Evidence map›Paper›PMID 32732190›Full record

SynthesisBMJ (Clinical research ed.)2020

Drug treatments for covid-19: living systematic review and network meta-analysis

Reed Ac Siemieniuk, Jessica J Bartoszko, Dena Zeraatkar, Elena Kum, Anila Qasim, Juan Pablo Díaz Martinez, Ariel Izcovich, Francois Lamontagne, Mi Ah Han, Arnav Agarwal and 40 more

Erratum issuedOpen access · hybridAbstract readComparative StudyNetwork Meta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMJ (Clinical research ed.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 464 papers, 35 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
464citing papers in PubMed, 35 pooled it
70.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

464 citing papers in PubMed, 35 syntheses or guidelines pooled it, 908 citations in OpenAlex.

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  9. Molnupiravir for treatment of adults with mild or moderate COVID-19: a systematic review and meta-analysis of randomized controlled trials.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2023
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404 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

50 authors at 20 institutions in 12 countries.

Reed Ac SiemieniukDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada reed.siemieniuk@medportal.ca.ORCID 0000-0002-3725-3031
Jessica J BartoszkoDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Dena ZeraatkarDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Elena KumDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Anila QasimDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Juan Pablo Díaz MartinezDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Ariel IzcovichServicio de Clinica Médica del Hospital Alemán, Buenos Aires, Argentina.
Francois LamontagneDepartment of Medicine and Centre de recherche du CHU de Sherbrooke, Sherbrooke, Quebec, Canada.
Mi Ah HanDepartment of Preventive Medicine, College of Medicine, Chosun University, Gwangju, Republic of Korea.
Arnav AgarwalDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Thomas AgoritsasDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Maria AzabDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada reed.siemieniuk@medportal.ca.
Gonzalo BravoDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada reed.siemieniuk@medportal.ca.
Derek K ChuDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Rachel CoubanDepartment of Anesthesia, McMaster University, Hamilton, ON, Canada.
Tahira DevjiDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Zaira EscamillaDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada reed.siemieniuk@medportal.ca.
Farid ForoutanDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Ya GaoDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada reed.siemieniuk@medportal.ca.
Long GeEvidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, Gansu, China.
Maryam GhadimiDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Diane Heels-AnsdellDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Kimia HonarmandDepartment of Medicine, Western University, London, ON, Canada.
Liangying HouEvidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, Gansu, China.
Quazi IbrahimDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Assem KhamisWolfson Palliative Care Research Centre, Hull York Medical School, Hull, UK.
Bonnie LamDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Christian MansillaDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada reed.siemieniuk@medportal.ca.
Mark LoebDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Anna MiroshnychenkoDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada reed.siemieniuk@medportal.ca.
Maura MarcucciDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Shelley L McLeodSchwartz/Reisman Emergency Medicine Institute, Sinai Health, Toronto, ON, Canada.
Sharhzad MotaghiDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Srinivas MurthyDepartment of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Reem A MustafaDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Hector Pardo-HernandezIberoamerican Cochrane Centre, Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain.
Gabriel RadaEpistemonikos Foundation, Santiago, Chile.
Yamna RizwanDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada reed.siemieniuk@medportal.ca.
Pakeezah SaadatDepartment of Medicine, University of Toronto, Toronto, ON, Canada.
Charlotte SwitzerDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Lehana ThabaneDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
George TomlinsonDepartment of Medicine, University Health Network, Toronto, ON, Canada.
Per O VandvikWilliam Osler Health Network, Toronto, ON, Canada.
Robin Wm VernooijDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands.
Andrés Viteri-GarcíaEpistemonikos Foundation, Santiago, Chile.
Ying WangDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Liang YaoDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Yunli ZhaoDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada reed.siemieniuk@medportal.ca.
Gordon H GuyattDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Romina Brignardello-PetersenDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.
Impact · CAUniversity of Toronto · CALanzhou University · CNCentre Hospitalier Universitaire de Sherbrooke · CAChosun University · KRHospital Alemán · ARHull York Medical School · GBIberoamerican Cochrane Centre · ESLovisenberg Diakonale Høgskole · NOMcMaster University · CAPontificia Universidad Católica de Chile · CLToronto General Hospital · CAUniversidad UTE · ECUniversity Health Network · CAUniversity Hospital of Geneva · CHUniversity of British Columbia · CAUniversity of Calgary · CAUniversity of Kansas Medical Center · USUtrecht University · NLWestern University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo compare the effects of treatments for coronavirus disease 2019 (covid-19).

designLiving systematic review and network meta-analysis. DATA SOURCES: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis. STUDY SELECTION: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.

methodsAfter duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using 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, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.

results463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty).

conclusionCorticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol is publicly available in the supplementary material. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

Indexed as

Antiviral AgentsBetacoronavirusCoronavirus InfectionsPneumonia, ViralRespiration, ArtificialAdenosine MonophosphateAlanineCenters for Disease Control and Prevention, U.S.ChinaCOVID-19COVID-19 Drug TreatmentDatabases, FactualDrug CombinationsEvidence-Based MedicineGlucocorticoidsHumansAdenosine MonophosphateAlanineAntiviral AgentsDrug CombinationsGlucocorticoidsHydroxychloroquineLopinavirlopinavir-ritonavir drug combinationremdesivirRitonavir

Identifiers

PMID32732190
PMCPMC7390912
OpenAlexW3046396978

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.