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Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial · 10.1016/j.ijantimicag.2020.105949

Name: Verified Rigor Record — Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial · 10.1016/j.ijantimicag.2020.105949
Item: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial · 10.1016/j.ijantimicag.2020.105949
Rating: 63
Author: Αlpha¹

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · July 6, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

WARN

Warnings to address · Interventional Study

Eight dimensions — click a segment for details

Critical

High-priority

Model-reported confidence: moderateReviewer agreement: lowEngine: 7.6.0Source: full text

Not verified in this report

No data or code availability links were detected to verify.

This Αlpha¹ Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This open-label non-randomized clinical trial of hydroxychloroquine for COVID-19 has a clear scientific premise and meets ethical approval standards, but suffers from major design weaknesses (no randomization, no blinding, differential sampling, no ITT analysis). Key resources are poorly identified, no data are available, and the conclusions are overstated relative to the evidence. Statistical reporting is incomplete.

All eight dimensions were scored based on evidence from three independent reviewers. All dimensions were applicable. A key divergence was on study design (pass/fail/warn), resolved to warn. Another divergence was on key resources (fail/warn), resolved to fail. The statistics recheck found 4/4 recomputed tests consistent, but this does not validate the overall analysis.

6 major claims checked against the paper's own evidence: 2 not fully backed by the presented evidence (unsupported or overstated).

Recomputed 4 tests: 4 consistent, 0 inconsistent, 4 via agent-written checks.

7 integrity concerns flagged (0 high).

Rigor

Eight Dimensions2 pass · 3 warn · 3 fail

6 major claims1 unsupported1 overstated4 partial

The introduction cites in vitro data on chloroquine and hydroxychloroquine against SARS-CoV-2, a Chinese clinical trial showing chloroquine efficacy, and the team's extensive experience with hydroxychloroquine for intracellular bacterial diseases. It identifies the urgent need for treatment and logically links the known safety profile of hydroxychloroquine to the trial objectives. Limitations of prior work (small sample, need for more data) are implicitly acknowledged by the study design. All three sub-criteria are adequately addressed.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

The scientific premise is well-established with adequate citations and rationale, though limitations of prior work are not explicitly addressed.

Evidence

direct quote[Introduction, paragraph 2]

“A recent paper reported an inhibitor effect of remdesivir (a new antiviral drug) and chloroquine (an old antimalarial drug) on the growth of SARS-CoV-2 in vitro, and an early clinical trial conducted in Chinese COVID-19 patients, showed that chloroquine had a significant effect, both in terms of clinical outcome and viral clearance, when compared to controls groups.”

direct quote[Introduction, paragraph 3]

“Hydroxychloroquine (an analogue of chloroquine) has been demonstrated to have an anti-SARS-CoV activity in vitro.”

absence[Introduction]

Limitations of prior research are not addressed.

PASSReviewer 2· 95% conf

The premise is well-established: prior in vitro and Chinese clinical evidence for chloroquine/hydroxychloroquine against SARS-CoV-2 is cited, and the study's rationale is logically built from that evidence.

Evidence

direct quote[Introduction, paragraph 3]

direct quote[Introduction, paragraph 4]

“Our team has a very comprehensive experience (over 20 years) in successfully treating patients with chronic diseases due to intracellular bacteria ... with long-term hydroxychloroquine treatment (600 mg/day for 12 to 18 months).”

direct quote[Introduction, paragraph 2]

“Thus, there is an urgent need for an effective treatment to treat symptomatic patients but also to decrease the duration of virus carriage in order to limit the transmission in the community.”

PASSReviewer 3· 85% conf

The paper cites prior work on chloroquine/hydroxychloroquine against SARS-CoV-2 and establishes a logical rationale for testing hydroxychloroquine, but does not discuss limitations of prior research.

Evidence

direct quote[Introduction, paragraphs 1-3]

absence[Introduction, entire section]

Limitations of prior research are not discussed.

The study explicitly states it is 'open-label non-randomized'. No randomization method or unit is reported. Blinding is not attempted, and no rationale is given for its absence. A power analysis is reported, but the target sample of 48 was not reached (only 36 were analyzed), making the power analysis post-hoc and inadequate. Inclusion/exclusion criteria are described. Outlier handling is not addressed; six treated patients were excluded from analysis due to early treatment cessation, but their data are not included in an intention-to-treat analysis, and the reasons provided (transfer to ICU, death, nausea, leaving) represent informative censoring that can bias results. No independent replication is reported. Control patients were not sampled daily, creating a differential ascertainment bias that is acknowledged but not corrected. The scoring rule yields <30% applicable adequate (only 1 of 9: inclusion_exclusion), thus fail.

Sub-criteria

controlsN/A

power analysisINADEQUATE

blinding levelsNOT REPORTED

outlier handlingNOT REPORTED

randomization unitNOT REPORTED

inclusion exclusionADEQUATE

randomization methodNOT REPORTED

replicate distinctionN/A

independent replicationNOT REPORTED

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Study design reporting is adequate for an open-label non-randomized trial, with a power analysis and inclusion/exclusion criteria, though handling of dropouts is not pre-specified.

Evidence

direct quote[Title]

“Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial”

direct quote[Section 2.10 Statistics]

“Assuming a 50% efficacy of hydroxychloroquine in reducing the viral load at day 7, an 85% power, a type I error rate of 5% and 10% loss to follow-up, we calculated that a total of 48 COVID-19 patients (ie, 24 cases in the hydroxychloroquine group and 24 in the control group) would be required for the analysis (Fleiss with CC).”

absence[Section 2.10 Statistics]

Pre-specified handling of dropouts is not reported.

FAILReviewer 2· 95% conf

The study is an open-label, non-randomized trial with major design flaws: no randomization, no blinding, a post-hoc control group that differs in age and sampling frequency, and a high dropout rate without adequate handling.

Evidence

direct quote[Title]

“Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial”

paraphrase[Results, paragraph 1]

“Six hydroxychloroquine-treated patients were lost during follow-up (transfer to ICU, death, nausea, leaving), and the analysis is restricted to the remaining 20 treated patients.”

direct quote[Table 2 footnote]

“a control patients from centers other than Marseille did not undergo daily sampling, but were sampled every other day in most cases, they were considered positive for PCR when actually positive the day(s) before and the day(s) after the day(s) with missing data.”

WARNReviewer 3· 80% conf

The study is non-randomized and open-label with no justification for the lack of blinding; a power analysis is reported, but there is no randomization method, and the handling of dropouts is inadequate.

Evidence

direct quote[Title and Methods, section 2.2]

“open-label non-randomized clinical trial”

direct quote[Methods, section 2.10]

paraphrase[Results, section 3.1]

“Six hydroxychloroquine-treated patients were lost during follow-up and excluded from the analysis; results presented are for 20 treated and 16 control patients.”

Table 1 reports age and sex for all patients, and clinical status is given. However, weight is not reported, and no information on race/ethnicity or comorbidities is provided.

Sub-criteria

demographicsINADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthINADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 75% conf

Sex and age are reported, but weight and detailed demographics (race/ethnicity, comorbidities) are not provided.

Evidence

direct quote[Table 1]

“15 patients were male (41.7%)”

direct quote[Table 1]

“Mean age of 45.1 years”

absence[Results, Section 3.1]

Race/ethnicity and comorbidities are not reported.

PASSReviewer 2· 90% conf

For a human clinical trial, key biological variables (age, sex, clinical status, symptom duration) are reported in Table 1. Sex is reported for the overall cohort. Age and clinical status are adequately detailed. No species/strain/housing criteria apply.

Evidence

direct quote[Table 1]

“Age (years) 51.2 ± 18.7 ... 37.3 ± 24.0 ... Male gender 9 (45.0%) ... 6 (37.5%) ... Clinical status Asymptomatic 2 (10.0%) ... URTI 12 (60.0%) ... LRTI 6 (30.0%)”

direct quote[Results, paragraph 1]

“Overall, 15 patients were male (41.7%), with a mean age of 45.1 years.”

WARNReviewer 3· 70% conf

Sex and age are reported, but weight is not reported, and race/ethnicity and comorbidities are not reported.

Evidence

direct quote[Results, Table 1]

“Age (years) Mean ± SD ... Male gender n (%) ... Hydroxychloroquine treated patients (N=20) 51.2 ± 18.7 ... 9 (45.0) ... Control patients (N=16) 37.3 ± 24.0 ... 6 (37.5)”

absence[Results, Table 1 and demographics paragraph]

Weight is not reported.

absence[Results, demographics section]

Race/ethnicity and comorbidities are not reported.

The paper names the ANSM and CPP Ile de France, provides protocol numbers, and describes written informed consent. Compliance with ICH-GCP and the Declaration of Helsinki is stated.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approvals and informed consent are clearly reported, including named ethics committees and protocol numbers.

Evidence

direct quote[Section 2.3 Informed consent]

“The protocol, appendices and any other relevant documentation were submitted to the French National Agency for Drug Safety (ANSM) (2020-000890-25) and to the French Ethic Committee (CPP Ile de France) (20.02.28.99113) for reviewing and were approved on 5th and 6th March, 2020, respectively.”

direct quote[Section 2.3 Informed consent]

“Written informed signed consent was obtained from adult participants (≥ 18 years) or from parents or legal guardians for minors (<18 years).”

direct quote[Section 2.3 Informed consent]

“The study was conducted in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines of good clinical practice, the Helsinki Declaration, and applicable standard operating procedures.”

PASSReviewer 2· 95% conf

Ethics approval by a named committee (CPP Ile de France) and regulatory approval by the French National Agency for Drug Safety (ANSM) are reported with protocol numbers. Informed consent is described. The trial is registered. Regulatory compliance with ICH-GCP and the Declaration of Helsinki is stated.

Evidence

direct quote[Section 2.3, paragraph 2]

direct quote[Section 2.3, paragraph 1]

“Written informed signed consent was obtained from adult participants (≥ 18 years) or from parents or legal guardians for minors (<18 years).”

direct quote[Section 2.3, paragraph 2]

PASSReviewer 3· 95% conf

The paper reports ethics committee approval with protocol numbers, describes informed consent, and states compliance with ICH-GCP and the Declaration of Helsinki.

Evidence

direct quote[Methods, section 2.3]

“Written informed signed consent was obtained from adult participants (≥ 18 years) or from parents or legal guardians for minors (<18 years).”

direct quote[Methods, section 2.3]

The doses of hydroxychloroquine and azithromycin are given, but no manufacturer or lot numbers are provided. Vero E6 cells are sourced from ATCC but not authenticated, and no mycoplasma testing is reported. Statistical software (Stata 14.2) is identified.

Sub-criteria

mycoplasma testingNOT REPORTED

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationINADEQUATE

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 80% conf

Key resources are inadequately identified: the investigational drugs lack manufacturer/source, and cell line authentication and mycoplasma testing are not reported.

Evidence

direct quote[Section 2.4 Procedure]

“All patients in the Marseille center were proposed oral hydroxychloroquine sulfate 200 mg, three times per day for ten days”

direct quote[Section 2.8 Culture]

“4 wells contained Vero E6 cells (ATCC CRL-1586)”

absence[Section 2.8 Culture]

Mycoplasma testing not reported.

WARNReviewer 2· 90% conf

The investigational drug (hydroxychloroquine) and the antibiotic (azithromycin) are identified, but their manufacturers, lot numbers, and full formulation details are not provided. The cell line (Vero E6) is identified with an ATCC number. Software (Stata) is identified with version.

Evidence

direct quote[Section 2.4, paragraph 1]

“all patients in the Marseille center were proposed oral hydroxychloroquine sulfate 200 mg, three times per day for ten days ... Hydroxychloroquine was provided by the National Pharmacy of France on nominative demand.”

direct quote[Section 2.8]

“4 wells contained Vero E6 cells (ATCC CRL-1586)”

direct quote[Section 2.10]

“Analyses were performed in Stata version 14.2.”

FAILReviewer 3· 70% conf

The investigational drugs are identified, but the wet-lab component (viral culture) lacks cell line authentication, mycoplasma testing, and detailed reagent identification; only software is adequately identified.

Evidence

direct quote[Methods, section 2.8]

“Vero E6 cells (ATCC CRL-1586)”

absence[Methods, section 2.8]

Mycoplasma testing is not reported.

direct quote[Methods, section 2.10]

“Analyses were performed in Stata version 14.2.”

The paper names Pearson's chi-square or Fisher's exact tests for categorical variables and Student's t-test for means. Exact p-values are reported in Tables 2 and 3 and are reproducible from the reported fractions (e.g., chi-square test on Day6 data: 14/20 vs 2/16 yields p≈0.001). No assumptions (normality, equal variance) for t-tests are verified. No effect sizes or confidence intervals are reported. Data presentation shows per-group n and percentages, but not individual data points; error bars are not used. Mathematical plausibility: the reported mean age and SD for subgroups are plausible given the total N. The p-value consistency check passes. The score is warn because 4 of 7 applicable criteria are adequate (tests_named, exact_p_values, software_identified, mathematical_plausibility), but 3 are inadequate (assumptions_verified, effect_sizes_ci, data_presentation).

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciNOT REPORTED

data presentationINADEQUATE

software identifiedADEQUATE

assumptions verifiedNOT REPORTED

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Statistical tests and software are named, exact p-values are reported, and numbers appear plausible. However, effect sizes/confidence intervals are not reported, and data presentation lacks individual points and dispersion.

Evidence

direct quote[Section 2.10 Statistics]

“Statistical differences were evaluated by Pearson's chi-square or Fisher's exact tests as categorical variables, as appropriate. Means of quantitative data were compared using Student's t-test.”

direct quote[Table 2]

“At day6 post-inclusion, 70% of hydroxychloroquine-treated patients were virologically cured compared to 12.5% in the control group (p= 0.001).”

absence[Results]

Effect sizes and confidence intervals are not reported.

WARNReviewer 2· 85% conf

Statistical tests are named (chi-square, Fisher's exact, Student's t), software is identified, and p-values are largely exact. However, test assumptions are not verified, effect sizes with confidence intervals are not reported, and the per-group sample sizes are very small. Mathematical plausibility checks are limited by continuous outcome data.

Evidence

direct quote[Section 2.10]

“Statistical differences were evaluated by Pearson's chi-square or Fisher's exact tests as categorical variables, as appropriate. Means of quantitative data were compared using Student's t-test.”

direct quote[Table 2]

“p= 0.001”

direct quote[Section 2.10]

“Analyses were performed in Stata version 14.2.”

WARNReviewer 3· 80% conf

Statistical tests are named and software is identified, but assumptions are not verified, exact p-values are not consistently reported, effect sizes and confidence intervals are absent, and data presentation lacks individual data points.

Evidence

direct quote[Methods, section 2.10]

“Statistical differences were evaluated by Pearson's chi-square or Fisher's exact tests as categorical variables, as appropriate. Means of quantitative data were compared using Student's t-test.”

direct quote[Results, Table 2 and Table 3]

“p<0.001”

absence[Results, entire section]

Effect sizes and confidence intervals are not reported.

The paper does not include any statement about data availability, repository deposit, or code sharing. For a clinical trial, a data availability statement is mandatory.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementNOT REPORTED

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 95% conf

No data availability statement is provided, which is required for a clinical trial.

Evidence

absence[Entire paper]

No data availability statement.

WARNReviewer 2· 95% conf

No data or code availability statement is provided. The paper does not mention any repository deposition, accession numbers, or code sharing. For a clinical trial, a data availability statement is required; its complete absence is a significant omission.

Evidence

absence[Throughout paper]

No data availability statement found in the paper.

FAILReviewer 3· 90% conf

No data availability statement is provided, and no data or code are deposited in a repository.

Evidence

absence[Entire paper]

No data availability statement is present.

The methods section provides detailed procedures, dosing, and assays. The trial registration number (2020-000890-25) is provided. Funding sources are acknowledged (ANR grant). The discussion acknowledges limitations (small sample, dropout). However, no reporting guideline (e.g., CONSORT) is mentioned. The secondary outcomes 'clinical follow-up and occurrence of side-effects' are deferred to a later paper, making it impossible to verify that all pre-specified outcomes are reported. Conclusions are somewhat proportional given the acknowledged limitations but are also strongly advocative ('We therefore recommend that COVID-19 patients be treated...'). The score is warn because 4 of 7 applicable criteria are adequate (methods_completeness, trial_registration, limitations_discussed, funding_coi), but 3 are inadequate (reporting_guideline, all_outcomes_reported, conclusions_proportional).

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedINADEQUATE

limitations discussedADEQUATE

conclusions proportionalINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

The trial is registered, methods are detailed, and limitations are acknowledged. However, no reporting guideline is referenced, clinical outcomes are deferred, conclusions may overstate the evidence, and a conflicts-of-interest statement is missing.

Evidence

direct quote[Section 2.3 Informed consent]

“This trial is registered in EU Clinical Trials Register with number 2020-000890-25.”

direct quote[Discussion]

“Our study has some limitations including a small sample size, limited long-term outcome follow-up, and dropout of six patients from the study”

direct quote[Discussion]

“We therefore recommend that COVID-19 patients be treated with hydroxychloroquine and azithromycin to cure their infection and to limit the transmission of the virus to other people in order to curb the spread of COVID-19 in the world.”

WARNReviewer 2· 90% conf

Methods are described in sufficient detail for replication, the trial is registered, funding and COI are stated, and limitations are discussed. However, no reporting guideline checklist (CONSORT) is referenced, and some pre-specified secondary outcomes are deferred to a future paper, which raises concerns about selective outcome reporting.

Evidence

direct quote[Section 2.3]

“This trial is registered in EU Clinical Trials Register with number 2020-000890-25.”

direct quote[Results, paragraph 1]

“Clinical follow-up and occurrence of side-effects will be described in a further paper at the end of the trial.”

direct quote[Discussion, paragraph 5]

WARNReviewer 3· 80% conf

Methods are adequately described and the trial is registered, but no reporting guideline is followed, not all outcomes are reported, the conclusions are overstated, and a conflicts-of-interest statement is missing.

Evidence

direct quote[Methods, section 2.3]

“This trial is registered in EU Clinical Trials Register with number 2020-000890-25.”

direct quote[Results, section 3.1]

“Clinical follow-up and occurrence of side-effects will be described in a further paper at the end of the trial.”

direct quote[Discussion, last paragraph]

18 copyedit issues flagged: mostly typo, clarity, grammar.

Checked 20 references: 19 verified — 1 unresolved.

Reproducibility

Registration stated in text, but no registry ID was detected. No reporting guideline cited.

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

This published paper is not robust. An informed reader should weigh the major design flaws (non-randomized, open-label, differential sampling, no ITT) and the absence of data sharing as serious threats to the validity and reproducibility of the findings. The overstated conclusions warrant critical scrutiny. An erratum or correction addressing the conclusions and data availability is needed.

1.
HIGHrigor
Retract or tone down the recommendation 'We therefore recommend that COVID-19 patients be treated with hydroxychloroquine and azithromycin to cure their infection and to limit the transmission' because it is unsupported by the non-randomized, open-label study design.
The claim audit flagged this as unsupported/overstated; a recommendation for global treatment requires robust evidence from randomized trials.
2.
HIGHdata code
Add a data availability statement specifying how de-identified individual patient data can be accessed (e.g., via a managed-access platform or on reasonable request from the corresponding author).
Without a data availability statement, reproducibility is impossible, and journals require this for clinical trials.
3.
HIGHreporting
Reference the CONSORT reporting guideline for non-randomized trials in the Methods and provide a completed checklist as supplementary material.
No reporting guideline is cited; adherence to CONSORT improves completeness and transparency.
4.
HIGHstatistics
Report effect sizes (e.g., risk differences, odds ratios) with 95% confidence intervals for all primary and secondary comparisons in Results and Tables 2-3.
Effect sizes and confidence intervals are essential for interpreting the magnitude and precision of treatment effects.
5.
HIGHreporting
Provide exact p-values (e.g., p=0.0012) instead of threshold values (p<0.001) throughout the Results and Tables.
Threshold p-values are less informative; exact values allow the reader to assess the evidence precisely.
6.
HIGHreporting
Add a conflicts-of-interest statement at the end of the manuscript (e.g., 'The authors declare no competing interests').
A COI statement is a standard ethical disclosure; its absence is a reporting gap.
7.
HIGHreporting
Submit the trial registration data to a public clinical trials registry and ensure the record contains all pre-specified outcomes.
The trial is registered (2020-000890-25), but secondary outcomes are deferred to a future paper, raising concern for selective outcome reporting.
8.
HIGHreporting
Report all pre-specified secondary outcomes (clinical follow-up, side-effects) in this paper, or clearly explain why they are not yet available, rather than deferring them entirely.
Deferring outcomes undermines the ability to assess the completeness of the trial report and risks selective reporting.
9.
HIGHrigor
Add an intention-to-treat (ITT) analysis including all 42 enrolled patients, with appropriate handling of dropouts (e.g., sensitivity analysis).
Excluding 6/26 treated patients without ITT analysis introduces informative censoring bias; the asymmetric dropout (0/16 controls lost) is a validity threat.
10.
HIGHrigor
Justify the open-label design (e.g., feasibility, ethical constraints) in the Methods, and explicitly state who was aware of treatment allocation.
The lack of blinding in a non-randomized study is a major source of bias; justification is missing.
11.
MEDIUMreporting
Provide a CONSORT flow diagram showing participant flow from enrollment (42) through analysis (36), including reasons for dropout.
A flow diagram clarifies the discrepancy between enrolled and analyzed patients and is required by CONSORT.
12.
MEDIUMrigor
Discuss the asymmetric dropout (6/26 treated, 0/16 control) explicitly as a limitation, and note that it could bias results toward the treated group.
The current limitations paragraph mentions dropout but does not address the asymmetry's potential for bias.
13.
MEDIUMreporting
Standardize PCR sampling frequency between groups or apply a standard imputation method and report its impact in sensitivity analysis.
The differential sampling frequency (daily for treated, every other day for controls) and the non-standard imputation method used are potential biases.
14.
MEDIUMreporting
Add a statement on mycoplasma testing for Vero E6 cells, and include authentication results (e.g., STR profiling) in the Methods (Section 2.8).
Mycoplasma testing and cell line authentication are required for reproducible cell culture experiments.
15.
MEDIUMreporting
State the manufacturer, catalog/lot numbers for hydroxychloroquine, azithromycin, and the PCR kit used in Sections 2.4 and 2.6.
Reagent traceability is essential for reproducibility; the current description is inadequate.
16.
LOWcopyedit
Correct typos: 'litterature' to 'literature' (Introduction, Abstract), 'lenght' to 'length' (Section 2.9), 'centrifigation' to 'centrifugation' (Section 2.8).
These typographical errors reduce the manuscript's professionalism.
17.
LOWcopyedit
Fix the awkward phrase 'cost benefits of the risk should be evaluated' to 'risk-benefit should be evaluated individually' in the Discussion.
The phrasing is unclear and grammatically awkward.
18.
LOWother
Verify the reference 'Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia' (DOI: 10.3760/cma.j.issn.1001-0939.2020.03.009) that was not found in the registry, and correct or remove it.
A reference that cannot be located in Crossref/OpenAlex may be fabricated or contain an incorrect DOI.

Full text (22,576 chars)Analyzed: Jul 6, 2026

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