Azithromycin and Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19

Main Article Content

Violaine Guérin
Pierre Lévy
Jean-Louis Thomas
Thierry Lardenois
Philippe Lacrosse
Emmanuel Sarrazin
Natacha Regensberg-de Andreis
Martine Wonner

Abstract

Aims: The challenge regarding COVID-19 is to prevent complications and fatal evolution. Azithromycin (AZM) and hydroxychloroquine (HCQ) have proven their antiviral effect in vitro. We aimed to assess the efficacy and safety of AZM alone or combined to HCQ, prescribed, at an early stage, in patients with Covid-19, in a primary care setting.

Study Design: Retrospective observational study.

Place and Duration of Study: Patients have been followed by private practitioners in France, between March and April 2020.

Methodology: Eighty-eight patients received either no or a symptomatic treatment (NST) (n=34) or AZM alone (n=34) or AZM+HCQ (n=20). The efficacy end point was the time to clinical recovery and the safety end point was the occurrence of cardiovascular events. To improve the evidence level, a case-control analysis was performed on a sample of 57 patients (19/group) matched for age, sex and BMI.

Results: The mean (SD) times to achieve clinical recovery were respectively 25.8 days (11.1), 12.9 days (13.4) and 9.2 days (9.3), showing a statistically significant difference between NST and AZM alone (p<0.0001) or AZM+HCQ (p<0.0001). The statistical difference between NST and AZM was confirmed (p=0.0149) as well as the difference with AZM+HCQ (p=0.0002). No cardiac toxicity was recorded in any patient. No statistical difference was shown between AZM and AZM+HCQ groups, although the dual therapy tended to be more effective in patients over 50 years, based on an analysis using the cox model.

Conclusion: AZM and AZM+HCQ favourably impacted the course of the disease. We need trials, ideally prospective/double blind, to show if a statistical difference can be evidenced with a broader group, and clarify the indications of each treatment depending on initial clinical presentation.

Keywords:
COVID-19, SARS-CoV-2, azithromycin, hydroxychloroquine, primary care.

Article Details

How to Cite
Guérin, V., Lévy, P., Thomas, J.-L., Lardenois, T., Lacrosse, P., Sarrazin, E., Andreis, N. R.- de, & Wonner, M. (2020). Azithromycin and Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19. Asian Journal of Medicine and Health, 18(7), 45-55. https://doi.org/10.9734/ajmah/2020/v18i730224
Section
Original Research Article

References

Agrawal S., Goel DA, Gupta N. Emerging prophylaxis strategies against COVID-19. Monaldi Archives for Chest Disease. 2020; 90:1289.

DOI: 10.4081/monaldi.2020.1289

Gao J, Tian Z, Yang X. Break through: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14:72–3.

DOI: 10.5582/bst.2020.01047

Yan Y, Zou Z, Sun Y, Li X, Xu KF, Wei Y, et al. Anti-malaria drug chloroquine is highly effective in treating avian Influenza A HRN1 virus infection in a animal model. Cell Res. 2013;23:300-2.

DOI: 10.1038/cr.2012.165

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.

DOI: 10.1186/1743-422X-2-69

Savarino A, Trani LD, Donatelli I, Cauda R, Cassone A. New insights into the antiviral effects of chloroquine. Lancet Infect Dis. 2006;6(2):67-9.

DOI: 10.1016/S1473-3099(06)70361-9

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-71.

DOI: 10.1038/s41422-020-0282-0

Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun. 2004;323(1):264-8.

DOI: 10.1016/j.bbrc.2004.08.085

Mackenzie AH. Dose refinement in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med. 1983;75(1):40-5.

DOI: 10.1016/0002-9343(83)91269.

Meo SA, Klonoff DC, Akram J. Efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19. Eur Rev Med Pharmacol Sci. 2020;24(8):4539-4547.

DOI: 10.26355/eurrev_202004_21038.

Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, 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.

DOI: 10.1093/cid/ciaa237

Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6:16.

DOI: 10.1038/s41421-020-0156-0

Menzel M, Akbarshahi H, Bjermer L, Uller N. Azithomycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients. Sci Rep. 2016;6:28698.

DOI: 10.1038/srep28698.

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, 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;105949.

DOI:10.1016/j.ijantimicag.2020.105949.

Fox RI. Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum. 1993;23(2 Suppl 1):82-91.

DOI: 10.1016/s0049-0172(10)80012-5

Barbosa R, Souza da Silva R, Teichi Costa F, Machado Castro M, Razuk-Filho A, Benedito Batista P, et al. Empirical treatment with hydroxychloroquine and azithromycin for suspected cases of COVID-19 followed by telemedicine. 2020 - ClinicalTrials.gov Identifier: NCT04348474 (under submission); 2020.

Available:https://pgibertie.files.wordpress.com/2020/04/2020.04.15-journal-manuscript-final.pdf 10/05/2020

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. for the China medical treatment expert group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. New Engl J Med. 2020;382:1708-20.

DOI: 10.1056/NEJMoa2002032

Chen Z, Hu J, Zhang Z, Jiang S, Han S, Zhuang R, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. Med Rxiv 2020;20040758.

DOI: 10.1101/2020.03.22.20040758

Million M, Lagier JC, Gautret P, Colson P, Fournier PE, Amrane S,et al. Early treatment of 1061 COVID-19 patients with hydroxychloroquine and azithromycin, Marseille, France. Travel Med Infect Dis. 2020;101738.

DOI.org/10.1016/j.tmaid.2020.101738

Arshad S, Kilgore P, Chaudhry ZS, Jacobsen G, Wang DD, Huitsing K, et al. Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19. Int J Infect Dis; 2020.

DOI:10.1016/j.ijid.2020.06.099

Lagier JC, Million M, Gautret P, Colson P, Cortaredona S, Giraud-Gatineau A, et al. Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/ azithromycin and other regimens in Marseille, France: A retrospective analysis. Travel Med Infect Dis; 2020.

DOI: 10.1016/j.tmaid.2020.101791.

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Sevestre J, et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: a pilot observational study. Travel Med Infect Dis. 2020;101663.

DOI: 10.1016/j.tmaid.2020.101663.

Kim MS, Jang SW, Parl YK, Kim BO, Hwang TH, Kang SH, et al. Treatment response to hydroxychloroquine, lopinavir-ritonavir, and antibiotics for moderate COVID-19: A first report on the pharmacological outcomes from South Korea. Med Rxiv 2020;20094193.

DOI: 10.1101/2020.05.13.20094193

Garcia-Cremades M, Solans BP, Hughes E, Ernest JP, Wallender E, Aweeka F, et al. Optimizing hydroxychloroquine dosing for patients with COVID‐19: An integrative modeling approach for effective drug repurposing. Clin Pharmacol Ther; 2020.

DOI: 10.1002/cpt.1856

Saleh M, Gabriels J, Chang D, Kim BS, Mansoor A, Mahmood E, et al. The effect of chloroquine, hydroxychloroquine and azithromycin on the corrected QT interval in patients with SARS-CoV-2 infection. Circ Arrhythm Electrophysiol; 2020.

DOI: 10.1161/CIRCEP.120.008662