Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: a population-based cohort study
Sun-Young Jung, Myo-Song Kim, Min-Chul Kim, Seong-Ho Choi, Jin-Won Chung, Sang Tae Choi
Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.12.003
Objectives: Early in vitro studies have suggested that hydroxychloroquine (HCQ) is a potentially useful drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study was conducted to determine whether HCQ had a preventive effect on coronavirus disease 2019 (COVID-19) in rheumatic disease patients who were taking HCQ. Methods: We conducted a population-based retrospective cohort study using the records of the Korean Health Insurance Review and Assessment (HIRA) claim records. The clinical data of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) who were tested for SARS-CoV-2 were investigated. We compared the attack rate of COVID-19 between those who underwent HCQ therapy within 14 days before the test for SARS-CoV-2 (HCQ users) and HCQ non-users. Data were analysed using logistic regression models, c 2 , and Student's t-tests. Results: As of 15th May 2020, 2066 patients with RA or SLE were tested for COVID-19. Among them, 31.4% (649/2066) were treated with HCQ. Most HCQ users (93.7%, 608/649) were taking 200e400 mg/ day recommended for the treatment of rheumatic diseases. The attack rate of COVID-19 in the HCQ users (2.3%, 15/649) did not differ from that in the HCQ non-users (2.2%, 31/1417) (p 0.86). Conclusions: HCQ prophylactic use at a usual dose did not prevent COVID-19 in patients with rheumatic disease.
Author contributions Conceptualization: SYJ, MCK, SHC, JWC and STC. Methodology and software: SYJ and MSK. Validation: SYJ, SHC and STC. Formal analysis: SYJ, SHC and STC. Investigation: SYJ, MSK, SHC and STC. Data curation: SYJ and MSK. Writingdoriginal draft: SYJ, SHC and STC. Writingdreview and editing: SYJ, MSK, MCK, SHC, JWC and STC. Visualization: SYJ, SHC and STC. Project administration: SYJ, MCK, JWC and STC.
Transparency declaration The authors declare that there are no competing interests. Seong-Ho Choi was supported by the National Research Foundation of Korea Grant funded by the Korea Government (Ministry of Science and ICT) (2019R1C1C1006417). Sang Tae Choi was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Republic of Korea (2018R1D1A1B07049248).
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.cmi.2020.12.003.
References
Abella, Jolkovsky, Biney, Uspal, Hyman et al., Efficacy and safety of hydroxychloroquine vs placebo for pre-exposure SARS-CoV-2 prophylaxis among health care workers: a Randomized clinical trial, JAMA Intern Med,
doi:10.1001/jamainternmed.2020.6319Austin, An introduction to propensity score methods for reducing the effects of confounding in observational studies, Multivariate Behav Res
Bae, Lim, Han, Jung, Choi et al., Trend of prevalence and incidence of systemic lupus erythematosus in South Korea, 2005 to 2015: a nationwide population-based study, Korean J Intern Med
Boulware, Pullen, Bangdiwala, Pastick, Lofgren et al., A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19, N Engl J Med
Charlson, Pompei, Ales, Mackenzie, A new method of classifying prognostic comorbidity in longitudinal studies: development and validation, J Chronic Dis
Chen, Hu, Zhang, Jiang, Han et al., Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial
Choi, Han, Im, Baek, The prevalence and clinical features of musculoskeletal diseases in Incheon: results from chronic disease management surveys, J Rheum Dis
Fiolet, Guihur, Rebeaud, Mulot, Peiffer-Smadja et al., Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis, Clin Microbiol Infect
Gao, Tian, Yang, Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies, Biosci Trends
Geleris, Sun, Platt, Zucker, Baldwin et al., Observational study of hydroxychloroquine in hospitalized patients with Covid-19, N Engl J Med
Hoffmann, Mosbauer, Hofmann-Winkler, Kaul, Kleine-Weber et al., Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2, Nature
Konig, Kim, Scheetz, Graef, Liew et al., Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19, Ann Rheum Dis
Lê, Peiffer-Smadja, Guedj, Neant, Mentre et al., Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trialdauthors' response, J Antimicrob Chemother
Mahevas, Tran, Roumier, Chabrol, Paule et al., Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data, BMJ
Maisonnasse, Guedj, Contreras, Behillil, Solas et al., Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates, Nature
Marmor, Kellner, Lai, Melles, Mieler, American Academy of Ophthalmology. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 Revision), Ophthalmology
Mathian, Mahevas, Rohmer, Roumier, Cohen-Aubart et al., Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine, Ann Rheum Dis
Pastick, Okafor, Wang, Lofgren, Skipper et al., Review: hydroxychloroquine and chloroquine for treatment of SARS-CoV-2 (COVID-19), Open Forum Infect Dis
Petri, Elkhalifa, Li, Magder, Goldman, Hydroxychloroquine blood levels predict hydroxychloroquine retinopathy, Arthritis Rheumatol
Smolen, Landewe, Bijlsma, Burmester, Dougados et al., EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update, Ann Rheum Dis
Tang, Cao, Han, Wang, Chen et al., Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ
Tang, Comish, Kang, The hallmarks of COVID-19 disease, PLoS Pathog
Vincent, Bergeron, Benjannet, Erickson, Rollin et al., Chloroquine is a potent inhibitor of SARS coronavirus infection and spread, Virol J
Wallace, Tse, Hanrahan, Davies, Petri, Hydroxychloroquine usage in US patients, their experiences of tolerability and adherence, and implications for treatment: survey results from 3127 patients with SLE conducted by the Lupus Foundation of America, Lupus Sci Med
Won, Cho, Kim, Han, Lee et al., Update on the prevalence and incidence of rheumatoid arthritis in Korea and an analysis of medical care and drug utilization, Rheumatol Int
Yao, Ye, Zhang, Cui, Huang 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
Yu, Li, Chen, Zhou, Wang et al., Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19, Sci China Life Sci
