Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial

Objective: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). Design: Multicentre, open label, randomised controlled trial. Setting 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. Participants: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). Interventions Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). Main outcome measure: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone.

Retrospective analysis of the effect of current clinical medications and clinicopathological factors on viral shedding in COVID-19 patients.

The aim of the present study was to identify the risk factors associated with prolonged shedding in patients with coronavirus disease 2019 (COVID-19), and to evaluate the effects of current clinical and clinicopathological factors on viral shedding in patients. A total of 186 COVID-19 inpatients were enrolled in this multicentre retrospective analysis. Detailed clinical data of each patient were collected, and the factors that affected the duration of viral shedding were retrospectively analysed. The median duration of viral shedding in the 186 COVID-19 patients was 13 days. The median duration of viral shedding was 12 days in non-severe patients, and 17 days in severe patients, and there was a significant difference between the two groups (P<0.001). Multi-factor regression analysis suggested that the onset-hospitalization interval [odds ratio (OR), 1.27; 95% confidence interval (CI), 1.15-1.41; P<0.001] and comorbidity with a chronic disease (OR, 2.43; 95% CI, 1.14-5.17; P=0.021) were independent risk factors for prolonged viral shedding, whereas lopinavir/ritonavir (LPV/r) was an independent protective factor (OR, 0.28; 95% CI, 0.11-0.75; P=0.011). Spearman's rank correlation analysis showed that the onset-drug interval was positively correlated with the duration of viral shedding (r=0.446; P<0.0001). Umifenovir, and low and short courses of glucocorticoids were not associated with prolonged viral shedding. The prolonged viral shedding was the initial causative factor of persistent aggravation of the patient's conditions. The interval between presentation of symptoms and hospitalization as well as complications with a comorbid chronic disease were independent risk factors for prolonged viral shedding. LPV/r shortened the duration of viral shedding, and the smaller the interval between presentation and LPV/r onset was, the faster viral shedding occurred.

[A single arm clinical study of 86 patients with common type of coronavirus disease 2019 treated by integrated traditional Chinese and Western medicine: multicenter case observation from 7 designated hospitals in Henan Province].

OBJECTIVE: To evaluate the clinical effect of integrated traditional Chinese and Western medicine on common type of coronavirus disease 2019 (COVID-19) in Henan Province. METHODS: A prospective single arm clinical study was performed. Patients with common type of COVID-19 admitted to seven designated hospitals for COVID-19 in Henan Province from January 25th to February 26th, 2020 were enrolled, and treated with integrated traditional Chinese and Western medicine. The negative transformation of 2019 novel coronavirus (2019-nCoV) nucleic acid, disease outcome, hospital stay, clinical symptoms and signs scores, and chest imaging performance were observed. RESULTS: Totally 86 cases were included in the analysis, including 48 males (55.8%), aged 43.5 (35.0, 53.3) years old, 24 patients (27.9%) with previous medical history. Fifty-eight patients were primarily diagnosed COVID-19 and 28 patients were transferred. The 2019-nCoV nucleic acid of 86 cases (100%) turned negative, and the median time of turning negative was 10 (7, 14) days. Eighty-six cases (100%) were discharged from hospital, and none turned into the severe type; the average length of hospital stay was (13.8±5.6) days. The scores of fever, cough, chest tightness, shortness of breath, and fatigue decreased with the treatment time, and the scores of 7 days and 14 days after treatment were significantly lower than those before treatment [fever (points): 0 (0, 0), 0 (0, 0) vs. 1 (0, 1); cough (points): 1 (0, 1), 0 (0, 1) vs. 1 (0, 2); chest tightness (points): 0 (0, 0), 0 (0, 0) vs. 0 (0, 1); shortness of breath (points): 0 (0, 0), 0 (0, 0) vs. 0 (0, 1); fatigue (points): 0 (0, 1), 0 (0, 1) vs. 1 (0, 1); all P < 0.05]. The improvement rate of X ray and CT image was 42.9% (12/28) and 81.0% (64/79), respectively. CONCLUSIONS: The treatment with integrated traditional Chinese and Western medicine has good curative effect on common type of COVID-19 in 7 designated hospitals of Henan Province. It can improve the clinical symptoms, promote the absorption of pulmonary inflammation, and to some extent control the progress of disease and shorten the time of turning negative of virus nucleic acid and hospital stay.

Clinical characteristics of 71 patients with coronavirus disease 2019. / 71例2019å† çŠ¶ç— æ¯’ç— ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To analyze the clinical characteristics of 71 patients with coronavirus disease 2019 (COVID-19). METHODS: The general data, epidemiological data, laboratory tests, imaging examinations, and treatment of 71 patients with COVID-19 admitted to the Sixth People's Hospital of Zhengzhou from January 19, 2020 to March 3, 2020 were retrospectively analyzed. RESULTS: Of the 71 COVID-19 patients, the ages were 4-84 (41.29±15.21) years, 38 (53.5%) patients were male, 33 (46.5%) were female, and 52 (73.2%) were in 22 clusters. The main clinical manifestations were fever (78.9%), cough (64.8%), and sputum (38.0%). The fever was mainly low and moderate, with 49 patients (69.0%) at 37.3-39.0 ℃. Most of the leukocytes, neutrophils, and lymphocytes were normal, accounting for 47 (66.2%), 51 (71.8%), and 51 (71.8%) patients, respectively; a few of them were decreased, accounting for 21 (29.6%), 16 (22.5%), and 20 (28.2%) patients, respectively. There were 38 (53.5%) and 31 (43.7%) patients with the decreased CD4+ and CD8+ T cell counts, respectively. There were 41 (57.7%), 38 (53.5%), 32 (45.1%), 26(36.6%), 22 (31.0%), 20 (28.2%), 14 (19.7%), 14 (19.7%), and 9 (12.7%) patients with the increased levels of C-reactive protein, erythrocyte sedimentation rate, procalcitonin, fibrinogen,interleukin 6, lactate dehydrogenase,D-dimer,alanine aminotransferase, and aspartate aminotransferase, respectively. Of the 71 patients, the lung was involved in 60 (84.5%) patients, the double lung was involved in 47 (66.2%) patients, and the single lung was involved in 13 (18.3%) patients. The course of the disease was long, and the time from symptom onset to the second severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid negative transformation was (17.22±6.34) days.There were no significant differences in the incubation period (t=-0.453, P>0.05), the complicates (χ2=0.042, P>0.05), and the time from symptom onset to diagnosis (t=-1.330, P>0.05) in patients between the non-severe group and the severe group. The onset age, gender, SARS-CoV-2 nucleic acid negative time, lymphocyte count, D-dimer, C-reactive protein, total bilirubin, direct bilirubin, lactate dehydrogenase, calcium ion, CD4+ T cell count, CD8+ T cell count, calcitonin, procalcitonin, and troponin were significantly different between the severe group and the non-severe group (all P<0.05). Among the 71 patients, 4 (5.6%) patients were mild, 59 (83.1%) were normal, and 8 (11.3%) were severe or critical. CONCLUSIONS: The aggregation phenomenon of COVID-19 is obvious. Fever and cough are the main clinical manifestations. White blood cells, neutrophils, and lymphocytes in the most patients in the early onset are normal. Most COVID-19 patients are light and ordinary type, with good prognosis.