Global Health Outbreaks and Updates

Chloroquine Myths and Facts in a Time of COVID-19

There is a lot of hope and expectation being laid at the feet of chloroquine for use in SARS-CoV-2 and COVID19. This article will attempt to aggregate current understandings and information, examine a few trials that have been published already and look ahead at current research.


Chloroquine (CQ) Background[i]

  • To understand chloroquine, we must go back to its precursor molecule Quinine
  • Quinine traces is roots back to the bark of a tree native to South America
  • The bark was named Cinchona by Linneaus in 1742
  • In 1820, two French chemists isolated quinine from the Cinchona bark
  • Quinine became a recognized treatment for intermittent fever
  • German scientists began researching a substitute to quinine and developed chloroquine and 3-methly-chloroquine in 1934

Chloroquine phosphate current uses

  • Malaria prophylaxis (dose 300mg, by mouth, once per week)
  • t (dose (600mg by mouth x 1 then 300mg X 1 at 6 hours, 24 and 48 hours)
  • Anti-ameba (dose 600mg by mouth for two days then 300mg per day x 2-3 weeks)

Chloroquine Pharmacology

  • Partially metabolized by the liver; CYP450: 2D6 inhibitor
  • Excreted in the urine 95% and feces with a half life of 1-2 months
  • Mechanism of action: unknown but binds hemazoin in parasitized erythrocytes, causing cell lysis
  • Renal dosing for Creatinine clearance <10 is to decrease dose by 50%

versus Hydroxychloroquine (HCQ)[ii]

  • Hydroxychloroquine sulfate is a derivative of CQ
  • HCQ was first synthesized in 1946 by adding a hydroxyl group to CQ
  • HCQ is demonstrated to be 40% less toxic than CQ in animal models[iii]

Hydroxychloroquine current uses

  • Malaria prophylaxis (400mg PO q week)
  • Malaria treatment (800mg PO x 1 then 400mg PO x 1 at 6 hours, 24 and 48 hours)
  • Systemic Lupus Erythematosus (200-400mg/day PO divided qday to BID)
  • Rheumatoid arthritis (200-400mg/day PO divided qday to BID)


Chloroquine and Hydroxychloroquine in SARS-CoV-2 and COVID19 Proposed Mechanism of Action[iv]

  • Chloroquine is known to block virus infection by increasing endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors of SARS-CoV
  • Appears to interfere with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2. This may negatively influence the virus-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting in the inhibition of infection and spread of SARS CoV at clinically admissible concentrations


Previous Studies and Trials

  • Perhaps the most readily cited communication of CQ and HCQ was detailed by Dr Raoult et al in a communication to The International Journal of Antimicrobial Agents[v]
    • 600mg of HCQ daily (no comment on duration of treatment)
    • + / – addition of azithromycin (this only serves to confound their report)
    • Presence of the virus at day six was considered the endpoint
    • 20 cases were treated and showed a significant reduction in viral loads at day 6 as compared to controls
    • Addition of azithromycin was also shown to be significantly more efficient for virus elimination
  • A letter to the Editor of Nature was cited prominently in the above study[vi]
    • The letter explored previous treatments versus SARS and MER CoV
    • Ribavirin, Favipiravir, Nafamostat, Remdesivir and Chloroquine were discussed
    • “Besides its antiviral activity, chloroquine has an immune-modulating activity, which may synergistically enhance its antiviral effect in vivo”
    • The authors concluded that Remdesivir and Chloroquine were effective
  • The Journal of Critical Care published a literature review on CQ in COVID19[vii]
    • Six articles were reviewed (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents)
    • 23 currently ongoing trials in China (at time of writing) were reviewed
    • Their conclusion was “There is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clinical use for other indications to justify clinical research on chloroquine in patients with COVID-19. However, clinical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial as stated by the World Health Organization”
    • This review cited previous literature reviews and sources from China[viii]
      • The drug is recommended to be included in the next version of the Guidelines for the Prevention, Diagnosis, and Treatment of Pneumonia Caused by COVID-19 issued by the National Health Commission of the People’s Republic of China for treatment of COVID-19 infection in larger populations in the future.
    • The review by Gao, Tian and Yang aggregated several prior studies
      • A listing of current clinical trials in China as listed by the above review can be found here[ix] and was viewed with help of google translate
      • Of interest were several older papers that explored CQ efficacy on viruses
        • Lancet Infect Dis. 2003 Nov;3(11):722-7. Effects of chloroquine on viral infections: an old drug against today’s diseases? Savarino A1, Boelaert JR, Cassone A, Majori G, Cauda R.
        • Yan, Y., Zou, Z., Sun, Y. et al.Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model. Cell Res 23, 300–302 (2013)


Up-coming clinical trials

  • Chloroquine Prevention of Coronavirus Disease (COVID-19) in the Healthcare Setting (COPCOV)[x] double-blind, randomised, placebo-controlled trial that will be conducted in health care settings average of 200 participants per site in 50 sites
  • Explores high-risk healthcare workers using CQ as a prophylaxis
  • A loading dose of 10mg base/kg, followed by 150 mg daily (250mg chloroquine phosphate salt) which will be taken for 3 months or until they are diagnosed with COVID-19.
  • Norway is conducting a trial in hospitalized patients[xi]
    • 202 participants
    • 400 mg hydroxychloroquine sulphate (equalling 310 mg base) twice daily for seven days
  • World Health Organization SOLIDARITY trial[xii]
    • Balancing scientific rigor and speed are concerns here
    • This is not a randomized trial
    • The drugs trialed include
      • Remdesivir
      • CQ and HCQ
      • Ritonavir/lopinavir
      • Ritonavir/lopinavir and interferon beta


Putting it into Practice

  • There are anecdotal reports of CQ and HCQ being effective against SARS CoV-2 and COVID19
  • Currently there are multiple trials, globally, to explore efficacy
  • What are we, as clinicians willing to accept as “quality evidence” in this rapidly evolving time
  • The CDC has information on dosing listed as the following[xiii]:
    • There are no currently available data from Randomized Clinical Trials (RCTs) to inform clinical guidance on the use, dosing, or duration of hydroxychloroquine for prophylaxis or treatment of SARS-CoV-2 infection.  Although optimal dosing and duration of hydroxychloroquine for treatment of COVID-19 are unknown, some U.S. clinicians have reported anecdotally different hydroxychloroquine dosing such as: 400mg BID on day one, then daily for 5 days; 400 mg BID on day one, then 200mg BID for 4 days; 600 mg BID on day one, then 400mg daily on days 2-5.



References & Links



[iii] McChesney, E. W. Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate. Am. J. Med. 75, 11–18 (1983)




[viii] J. Gao, Z. Tian, X. Yang Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies







  1. Great analysis! Thank you:

    Please consider also the following:

    15 February 2020 Conference on early results of studies of Chloroquine as treatment for Covid 19 reporting results of trial on 100 patients. (Not randomised or blind.) Conference participants including experts from government and regulatory authorities and organizers of clinical trials reached an agreement that chloroquine phosphate has potent activity against COVID-19.

    17 February 2020 – See
    Sun Yanrong, deputy head of the China National Center for Biotechnology Development under the Ministry of Science and Technology (MOST) announces that experts have “unanimously” suggested the drug be included in the next version of the treatment guidelines and that further clinical trials must begin immediately.

    17 February 2020 the official new Diagnosis And Treatment Protocol for Covid-19 is published by China CDC at
    It includes under Treatment recommendation (Part 4 at page 7): “Chloroquine phosphate (for adults (18-65 years old): if weight >50kg, 500 mg each time, twice a day for 7 days; if weight <50kg, 500 mg each time and twice a day on the first and second days, 500 mg each time and once a day for the third to seventh days) "

    19 February Dr Gao publishes letter in Bio Science Trends reporting the above:
    "In the early in vitro studies, chloroquine was found to block COVID-19 infection at low-micromolar concentration, with a half-maximal effective concentration (EC50) of 1.13 μM and a half-cytotoxic concentration (CC50) greater than 100 μM (4). A number of subsequent clinical trials (ChiCTR2000029939, ChiCTR2000029935, ChiCTR2000029899, ChiCTR2000029898, ChiCTR2000029868, ChiCTR2000029837, ChiCTR2000029826, ChiCTR2000029803, ChiCTR2000029762, ChiCTR2000029761, ChiCTR2000029760, ChiCTR2000029740, ChiCTR2000029609, ChiCTR2000029559, and ChiCTR2000029542) have been quickly conducted in China to test the efficacy and safety of chloroquine or hydroxychloroquine in the treatment of COVID-19 associated pneumonia in more than 10 hospitals in Wuhan, Jingzhou, Guangzhou, Beijing, Shanghai, Chongqing, and Ningbo (5). Thus far, results from more than 100 patients have demonstrated that chloroquine phosphate is superior to the control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus-negative conversion, and shortening the disease course according to the news briefing. Severe adverse reactions to chloroquine phosphate were not noted in the aforementioned patients."

    28 February WHO Joint Mission Report records the use of Chloroquine in Covid-19 treatment in China – see p.33:

    3 March 7 Day Randomised trial of 30 patients (15 of whom acted as control) using 400mg HQ daily is inconclusive showing no difference with control group See Journal of Zhejiang University at

    4 March International Journal of Antimicrobial Agents publishes a paper by Raoualt setting out his experience and reasoning.
    Chloroquine and hydroxychloroquine as available weapons to fight COVID-19

    19 March Trial announced in Queensland Further trials announced in Australia

    26 March mass trial in New York announced

Leave a Reply

%d bloggers like this: