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The American Journal of Medicine Now Recommends HCQ for COVID19

Written by The American Journal of Medicine

The American Journal of Medicine now (Jan. 2021) now recommends Hydroxychloroquine, Azithromycin, and Zinc  for the treatment of Covid 19 outpatients.

The irony is this is the treatment that former US President, Donald Trump promoted last year. The timing, right after the election, is interesting.

Select extracts are below:


Approximately 9 months of the severe acute respiratory syndrome coronavius-2 (SARS-CoV-2 [COVID-19]) spreading across the globe has led to widespread COVID-19 acute hospitalizations and death.

This article outlines key pathophysiological principles that relate to the patient with early infection treated at home. Therapeutic approaches based on these principles include 1) reduction of reinoculation, 2) combination antiviral therapy, 3) immunomodulation, 4) antiplatelet/antithrombotic therapy, and 5) administration of oxygen, monitoring, and telemedicine. Future randomized trials testing the principles and agents discussed will undoubtedly refine and clarify their individual roles; however, we emphasize the immediate need for management guidance in the setting of widespread hospital resource consumption, morbidity, and mortality.

Zinc Lozenges and Zinc Sulfate

Zinc is a known inhibitor of coronavirus replication. Clinical trials of zinc lozenges in the common cold have demonstrated modest reductions in the duration and or severity of symptoms.18 By extension, this readily available nontoxic therapy could be deployed at the first signs of COVID-19.19 Zinc lozenges can be administered 5 times a day for up to 5 days and extended if needed if symptoms persist. The amount of elemental zinc lozenges is <25% of that in a single 220-mg zinc sulfate daily tablet. This dose of zinc sulfate has been effectively used in combination with antimalarials in early treatment of high-risk outpatients with COVID-19.20


Hydroxychloroquine (HCQ) is an antimalarial/anti-inflammatory drug that impairs endosomal transfer of virions within human cells. HCQ is also a zinc ionophore that conveys zinc intracellularly to block the SARS-CoV-2 RNA-dependent RNA polymerase, which is the core enzyme of the virus replication.21 The currently completed retrospective studies and randomized trials have generally shown these findings: 1) when started late in the hospital course and for short durations of time, antimalarials appear to be ineffective, 2) when started earlier in the hospital course, for progressively longer durations and in outpatients, antimalarials may reduce the progression of disease, prevent hospitalization, and are associated with reduced mortality.22232425 In a retrospective inpatient study of 2541 patients hospitalized with COVID-19, therapy associated with an adjusted reduction in mortality was HCQ alone (hazard ratio [HR] = 0.34, 95% confidence interval [CI] 0.25-0.46, P <0.001) and HCQ with azithromycin (HR = 0.29, 95% CI 0.22-0.40, P <0.001).23 HCQ was approved by the US Food and Drug Administration in 1955, has been used by hundreds of millions of people worldwide since then, is sold over the counter in many countries, and has a well-characterized safety profile that should not raise undue alarm.25,26 Although asymptomatic QT prolongation is a well-recognized and infrequent (<1%) complication of HCQ, it is possible that in the setting of acute illness symptomatic arrhythmias could develop. Data safety and monitoring boards have not declared safety concerns in any clinical trial published to date. Rare patients with a personal or family history of prolonged QT syndrome and those on additional QT prolonging, contraindicated drugs (eg, dofetilide, sotalol) should be treated with caution and a plan to monitor the QTc in the ambulatory setting. A typical HCQ regimen is 200 mg bid for 5 days and extended to 30 days for continued symptoms. A minimal sufficient dose of HCQ should be used, because in excessive doses the drug can interfere with early immune response to the virus.


Azithromycin is a commonly used macrolide antibiotic that has antiviral properties mainly attributed to reduced endosomal transfer of virions as well as established anti-inflammatory effects.27 It has been commonly used in COVID-19 studies initially based on French reports demonstrating markedly reduced durations of viral shedding, fewer hospitalizations, and reduced mortality combination with HCQ as compared to those untreated.28,29 In the large inpatient study (n = 2451) discussed previously, those who received azithromycin alone had an adjusted HR for mortality of 1.05, 95% CI 0.68-1.62, and P = 0.83.23 The combination of HCQ and azithromycin has been used as standard of care in other contexts as a standard of care in more than 300,000 older adults with multiple comorbidities.30 This agent is well-tolerated and like HCQ can prolong the QTc in <1% of patients. The same safety precautions for HCQ listed previously could be extended to azithromycin with or without HCQ. Azithromycin provides additional coverage of bacterial upper respiratory pathogens that could potentially play a role in concurrent or secondary infection. Thus, this agent can serve as a safety net for patients with COVID-19 against clinical failure of the bacterial component of community-acquired pneumonia.31,32 The same safety precautions for HCQ could be extended to azithromycin with or without HCQ. Because both HCQ and azithromycin have small but potentially additive risks of QTc prolongation, patients with known or suspected arrhythmias or taking contraindicated medications or should have more thorough workup (eg, review of baseline electrocardiogram, imaging studies, etc.) before receiving these 2 together. One of many dosing schemes is 250 mg po bid for 5 days and may extend to 30 days for persistent symptoms or evidence of bacterial superinfection.

Read the full study at





  1. There are two anonymous commenters so far saying this article is not true. The links they provided are old. If you click on the link at the bottom of the article, it will take you here:
    The American Journal of Medicine
    Volume 134, Issue 1, January 2021, Pages 16-22

  2. I tried looking up this information and could not find it on the American Journal of Medicine’s site. I VERY MUCH want to see that firsthand myself. There wasn’t a way to read those pages without purchasing the subscription for $316/year.

    Can you provide a link?

  3. that study actually only references another study which actually says the hydroxychloroquine has statistically invalid results…

    Full Study:

    The Studies that Study References (# 22, 23, 24, 25):

    22 –

    “The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). ”

    23 –

    “Overall in-hospital mortality was 18.1% (95% CI:16.6%–19.7%); by treatment: hydroxychloroquine + azithromycin, 157/783 (20.1% [95% CI: 17.3%–23.0%]), hydroxychloroquine alone,162/1202 (13.5% [95% CI: 11.6%–15.5%]), azithromycin alone, 33/147 (22.4% [95% CI: 16.0%–30.1%]), and neither drug, 108/409 (26.4% [95% CI: 22.2%–31.0%]). Primary cause of mortality was respiratory failure(88%)”

    24 –

    “The majority of hospitalized patients received hydroxychloroquine (74.6% of survivors and 71.3% of non-survivors) and azithromycin (67.4% of survivors and 71.3% of non-survivors). Fewer hospitalized patients received other medications such as remdesivir, anakinra, tocilizumab, or sarilumab (Table 2). The majority of ambulatory patients did not receive hydroxychloroquine or azithromycin. Kaplan-Meier estimate showed lower mortality in hospitalized patients who received hydroxychloroquine (log rank P value < 0.001) (Supplementary Figure 4)." (it doesn't actually post anything that indicates that tho – spends most of the time explaining their study which is a big sign it didn't find what they were looking for)

    "Our study has several limitations. First, we have no long-term follow up data for ambulatory and discharged patients; hence, the clinical outcome observed may not be reflective of the true eventual outcome, particularly in the ambulatory group. Second, we have patients who remained hospitalized at the time of our analyses and did not have our outcomes, such as discharge or mortality, and were excluded for our comparison of survivors and non-survivors. Third, due to limitations and local testing policy during the study duration, there are an unknown number of patients who were not diagnosed with COVID-19 because of a lack of severe symptoms and/or hospitalization. Fourth, we are not able to adjust for unknown confounders that may affect the true treatment effect. These limitations prevent any definitive conclusions on the efficacy of any treatment."

    25 –
    (this study doesn't actually look into hydrox's efficacy against Covid-19 specifically)
    "The antimalarial drugs hydroxychloroquine and chloroquine are DMARDs introduced serendipitously…"
    "Although hydroxychloroquine and chloroquine are well-known DMARDs that have been used for the treatment of patients with rheumatic diseases for many years, their exact mechanisms of action are only beginning to be understood. Important to the pharmacokinetic, pharmacodynamics and toxic properties of these drugs is their ability to accumulate in acidic compartments such as lysosomes, as well as inflamed (acidic) tissues. The large volume distribution and long half-lives of these drugs can explain some of their clinical characteristics, such as their slow onset of action and prolonged effects after drug discontinuation. At the cellular level, several direct and indirect mechanisms have been described that account for the immunomodulatory effects of hydroxychloroquine and chloroquine. In particular, inhibition of autophagy prevents immune activation of different cell types, which inhibits cytokine production and modulates CD154 expression on T cells. Renal failure and certain drug interactions (such as interactions with tamoxifen, glycosides, methotrexate and ciclosporin) can influence the pharmacokinetics of hydroxychloroquine and chloroquine and hence require consideration. Although hydroxychloroquine and chloroquine are considered safe to use, these drugs are associated with an increased risk of retinopathy. This increased risk has resulted in ophthalmology guidelines recommending a maximal daily dose of 5.0 mg/kg actual body weight for hydroxychloroquine, which is debated among rheumatologists. Ultimately, drug level monitoring studies are needed to reassess the risk to benefit profile of this dosing strategy. Preclinical studies of compounds targeting lysosome and autophagosome activity are underway and should reveal whether such strategies have value in the treatment of systemic autoimmune diseases."

  4. I’m of the opinion that attacks on HCQ were specifically driven by TDS. I also believe that the treatment can be effective and that doctors should be allowed to prescribe as they see fit. But I see this as an article that was submitted to and published by the Journal, not a recommendation BY the Journal.
    It doesn’t seem to be a study that has specifics as to outcomes from a clinical trial, but a recommendation based on the fact that “gold standard” trials aren’t fast enough to respond to this epidemic; a recommendation I wholeheartedly agree with.

    Am I missing something?

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