Chloroquine, hydroxychloroquine, and COVID-19, the Libyan prospective

Chloroquine (CQ) and its structural analog hydroxychloroquine (HCQ) were used as the primary and most successful drugs against malaria. They are also efficacious anti-inflammatory agents for the treatment of rheumatoid arthritis and lupus erythematosus.[[1]]

CQ was reported in 2005 to be effective in preventing the spread of coronavirus (CoV) that caused severe acute respiratory syndrome (SARS) in cell culture.[[2]] It was also found to inhibit HIV replication and glycosylation in CD4 cell lines in a dose-dependent manner.[[3]] This broad-spectrum antiviral activity of CQ was suggested to be due to an increase in the endosomal pH required for virus entry and replication,[[4]] and as well as to the reduced glycosylation of ACE₂ which is believed to be the entry point of COVID-19 into the cell.[[5]]

The interest in HQ and HCQ has been raised again by the emergence of coronavirus disease 2019 (COVID-19) in Wuhan, China, in December 2019. Because of its previously reported effectiveness against SARS CoV, CQ, and HCQ were suggested as a possible treatment of COVID-19-associated pneumonia. The first multicenter clinical trials conducted in China showed that CQ has apparent efficacy and acceptable safety against COVID-19-associated pneumonia.[[5]],[[6]] Another study conducted on 36 patients in France showed that patients treated with HCQ were significantly more likely to test negative for the virus on Day 6 than patients in the control group (70% vs. 12.5% virologically cured, P < 0.001).[[7]] These clinical studies suffer from many limitations; most important is the small number of patients included, which would lower the statistical power. Consequently, many other countries, including Britain, Canada, USA, Germany, and France, are conducting clinical trials on the use of CQ and HCQ in COVID-19 using a large number of patients and well-defined endpoints.[[8]] The results of these studies will be available in a few months. Up-to-date, there are no specific pharmacological treatments for COVID-19. Considering the current Libyan situation, HQ and HCQ, with their known clinical safety profile from long-time clinical use, would provide a rationale choice for patients with COVID-19. However, this off-label use should be done as a clinical trial through a certain framework ethically approved by the ministry of health and as stated by the World Health Organization.[[9]],[[10]]

No conflict of interest has been declared by the author(s).

• References

• 1 Mackenzie AH. Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med 1983;75:40-5.
• 2 Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005;2:69.
• 3 Savarino A, Lucia MB, Rastrelli E, Rutella S, Golotta C, Morra E, et al. Anti-HIV effects of chloroquine: Inhibition of viral particle glycosylation and synergism with protease inhibitors. J Acquir Immune Defic Syndr 2004;35:223-32.
• 4 Savarino A, Shytaj IL. Chloroquine and beyond: Exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS. Retrovirology 2015;12:51.
• 5 Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270-3.
• 6 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;14:72-3.
• 7 Gautret P, Lagier JC, Parola P, Meddeb L, Mailhe M, Doudier B, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrobial Agents 2020 Mar 20:105949.
• 8 Aronson J, Ferner R, DeVito N, Heneghan C. COVID-19 Trials Registered up to 8 March 2020 – An Analysis of 382 Studies; 2020. Available from: https://www.cebm.net/oxford-covid-19/covid-19-registered-trials-and-analysis/. [Last accessed on 2020 Apr 13].
• 9 International Standards for Clinical Trial Registries – Version 3.0. License: CC BY-NC-SA 3.0 IGO. Geneva: World Health Organization; 2018.
• 10 World Health Organization. Monitored Emergency use of Unregistered and Experimental Interventions (MEURI). Available from: http://www.who.int/ethics/publications/infectious-disease-outbreaks/en/. [Last accessed on 2020 Apr 13].

Publication History

Received: 14 April 2020

Accepted: 14 April 2020

Article published online:
14 June 2022