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How effective are chloroquine, hydroxychloroquine, or azithromycin in COVID-19?

posted on 6:51 PM, April 14, 2020

Clinical trials are underway to study the efficacy of chloroquine, hydroxychloroquine, and azithromycin in humans with COVID-19 compared with controls. Current evidence is limited to in vitro studies, animal studies and case series. A non-randomized, open-label study has evaluated hydroxychloroquine and azithromycin versus controls in COVID-19 infection and demonstrated a significant decrease in the viral load, and duration of carrying the virus. This effect seemed more pronounced when the drug was combined with azithromycin.  (Gautret 2020) This study has been widely criticized as assessing mildly ill (and many asymptomatic) patients, not demonstrating improved clinical outcomes, methodological limitations, and other issues (Int Soc Antimicrob Chemother 2020; Mégarbane 2020).

Chloroquine and hydroxychloroquine have interesting biochemical cellular effects that theoretically, may render them effective against viral infections. Chloroquine and hydroxychloroquine have immunomodulatory effects, accounting for their widespread use in rheumatological illnesses. The suppression of tumor necrosis factor α and interleukin 6, potentially important intermediaries in viral inflammatory response, is a plausible shared mechanism between rheumatological and infectious conditions. In addition, inhibition of viral replication in host cells has been demonstrated in a number of models, and attributed to pH changes in acidic intracellular endosomes and lysosomes evoked by the weak base properties of chloroquine and hydroxychloroquine, thus inhibiting membrane fusion and exocytosis of new virions. There is also in vitro evidence that chloroquine inhibits SARS-Cov-2 cell entry via alteration of ACE2 receptor and spike protein. 

A small Chinese study (Chen 2020) published in March 2020 reported no significant difference in patients’ hospital length of stay and return to afebrile status between the hydroxychloroquine group and a control group. At this time, more research is needed to determine whether the effects of hydroxychloroquine or chloroquine have efficacy in reducing viral load or improving clinical outcomes in COVID-19 illness.  There are a number of clinical trials underway to determine the efficacy of these drugs for use in COVID-19 from which we will be able to determine its clinical outcome benefit.

 

References:

Chen J, Liu D, Liu L, Liu P, Xu Q, et al. "A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19)." Journal of Zhejiang University (Medical Science) 2020:49.1: 0-0. https://doi.org/10.3785/j.issn.1008-9292.2020.03.03

Gautret P, Lagiera JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020. https://doi.org/10.1016/j.ijantimicag.2020.105949  

International Society of Antimicrobial Chemotherapy. Hydroxychloroquine for COVID-19 study did not meet ‘Expected Standard.’ Available at: Retraction Watch Web Portal. https://retractionwatch.com/2020/04/06/hydroxychlorine-covid-19-study-did-not-meet-publishing-societys-expected-standard/. [Accessed April 11, 2020].

Liu, J., Cao, R., Xu, M. et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov 2020;6:16. https://doi.org/10.1038/s41421-020-0156-0

Mégarbane B. Chloroquine and hydroxychloroquine to treat COVID-19: between hope and caution. Clin Toxicol 2020;2:1-2. doi: 10.1080/15563650.2020.1748194.)

Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003;3(11):722–727. https://doi:10.1016/s1473-3099(03)00806-5 

Vincent MJ, Bergeron E, Benjannet S. et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005;2:69. https://doi.org/10.1186/1743-422X-2-69