Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients with COVID-19: A Nationwide Observational Study of 8075 Participants

Catteau, Lucy; Dauby, Nicolas; Montourcy, Marion; Bottieau, Emmanuel; Hautekiet, Joris; Goetghebeur, Els; van Ierssel, Sabrina; Duysburgh, Els; Van Oyen, Herman; Wyndham-Thomas, Chloé; Van Beckhoven, Dominique

BACKGROUND: Hydroxychloroquine (HCQ) has been largely used and investigated as therapy of COVID-19 across various settings, at total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use of low-dose HCQ (2400 mg in total over five days) was recommended for hospitalized patients with COVID-19. METHODS: We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19 hospital surveillance data. Patients treated either with HCQ alone and supportive care (HCQ group) were compared to patients treated with supportive care only (no-HCQ group) using a competing risks proportional hazards regression with discharge alive as competing risk, adjusted for demographic and clinical features with robust standard errors. RESULTS: Of 8075 patients with complete discharge data on 24(th) of May and diagnosed before the 1(st) of May, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the multivariable analysis, the mortality was lower in the HCQ group compared to the no-HCQ group (adjusted hazard ratio [HR] 0.684, 95% confidence interval [CI] 0.617–0.758). Compared to the no-HCQ group, mortality in the HCQ group was reduced both in patients diagnosed ≤ 5 days (n=3975) and > 5 days (n=3487) after symptom onset (adjusted HR 0.701, 95% CI 0.617–0.796 and adjusted HR 0.647, 95% CI 0.525–0.797, respectively). CONCLUSIONS: Compared to supportive care only, low-dose HCQ monotherapy was independently associated with lower mortality in hospitalized patients with COVID-19 diagnosed and treated early or later after symptom onset.