Outcomes of 2111 COVID-19 Hospitalized Patients Treated with Hydroxychloroquine/Azithromycin and Other Regimens in Marseille, France, 2020: A Monocentric Retrospective Analysis

References

• Johns Hopkins University. Coronavirus Resource Center. COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Available from: https://coronavirus.jhu.edu/map.html. Accessed January 17, 2022.
   Google Scholar
• 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):72–73. doi:10.5582/bst.2020.01047
   PubMed Web of Science ®Google Scholar
• 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. doi:10.1038/s41421-020-0156-0
   PubMed Web of Science ®Google Scholar
• Andreani J, Le Bideau M, Duflot I, et al. In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect. Microb Pathog. 2020;145:104228. doi:10.1016/j.micpath.2020.104228
   PubMed Web of Science ®Google Scholar
• Gautret P, Lagier 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;56:105949. doi:10.1016/j.ijantimicag.2020.105949
   PubMed Web of Science ®Google Scholar
• Gautret P, Lagier JC, Parola P, 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: an observational study. Travel Med Infect Dis. 2020;34:101663. doi:10.1016/j.tmaid.2020.101663
   PubMed Web of Science ®Google Scholar
• Million M, Lagier JC, Gautret P, et al. Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: a retrospective analysis of 1061 cases in Marseille, France. Travel Med Infect Dis. 2020;35:101738. doi:10.1016/j.tmaid.2020.101738
   PubMed Web of Science ®Google Scholar
• Cao B, Wang Y, Wen D, et al. A trial of Lopinavir-Ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382:1787–1799. doi:10.1056/NEJMoa2001282
   PubMed Web of Science ®Google Scholar
• Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet Infect Dis. 2020;395:1569–1578.
   Google Scholar
• RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693–704. doi:10.1056/NEJMoa2021436
   PubMed Web of Science ®Google Scholar
• 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):264–268. doi:10.1016/j.bbrc.2004.08.085
   PubMed Web of Science ®Google Scholar
• Vincent MJ, Bergeron E, Benjannet S, 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
   PubMed Web of Science ®Google Scholar
• de Wilde AH, Jochmans D, Posthuma CC, et al. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of middle east respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother. 2014;58(8):4875–4884. doi:10.1128/AAC.03011-14
   PubMed Web of Science ®Google Scholar
• Gordon DE, Jang GM, Bouhaddou M, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020;583(7816):459–468. doi:10.1038/s41586-020-2286-9
   PubMed Web of Science ®Google Scholar
• Gordon DE, Hiatt J, Bouhaddou M, et al. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science. 2020;370(6521):eabe9403. doi:10.1126/science.abe9403
   PubMed Web of Science ®Google Scholar
• Gautret P, Million M, Jarrot PA, et al. Natural history of COVID-19 and therapeutic options. Expert Rev Clin Immunol. 2020;16(12):1159–1184. PMID: 33356661. doi:10.1080/1744666X.2021.1847640
   PubMed Web of Science ®Google Scholar
• Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020;55(5):105938. doi:10.1016/j.ijantimicag.2020.105938
   PubMed Web of Science ®Google Scholar
• Ostrov DA, Bluhm AP, Li D, et al. Highly specific sigma receptor ligands exhibit anti-viral properties in SARS-CoV-2 infected cells. Pathogens. 2021;10(11):1514. doi:10.3390/pathogens10111514
   PubMed Web of Science ®Google Scholar
• Tesei A, Cortesi M, Zamagni A, et al. Sigma receptors as endoplasmic reticulum stress “Gatekeepers” and their modulators as emerging new weapons in the fight against cancer. Front Pharmacol. 2018;9:711. doi:10.3389/fphar.2018.00711
   PubMed Web of Science ®Google Scholar
• RECOVERY Collaborative Group, Horby P, Mafham M, et al. Effect of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020;383:2030. doi:10.1056/NEJMoa2022926
   PubMed Web of Science ®Google Scholar
• Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;369:m1849. doi:10.1136/bmj.m1849
   PubMed Web of Science ®Google Scholar
• Cavalcanti AB, Zampieri FG, Rosa RG, et al. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. N Engl J Med. 2020;383:2041. doi:10.1056/NEJMoa2019014
   PubMed Web of Science ®Google Scholar
• Self WH, Semler MW, Leither LM, et al. Effect of hydroxychloroquine on clinical status at 14 days in hospitalized patients with COVID-19: a randomized clinical trial. JAMA. 2020;324:2165. doi:10.1001/jama.2020.22240
   PubMed Web of Science ®Google Scholar
• Geleris J, Sun Y, Platt J, et al. Observational study of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020;382(25):2411–2418. doi:10.1056/NEJMoa2012410
   PubMed Web of Science ®Google Scholar
• Lagier JC, Raoult D. Whipple’s disease and Tropheryma whipplei infections: when to suspect them and how to diagnose and treat them. Curr Opin Infect Dis. 2018;31(6):463–470. doi:10.1097/QCO.0000000000000489
   PubMed Web of Science ®Google Scholar
• Melenotte C, Million M, Raoult D. New insights in Coxiella burnetii infection: diagnosis and therapeutic update. Expert Rev Anti Infect Ther. 2020;18(1):75–86. PMID: 31782315. doi:10.1080/14787210.2020.1699055
   PubMed Web of Science ®Google Scholar
• Fried MW, Crawford JM, Mospan AR, et al. Patient characteristics and outcomes of 11 721 patients with coronavirus disease 2019 (COVID-19) hospitalized across the United States. Clin Infect Dis. 2021;72(10):e558–e565. doi:10.1093/cid/ciaa1268
   PubMed Web of Science ®Google Scholar
• Skipper CP, Pastick KA, Engen NW, et al. Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial. Ann Intern Med. 2020;173:623e31. doi:10.7326/M20-4207
   Web of Science ®Google Scholar
• Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for covid-19. N Engl J Med. 2020;383:517e25. doi:10.1056/NEJMoa2016638
   Web of Science ®Google Scholar
• Ader F, Peiffer-Smadja N, Poissy J, et al. An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19. Clin Microbiol Infect. 2021;27:1826–1837. doi:10.1016/j.cmi.2021.05.020
   PubMed Web of Science ®Google Scholar
• Sulaiman T, Mohana A, Alawdah L, et al. The effect of early hydroxychloroquine-based therapy in COVID-19 patients in ambulatory care settings: a nationwide prospective cohort study. medRxiv. 2020. doi:10.1101/2020.09.09.20184143
   Google Scholar
• Mokhtari M, Mohraz M, Gouya MM, et al. Clinical outcomes of patients with mild COVID-19 following treatment with hydroxychloroquine in an outpatient setting. Int Immunopharmacol. 2021;96:107636. PMID: 34015598; PMCID: PMC8023208. doi:10.1016/j.intimp.2021.107636
   PubMed Web of Science ®Google Scholar
• Global HCQ/CQ studies. Available from: https://c19study.com. Accessed May 24, 2022.
   Google Scholar
• Lagier JC, Million M, Gautret P, et al. Outcomes of 3737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: a retrospective analysis. Travel Med Infect Dis. 2020;36:101791. doi:10.1016/j.tmaid.2020.101791
   PubMed Web of Science ®Google Scholar
• Million M, Lagier JC, Tissot-DuPont H, et al. Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients. Rev Cardiovasc Med. 2021;22(3):1063–1072. PMID: 34565108. doi:10.31083/j.rcm2203116
   PubMed Web of Science ®Google Scholar
• Carlucci PM, Ahuja T, Petrilli C, Rajagopalan H, Jones S, Rahimian J. Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients. J Med Microbiol. 2020;69(10):1228–1234. PMID: 32930657; PMCID: PMC7660893. doi:10.1099/jmm.0.001250
   PubMed Web of Science ®Google Scholar
• Amrane S, Tissot-DuPont H, Doudier B, et al. 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;36:101632. doi:10.1016/j.tmaid.2020.101632
   PubMed Web of Science ®Google Scholar
• Brouqui P, Drancourt M, Raoult D. On behalf of the ihu task force. COVID-19 management at ihu méditerranée infection: a one-year experience. J Clin Med. 2021;10(13):2881. PMID: 34209634; PMCID: PMC8268723. doi:10.3390/jcm10132881
   PubMed Web of Science ®Google Scholar
• Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245–1251. doi:10.1016/0895-4356(94)90129-5
   PubMed Web of Science ®Google Scholar
• Liao X, Wang B, Kang Y. Novel coronavirus infection during the 2019-2020 epidemic: preparing intensive care units-The experience in Sichuan Province, China. Intensive Care Med. 2020;46:357–360. doi:10.1007/s00134-020-05954-2
   PubMed Web of Science ®Google Scholar
• Edouard S, Colson P, Melenotte C, et al. Evaluating the serological status of COVID-19 patients using an indirect immunofluorescent assay, France. Eur J Clin Microbiol Infect Dis. 2021;40(2):361–371. doi:10.1007/s10096-020-04104-2
   PubMed Web of Science ®Google Scholar
• Wurtz N, Penant G, Jardot P, Duclos N, La Scola B. Culture of SARS-CoV-2 in a panel of laboratory cell lines, permissivity, and differences in growth profile. Eur J Clin Microbiol Infect Dis. 2021;40(3):477–484. PMID: 33389257. doi:10.1007/s10096-020-04106-0
   PubMed Web of Science ®Google Scholar
• Leger T, Jacquier A, Barral PA, et al. Low-dose chest CT for diagnosing and assessing the extent of lung involvement of SARS-CoV-2 pneumonia using a semi quantitative score. PLoS One. 2020;15(11):e0241407. doi:10.1371/journal.pone.0241407
   PubMed Web of Science ®Google Scholar
• Susen S, Tacquard CA, Godon A, Mansour A, Garrigue D, Nguyen P, Godier A,Testa S, Levy JH, Albaladejo P, Gruel Y; GIHP and GFHT. Prevention of thromboticrisk in hospitalized patients with COVID-19 and hemostasis monitoring. CritCare. 2020 Jun 19;24(1):364. doi:10.1186/s13054-020-03000-7. PMID: 32560658;PMCID: PMC7303590.
   Google Scholar
• Lagier JC, Amrane S, Mailhe M, et al. High-flow oxygen therapy in elderly patients infected with SARS-CoV2 with a contraindication for transfer to an intensive care unit: a preliminary report. Int J Infect Dis. 2021;108:1–3. doi:10.1016/j.ijid.2021.03.087
   PubMed Web of Science ®Google Scholar
• Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res. 2011;46(3):399‑42. doi:10.1080/00273171.2011.568786
   Web of Science ®Google Scholar
• Gautret P, Raoult D. Nullane salus extra ecclesiam. New Microbes New Infect. 2020;37:100714. doi:10.1016/j.nmni.2020.100714
   PubMed Web of Science ®Google Scholar
• Anglemyer A, Horvath HT, Bero L. Healthcare outcomes assessed with observational study designs compared with those assessed in randomized trials. Cochrane Database Syst Rev. 2014;(4):MR000034. doi:10.1002/14651858.MR000034.pub2
   PubMed Web of Science ®Google Scholar
• Janket SJ, Ackerson LK, Diamandis E. Simpson’s paradox in proof-of-concept studies. Nat Med. 2019;25:1640. doi:10.1038/s41591-019-0624-y
   PubMed Web of Science ®Google Scholar
• Million M, Dudouet P, Chabrière E, et al. Predictive factors of clinical assays on hydroxychloroquine for COVID-19 mortality during the first year of the pandemic: a meta-synthesis. Afr J Clin Exp Microbiol. 2022;23:1–13. doi:10.4314/ajcem.v23i1.1
   Google Scholar
• Aherfi S, Pradines B, Devaux C, et al. Drug repurposing against SARS-CoV-1, SARS-CoV-2 and MERS-CoV. Future Microbiol. 2021;16:1341–1370. PMID: 34755538; PMCID: PMC8579950. doi:10.2217/fmb-2021-0019
   PubMed Web of Science ®Google Scholar
• Hayashi K. Molnupiravir might be dangerous without clarification of its indications. BMJ. 2022;377:o1030. doi:10.1136/bmj.o1030
   PubMed Web of Science ®Google Scholar
• Colson P, Fournier PE, Chaudet H, et al. Analysis of SARS-CoV-2 variants from 24,181 patients exemplifies the role of globalization and zoonosis in pandemics. Front Microbiol. 2022;12:786233. PMID: 35197938; PMCID: PMC8859183. doi:10.3389/fmicb.2021.786233
   PubMed Web of Science ®Google Scholar
• Feikin DR, Higdon MM, Abu-Raddad LJ, et al. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression. Lancet. 2022;399:924–944. PMID: 35202601. doi:10.1016/S0140-6736(22)00152-0
   PubMed Web of Science ®Google Scholar