Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

Philippe Gautret, Jean-Christophe Lagier, Philippe Parola, Van Thuan Hoang, Line Meddeb, Morgane Mailhe, Barbara Doudier, Johan Courjon, Valérie Giordanengo, Vera Esteves Vieira, Hervé Tissot Dupont, Stéphane Honoré, Philippe Colson, Eric Chabrière, Bernard La Scola, Jean-Marc Rolain, Philippe Brouqui, Didier Raoult, Philippe Gautret, Jean-Christophe Lagier, Philippe Parola, Van Thuan Hoang, Line Meddeb, Morgane Mailhe, Barbara Doudier, Johan Courjon, Valérie Giordanengo, Vera Esteves Vieira, Hervé Tissot Dupont, Stéphane Honoré, Philippe Colson, Eric Chabrière, Bernard La Scola, Jean-Marc Rolain, Philippe Brouqui, Didier Raoult

Abstract

Background: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads.

Patients and methods: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point.

Results: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.

Conclusion: Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

Keywords: 2019-nCoV; Azithromycin; COVID-19; Clinical trial; Hydroxychloroquine; SARS-CoV-2.

Copyright © 2020. Published by Elsevier B.V.

Figures

Fig. 1
Fig. 1
Percentage of patients with PCR-positive nasopharyngeal samples from inclusion to day6 post-inclusion in COVID-19 patients treated with hydroxychloroquine and in COVID-19 control patients.
Fig. 2
Fig. 2
Percentage of patients with PCR-positive nasopharyngeal samples from inclusion to day6 post-inclusion in COVID-19 patients treated with hydroxychloroquine only, in COVID-19 patients treated with hydroxychloroquine and azithromycin combination, and in COVID-19 control patients.

References

    1. Lai C.C., Shih T.P., Ko W.C., Tang H.J., Hsueh P.R. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents. 2020 Feb 17 doi: 10.1016/j.ijantimicag.2020.105924. [Epub ahead of print]
    1. Wang L.S., Wang Y.R., Ye D.W., Liu Q.Q. A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence”. Int J Antimicrob Agents. 2020 [Epub ahead of print]
    1. WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. []
    1. Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24 doi: 10.1001/jama.2020.2648. [Epub ahead of print]
    1. Santé Publique France. Infection au nouveau Coronavirus (SARS-CoV-2), COVID-19, France et Monde []
    1. Colson P., Rolain J.M., Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents. 2020 Feb 15 doi: 10.1016/j.ijantimicag.2020.105923. [Epub ahead of print]
    1. Colson P., Rolain J.M., Lagier J.C., Brouqui P., Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020 [Epub ahead of print]
    1. Wang M., Cao R., Zhang L., Yang X., Liu J., Xu M. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020:10–0282.
    1. 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 Feb 19 doi: 10.5582/bst.2020.01047. [Epub ahead of print]
    1. Chinese Clinical Trial Registry. .
    1. 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 Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia] Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):185–188. doi: 10.3760/cma.j.issn.1001-0939.2020.03.009.
    1. Biot C., Daher W., Chavain N., Fandeur T., Khalife J., Dive D. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem. 2006;49:2845–2849.
    1. Marmor M.F., Kellner U., Lai T.Y., Melles R.B., Mieler W.F., American Academy of Ophthalmology Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision) Ophthalmology. Jun 2016;123(6):1386–1394. doi: 10.1016/j.ophtha.2016.01.058. Epub 2016 Mar 16.
    1. Yao X., Ye F., Zhang M., Cui C., Huang B., Niu P. 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 Mar 9 doi: 10.1093/cid/ciaa237. pii: ciaa237[Epub ahead of print]
    1. Raoult D., Houpikian P., Tissot Dupont H., Riss J.M., Arditi-Djiane J., Brouqui P. Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern Med. 1999 Jan 25;159(2):167–173.
    1. Lagier J.C., Raoult D. Whipple's disease and Tropheryma whipplei infections: when to suspect them and how to diagnose and treat them. Curr Opin Infect Dis. Dec 2018;31(6):463–470. doi: 10.1097/QCO.0000000000000489. [x] Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):185-188. doi: 10.3760/cma.j.issn.1001-0939.2020.03.009.
    1. Amrane S., Tissot-Dupont H., Doudier B., Eldin C., Hocquart M., Mailhe M. Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infectious diseases referral hospital in Marseille, France, - January 31st to March 1st, 2020: A respiratory virus snapshot. Travel Med Infect Dis. 2020 [Epub ahead of print]
    1. Armstrong N., Richez M., Raoult D., Chabriere E. Simultaneous UHPLC-UV analysis of hydroxychloroquine, minocycline and doxycycline from serum samples for the therapeutic drug monitoring of Q fever and Whipple's disease. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2017;1060:166–172.
    1. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 11 doi: 10.1016/S0140-6736(20)30566-3. pii: S0140-6736(20)30566-3[Epub ahead of print]
    1. Retallack H., Di Lullo E., Arias C., Knopp K.A., Laurie M.T., Sandoval-Espinosa C. Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14408–14413. Epub 2016 Nov 29.
    1. Madrid P.B., Panchal R.G., Warren T.K., Shurtleff A.C., Endsley A.N., Green C.E., Kolokoltsov A. Evaluation of Ebola Virus Inhibitors for Drug Repurposing. ACS Infect Dis. 2015 Jul 10;1(7):317–326. doi: 10.1021/acsinfecdis.5b00030. Epub 2015 May 11.
    1. Bosseboeuf E., Aubry M., Nhan T., de Pina J.J., Rolain J.M., Raoult D. Azithromycin inhibits the replication of Zika virus. J Antivirals Antiretrovirals. 2018;10(1):6–11. doi: 10.4172/1948-5964.1000173.
    1. Bacharier L.B., Guilbert T.W., Mauger D.T., Boehmer S., Beigelman A., Fitzpatrick A.M. Early administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses: A randomized clinical trial. JAMA. 2015 Nov 17;314(19):2034–2044. doi: 10.1001/jama.2015.13896.

Source: PubMed

3
Abonnere