The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort
Abdulkarim Abdulrahman, Islam Alsayed, Marwa Almadhi, Jumana Alarayed, Sara Jaafar Mohammed, Aesha Khalid Sharif, Khadija Alansari, Abdulla I Alawadhi, Manaf Alqahtani
doi:10.1101/2020.11.25.20234914
Background Hydroxychloroquine is an antimalarial drug that received worldwide news and media attention in the treatment of COVID-19 patients. This drug was used based on its antimicrobial and antiviral properties despite lack of definite evidence of clinical efficacy. In this study, we aim to assess the efficacy and safety of using Hydroxychloroquine in treatment of COVID-19 patients who are admitted in acute care hospitals in Bahrain.
Methodology We conducted retrospective cohort study on a random sample of admitted COVID19 patients between 24 February and 31 July 2020. The study was conducted in four acute care COVID19 hospitals in Bahrain. Data was extracted from the medical records. The primary endpoint was the requirement of non-invasive ventilation, intubation or death. Secondary endpoint was length of hospitalization for survivors. Three methods of analysis were used to control for confounding factors: logistic multivariate regression, propensity score adjusted regression and matched propensity score analysis.
Results A random sample of 1571 patients were included, 440 of which received HCQ (treatment group) and 1131 did not receive it (control group). Our results showed that HCQ did not have a significant effect on primary outcomes due to COVID-19 infection when compared to controls after adjusting for confounders (OR 1.43 95% CI 0.85 to 2.37, P value=0.17). Co-administration of azithromycin had no effect on primary outcomes (OR 2.7 95% CI 0.82 to 8.85 P value =0.10). HCQ was found to be associated with increased risk of hypoglycemia (OR 10.9 95% CI 1.72 -69.49, P value =0.011) and diarrhea(OR 2.8, 95% CI 1.4-5.5, P value =0.003), but not QT prolongation(OR=1.92, 95% CI 0.95-3.9, P value =0.06) or cardiac arrhythmia.(OR=1.06, 95% CI 0.55-2.05, P value =0.85).
Conclusion Our results showed no significant beneficial effect of using hydroxychloroquine on the outcome of COVID-19 patients. Moreover, the risk of hypoglycemia due to hydroxychloroquine would possess a significant risk for out of hospital use.
Declarations
References
Agstam, Yadav, Kumar, Gupta, Hydroxychloroquine and QTc prolongation in patients with COVID-19: A systematic review and meta-analysis, Indian Pacing Electrophysiol J
Almazrou, Almalki, Alanazi, Alqahtani, Alghamd, Comparing the impact of Hydroxychloroquine based regimens and standard treatment on COVID-19 patient outcomes: A retrospective cohort study, Saudi Pharm J
Andreani, Bideau, Duflot, Jardot, Rolland et al., In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, Microb Pathog
Arrayed, Campaign to control genetic blood diseases in Bahrain, Community Genet
Bacharier, Guilbert, Mauger, Boehmer, Beigelman et al., Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial, JAMA
Beauverd, Adam, Assouline, Samii, COVID-19 infection and treatment with hydroxychloroquine cause severe haemolysis crisis in a patient with glucose-6-phosphate dehydrogenase deficiency, Eur J Haematol
Bhargava, Fukushima, Levine, Zhao, Tanveer et al., Predictors for Severe COVID-19 Infection, Clin Infect Dis
Blazar, Whitley, Kitabchi, Tsai, Santiago et al., In vivo chloroquine-induced inhibition of insulin degradation in a diabetic patient with severe insulin resistance, Diabetes
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
Capel, Herring, Kalla, Yavari, Mirams et al., Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential, Heart Rhythm
Cavalcanti, Zampieri, Rosa, Azevedo, Veiga et al., Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19, N Engl J Med
Chen, Dai, Mo, Li, Ma et al., Clinical Characteristics and Outcomes of Older Patients with Coronavirus Disease 2019 (COVID-19) in Wuhan, China: A Single-Centered, Retrospective Study, J Gerontol A Biol Sci Med Sci
Chen, Wu, Chen, Yang, Chen, Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study, BMJ
Cheng, Luo, Wang, Zhang, Wang et al., Kidney disease is associated with in-hospital death of patients with COVID-19, Kidney Int
Costedoat-Chalumeau, Hulot, Amoura, Leroux, Lechat et al., Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases, Rheumatology
Cucinotta, Vanelli, WHO Declares COVID-19 a Pandemic, Acta Biomed
Feng, Yu, Yao, Luo, Zhou et al., Early prediction of disease progression in COVID-19 pneumonia patients with chest CT and clinical characteristics, Nat Commun
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 Agents
Geleris, Sun, Platt, Zucker, Baldwin et al., Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19, N Engl J Med
Horby, Mafham, Linsell, Bell, Staplin et al., Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19, N Engl J Med
Huang, Wang, Li, Ren, Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet
Kalligeros, Shehadeh, Atalla, Mylona, Aung et al., Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study, J Glob Antimicrob Resist
Lenzer, Covid-19: US gives emergency approval to hydroxychloroquine despite lack of evidence, BMJ
Li, Chen, Nie, Ma, Guo et al., Identification of Symptoms Prognostic of COVID-19 Severity: Multivariate Data Analysis of a Case Series in Henan Province, J Med Internet Res
Liu, Cao, Xu, Wang, Zhang et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discov
Liu, Mao, Liang, Yang, Lu et al., Association between age and clinical characteristics and outcomes of COVID-19, Eur Respir J
Lofgren, Nicol, Bangdiwala, Pastick, Okafor et al., Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19
Marmor, Kellner, Lai, Melles, Mieler et al., Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision), Ophthalmology
Mehra, Desai, Ruschitzka, Patel, RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis, Lancet
Mingo, Simmons, Shoemaker, Nelson, Schornberg et al., Ebola virus and severe acute respiratory syndrome coronavirus display late cell entry kinetics: evidence that transport to NPC1+ endolysosomes is a rate-defining step, J Virol
Nabil, Uto, Elshemy, Soliman, Hassan et al., Current coronavirus (SARS-CoV-2) epidemiological, diagnostic and therapeutic approaches: An updated review until June 2020, EXCLI J
Rees, Smith, Effect of chloroquine on insulin and glucose homeostasis in normal subjects and patients with non-insulin dependent diabetes mellitus, Br Med J (Clin Res Ed)
Rismanbaf, Zarei, Liver and Kidney Injuries in COVID-19 and Their Effects on Drug Therapy; a Letter to Editor, Arch Acad Emerg Med
Romero Starke, Petereit-Haack, Schubert, Kämpf, Schliebner et al., The Age-Related Risk of Severe Outcomes Due to COVID-19 Infection: A Rapid Review, Meta-Analysis, and Meta-Regression, Int J Environ Res Public Health
Rosenberg, Dufort, Udo, Wilberschied, Kumar et al., Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State, JAMA
Schrezenmeier, Dörner, Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology, Nat Rev Rheumatol
Self, Semler, Leither, Casey, Angus et al., Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial, JAMA
Silva, Mariz, Rocha, Oliveira, Dantas et al., Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients, Clinics
Tang, Cao, Han, Wang, Chen et al., Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ
Uzelac, Iravanian, Ashikaga, Bhatia, Herndon et al., Fatal arrhythmias: Another reason why doctors remain cautious about chloroquine/hydroxychloroquine for treating COVID-19, Heart Rhythm
Who, Noncommunicable diseases country profiles
Who, Solidarity" clinical trial for COVID-19 treatments
Who, WHO Coronavirus Disease (COVID-19) Dashboard
Zhang, Shi, Wang, Liver injury in COVID-19: management and challenges
Zhou, Dai, Tong, COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression, J Antimicrob Chemother
Zhou, Yang, Dong, Lv, Shen, Comorbidities and the risk of severe or fatal outcomes associated with coronavirus disease 2019: A systematic review and meta-analysis, Int J Infect Dis
