Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19
Bo Yu, Chenze Li, Peng Chen, Ning Zhou, Luyun Wang, Jia Li, Hualiang Jiang, Dao-Wen Wang
Science China Life Sciences, doi:10.1007/s11427-020-1732-2
Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high fatality. The most urgent need is to find effective treatments. We sought to determine whether hydroxychloroquine (HCQ) application may reduce the death risk of critically ill COVID-19 patients. In this retrospective study, we included 550 critically ill COVID-19 patients who need mechanical ventilation in Tongji Hospital, Wuhan, from February 1, 2020 to April 4, 2020. All 550 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them were treated with oral HCQ treatment (200 mg twice a day for 7-10 days) in addition to the basic treatments. Primary endpoint is fatality of patients, and inflammatory cytokine levels were compared between HCQ and non-hydroxychloroquine (NHCQ) treatments. We found that fatalities are 18.8% (9/48) in HCQ group, which is significantly lower than 47.4% (238/502) in the NHCQ group (P<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4-14) days for the HCQ and NHCQ groups, respectively (P<0.05). The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 (8.3-118.9) pg mL -1 at the beginning of the treatment to 5.2 (3.0-23.4) pg mL -1 (P<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. These data demonstrate that addition of HCQ on top of the basic treatments is highly effective in reducing the fatality of critically ill patients of COVID-19 through attenuation of inflammatory cytokine storm. Therefore, HCQ should be prescribed as a part of treatment for critically ill COVID-19 patients, with possible outcome of saving lives.
References
Al-Bari, Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases, J Antimicrob Chemother,
doi:10.1093/jac/dkv018
Bian, Shi, Chen, Cai, Wang et al., Aveolar macrophage activation and cytokine storm in the pathogenesis of severe COVID-19, Immunol Pathol,
doi:10.21203/rs.3.rs-19346/v1
Gautret, Lagier, Parola, Hoang, Meddeb et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Ag,
doi:10.1016/j.ijantimicag.2020.105949
Geleris, Sun, Platt, Zucker, Baldwin et al., Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19
Grein, Ohmagari, Shin, Diaz, Asperges et al., Compassionate use of remdesivir for patients with severe Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2007016
Guan, Ni, Hu, Liang, Ou et al., Clinical characteristics of coronavirus disease 2019 in China, N Engl J Med,
doi:10.1056/NEJMoa2002032
He, Xu, Zhang, Gao, Dykema et al., Identification of a lysosomal pathway that modulates glucocorticoid signaling and the inflammatory response, Sci Signal,
doi:10.1126/scisignal.2001450
Luo, Liu, Qiu, Liu, Liu et al., Tocilizumab treatment in COVID-19: a single center experience, J Med Virol,
doi:10.1002/jmv.25801
Magagnoli, Narendran, Pereira, Cummings, Hardin et al., Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19, MedRxiv,
doi:10.1101/2020.04.16.20065920
Mahevas, Thi Tran, Roumier, Chabrol, Paule et al., No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial, MedRxiv,
doi:10.1101/2020.04.10.20060699
Plantone, Koudriavtseva, Current and future use of chloroquine and hydroxychloroquine in infectious, immune, neoplastic, and neurological diseases: a mini-review, Clin Drug Invest,
doi:10.1007/s40261-018-0656-y
Rainsford, Parke, Clifford-Rashotte, Kean, Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases, Inflammopharmacology,
doi:10.1007/s10787-015-0239-y
Sarzi-Puttini, Giorgi, Sirotti, Marotto, Ardizzone et al., COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome?, Clin Exp Rheumatol
Shiratori, Feinweber, Luckhardt, Wallner, Geisslinger et al., An in vitro test system for compounds that modulate human inflammatory macrophage polarization, Eur J Pharmacol,
doi:10.1016/j.ejphar.2018.06.017
Snijder, Van Der Meer, Zevenhoven-Dobbe, Onderwater, Van Der Meulen et al., Ultrastructure and origin of membrane vesicles associated with the severe acute respiratory syndrome coronavirus replication complex, JVI,
doi:10.1128/JVI.02501-05
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,
doi:10.1093/cid/ciaa237
Zhang, Wu, Li, Zhao, Wang, The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality, Int J Antimicrob Ag,
doi:10.1016/j.ijantimicag.2020.105954