk[SUP] 3 4 2 [/SUP], María José Oliveros[SUP] 1 5 2 [/SUP], Nazmul Islam[SUP] 1 2 [/SUP], Juan Pablo Díaz Martinez[SUP] 1 2 [/SUP], Ariel Izcovich[SUP] 6 [/SUP], Anila Qasim[SUP] 1 [/SUP], Yunli Zhao[SUP] 1 [/SUP], Carlos Zaror[SUP] 1 7 [/SUP], Liang Yao[SUP] 1 [/SUP], Ying Wang[SUP] 1 [/SUP], Per O Vandvik[SUP] 8 9 [/SUP], Yetiani Roldan[SUP] 1 [/SUP], Bram Rochwerg[SUP] 1 4 [/SUP], Gabriel Rada[SUP] 10 11 [/SUP], Manya Prasad[SUP] 12 [/SUP], Hector Pardo-Hernandez[SUP] 13 14 [/SUP], Reem A Mustafa[SUP] 1 15 [/SUP], Fatemeh Mirzayeh Fashami[SUP] 1 [/SUP], Anna Miroshnychenko[SUP] 1 [/SUP], Shelley L McLeod[SUP] 16 17 [/SUP], Cristian Mansilla[SUP] 1 [/SUP], Francois Lamontagne[SUP] 18 [/SUP], Azin Khosravirad[SUP] 1 [/SUP], Kimia Honarmand[SUP] 19 [/SUP], Maryam Ghadimi[SUP] 1 [/SUP], Ya Gao[SUP] 20 [/SUP], Farid Foroutan[SUP] 1 21 [/SUP], Tahira Devji[SUP] 22 [/SUP], Rachel Couban[SUP] 23 [/SUP], Derek K Chu[SUP] 1 4 [/SUP], Saifur Rahman Chowdhury[SUP] 1 [/SUP], Yaping Chang[SUP] 1 24 [/SUP], Gonzalo Bravo-Soto[SUP] 1 [/SUP], Claudia Bosio[SUP] 10 [/SUP], Diana Biscay[SUP] 10 [/SUP], Gurleen Bhogal[SUP] 25 [/SUP], Maria Azab[SUP] 22 [/SUP], Thomas Agoritsas[SUP] 1 26 [/SUP], Arnav Agarwal[SUP] 1 4 [/SUP], Gordon H Guyatt[SUP] 1 4 [/SUP], Romina Brignardello-Petersen[SUP] 1 [/SUP]
Affiliations
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.
. 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[SUP] 1 2 [/SUP], Reed A C Siemieniuk[SUP] 3 4 2 [/SUP], María José Oliveros[SUP] 1 5 2 [/SUP], Nazmul Islam[SUP] 1 2 [/SUP], Juan Pablo Díaz Martinez[SUP] 1 2 [/SUP], Ariel Izcovich[SUP] 6 [/SUP], Anila Qasim[SUP] 1 [/SUP], Yunli Zhao[SUP] 1 [/SUP], Carlos Zaror[SUP] 1 7 [/SUP], Liang Yao[SUP] 1 [/SUP], Ying Wang[SUP] 1 [/SUP], Per O Vandvik[SUP] 8 9 [/SUP], Yetiani Roldan[SUP] 1 [/SUP], Bram Rochwerg[SUP] 1 4 [/SUP], Gabriel Rada[SUP] 10 11 [/SUP], Manya Prasad[SUP] 12 [/SUP], Hector Pardo-Hernandez[SUP] 13 14 [/SUP], Reem A Mustafa[SUP] 1 15 [/SUP], Fatemeh Mirzayeh Fashami[SUP] 1 [/SUP], Anna Miroshnychenko[SUP] 1 [/SUP], Shelley L McLeod[SUP] 16 17 [/SUP], Cristian Mansilla[SUP] 1 [/SUP], Francois Lamontagne[SUP] 18 [/SUP], Azin Khosravirad[SUP] 1 [/SUP], Kimia Honarmand[SUP] 19 [/SUP], Maryam Ghadimi[SUP] 1 [/SUP], Ya Gao[SUP] 20 [/SUP], Farid Foroutan[SUP] 1 21 [/SUP], Tahira Devji[SUP] 22 [/SUP], Rachel Couban[SUP] 23 [/SUP], Derek K Chu[SUP] 1 4 [/SUP], Saifur Rahman Chowdhury[SUP] 1 [/SUP], Yaping Chang[SUP] 1 24 [/SUP], Gonzalo Bravo-Soto[SUP] 1 [/SUP], Claudia Bosio[SUP] 10 [/SUP], Diana Biscay[SUP] 10 [/SUP], Gurleen Bhogal[SUP] 25 [/SUP], Maria Azab[SUP] 22 [/SUP], Thomas Agoritsas[SUP] 1 26 [/SUP], Arnav Agarwal[SUP] 1 4 [/SUP], Gordon H Guyatt[SUP] 1 4 [/SUP], Romina Brignardello-Petersen[SUP] 1 [/SUP]
Affiliations
- PMID: 40441732
- DOI: 10.1136/bmj-2024-081165
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.