c19early.org COVID-19 treatment researchCOVID-19 treatments

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

He et al., Frontiers of Medicine, doi:10.1007/s11684-025-1123-9, NCT05615792, Mar 2025
Late treatmentRetrospective · 53,030 patients · China · Dec 2019 – Aug 2021
HCQ for COVID-19
He et al. Frontiers of Medicine · March 2025 · NCT05615792
Lower mortality and ventilation
Statistically significant only for mortality · p < 0.0001 (mortality) and p = 0.05 (ventilation)

HCQ for COVID-19

1st treatment shown to reduce risk in March 2020, now with p < 0.0000000001 from 426 studies, used in 59 countries.
Lower risk for mortality, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective.
Protocols combine treatments.

6,700+ studies · 220+ treatments

c19early.org
Meta-analysis
PSM retrospective 53,030 hospitalized patients in China showing low dose HCQ treatment associated with significantly lower all-cause mortality, mechanical ventilation, acute heart injury, and acute kidney injury, with benefits consistent across mild and critically ill patients.
Standard of Care (SOC) for COVID-19 in the study country, China, is average with moderate efficacy for approved treatments1.
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OutcomeImprovementEffect · pTreatmentControl
risk of death 66.0% lower · HR 0.34 · p < 0.001*** 66.0% lowerHR 0.34p < 0.001*** 830 830 treatment 830, control 830all patientspropensity score matchingKaplan-Meier
risk of death 74.0% lower · HR 0.26 · p < 0.001*** 74.0% lowerHR 0.26p < 0.001*** 800 800 treatment 800, control 800low dosepropensity score matchingKaplan-Meier
risk of mechanical ventilation 24.8% lower · HR 0.75 · p = 0.05* 24.8% lowerHR 0.75p = 0.05* 841 52,189 treatment 841, control 52,189all patientsinverted to make HR<1 favor treatmentKaplan-Meier
risk of mechanical ventilation 27.0% lower · HR 0.73 · p = 0.04* 27.0% lowerHR 0.73p = 0.04* 800 52,189 treatment 800, control 52,189low doseKaplan-Meier
ARDS 40.8% lower · HR 0.59 · p = 0.21 40.8% lowerHR 0.59p = 0.21 841 52,189 treatment 841, control 52,189all patientsinverted to make HR<1 favor treatmentKaplan-Meier
ARDS 49.0% lower · HR 0.51 · p = 0.13 49.0% lowerHR 0.51p = 0.13 800 52,189 treatment 800, control 52,189low doseKaplan-Meier
AKI 31.0% lower · HR 0.69 · p = 0.005** 31.0% lowerHR 0.69p = 0.005** 841 52,189 treatment 841, control 52,189all patientsinverted to make HR<1 favor treatmentKaplan-Meier
AKI 30.0% lower · HR 0.70 · p = 0.008** 30.0% lowerHR 0.70p = 0.008** 800 52,189 treatment 800, control 52,189low doseKaplan-Meier
acute heart injury 37.9% lower · HR 0.62 · p = 0.03* 37.9% lowerHR 0.62p = 0.03* 841 52,189 treatment 841, control 52,189all patientsinverted to make HR<1 favor treatmentKaplan-Meier
acute heart injury 39.0% lower · HR 0.61 · p = 0.02* 39.0% lowerHR 0.61p = 0.02* 800 52,189 treatment 800, control 52,189low doseKaplan-Meier

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates. * p < 0.05   ** p < 0.01   *** p < 0.001

He et al., 4 Mar 2025, retrospective, China, peer-reviewed, 9 authors, study period 29 December, 2019 - 31 August, 2021, trial NCT05615792 (history). Contact: dwwang@tjh.tjmu.edu.cn.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2026 China Angola Colombia Kenya Mozambique Myanmar South Africa Peru Philippines USA Brazil France Italy Canada Pakistan Spain Vietnam Japan Nepal Iran Bangladesh Ethiopia Ghana Germany Mexico South Korea United Kingdom Saudi Arabia Algeria Morocco Yemen Poland Thailand Uganda Egypt Nigeria Taiwan Fiji Zambia Bosnia-Herzegovina Dominican Republic Bolivia Côte d'Ivoire Eritrea Togo Bulgaria Greece Slovakia Iceland New Zealand Trinidad and Tobago Mongolia Czechia Belarus Israel Haiti North Macedonia Hong Kong Qatar Panama Serbia Benin Burundi Cameroon CAR China favored low-cost treatments.The average efficacy of treatments was moderate.Low-cost treatments improve early treatment, andprovide complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2026 China Angola Colombia Kenya Mozambique Myanmar South Africa Peru Philippines USA Brazil France Italy Canada Pakistan Spain Vietnam Japan Iran Bangladesh Ethiopia Ghana Germany Mexico South Korea United Kingdom Saudi Arabia Algeria Morocco Yemen Poland Thailand Uganda Egypt Nigeria Taiwan Fiji Zambia Dominican Rep. Bolivia Côte d'Ivoire Eritrea Togo Sri Lanka Bulgaria Greece Slovakia New Zealand Trinidad and Tobago Mongolia Czechia Belarus Israel North Macedonia Hong Kong Qatar Panama Serbia Benin Burundi CAR Syria China favored low-cost treatments.The average efficacy was moderate.Low-cost protocols improve early treatment,and add complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
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..
Late treatment
is less effective