Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: a multi-center observational study

  1. Andrew Ip
  2. Jaeil Ahn
  3. Yizhao Zhou
  4. Andre H. Goy
  5. Eric Hansen
  6. Andrew L. Pecora
  7. Brittany A. Sinclaire
  8. Urszula Bednarz
  9. Michael Marafelias
  10. Ihor S. Sawczuk
  11. Joseph P. Underwood
  12. David M. Walker
  13. Rajiv Prasad
  14. Robert L. Sweeney
  15. Marie G. Ponce
  16. Samuel La Capra
  17. Frank J. Cunningham
  18. Arthur G. Calise
  19. Bradley L. Pulver
  20. Dominic Ruocco
  21. Greggory E. Mojares
  22. Michael P. Eagan
  23. Kristy L. Ziontz
  24. Paul Mastrokyriakos
  25. Stuart L. Goldberg

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Abstract

Background

Hydroxychloroquine has not been associated with improved survival among hospitalized COVID-19 patients in the majority of observational studies and similarly was not identified as an effective prophylaxis following exposure in a prospective randomized trial. We aimed to explore the role of hydroxychloroquine therapy in mildly symptomatic patients diagnosed in the outpatient setting.

Methods

We examined the association between outpatient hydroxychloroquine exposure and the subsequent progression of disease among mildly symptomatic non-hospitalized patients with documented SARS-CoV-2 infection. The primary outcome assessed was requirement of hospitalization. Data was obtained from a retrospective review of electronic health records within a New Jersey USA multi-hospital network. We compared outcomes in patients who received hydroxychloroquine with those who did not applying a multivariable logistic model with propensity matching.

Results

Among 1274 outpatients with documented SARS-CoV-2 infection 7.6% were prescribed hydroxychloroquine. In a 1067 patient propensity matched cohort, 21.6% with outpatient exposure to hydroxychloroquine were hospitalized, and 31.4% without exposure were hospitalized. In the primary multivariable logistic regression analysis with propensity matching there was an association between exposure to hydroxychloroquine and a decreased rate of hospitalization from COVID-19 (OR 0.53; 95% CI, 0.29, 0.95). Sensitivity analyses revealed similar associations. QTc prolongation events occurred in 2% of patients prescribed hydroxychloroquine with no reported arrhythmia events among those with data available.

Conclusions

In this retrospective observational study of SARS-CoV-2 infected non-hospitalized patients hydroxychloroquine exposure was associated with a decreased rate of subsequent hospitalization. Additional exploration of hydroxychloroquine in this mildly symptomatic outpatient population is warranted.

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  1. ScreenIT

    SciScore for 10.1101/2020.08.20.20178772: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Institutional Review Board (IRB) approval was obtained for access to the prospective observational database.
    Consent: The requirement for patient informed consent was waived by the IRB as this project represented a non-interventional study utilizing routinely collected data for secondary research purposes.
    RandomizationAssignment of patients to our data team occurred in real-time but was not randomized.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data abstracted by the team were entered utilizing Research Electronic Data Capture (REDCap).
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    R Project for Statistical Computing).
    R Project for Statistical
    suggested: (R Project for Statistical Computing, RRID:SCR_001905)

    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:
    This limitation biased against finding a difference between cohorts, as non-adherent patients would be categorized within the hydroxychloroquine cohort even though in actuality they did not have drug exposure. Thus, our reduction in hospitalization association may be an underestimate of the effect size. Conversely, it is possible that some outpatients received prescriptions for hydroxychloroquine outside the HMH network and were misclassified in the opposite direction, although this is less likely as patients underwent initial testing within our hospital network and would have been contacted by HMH personnel to discuss testing results and/or had notation of a prescription fill in the EPIC pharmacy section. Our study was conducted early in the United States pandemic during a timeframe when testing for COVID-19 was largely limited to individuals with symptomatic disease. Thus, we suspect that those included in our observational cohort represent a bias towards more advanced disease with a higher likelihood of hospitalization. Indeed 30.6% of our cohort subsequently required hospital based care, which is higher than current state and national hospitalization rates.1,2 Our findings need to be taken into context of current testing availability. This observational study has several additional limitations. We recorded hospitalizations based on EHR documentation, but we have not accounted for hospitalizations outside the HMH network. Since the patients in our series received outpatien...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04347993RecruitingA Prospective "Universal" Observational Database for COVID-1…

    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 10.1186/s12879-021-05773-w
  3. Version published to 10.1101/2020.08.20.20178772 on medRxiv