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Cited by 846COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchRespiratory Support and Mechanisms

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

Open access
Siemieniuk, Reed AC, Bartoszko, Jessica J, Zeraatkar, Dena, Kum, Elena, Qasim, Anila, Díaz Martinez, Juan Pablo, Izcovich, Ariel, Rochwerg, Bram +44 more·2020·BMJ
DOI 10.1136/bmj.m2980PMC PMC7390912
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Abstract

Objective: To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design: Living 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. Methods: After 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. Results: 463 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). Conclusion: Corticosteroids, 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.

AI snapshot

Written from the paper’s full text.

TL;DR

This fifth version of a living systematic review and Bayesian network meta-analysis included 463 randomized trials (166,581 patients) of drug treatments for covid-19. It found that systemic corticosteroids, IL-6 receptor antagonists with corticosteroids, and Janus kinase inhibitors probably reduce mortality in severe covid-19, while molnupiravir and nirmatrelvir/ritonavir probably reduce hospital admission in non-severe covid-19.

Key findings

  • In patients with mostly severe disease, compared with standard care, mortality was reduced by systemic corticosteroids (risk difference 23 fewer per 1000, 95% CrI 40 fewer to 7 fewer; moderate certainty), IL-6 receptor antagonists 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).
  • In non-severe disease, compared with standard care, hospital admission was probably reduced by 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 admission (29 fewer per 1000, 40 fewer to 6 fewer; low certainty). Only molnupiravir had at least moderate-quality evidence of reduced time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer; moderate certainty).
  • Other benefits: Janus kinase inhibitors probably reduce duration of mechanical ventilation (−3.2 days, −5.9 to −0.5; high certainty); IL-6 receptor antagonists with corticosteroids reduce length of hospital stay (−4.7 days, −8.9 to −0.5; moderate certainty), as do Janus kinase inhibitors (−1.1 days, −1.9 to −0.4; moderate certainty). Full-dose anticoagulation may reduce venous thromboembolism (OR 0.50, 0.32 to 0.78; low certainty) but may increase clinically important bleeding (OR 2.15, 1.35 to 3.52; low certainty).
  • Adverse effects leading to discontinuation were increased by hydroxychloroquine (13 more per 1000, 2 more to 24 more; low certainty), lopinavir-ritonavir (49 more per 1000, 27 more to 72 more; moderate certainty), and tyrosine kinase inhibitors (62 more per 1000, 19 more to 105 more; moderate certainty). Hydroxychloroquine probably increases mechanical ventilation (moderate certainty). Several interventions showed no important benefit on patient-important outcomes, including ACE inhibitors, aspirin, azithromycin, colchicine, hydroxychloroquine, inhaled corticosteroids, intranasal corticosteroids, interferon beta, ivermectin, lopinavir-ritonavir, umifenovir, and vitamin C.

Methods

  • Living systematic review and Bayesian network meta-analysis of randomized clinical trials in people with suspected, probable, or confirmed covid-19, comparing drug treatments with one another or with no intervention, placebo, or standard care; no restrictions by language, publication status, illness severity, or setting. Excluded vaccination, blood products/antibody-based antivirals, nutrition, traditional Chinese herbal/alternative medicines, and non-drug supportive care.
  • Searched WHO covid-19 database up to 3 December 2021 and six Chinese databases up to 20 February 2021; included 463 trials enrolling 166,581 patients; 265 trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in analyses.
  • Used random-effects Bayesian network meta-analysis with odds ratios or mean differences and 95% credible intervals; assessed risk of bias with a modification of Cochrane RoB 2.0 and certainty with GRADE; calculated absolute effects using baseline risks from observational data and standard-care medians; assessed incoherence with node-splitting models and performed subgroup/sensitivity analyses.

Limitations

  • Paper-stated: the primary limitation for most interventions was lack of blinding, which might introduce bias through differences in co-interventions; unblinded standard care and placebo groups were combined in the same node, so co-interventions may have differed systematically. Reporting concerns and inconsistent outcome measurement across studies were also noted.
  • Paper-stated: the living nature could temporarily amplify publication bias, though inclusion of preprints with negative results might reduce this; preprints may introduce bias from errors and reporting limitations. Sparse data produced uninformative or implausible estimates, so only treatments with at least 100 patients or 20 events were reported; observational data used for some absolute risk estimates can affect GRADE imprecision. The review was not registered (abstract states), though the protocol is publicly available.
  • Evident from text: network meta-analysis assumes transitivity; no statistical incoherence was detected, but excluded trials (same treatment node, different doses/durations, insufficient data, or no outcomes of interest) and sparse nodes limit inference. This is the final version of this particular living review, with future separate reviews planned for non-severe and severe covid-19.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1136/bmj.m2980

Cites

222 of 222 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 14 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Lopinavir-ritonavir does not suggest benefit for mortality (odds ratio 1.06, 95% credible interval 0.88 to 1.28; low certainty).

    “lopinavir-ritonavir (1.06, 0.88 to 1.28; low certainty)”
    Quote in the paperSubstantial claim
  • Findingown data

    Interleukin-6 receptor antagonists when given with corticosteroids reduce mortality compared with standard care (23 fewer per 1000, 36 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)”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline risks for outcomes derived from observational data are representative of the usual care groups in the included randomised trials.
  • Findingown data

    Hydroxychloroquine does not suggest benefit for mortality (odds ratio 1.08, 95% credible interval 0.92 to 1.27; moderate certainty).

    “hydroxychloroquine (1.08, 0.92 to 1.27; moderate certainty)”
    Quote in the paperSubstantial claim
  • Findingown data

    121 studies were judged at low risk of bias in all domains for at least one outcome.

    “121 studies were judged at low risk of bias in all domains for at least one outcome.”
    Quote in the paperNot a substantial claim
  • Findingown data

    265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses.

    “265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 26
  • May combine two claims. 12
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    267 (57.7%) trials and 89,814 (53.9%) patients are new from the previous iteration.

    “267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Thirty two studies had discrepancies in outcome reporting between the preprint and peer-reviewed publication, 32 studies had discrepancies with patient baseline characteristics, and 14 studies had discrepancies in reporting that led to changes in risk of bias ratings.

    “Thirty two studies had discrepancies in outcome reporting between the preprint and peer-reviewed publication, 32 studies had discrepancies with patient baseline characteristics, and 14 studies had discrepancies in reporting that led to changes in risk of bias ratings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    No substantive differences were found for 26 studies.

    “No substantive differences were found for 26 studies.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Fifty seven different interventions were included in the mortality network meta-analysis.

    “Fifty seven different interventions were included”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    We stopped searching the Chinese databases on 20 February 2021 because they had not provided studies that meaningfully altered the evidence for any intervention.

    “We stopped searching the Chinese databases on 20 February 2021 because they had not provided studies that meaningfully altered the evidence for any intervention.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    Many of the data also had reporting concerns.

    “Many of the data also had reporting concerns.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    To date, we are aware of two other similar efforts to ours.

    “To date, we are aware of two other similar efforts to ours.42 43”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [42] Boutron I, Chaimani A, Devane D, et al. Interventions for preventing and treating COVID-19: protocol for a living mapping of research and a living systematic review. Zenodo 2020. https://zenodo.org/record/3744600#.X1igcnlKiN5. source

      Not checked in the free run.

    • cites [43] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    This is the final version of this particular living systematic review and network meta-analysis.

    “This is the final version of this particular living systematic review and network meta-analysis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    All other interventions either are probably not beneficial, or the evidence remains highly uncertain regarding their impacts on patient-important outcomes.

    “All other interventions either are probably not beneficial, or the evidence remains highly uncertain regarding their impacts on patient-important outcomes.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Molnupiravir probably reduces hospitalisation in patients with non-severe covid-19 (odds ratio 0.54, 95% credible interval 0.30 to 0.90; moderate certainty).

    “Molnupiravir (odds ratio 0.54, 0.30 to 0.90; moderate certainty)”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based). May combine two claims.

    Findingnone given

    We also include a more comprehensive search for the evidence and several differences in analytical methods, which we believe are best suited for this evidence.

    “We also include a more comprehensive search for the evidence and several differences in analytical methods, which we believe are best suited for this evidence.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    Some others use fixed rather than random effects meta-analysis and provide estimates for pairwise comparisons only.

    “For example, some others use fixed rather than random effects meta-analysis and provide estimates for pairwise comparisons only.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    We assessed the certainty of evidence using the GRADE approach for network meta-analysis.

    “We assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach for network meta-analysis.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    We used node splitting models to assess local incoherence.

    “We used node splitting models to assess local incoherence and to obtain indirect estimates.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    Pairs of reviewers independently screened all titles and abstracts, followed by full texts of trials that were identified as potentially eligible.

    “pairs of reviewers, following training and calibration exercises, independently screened all titles and abstracts, followed by full texts of trials that were identified as potentially eligible.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Living systematic reviews deal with the main limitation of traditional reviews-that of providing an overview of the relevant evidence only at a specific time.

    “Living systematic reviews deal with the main limitation of traditional reviews—that of providing an overview of the relevant evidence only at a specific time.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Reviewers used a revision of the Cochrane tool for assessing risk of bias in randomised trials (RoB 2.0) to rate trials.

    “used a revision of the Cochrane tool for assessing risk of bias in randomised trials (RoB 2.0)20 to rate trials”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Pairs of reviewers extracted data independently using a standardised, pilot tested data extraction form.

    “pairs of reviewers, following training and calibration exercises, extracted data independently using a standardised, pilot tested data extraction form.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Two people with experience in using GRADE rated each domain for each comparison separately and resolved discrepancies by consensus.

    “Two people with experience in using GRADE rated each domain for each comparison separately and resolved discrepancies by consensus.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The RECOVERY trial randomized 8156 patients to baricitinib or standard care and was published after our analyses were completed.

    “The RECOVERY trial, which randomized 8156 patients to baricitinib or standard care, was published after our analyses were completed.38”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Horby PW Emberson JR Mafham M RECOVERY Collaborative Group . Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis. medRxiv 2022:2022.03.02.22271623.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    This living systematic review and network meta-analysis provides a comprehensive overview and assessment of the evidence published as of 3 December 2021.

    “This living systematic review and network meta-analysis provides a comprehensive overview and assessment of the evidence published as of 3 December 2021”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Our team is composed of clinical and methods experts who have undergone training and calibration exercises for all stages of the review process.

    “To ensure expertise in all areas, our team is composed of clinical and methods experts who have undergone training and calibration exercises for all stages of the review process.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    In this living systematic review and network meta-analysis, we use a minimally contextualised approach for rating the certainty of the evidence, whereas the guideline panels use a fully contextualised approach.

    “In this living systematic review and network meta-analysis, we use a minimally contextualised approach for rating the certainty of the evidence, whereas the guideline panels use a fully contextualised approach in which the thresholds of importance of magnitudes of effects depend on all other outcomes and factors involved in the decision.29”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The inclusion of preprints, many of which have negative results, might reduce this risk.

    “The inclusion of preprints, many of which have negative results, might reduce this risk.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Our search strategy and eligibility criteria were comprehensive, without restrictions on language of publication or publication status.

    “Our search strategy and eligibility criteria were comprehensive, without restrictions on language of publication or publication status.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Differences in baseline risk can impact GRADE assessments for imprecision.

    “We used observational data to inform the absolute risk estimates for some outcomes; differences in baseline risk can impact GRADE assessments for imprecision.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The contextualisation explains differences in the certainty of the evidence between the two.

    “The contextualisation explains differences in the certainty of the evidence between the two.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    We decided to report evidence on treatments for which at least 100 people were randomised or for which there were at least 20 events.

    “For that reason, we decided to report evidence on treatments for which at least 100 people were randomised or for which there were at least 20 events.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    The primary limitation of the evidence for most interventions is lack of blinding, which might introduce bias through differences in co-interventions between randomised groups.

    “The primary limitation of the evidence for most interventions is lack of blinding, which might introduce bias through differences in co-interventions between randomised groups.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The living nature of our systematic review and network meta-analysis could conceivably amplify publication bias, because studies with promising results are more likely to be published and are published sooner than studies with negative results.

    “The living nature of our systematic review and network meta-analysis could conceivably (at least temporarily) amplify publication bias, because studies with promising results are more likely to be published and are published sooner than studies with negative results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The inclusion of preprints in our network meta-analysis might introduce bias from simple errors and the reporting limitations of preprints.

    “However, the inclusion of preprints in our network meta-analysis might introduce bias from simple errors and the reporting limitations of preprints.”
    Quote in the paperNot a substantial claim
31 of 31

  • The paper relies on this without support.

    Baseline risks for outcomes derived from observational data are representative of the usual care groups in the included randomised trials.

    “When available, we inferred baseline risk in the usual care group for each outcome from representative observational data (supplementary material).”

  • The paper relies on this without support.

    Evidence for effective treatment for covid-19 remains limited despite huge efforts.

    “Despite huge efforts to identify effective drug interventions for coronavirus disease 2019 (covid-19), evidence for effective treatment remains limited”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Percentage of studies conducted in China is incorrect

    Minor

    Table 1 describes 420 studies. Its 41 studies from China represent 9.8% to one decimal place, not 10.0%.

    Reported 10 · recomputed 9.761905

  • Mortality analysis includes more trials than the stated overall analysis

    Minor

    The paper says 265 trials were analysed overall, but says 267 trials were included in the mortality network meta-analysis. An analysis of one outcome cannot contain more trials than the overall set analysed.

  • Standard-care trial count exceeds the hospital-admission analysis total

    Minor

    The hospital-admission analysis is said to include 35 trials, but its standard-care intervention is reported in 36 trials.

  • Remdesivir's hospital-admission benefit is described as both possible and probable

    Minor

    The abstract distinguishes remdesivir as a treatment that may reduce admission, while the discussion groups it with treatments that probably reduce admission.

4 of 4

Cites

6 retracted

Flagged first, then by citations

Research works printed but not linked: 9

  1. 10.1016/j.jclinepi.2017.08.010 · DOI · Paper page
  2. 10.1002/jrsm.1287 · DOI · Paper page
  3. 10.1016/j.jclinepi.2017.08.010 · DOI · Paper page
  4. 10.1002/jrsm.1287 · DOI · Paper page
  5. Covidence systematic review software [program]. Melbourne, Australia: Veritas Health Innovation.
  6. 10.1016/j.jclinepi.2017.10.005 · DOI · Paper page
  7. 10.1016/j.jclinepi.2018.11.025 · DOI
  8. 10.1016/j.jclinepi.2017.05.006 · DOI · Paper page
  9. ISARIC (International Severe Acute Respiratory and Emerging Infections Consortium). COVID-19 Report: 08 June 2020. medRxiv 2020. .

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Authors
Siemieniuk, R. A., Bartoszko, J. J., Zeraatkar, D., Kum, E., Qasim, A., Díaz Martinez, J. P., Izcovich, A., Rochwerg, B., Lamontagne, F., Han, M. A., Agarwal, A., Agoritsas, T., Azab, M., Bravo, G., Chu, D. K., Couban, R., Cusano, E., Devji, T., Escamilla, Z., Foroutan, F., Gao, Y., Ge, L., Ghadimi, M., Heels-Ansdell, D., Honarmand, K., Hou, L., Ibrahim, S., Khamis, A., Lam, B., Mansilla, C., Loeb, M., Miroshnychenko, A., Marcucci, M., McLeod, S. L., Motaghi, S., Murthy, S., Mustafa, R. A., Pardo-Hernandez, H., Rada, G., Rizwan, Y., Saadat, P., Switzer, C., Thabane, L., Tomlinson, G., Vandvik, P. O., Vernooij, R. W., Viteri-García, A., Wang, Y., Yao, L., Zhao, Y., Guyatt, G. H., & Brignardello-Petersen, R.
Affiliations
  • McMaster University (CA)
  • Hospital Alemán (AR)
  • Chosun University (KR)
  • University of Toronto (CA)
  • University Hospital of Geneva (CH)
  • University of Calgary (CA)
  • Toronto General Hospital (CA)
  • Lanzhou University (CN)
  • Western University (CA)
  • Hull York Medical School (GB)
  • University of British Columbia (CA)
  • University of Kansas Medical Center (US)
  • University Health Network (CA)
  • Lovisenberg Diakonale Sykehus (NO)
  • Utrecht University (NL)
  • Universidad UTE (EC)
ORCID
Venue
BMJ
Publisher
BMJ
Published
2020-07-30
Volume
370
Pages
m2980
ISSN
1756-1833 (ISSN-L)
DOI
10.1136/bmj.m2980
PMC
PMC7390912
OpenAlex
W3046396978
Semantic Scholar
d8275101c32fa34be950ad4fdd4da76da9869f7c
Cited by
846
References
222
Citations by year
2026: 14 · 2025: 30 · 2024: 73 · 2023: 131 · 2022: 213 · 2021: 304 · 2020: 80
FWCI
8.60
Type
journal article
Language
en
Update notices
correction (2021-04-13)
Open access
Licence
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • cIRcle (University of British Columbia) (publishedVersion, cc-by-nc)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
  • Monash University Research Portal (Monash University) (submittedVersion, cc-by-nc)
  • Lanzhou University Institutional Repository (submittedVersion, cc-by-nc-sa)
  • Lanzhou University Institutional Repository (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
  • MacSphere (McMaster University) (submittedVersion, cc-by-nc)
  • HighWire Press Open Archive (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by-nc)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc)
Funders
Canadian Institutes of Health Research (Research CIHR-IRSC:057900132, 170359_1, CIHR-IRSC:057900132)
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 › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
Keywords
COVID-19 pandemic, antiviral agents, systemic corticosteroids, IL-6 receptor inhibitor, JAK inhibitors, nirmatrelvir/ritonavir, molnupiravir, remdesivir, tocilizumab, hydroxychloroquine, dexamethasone, mortality, hospitalization
MeSH terms
Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Adenosine Monophosphate, Alanine, Antiviral Agents, Centers for Disease Control and Prevention, U.S., China, Drug Combinations, Glucocorticoids, Humans, Hydroxychloroquine, Pneumonia, Viral, Respiration, Artificial, Severity of Illness Index, United States, Randomized Controlled Trials as Topic, Databases, Factual, Treatment Outcome, Coronavirus Infections, Evidence-Based Medicine, Ritonavir, Pandemics, Standard of Care, Lopinavir

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