Low dose of hydroxychloroquine is associated with reduced COVID-19 mortality: a multicenter study in China

Abstract: Front. Med. https://doi.org/10.1007/s11684-025-1123-9 LETTER TO FRONTIERS OF MEDICINE Low dose of hydroxychloroquine is associated with reduced COVID-19 mortality: a multicenter study in China ✉)1 Wu He1,*, Ke Xu1,*, Yongcui Yan1, Gen Li1, Bo Yu1, Junfang Wu1, Kaineng Zhong2, Da Zhou2, Dao Wen Wang ( 1Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China; 2Health Commission of Hubei Province, Wuhan 430079, China © Higher Education Press 2025 Dear Editor, Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has widely spread worldwide, and we have been fighting against coronavirus disease 2019 (COVID-19) for more than 4 years [1]. According to the statistics of the World Health Organization (WHO), more than 775 million individuals have incurred COVID-19, and 7 million deaths have been recorded. The COVID-19 outbreak has become a devastating global health crisis, and the challenges faced by humanity due to this disease are continuing [2]. In the past 4 years, an old antimalarial drug, hydroxychloroquine (HCQ), has been evaluated by doctors and scientists [3]. Its effects on the immune system have been fully confirmed, including inhibition of Toll-like receptor signals and lymphocyte receptors; interference with lysosomal acidification, antigen presentation, and DNA binding and stabilization; and reduction of proinflammatory cytokines produced by macrophages (especially IL-1, IL-6, and TNF-α) [4]. In vitro experiment of HCQ showed its efficacy in inhibiting novel coronaviruses and its greater effectiveness than chloroquine [5]. Our previous clinical results also supported that HCQ has good therapeutic effects on patients with COVID-19 [6]. An observational study revealed that the use of HCQ was associated with a reduced hospitalization rate among patients with COVID19 [7]. Nevertheless, some studies reported neutral or negative findings on the clinical results and meta-analysis of patients with COVID-19 treated with HCQ [8], leading to doubts and restrictions on the clinical use of HCQ on patients with COVID-19 to a certain extent. We conducted a multicenter retrospective study of Received August 5, 2024; accepted December 16, 2024 Correspondence: Dao Wen Wang, dwwang@tjh.tjmu.edu.cn *These authors contributed equally to this work. 53 030 patients with COVID-19 (discharged or deceased) in 138 hospitals in Hubei Province to clarify the effects of different HCQ doses on the mortality of patients with COVID-19 (Trial registration: NCT05615792). Under China and WHO interim guidance, all the patients diagnosed with COVID-19 between Dec 29, 2019 (i.e., when the first patients were admitted) and Aug 31, 2021 were screened, and those who had died or were discharged were included in this study. The patients were divided into HCQ group and non-HCQ group according to whether or not they were administered with HCQ. A 1:1 propensity score matching (PSM) analysis was used to balance the confounding factors between HCQ group and non-HCQ group. The HCQ group consisted of patients with COVID-19 who continuously received HCQ for more than 3 days. According to the dosage, the HCQ group was subdivided into high-dose (≥ 400 mg/d) and low-dose (< 400 mg/d) groups. This study included 68 128 patients with COVID-19 from 138 hospitals..