Comparing the impact of Hydroxychloroquine based regimens and standard treatment on COVID-19 patient outcomes: A retrospective cohort study
Saja H Almazrou, Ziyad S Almalki, Abdullah S Alanazi, Abdulhadi M Alqahtani, Saleh M Alghamd
Saudi Pharmaceutical Journal, doi:10.1016/j.jsps.2020.09.019
Background: Pharmacological treatments including antivirals (Lopinavir/Ritonavir), Immuno-modulatory and anti-inflammatory drugs including, Tocilizumab and Hydroxychloroquine (HCQ) has been widely investigated as a treatment for COVID-19. Despite the ongoing controversies, HCQ was recommended for managing mild to moderate cases in Saudi Arabia . However, to our knowledge, no previous studies have been conducted in Saudi Arabia to assess its effectiveness. Methods: A hospital-based retrospective cohort study involving 161 patients with COVID-19 was conducted from March 1 to May 20, 2020. The study was conducted at Prince Mohammed bin Abdul Aziz Hospital (PMAH). The population included hospitalized adults (age ! 18 years) with laboratory-confirmed COVID-19. Each eligible patient was followed from the time of admission until the time of discharge. Patients were classified into two groups according to treatment type: in the HCQ group, patients were treated with HCQ; in the SC group, patients were treated with other antiviral or antibacterial treatments according to Ministry of Health (MOH) protocols. The outcomes were hospitalization days, ICU admission, and the need for mechanical ventilation. We estimated the differences in hospital length of stay and time in the ICU between the HCQ group and the standard care (SC) group using a multivariate generalized linear regression. The differences in ICU admission and mechanical ventilation were compared via logistic regression. All models were adjusted for age and gender variables. Results: A total of 161 patients fulfilled the inclusion criteria. Approximately 59% (n = 95) received HCQbased treatment, and 41% (n = 66) received SC. Length of hospital stay and time in ICU in for patients who received HCQ based treatment was shorter than those who received SC. Similarly, there was less need for ICU admission and mechanical ventilation among patients who received HCQ based treatment compared with SC, (8.6% vs. 10.7 and 3.1% vs. 9.1%). However, the regression analysis showed no significant difference between the two groups in terms of patient outcomes. Conclusion: HCQ had a modest effect on hospital length stay and days in ICU compared with SC. However, these results need to be interpreted with caution. Larger observational studies and
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References
Almalki, Fitzgerald, Clark, Health care system in Saudi Arabia: an overview, East Mediterr Health J
Alsofayan, Althunayyan, Khan, Hakawi, Assiri, Clinical characteristics of COVID-19 in Saudi Arabia: A national retrospective study, Journal of Infection and Public Health
Bartsch, Ferguson, Mckinnell, O'shea, Wedlock et al., The Potential Health Care Costs And Resource Use Associated With COVID-19 In The United States: A simulation estimate of the direct medical costs and health care resource use associated with COVID-19 infections in the United States, Health Affairs
Chen, Hu, Zhang, Zongwei, Jiang et al., Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial,
doi:10.1101/2020.03.22.20040758Colson, Rolain, Lagier, Brouqui, Raoult, Chloroquine and hydroxychloroquine as available weapons to fight COVID-19, International Journal of Antimicrobial Agents,
doi:10.1016/j.ijantimicag.2020.105932Cortegiani, Ingoglia, Ippolito, Giarratano, Einav, A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19, Journal of Critical Care
Das, Bhowmick, Tiwari, Sen, An Updated Systematic Review of the Therapeutic Role of Hydroxychloroquine in Coronavirus Disease-19 (COVID-19), Clin Drug Investig
Geleris, Sun, Platt, Zucker, Baldwin et al., Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19, N Engl J Med
Keeley, Buchanan, Carolan, Pivodic, Tavabie et al., Symptom burden and clinical profile of COVID-19 deaths: A rapid systematic review and evidence summary, BMJ Support. Palliat. Care,
doi:10.1136/bmjspcare-2020-002368Keni, Alexander, Nayak, Mudgal, Nandakumar, COVID-19: Emergence, Spread, Possible Treatments, and Global Burden,
doi:10.3389/fpubh.2020.00216Mahévas, Tran, Roumier, Chabrol, Paule et al., Observational comparative study using routine care data,
doi:10.1136/bmj.m1844Matera, Rogliani, Calzetta, Cazzola, Pharmacological management of COVID-19 patients with ARDS (CARDS): A narrative review,
doi:10.1016/j.rmed.2020.106114Mohammed Bin, Hospital, None
Pascarella, Strumia, Piliego, Bruno, Del Buono et al., COVID-19 diagnosis and management: a comprehensive review, J Intern Med
Ponticelli, Moroni, Hydroxychloroquine in systemic lupus erythematosus (SLE), Expert Opinion on Drug Safety
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,
doi:10.1001/jama.2020.8630Shen, Wang, Zhao, Yang, Li et al., Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma, JAMA,
doi:10.1001/jama.2020.4783Siemieniuk, Bartoszko, Ge, Zeraatkar, Izcovich et al., Drug treatments for covid-19: living systematic review and network meta-analysis,
doi:10.1136/bmj.m2980Von Elm, Altman, Egger, Pocock, Gøtzsche et al., The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies, International Journal of Surgery
Yao, Ye, Zhang, Cui, Huang et al., 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/ciaa237Ye, Wang, Colunga-Lozano, Prasad, Tangamornsuksan et al., Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis, CMAJ
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