No benefit of hydroxychloroquine on SARS-CoV-2 viral load reduction in non-critical hospitalized patients with COVID-19
Klinger Soares Faíco-Filho, Danielle Dias Conte, Luciano Kleber De Souza Luna, Joseane Mayara Almeida Carvalho, Ana Helena Sitta Perosa, Nancy Bellei
Brazilian Journal of Microbiology, doi:10.1007/s42770-020-00395-x
Background Some studies have shown that hydroxychloroquine (HCQ) is an effective drug in reducing the in vitro replication of SARS-CoV-2. However, the in vivo effect of HCQ still unclear. Objectives This study aims to evaluate viral load clearance in patients with COVID-19 who underwent HCQ treatment in comparison with a control group that did not receive the drug. Study design This prospective study comprised consecutive viral load measurements in patients with COVID-19 hospitalized with a moderate illness. Patients received 400 mg of HCQ every 12 h for 10 days according to the medical decision. Nasal swab samples were collected from patients during early, intermediary, and final clinical stage of COVID-19. Results A total of 155 samples were collected from 66 patients with COVID-19 (60% female), with a median age of 58 years. The viral load between studied groups, assumed as a semiquantitative measure of cycle threshold (Ct) values, presented no significant difference within the three consecutive measures (ΔCt) (p > 0.05). We also analyzed the ΔCt viral load at different intervals of sample collection (Δt < 7; 7-12; and > 12 days) without significant differences at any ΔCt (p > 0.05). Conclusion In this study, we did not observe any change in viral load reduction in vivo with the use of HCQ.
References
Andreani, Bideau, Duflot, Jardot, Rolland et al., In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, Microb Pathog
Cdc, CDC 2019-Novel Coronavirus (2019-nCoV) Realtime RT-PCR diagnostic panel
Gautret, Lagier, Parola, Hoang, Meddeb 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
Geleris, Sun, Platt, Zucker, Baldwin et al., Observational study of hydroxychloroquine in hospitalized patients with Covid-19, N Engl J Med
Lescure, Bouadma, Nguyen, Parisey, Wicky et al., Clinical and virological data of the first cases of COVID-19 in Europe: a case series, Lancet Infect Dis
Lim, Jeon, Shin, Kim, Seong et al., Case of the index patient who caused tertiary transmission of COVID-19 infection in Korea: the application of lopinavir/ritonavir for the treatment of COVID-19 infected pneumonia monitored by quantitative RT-PCR, J Korean Med Sci
Liu, Yan, Wan, Xiang, Le et al., Viral dynamics in mild and severe cases of COVID-19, Lancet Infect Dis
Luo, Liu, Qiu, Liu, Liu et al., Tocilizumab treatment in COVID-19: a single center experience, J Med Virol
Savarino, Trani, Donatelli, Cauda, Cassone, New insights into the antiviral effects of chloroquine, Lancet Infect Dis
Thachil, The versatile heparin in COVID-19, J Thromb Haemost
Torjesen, Covid-19: Hydroxychloroquine does not benefit hospitalised patients, UK trial finds, BMJ: British Medical Journal (Online)
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 2019 (COVID-19)
Xu, Han, Li, Sun, Wang et al., Effective treatment of severe COVID-19 patients with tocilizumab, Proc Natl Acad Sci
Yan, Zou, Sun, Li, Xu et al., Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model, Cell Res
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
Zheng, Yu, Feng, Lou, Zou, Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January, BMJ
Zou, Ruan, Huang, Liang, Huang et al., SARS-CoV-2 viral load in upper respiratory specimens of infected patients, N Engl J Med
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