Evidence map›Paper›PMID 35236729›Full record

SynthesisBMJ open2022

Adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomised trials.

Ariel Izcovich, Reed Alexander Siemieniuk, Jessica Julia Bartoszko, Long Ge, Dena Zeraatkar, Elena Kum, Anila Qasim, Assem M Khamis, Bram Rochwerg, Thomas Agoritsas and 5 more

Open access · goldAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMJ open, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 5 pooled it
5.1field-weighted citation impact, top 3% 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

32 citing papers in PubMed, 5 syntheses or guidelines pooled it, 55 citations in OpenAlex.

  1. Pooled it
  2. Neurocognitive Impairment in Long COVID: A Systematic Review.Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists · 2025
    Pooled it
  3. Pooled it
  4. Remdesivir for the treatment of COVID-19.The Cochrane database of systematic reviews · 2023
    Pooled it
  5. Pooled it
  6. Article
  7. Anti-Inflammatory Mechanisms and Translational Relevance ofJournal of inflammation research · 2026
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Efficacy of Kan JangPharmaceuticals (Basel, Switzerland) · 2023
    Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 7 institutions in 7 countries.

Ariel IzcovichDepartment of Internal Medicine, Hospital Alemán de Buenos Aires, Buenos Aires, Argentina ariel.izcovich@gmail.com.ORCID 0000-0001-9053-4396
Reed Alexander SiemieniukDepartment of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0002-3725-3031
Jessica Julia BartoszkoDepartment of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0001-6743-3538
Long GeEvidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China.ORCID 0000-0002-3555-1107
Dena ZeraatkarDepartment of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0003-4287-0541
Elena KumDepartment of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
Anila QasimDepartment of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
Assem M KhamisHull York Medical School, University of Hull, York, UK.ORCID 0000-0002-5567-7065
Bram RochwergDepartment of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
Thomas AgoritsasDepartment of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0002-6182-9969
Derek K ChuDepartment of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
Shelley L McLeodSchwartz/Reisman Emergency Medicine Institute, Sinai Health System, Toronto, Ontario, Canada.
Reem A MustafaDepartment of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
Per VandvikMAGIC Evidence Ecosystem Foundation, Oslo, Norway.
Romina Brignardello-PetersenDepartment of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
Impact · CAEvidence Based Research (United States) · USGeneral Department of Preventive Medicine · VNHospital Alemán · ARUniversity of Hull · GBUniversity of Kansas Medical Center · USUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTo summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19.

methodsWe searched 32 databases through 27 October 2020. We included randomised trials comparing any of the drugs of interest to placebo or standard care, or against each other. We conducted fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation approach.

resultsWe included 16 randomised trials which enrolled 8152 patients. For most interventions and outcomes the certainty of the evidence was very low to low except for gastrointestinal adverse effects from hydroxychloroquine, which was moderate certainty. Compared with standard care or placebo, low certainty evidence suggests that remdesivir may not have an important effect on acute kidney injury (risk difference (RD) 8 fewer per 1000, 95% CI 27 fewer to 21 more) or cognitive dysfunction/delirium (RD 3 more per 1000, 95% CI 12 fewer to 19 more). Low certainty evidence suggests that hydroxychloroquine may increase the risk of cardiac toxicity (RD 10 more per 1000, 95% CI 0 more to 30 more) and cognitive dysfunction/delirium (RD 33 more per 1000, 95% CI 18 fewer to 84 more), whereas moderate certainty evidence suggests hydroxychloroquine probably increases the risk of diarrhoea (RD 106 more per 1000, 95% CI 48 more to 175 more) and nausea and/or vomiting (RD 62 more per 1000, 95% CI 23 more to 110 more) compared with standard care or placebo. Low certainty evidence suggests lopinavir/ritonavir may increase the risk of diarrhoea (RD 168 more per 1000, 95% CI 58 more to 330 more) and nausea and/or vomiting (RD 160 more per 1000, 95% CI 100 more to 210 more) compared with standard care or placebo. DISCUSSION: Hydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. Remdesivir may have no important effect on risk of acute kidney injury or cognitive dysfunction/delirium. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19.

Indexed as

COVID-19 Drug TreatmentHydroxychloroquineAdenosine MonophosphateAlanineDrug CombinationsHumansLopinavirRandomized Controlled Trials as TopicRitonavirSARS-CoV-2Adenosine MonophosphateAlanineDrug CombinationsHydroxychloroquineLopinavirlopinavir-ritonavir drug combinationremdesivirRitonaviradverse eventsCOVID-19infectious diseases

Identifiers

PMID35236729
PMCPMC8895418
OpenAlexW4214864289

What OpenQuestion 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 OpenQuestion graph.