Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial

ObjectivesTo assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. DesignMulticenter, open-label, randomized controlled trial. Setting16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. Participants150 patients hospitalized with laboratory confirmed COVID-19 were included in the intention to treat analysis. 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. InterventionsHCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). Main outcome measuresThe primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention-to-treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. ResultsAmong 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-} standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70). The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. ConclusionsThe administration of HCQ did not result in a significantly higher negative conversion probability than SOC alone in patients mainly hospitalized with persistent mild to moderate COVID-19. Adverse events were higher in HCQ recipients than in HCQ non-recipients. Trial registrationChiCTR2000029868 What is already known on this topic-- The pandemic of coronavirus disease 2019 (COVID-19) imposes substantial burdens on individuals, communities, health-care facilities, markets, governments, etc. globally. -- There is no specific treatment approved for COVID-19 or vaccine to prevent infection with the novel coronavirus. -- During the urgent pandemic, media headlines the utility of drugs without solid evidence but buries the side-effects of these drugs. What this study adds-- In this randomized clinical trial of patients mainly with persistent mild to moderate COVID-19, exposure to hydroxychloroquine led to a similar probability of virus elimination comparing to the current standard-of-care. -- Adverse events, mostly gastrointestinal related, were significantly increased in patients who received hydroxychloroquine. -- Overall, the results from our trial do not support the use of hydroxychloroquine in patients with persistent mild to moderate COVID-19. Print abstractO_ST_ABSStudy questionC_ST_ABSTo assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. MethodsThis is a multicenter, open-label, randomized controlled trial conducted in 16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. A total of 150 patients hospitalized with laboratory confirmed COVID-19 were included in the intention to treat analysis. Among them, 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). The primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention to treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. Study answer and limitationsAmong 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-} standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70) with two serious adverse events. The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. What this study addsOur trial does not support the use of hydroxychloroquine in patients with persistent mild to moderate COVID-19 due to limited effects on virus eliminating and significantly increased adverse events. Funding, competing interests, data sharingThis work was supported by the Emergent Projects of National Science and Technology (2020YFC0844500), National Natural Science Foundation of China (81970020, 81770025), National Key Research and Development Program of China (2016YFC0901104), Shanghai Municipal Key Clinical Specialty (shslczdzk02202, shslczdzk01103), National Innovative Research Team of High-level Local Universities in Shanghai, Shanghai Key Discipline for Respiratory Diseases (2017ZZ02014), National Major Scientific and Technological Special Project for Significant New Drugs Development (2017ZX09304007), Key Projects in the National Science and Technology Pillar Program during the Thirteenth Five-year Plan Period (2018ZX09206005-004, 2017ZX10202202-005-004, 2017ZX10203201-008). All authors declared no competing interests. Anonymized datasets can be made available on reasonable request after approval from the trial management committee. Study registrationChiCTR2000029868

Clinical features and prognosis of 496 patients with corona virus disease 2019 / 中华传染病杂志

Objective:To investigate the clinical features and prognosis of patients with corona virus disease 2019 (COVID-19).Methods:The clinical data and chest computed tomography (CT) results of 496 patients with COVID-19 admitted to Wuhan No.7 Hospital from January 22 to February 24, 2020 were retrospectively analyzed. The nucleic acid of 2019 novel coronavirus (2019-nCoV) was detected by real-time fluorescence reverse transcription polymerase chain reaction.Results:There were 246(49.6%) males and 250(50.4%) females. The patients ranged from 10 to 91 years old. All of the patients had a history of living in Wuhan City or close contact with diagnosed patients. The detection of nucleic acid of 2019-nCoV in 496 patients were all positive, and one patient was recuperation positive 14 days after cured and discharged. There were 13 mild cases, 101 ordinary cases, 337 severe cases and 45 critical cases. Twelve (2.4%) patients were asymptomatic, 417(84.1%) patients had fever, and 67(13.5%) had normal body temperature. Other major symptoms included dry cough (229 cases (46.2%)), fatigue (129 cases (26.0%)), short breath (77 cases (15.5%)), expectoration (86 cases (17.3%)), dyspnea (43 cases (8.7%)), chest pain (11 cases (2.2%)) and diarrhea (86 cases (17.3%)). Seventy-five cases (15.1%) showed decreased peripheral blood white blood cell counts and 305 cases (61.5%) showed decreased lymphocyte proportions. Serum alanine aminotransferase and aspartate aminotransferase elevations were presented in 91 cases (18.3%) and 176 cases (35.5%), respectively. Infiltrates on chest CT were seen in 483 cases (97.4%), with 68.7%(332/483) in both lungs, 20.3%(98/483) in right lung, 11.0%(53/483) in left lung. No infiltrates on chest CT were seen in 13(2.6%) patients. As of February 24, 2020, 120(24.2%) patients were cured and discharged, 102(20.6%) patients improved, 52(10.5%) patients died, and the remaining patients were still under treatment. Among the dead patients, 16 cases (30.8%) aged from 61 to 70 years old, 32 cases (61.5%) aged≥71 years old, and 38 cases (73.1%) had underlying diseases.Conclusions:The COVID-19 lesions mainly involve both lungs. The main clinical features are fever and dry cough. The CT imaging findings of the lungs are mostly frosted hyaline. Peripheral white blood cell and leukomonocyte counts are decreased or normal. Older individuals with underlying diseases have increased risk of death.

Clinical effect of artificial liver support system on serum hs -CRP level in patients with hepatic failure / 临床肝胆病杂志

Objective To evaluate the clinical effect of artificial liver support system (ALSS)on serum high -sensitivity C -reactive pro-tein (hs -CRP)level and investigate the influence of the change in hs -CRP level on clinical prognosis among patients with hepatic failure. Methods Patients were recruited into three groups:group one included 60 patients who received ALSS due to hepatic failure;group two in-cluded 37 patients with hepatic failure without ALSS treatment;and group three included 37 patients with chronic hepatitis B.The serum levels of hs -CRP were measured in groups two and three,and in group one before and after ALSS treatment.Comparison of continuous data between groups was made by t test,and comparison of categorical data was made by chi -square test.Results The levels of hs -CRP in group one before treatment and in groups two and three were 12.89 ±9.39,12.22 ±9.73,and 2.83 ±6.79,respectively.No significant difference in hs -CRP level between group one and group two was observed (P >0.05).However,the hs -CRP level in group three was significantly different from those in group one and group two (P <0.001 ).The improvement rate in group one after ALSS treatment (78.3%)was significantly higher compared with that in group two (54.05%)(χ2 =6.315,P <0.05).ALSS treatment (t =5.179,P <0.05).ALSS treatment was selectively effective in a subgroup of patients and greatly decreased the hs -CRP level in these patients (t =5.344,P =0.000),resulting in a significant difference from the patients who were unresponsive to ALSS treatment (t =2.368,P =0.038).Conclusion Artificial liver support system can decrease the hs -CRP level in patients with hepatic failure.Serum level of hs -CRP can be used as a clinical indicator of disease progression and predict the clinical outcomes of ALSS in patients with hepatic failure.