Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease

  1. Jihad Mallat
  2. Fadi Hamed
  3. Maher Balkis
  4. Mohamed A. Mohamed
  5. Mohamad Mooty
  6. Asim Malik
  7. Ahmad Nusair
  8. Maria-Fernanda Bonilla

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Abstract

There are conflicting data regarding the use of hydroxychloroquine (HCQ) in COVID-19 hospitalized patients. The objective of this study was to assess the efficacy of HCQ in increasing SARS-CoV-2 viral clearance.

Hospitalized adult patients with confirmed SARS-CoV-2 infection were retrospectively included in the study. The primary outcome was the time from a confirmed positive nasopharyngeal swab to turn negative. A negative nasopharyngeal swab conversion was defined as a confirmed SARS-CoV-2 case followed by 2 negative results using RT-PCR assay with samples obtained 24 hours apart. Multiple linear regression analysis was used to adjust for potential confounders.

Thirty-four confirmed COVID-19 patients completed the study. Nineteen (55.9%) patients presented with symptoms, and 14 (41.2%) had pneumonia. Only 21 (61.8%) patients received HCQ. The time to SARS-CoV-2 negativity nasopharyngeal test was significantly longer in patients who received HCQ than those who did not receive HCQ [17 (13–21) vs 10 (4–13) days, P  = .023]. HCQ was independently associated with time to negativity test after adjustment for potential confounders (symptoms, comorbidities, antiviral drugs, pneumonia, or oxygen therapy) in multivariable Cox proportional hazards regression analysis (hazard ratio = 0.33, 95% confidence interval: 0.13–0.9, P  = .024). On day 14, 47.8% (14/23) patients tested negative in the HCQ group compared with 90.9% (10/11) patients who did not receive HCQ ( P  = .016).

HCQ was associated with a slower viral clearance in COVID-19 patients with mild to moderate disease. Data from ongoing randomized clinical trials with HCQ should provide a definitive answer regarding the efficacy and safety of this treatment.

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  1. Version published to 10.1097/md.0000000000023720
  2. ScreenIT

    SciScore for 10.1101/2020.04.27.20082180: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The institutional Ethics Committee of Cleveland Clinic Abu Dhabi approved the study, and a waiver of informed consent was obtained due to the nature of the retrospective chart review.
    Consent: The institutional Ethics Committee of Cleveland Clinic Abu Dhabi approved the study, and a waiver of informed consent was obtained due to the nature of the retrospective chart review.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using SPSS software version 20.0 (IBM corporation). p <0.05 was considered statistically significant.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    The studies reported by Gautret et al. [8,9] had major limitations. In the first study [8], 6 (23%) patients in the HCQ group were removed from the analysis due to early cessation of treatment resulting from critical illness (transfer to ICU) or intolerance of the drugs. Also, no safety or clinical outcome was reported. The second study [9] had no control arm. Our findings are partly in line with other studies that found no effects of HCQ on viral clearance [11,12,17]. In a prospective study of 30 COVID-19 patients [11], the authors randomized patients to HCQ (400 mg daily for 5 days) and standard of care or standard care alone. They found no significant difference in the rate of virologic clearance at day 7 between patients with or without HCQ treatment (86.7% vs. 93.3%, respectively), and no difference in clinical outcomes. Molina et al. [17], in patients who received HCQ for 10 days and azithromycin for 5 days, found that 80% (8/10) of them were still positive for SARS-CoV-2 in nasopharyngeal swabs 5 to 6 days after treatment initiation. In a recent multicenter, open-label randomized trial (preprint published) [12], 75 patients were assigned to HCQ (for 2 to 3 weeks) plus standard of care, and 75 patients were assigned to standard of care alone (control group). The authors found that the overall 28-day conversion rate (primary outcome) was not significantly different between the two groups (85.4% for HCQ group vs. 81.3% for control group). Also, the time to SARS-CoV-2 nega...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.

  3. Version published to 10.1101/2020.04.27.20082180v1 on medRxiv