Letters21 October 2020

Update Alert 3: Hydroxychloroquine or Chloroquine for the Treatment or Prophylaxis of COVID-19

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    This report, the third update of a previously published living systematic review (1), focuses on treatment (not prophylaxis) of coronavirus disease 2019 (COVID-19) with hydroxychloroquine or chloroquine. The first and second updates covered evidence available through 1 July 2020 (2) and 1 August 2020 (3), respectively. This update evaluates evidence published through 21 September 2020.

    No new evidence about chloroquine was found. One new randomized trial (4) and 5 new cohort studies (5–9) evaluating hydroxychloroquine were found. None of the studies used zinc; all studies (5–8) except for 1 (9) with a hydroxychloroquine group and an azithromycin group evaluated hydroxychloroquine alone. The trial used a “standard care” control group (4) and had high risk of bias, whereas all of the cohort studies had serious risk of bias (5–9). The trial (4) and 3 of the new cohort studies (6, 7, 9) assessed hospital-initiated hydroxychloroquine, whereas 2 of the new cohort studies (5, 8) assessed prehospital initiation.

    The Supplement Table displays the following for outcomes of all identified trials (4, 10–16, 32, 34) and cohort studies (5–9, 17–31, 33, 35) that addressed treatment with hydroxychloroquine: risk-of-bias assessments, unadjusted estimates of effect, and overall ratings of strength of evidence. In trials, when hydroxychloroquine is initiated in the outpatient setting, there is low strength of evidence that it reduces hospitalizations (11, 12); in cohort studies, there remains insufficient evidence (5, 8, 33). There is now low strength of evidence that hydroxychloroquine has no positive effect on all-cause mortality and need for mechanical ventilation in both trials and cohort studies. Even with 3 new cohort studies assessing intensive care unit admission (5, 6, 8) and 1 trial (4) and 1 cohort study (9) assessing symptom resolution, there is still insufficient evidence for determining hydroxychloroquine's effect on both outcomes. No new trial or studies assessed any other outcome.

    It is becoming increasingly unlikely that in-hospital use of hydroxychloroquine will yield beneficial effects. The large SOLIDARITY-WHO and ORCHID-NIH trials have been prematurely discontinued, with press releases citing lack of efficacy (36, 37), but preprints or publications of these trials are still not available. However, the outpatient use of hydroxychloroquine is more promising. Trials with some concern of bias (11) and high risk of bias (12) found nonsignificant reductions in hospitalizations, whereas 2 cohort studies with serious risk of bias found significant reductions (5, 8). However, 1 cohort study with critical risk of bias found a significant increase (33). One of these cohort studies (5) found a significant reduction in intensive care unit admission with hydroxychloroquine use, whereas another found a nonsignificant reduction (8), which is in contrast to 2 cohort studies (6, 24) with serious risk of bias assessing inpatient use of hydroxychloroquine where intensive care unit admissions were significantly increased.


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    Vinu Arumugham21 October 2020
    How many will die because the medical community failed to get HCQ dosage and timing right?

    The authors write: "However, the outpatient use of hydroxychloroquine is more promising." 

    Tells you the importance of timing, as many have been pointing out forever.

    Ignore all the cited studies that used HCQ >400 mg/day as those are unacceptable overdoses. Looking at the rest of the studies, the benefit of HCQ is obvious. But 9 months later, the medical community has utterly failed to use this cheap, safe and effective drug correctly to save lives.

    Robert Stine, MD24 October 2020
    When will physicians help patients early in the covid19 viremia?

    Why is Covid19 allowed to go on unabated until the patient needs admission to the hospital?  Treating the patient should begin with prophylaxsis with vitamin D, vitamin C and Zinc since these are low or insufficient in many of the population , especially the  upper age group.   When the patient begins with symptoms the study for Covid19 should be done and as soon as possible get the report and start the patient on antivirals such as hydroxychloraquine, azythromymycin and aspirin to slow the viral replication as soon as possible and the aspirin to reduce the potential for clotting, rather than waitng for the cytokine storm and all the devastation.   CDC says it is up to the care taker and the patient, also the CDC reports it does not endorse any medication for the treatment of Covi19.  Therefore the physician has an obligation to go with the best information that he has and for the patients sake, I would hope that slowing the replication of the virus with what is available would rule the day unless the patient is allergic to those medications or due to cardiac problems they are contraindicated.  Also if there are chest symptoms bronchdilators and steroids should be started and pulse oximetry should be started even at home with levels under 94% or so indicating the need for admission to the hospital for more intensive treatments.


    Robert H Stine, MD