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COVID-19 and hydroxychloroquine: Let the available data speak for themselves

  • Ugo Paliani
    Correspondence
    Corresponding author.
    Affiliations
    Division of Internal Medicine and Sport Cardiology, Media Valle del Tevere Hospital, Todi, Umbria, Italy

    Umbria Covid Hospital, Todi, Umbria, Italy
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  • Andrea Cardona
    Affiliations
    Division of Internal Medicine and Sport Cardiology, Media Valle del Tevere Hospital, Todi, Umbria, Italy

    Umbria Covid Hospital, Todi, Umbria, Italy

    Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
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      Dear Editor,
      In our recent editorial on the role of hydroxychloroquine during SARS-Cov-2 pandemics [
      • Paliani U
      • Cardona A.
      Covid-19 and hydroxychloroquine: is the wonder drug failing?.
      ], leveraging on the available scientific evidence, we emphasized the need of using extreme caution when it comes to prescribing a potentially toxic drug, especially with higher dose compared to standard drug regimen and on a large scale population.
      We read with interest a comment from the group of Raoult and colleagues [
      • Matthieu Milliona YR
      • Raoult Didier
      Chloroquine and COVID-19: a western medical and scientific drift?.
      ]. We wish to thank the authors as they clearly understood our goal of stressing the need of being very careful in analyzing the literature at a time when scientific conflicts of this magnitude are taking place.
      Importantly, after our editorial, one of the papers we cited was retracted [
      • Mehra MR RF
      • Patel AN
      Retraction—hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis.
      ] and once more, this clearly underlines that, in the era of SARS-Cov-2 pandemics, owing to an unprecedented volume of research being conducted in such a short period of time and the large number of reports submitted to journals, high quality standards and meticulous peer-review process must be undertaken in order to convey objective and unbiased evidence [
      • Bauchner H
      • Fontanarosa PB
      • Golub RM
      Editorial evaluation and peer review during a pandemic: how journals maintain standards.
      ].
      Nevertheless, the vast majority of the available current scientific evidence, suggest, at the very least, that hydroxychloroquine is not ready for clinical prime time as standard therapy in Covid-19. Tang and colleagues recently published a randomized clinical trial of patients with mainly persistent mild to moderate Covid-19 in which exposure to hydroxychloroquine led to a similar probability of virus elimination compared to the current standard of care [
      • Tang W
      • Cao Z
      • Han M
      • Wang Z
      • Chen J
      • Sun W
      • et al.
      Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial.
      ].
      Therefore, taking together what studies have told so far, it is not surprising that the last update of the “Covid-19 treatment guidelines” (dated June 25th) on the use of chloroquine or hydroxychloroquine published by the National Institutes of Health (NIH) suggest the following:
      • -
        The Covid-19 Treatment Guidelines Panel recommends against the use of chloroquine or hydroxychloroquine for the treatment of Covid-19, except in a clinical trial – Class of Evidence AII.
      • -
        The Panel recommends against the use of high-dose chloroquine (600 mg twice daily for 10 days) for the treatment of Covid-19 – Class of Evidence AI.
      The last recommendation follows results from a randomized clinical trial comparing high-dose chloroquine and low-dose chloroquine in patients with Covid-19; the study was discontinued early when preliminary results showed higher rates of mortality and QTc prolongation in the high-dose chloroquine group [
      • Borba MGS
      • Val FFA
      • Sampaio VS
      • Alexandre MAA
      • Melo GC
      • Brito M
      • et al.
      Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial.
      ].
      Finally, it is important to note that hydroxychloroquine toxic effect is related to its volume of distribution and half-life. Hydroxychloroquine half-life is around 50 days (!) and has prolonged effects even after drug discontinuation (
      • Schrezenmeier E
      • Dorner T.
      Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology.
      ).
      In conclusion, as we wrote in our editorial, we stay firm in believing that evidence based medicine is our strongest ally. Now more than ever, in the era of Covid-19 pandemics, where heterogeneous treatments and different drug doses not supported by the evidence can lead to confusion, discordant results, poor reproducibility, and potentially higher mortality, the whole scientific community should stay united in advocating the most meticulous scientific approach.

      Declaration of Competing Interest

      None.

      References

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        • Cardona A.
        Covid-19 and hydroxychloroquine: is the wonder drug failing?.
        Eur J Intern Med. 2020;
        • Matthieu Milliona YR
        • Raoult Didier
        Chloroquine and COVID-19: a western medical and scientific drift?.
        Eur J Intern Med. 2020;
        • Mehra MR RF
        • Patel AN
        Retraction—hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis.
        Lancet. 2020; (Jun 5)
        • Bauchner H
        • Fontanarosa PB
        • Golub RM
        Editorial evaluation and peer review during a pandemic: how journals maintain standards.
        JAMA. 2020; https://doi.org/10.1001/jama.2020.11764
        • Tang W
        • Cao Z
        • Han M
        • Wang Z
        • Chen J
        • Sun W
        • et al.
        Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial.
        BMJ. 2020; (369:m1849)
        • Borba MGS
        • Val FFA
        • Sampaio VS
        • Alexandre MAA
        • Melo GC
        • Brito M
        • et al.
        Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial.
        JAMA Network Open. 2020; 3e208857
        • Schrezenmeier E
        • Dorner T.
        Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology.
        Nat Rev Rheumatol. 2020; 16: 155-166