Chronic treatment with hydroxychloroquine and SARS‐CoV‐2 infection

  1. António Ferreira
  2. António Oliveira‐e‐Silva
  3. Paulo Bettencourt

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Hydroxychloroquine sulfate (HCQ) is being scrutinized for repositioning in the treatment and prevention of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. This antimalarial drug is also chronically used to treat patients with autoimmune diseases. By analyzing the Portuguese anonymized data on private and public based medical prescriptions we have identified all cases chronically receiving HCQ for the management of diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases. Additionally, we have detected all laboratory confirmed cases of SARS‐CoV‐2 infection and all laboratory confirmed negative cases in the Portuguese population (mandatorily registered in a centrally managed database). Cross linking the two sets of data has allowed us to compare the proportion of HCQ chronic treatment (at least 2 grams per month) in laboratory confirmed cases of SARS‐CoV‐2 infection with laboratory confirmed negative cases. Out of 26 815 SARS‐CoV‐2 positive patients, 77 (0.29%) were chronically treated with HCQ, while 1215 (0.36%) out of 333 489 negative patients were receiving it chronically ( P  = .04). After adjustment for age, sex, and chronic treatment with corticosteroids and/or immunosuppressants, the odds ratio of SARS‐CoV‐2 infection for chronic treatment with HCQ has been 0.51 (0.37‐0.70). Our data suggest that chronic treatment with HCQ confer protection against SARS‐CoV‐2 infection.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.06.26.20056507: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics: This study was approved by the Ethics Review Board of Centro Hospitalar Universitário de São João and Faculdade de Medicina da Universidade do Porto.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    By analyzing these sets of data, we were able to detect all patients with SARS-CoV-2 confirmed infections and all clinically suspected but non-confirmed patients between Mars 2, 2020 (the date of the first Portuguese case) and the moment of the analysis.
    SARS-CoV-2
    suggested: (Active Motif Cat# 91351, RRID:AB_2847848)

    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:
    However, as study limitation, the authors stated that the duration of treatment was not documented and only 3 patients received HCQ in the positive cases group. An Indian study showed that HCQ (in the dosage currently used in the prophylaxis of malaria and after four maintenance doses) was effective in preventing SARS-CoV-2 infection in health care workers (19), while another paper showed no statistically significant effect of HCQ (in the dose of 600 mg/day for four days, after a loading dose of 800 mg plus 600 mg after 6 to 8 hours) in postexposure prevention (20). The first two studies evaluated the effectiveness of HCQ as pre-exposure prophylaxis, while the latter tested its effectiveness as post-exposure prophylaxis. Taken together, these results suggest that a relatively long period of HCQ treatment may be necessary in patients without prior contact with the virus to obtain a preventive effect. We believe our data supports this hypothesis. Available data show that there was a significant increase of HCQ prescriptions in March 2020 and in the first two weeks of April 2020. Additional studies are needed to understand whether this increase in HCQ consumption has had any effect on the evolution of the outbreak in Portugal and on the incidence of adverse events. In conclusion, our findings suggest that HCQ might have a preventive effect of SARS-CoV-2 infection. Statistical limitations: Despite having a considerable number of lab tests that were missing in the official electro...

    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.

    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 checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1002/jmv.26286
  3. ScreenIT

    SciScore for 10.1101/2020.06.26.20056507: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementEthics This study was approved by the Ethics Review Board of Centro Hospitalar Universitário de São João and Faculdade de Medicina da Universidade do Porto .Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variableSARS-CoV-2 positive patients were older and more frequently of the male gender than negative patients .

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    By analyzing these sets of data , we were able to detect all patients with SARS-CoV-2 confirmed infections and all clinically suspected but non-confirmed patients between Mars 2 , 2020 ( the date of the first Portuguese case ) and the moment of the analysis .
    SARS-CoV-2
    suggested: (Sino Biological Cat# 40143-R019, AB_2827973)

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

    • The fact that we do not have information on comorbidities may be a major limitation of the study, because it did not allow us to exclude a potential selection bias -for example, physicians may have decided to prescribe HCQ to patients with fewer comorbidities, and because it was not possible to adjust the effect of HCQ to such comorbidities.
    • Thus, the observed effect could be related to a better health status of patients and not to a preventive action of HCQ.
    • We do not have any data on the therapeutic compliance of patients, and this is a study limitation too.

    Results from OddPub: We did not find a statement about open data. We also did not find a statement about 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.

  4. Version published to 10.1101/2020.06.26.20056507v1 on medRxiv