Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort study
Min Joo Choi, Minsun Kang, So Youn Shin, Ji Yun Noh, Hee Jin Cheong, Woo Joo Kim, Jaehun Jung, Joon Young Song
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.062
We aimed to compare the antiviral effect of hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/r) in patients with COVID-19. Methods: Nationwide retrospective case-control study was conducted to compare the effect of HCQ and LPV/r on viral shedding duration among patients with mild-to-moderate COVID-19 using the reimbursement data of National Health Insurance Service. After propensity score matching (PSM), multivariate analysis was conducted to determine statistically significant risk factors associated with prolonged viral shedding. Results: Overall, 4197 patients with mild-to-moderate COVID-19 were included. Patients were categorized into three groups: LPV/r (n = 1268), HCQ (n = 801), and standard care without HCQ or LPV/r (controls, n = 2128). The median viral shedding duration was 23 (IQR 17-32), 23 , and 18 (IQR 12-25) days in the LPV/r, HCQ, and control groups, respectively. Even after PSM, the viral shedding duration was not significantly different between LPV/r and HCQ groups: 23 (IQR, 17-32) days versus 23 (IQR, 16-32) days. On multivariate analysis, old age, malignancy, steroid use, and concomitant pneumonia were statistically significant risk factors for prolonged viral shedding.
Conclusion: The viral shedding duration was similar between HCQ and LPV/r treatment groups. There was no benefit in improving viral clearance compared to the control group.
Conflict of interest We declare no conflict of interest.
Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.ijid.2020.10.062.
References
Arshad, Kilgore, Chaudhry, Jacobsen, Wang et al., Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19, Int J Infect Dis
Bai, Yao, Wei, Tian, Jin et al., Presumed asymptomatic carrier transmission of COVID-19, JAMA
Beigel, Manosuthi, Beeler, Bao, Hoppers et al., Effect of oral oseltamivir on virological outcomes in low-risk adults with influenza: a randomized clinical trial, Clin Infect Dis
Borba, Val, Sampaio, Alexandre, Melo et al., Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial, JAMA Netw Open
Cao, Wang, Wen, Liu, Wang et al., A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19, N Engl J Med
Catteau, Dauby, Montourcy, Bottieau, Hautekiet et al., Lowdose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants, Int J Antimicrob Agents
Choi, Kim, Kim, Nam, Sohn, Community treatment centers for isolation of asymptomatic and mildly symptomatic patients with coronavirus disease, South Korea, Emerg Infect Dis 2020b
Choi, Lee, Park, Cho, Kwon et al., Altered COVID-19 receptor ACE2 expression in a higher risk group for cerebrovascular disease and ischemic stroke, Biochem Biophys Res Commun 2020a
Chu, Cheng, Hung, Wong, Chan et al., Role of lopinavir/ ritonavir in the treatment of SARS: initial virological and clinical findings, Thorax
Eslami, Jalili, The role of environmental factors to transmission of SARS-CoV-2 (COVID-19), AMB Express
Freeling, Koehn, Shu, Sun, Ho, Long-acting three-drug combination anti-HIV nanoparticles enhance drug exposure in primate plasma and cells within lymph nodes and blood, AIDS
Fu, Han, Zhu, Bai, Yi et al., Risk factors for viral RNA shedding in COVID-19 patients, Eur Respir J
Gandhi, Yokoe, Havlir, Asymptomatic transmission, the Achilles' heel of current strategies to control Covid-19, N Engl J Med
Gautret, Lagier, Parola, Hoang, Meddeb et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial, Int J Antimicrob Agents
Girolamo, Claver, Olivé, Salazar-Mendiguchía, Manito et al., Dilated cardiomyopathy and hydroxychloroquine-induced phospholipidosis: from curvilinear bodies to clinical suspicion, Rev Esp Cardiol
Huang, Tang, Pang, Li, Ma et al., Treating COVID-19 with chloroquine, J Mol Cell Biol
Hung, Lung, Tso, Liu, Chung et al., Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial, Lancet
Kang, Seong, Choi, Kim, Choe et al., In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses, Korean J Intern Med
Keyaerts, Vijgen, Maes, Neyts, Van Ranst, In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine, Biochem Biophys Res Commun
Kim, Huh, Heo, Joo, Kim et al., Interim guidelines on antiviral therapy for COVID-19, Infect Chemother
Klimke, Hefner, Will, Voss, Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection, Med Hypotheses
Lee, Hong, Kim, Lee, Lee, Clinical course of asymptomatic and mildly symptomatic patients with coronavirus disease admitted to community treatment centers, South Korea, Emerg Infect Dis
Li, Xie, Lin, Cai, Wen et al., An exploratory randomized controlled study on the efficacy and safety of lopinavir/ritonavir or arbidol treating adult patients hospitalized with mild/moderate COVID-19, medRxiv,
doi:10.1101/2020.03.19.20038984v2Madjid, Safavi-Naeini, Solomon, Vardeny, Potential effects of coronaviruses on the cardiovascular system: a review, JAMA Cardiol
Maharaj, Wu, Hornik, Balevic, Hornik et al., Simulated assessment of pharmacokinetically guided dosing for investigational treatments of pediatric patients with coronavirus disease 2019, JAMA Pediatr
Mehra, Ruschitzka, Patel, Retraction-hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis, Lancet
Meschi, Selleri, Lalle, Bordi, Valli et al., Duration of viral shedding in hospitalized patients infected with pandemic H1N1, BMC Infect Dis
Mikami, Miyashita, Yamada, Harrington, Steinberg et al., Risk factors for mortality in patients with COVID-19 in New York City, J Gen Intern Med
Noh, Yoon, Seong, Choi, Sohn et al., Asymptomatic infection and atypical manifestations of COVID-19: comparison of viral shedding duration, J Infect
Nord, Shah, Rinaldi, Weisman, Hydroxychloroquine cardiotoxicity in systemic lupus erythematosus: a report of 2 cases and review of the literature, Semin Arthritis Rheum
Qamar, Alqahtani, Alamri, Chen, Structural basis of SARS-CoV-2 3CL (pro) and anti-COVID-19 drug discovery from medicinal plants, J Pharm Anal
Risk, Treatments (CORIST) Collaboration. Use of hydroxychloroquine in hospitalized COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study, Eur J Intern Med
Roviello, Roviello, Lower COVID-19 mortality in Italian forested areas suggests immunoprotection by mediterranean plants, Environ Chem Lett
Ryu, Ali, Jang, Kim, Cowling, Effect of nonpharmaceutical interventions on transmission of severe acute respiratory syndrome coronavirus 2, South Korea, 2020, Emerg Infect Dis
Sanders, Monogue, Jodlowski, Cutrell, Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review, JAMA
Tang, Cao, Han, Wang, Chen et al., Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
Who, Coronavirus disease (COVID-19) weekly epidemiological update
Yan, Liu, Zhu, Huang, Dan et al., Factors associated with prolonged viral shedding and impact of lopinavir/ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection, Eur Respir J
Zhou, He, Zhang, Xue, Liang et al., Prolonged SARS-CoV-2 viral shedding in patients with COVID-19 was associated with delayed initiation of arbidol treatment: a retrospective cohort study, MedRxiv,
doi:10.1101/2020.06.09.20076646v1
