The Role of Hydroxychloroquine in COVID-19 Treatment: A Systematic Review and Meta-Analysis
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Abstract
Objective: A systematic review and meta-analysis was carried out to examine the role of hydroxychloroquine (HCQ) in the treatment of COVID-19. Methods: We performed a systematic search in PubMed, Scopus, Embase, Cochrane- Library, Web of Science, Google-Scholar, and medRxiv pre-print databases using available MeSH terms for COVID-19 and hydroxychloroquine. Data from all studies that focused on the effectiveness of HCQ with or without the addition of azithromycin (AZM) in confirmed COVID-19 patients, which were published up to 12 September 2020, were collated for analysis using CMA v.2.2.064. Results: Our systematic review retrieved 41 studies. Among these, 37 studies including 45,913 participants fulfilled the criteria for subsequent meta-analysis. The data showed no significant difference in treatment efficacy between the HCQ and control groups (RR: 1.02, 95% CI, 0.81–1.27). Combination of HCQ with AZM also did not lead to improved treatment outcomes (RR: 1.26, 95% CI, 0.91–1.74). Furthermore, the mortality difference was not significant, neither in HCQ treatment group (RR: 0.86, 95% CI, 0.71–1.03) nor in HCQ+AZM treatment group (RR: 1.28, 95% CI, 0.76–2.14) in comparison to controls. Meta-regression analysis showed that age was the factor that significantly affected mortality (P<0.00001). Conclusion: The meta-analysis found that there was no clinical benefit of using either HCQ by itself or in combination with AZM for the treatment of COVID-19 patients. Hence, it may be prudent for clinicians and researchers to focus on other therapeutic options that may show greater promise in this disease. Keywords: Azithromycin, coronavirus outbreaks, pandemic, 2019-nCoV disease
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SciScore for 10.1101/2020.04.14.20065276: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization The Jadad scale, ROBINS-I tool and Newcastle-Ottawa Scale (NOS) checklists were used to value the selected randomized controlled trials, non-randomized controlled trials and observational studies respectively concerning various aspects of the methodology and study process. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources A systematic search was performed via databases of PubMed, Scopus, Embase, Cochrane Library, Web of Science and Google Scholar (intitle) as well as pre-print database of medRxiv up to July 19, 2020. PubMedsuggested: …SciScore for 10.1101/2020.04.14.20065276: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization The Jadad scale, ROBINS-I tool and Newcastle-Ottawa Scale (NOS) checklists were used to value the selected randomized controlled trials, non-randomized controlled trials and observational studies respectively concerning various aspects of the methodology and study process. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources A systematic search was performed via databases of PubMed, Scopus, Embase, Cochrane Library, Web of Science and Google Scholar (intitle) as well as pre-print database of medRxiv up to July 19, 2020. PubMedsuggested: (PubMed, RRID:SCR_004846)Embasesuggested: (EMBASE, RRID:SCR_001650)Cochrane Librarysuggested: (Cochrane Library, RRID:SCR_013000)Google Scholarsuggested: (Google Scholar, RRID:SCR_008878)The search strategy included all MeSH terms and free keywords found for COVID-19, SARS-CoV-2, and hydroxychloroquine. MeSHsuggested: (MeSH, RRID:SCR_004750)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Concerning all of the limitations and analyze difficulties, we have conducted this systematic review and meta-analysis with great caution and sensitivity in performing analyzes in order to try to overcome the current controversies regarding the effectiveness of HCQ in the treatment of COVID-19, at least at the base. Considering the matter, recent investigations indicated that a high concentration of cytokines in the plasma called cytokine storm would be related to severe COVID-19 patients. In this situation, medications transposition is a critical need to find effective anti-inflammatory agents to decrease the cytokines and pro-inflammatory factors production 45. In this regard, HCQ has been known as an effective anti-inflammatory agent for a long time (since the 1950s), especially in autoimmune disorders 46. Besides, the outcome of a new experimental study conducted by Liu et al. has been mentioned in the title of their publication as follows: “Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro”. This also has been investigated and resulted same as the in vitro study of Yao et al. 47. In addition, Pagliano et al. in their letter to the editor of Clinical Infectious Diseases (CID) journal, have been recommended the use of HCQ as pre/post-exposure prophylaxis against SARS-CoV-2 infection for health care staffs exposed to the virus in contaminated environments 48. In contrast, Maurizio Guastalegname and Alfredo V...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.04.14.20065276: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Our gratitude should also go to the Student Research Committee of Mazandaran University of Medical Sciences for approving this student research proposal with the code 7586. Randomization However , due to that most of the studies were non-randomized and results were not homogenous , selection bias was unavoidable and further large randomized clinical trials following comprehensive meta-analysis should be taken into account in order to achieve more reliable findings . Blinding not detected. Power Analysis The studies’ sample size ranged from 10 to 96,032 including 103,486 participants . Sex as a biological variable not detected. Table 2: Resources
Software … SciScore for 10.1101/2020.04.14.20065276: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Our gratitude should also go to the Student Research Committee of Mazandaran University of Medical Sciences for approving this student research proposal with the code 7586. Randomization However , due to that most of the studies were non-randomized and results were not homogenous , selection bias was unavoidable and further large randomized clinical trials following comprehensive meta-analysis should be taken into account in order to achieve more reliable findings . Blinding not detected. Power Analysis The studies’ sample size ranged from 10 to 96,032 including 103,486 participants . Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, Google Scholar and medRxiv pre-print database using all available MeSH terms for COVID-19 and hydroxychloroquine up to May 25, 2020. PubMedsuggested: (PubMed, SCR_004846)<div style="margin-bottom:8px"> <div><b>Google Scholar</b></div> <div>suggested: (Google Scholar, <a href="https://scicrunch.org/resources/Any/search?q=SCR_008878">SCR_008878</a>)</div> </div> <div style="margin-bottom:8px"> <div><b>MeSH</b></div> <div>suggested: (MeSH, <a href="https://scicrunch.org/resources/Any/search?q=SCR_004750">SCR_004750</a>)</div> </div> </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">A systematic search was performed via databases of PubMed , Scopus , Embase , Cochrane Library , Web of Science and Google Scholar ( intitle ) as well as preprint database of medRxiv up to May 6 , 2020 .</td><td style="min-width:100px;border-bottom:1px solid lightgray"> <div style="margin-bottom:8px"> <div><b>Embase</b></div> <div>suggested: (EMBASE, <a href="https://scicrunch.org/resources/Any/search?q=SCR_001650">SCR_001650</a>)</div> </div> <div style="margin-bottom:8px"> <div><b>Cochrane Library</b></div> <div>suggested: (Cochrane Library, <a href="https://scicrunch.org/resources/Any/search?q=SCR_013000">SCR_013000</a>)</div> </div> </td></tr></table>Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
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