LETTER


Chloroquine Phosphate is not Proved to be an Effective Treatment for Coronavirus: A Meta-analysis of Clinical Trials



Mohamed F. Allam1, *
1 Faculty of Medicine, Ain Shams University, Family Medicine, Cairo, Abbasia, Egypt


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Creative Commons License
© 2020 Mohamed F. Allam.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Faculty of Medicine, Ain Shams University, Family Medicine, Cairo, Abbasia; Tel: +2 011 43 55 99 46; E-mail: mailto:farouk.allam@med.asu.edu.eg




On 31 December 2019, the Chinese health authorities declared an outbreak of a novel coronavirus (COVID-19), which rapidly extended in many countries. On 11 March 2020, the World Health Organization (WHO), after reported outbreaks in more than 110 countries, declaring COVID-19 as a pandemic [1].

Currently, vaccines and antivirals for COVID-19 are being investigated around the world [2]. Several reports claimed that chloroquine phosphate (chloroquine) could be an effective treatment for patients with COVID-19, by inhibiting viral entry into the host cells [3].

The aim of this meta-analysis is to investigate the effectiveness of chloroquine in treating coronavirus, in general not only COVID-19, by pooling the results of Randomized Controlled Clinical Trials (RCTs).

A comprehensive PubMed search (from July 1966 until 15 March 2020) was conducted using a variety of Medical Subjects Headings and free text words: coronavirus and chloroquine and/or clinical trials. Additional searches were conducted in Cochrane Central Register of Controlled Trials, Trip Database, Science Direct, and previously published reviews. No attempts were made to locate any unpublished studies.

Only 28 publications were identified, none of which was a RCT. Identified studies were published between 1987 and 2020.

Of these 28 publications, 7 were published in 2020 and discussed the effectiveness of chloroquine against COVID-19 [4-10]:

  1. Multicenter clinical trials currently conducted in China with only promising results that chloroquine could be effective for treating COVID-19 (2 publications).
  2. Expert consensus on the usage of chloroquine for treating COVID-19 associated to pneumonia (1 publication).
  3. Reviews and recommendations in the light of old experiments (2 publications).
  4. in vitro experiments, with one comparing chloroquine with hydroxychloroquine (2 publications).

Table 1 summarizes the types of studies and the results of each.

Table 1. Summary of published studies in 2020 evaluating the effectiveness of chloroquine for treatment of COVID-19.
References Type of Study Results
Expert consensus [4] Expert consensus on the effectiveness of chloroquine for treatment of COVID-19 pneumonia. Chloroquine improves outcome and shortens hospital stay.
Yao et al. [5] In vitro Antiviral Activity of Hydroxychloroquine against Severe Acute Respiratory Syndrome COVID-19. Hydroxychloroquine was found to be more potent than chloroquine to inhibit COVID-19.
Dong et al. [6] Undergoing clinical studies to test the efficacy and safety in the treatment of COVID-19. Tested drugs include chloroquine, arbidol, remdesivir, and favipiravir.
Touret and de Lamballerie [7] Review and recommendations for the use of chloroquine in treating COVID-19. Information in light to previous experiments. Chloroquine could be effective in treating COVID-19.
Gao et al. [8] Multicenter clinical trials currently conducted in China to evaluate the efficacy of chloroquine in treating COVID-19 associated pneumonia. Chloroquine has apparent efficacy and acceptable safety against COVID-19 associated pneumonia. Recommended to be included in the Guidelines.
Colson et al. [9] Review and recommendations. Usage of chloroquine in treating COVID-19. Chloroquine could be used for treating COVID-19.
Wang et al. [10] in vitro usage of remdesivir and chloroquine to inhibit COVID-19. Remdesivir and chloroquine could inhibit COVID-19.

Till 15 March 2020, the final results of the clinical trials currently conducted in China were not available, only the preliminary results reported promising effectiveness of chloroquine against COVID-19 [11].

The other 21 publications not related to COVID-19 were distributed as follows; in vitro experiments (11 publications), in vivo experiments (5 publications), both in vitro and in vitro experiments (1 publication), and reviews (4 publications). Only 2 in vitro experiments were about Middle East Respiratory Syndrome coronavirus (MERS-CoV) and 5 publications (2 in vitro experiments, 2 reviews, and 1 in vivo experiment) were about Severe Acute Respiratory Syndrome coronavirus (SARS-CoV).

CONCLUSION

In conclusion, this meta-analysis could not prove that chloroquine is an effective treatment against coronavirus in general or COVID-19 in particular. Expanded access trials should be encouraged especially stating that chloroquine is available, cheap and relatively safe drug.

CONFLICT OF INTEREST

The author declares no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

[1] The World Health Organization. Rolling updates on coronavirus disease (COVID-19). Updated 11 March 2020. Available at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen
[2] Fauci AS, Lane HC, Redfield RR. Covid-19 - Navigating the uncharted. N Engl J Med 2020; 382(13): 1268-9.
[3] Harrison C. Coronavirus puts drug repurposing on the fast track. Nat Biotechnol 2020; 38(4): 379-81.
[4] Jie Z, He H, Xi H, Zhi Z. Multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia 2020; 43(3): 185-8.
[5] Yao X, Ye F, Zhang M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020.ciaa237
[6] Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther 2020; 14(1): 58-60.
[7] Touret F, de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res 2020; 177104762
[8] Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020; 14(1): 72-3.
[9] Colson P, Rolain JM, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents 2020; 55(3)105923
[10] Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30(3): 269-71.
[11] Chinese Clinical Trial Registry. Available at: http://www.chictr.org.cn/searchproj.aspx?title=%E6%B0%AF%E5%96%B9&officialname=&subjectid=&secondaryid=&applier=&studyleader=&ethicalcommitteesanction=&sponsor=&studyailment=&studyailmentcode=&studytype=0&studystage=0&studydesign=0&minstudyexecutetime=&maxstudyexecutetime=&recruitmentstatus=0&gender=0&agreetosign=&secsponsor=&regno=&regstatus=0&country=&province=&city=&institution=&institutionlevel=&measure=&intercode=&sourceofspends=&createyear=0&isuploadrf=&whetherpublic=&btngo=btn&verifycode=&page=1