A Novel Protein Drug, Novaferon, as the Potential Antiviral Drug for COVID-19

BackgroundNovaferon, a novel protein drug approved for the treatment of chronic hepatitis B in China, exhibits potent antiviral activities. We aimed to determine the anti-SARS-CoV-2 effects of Novaferon in vitro, and conducted a randomized, open-label, parallel group study to explore the antiviral effects of Novaferon for COVID-19. MethodsIn laboratory, the inhibition of Novaferon on viral replication in cells infected with SARS-CoV-2, and on SARS-CoV-2 entry into healthy cells was determined. Antiviral effects of Novaferon were evaluated in COVID-19 patients with treatment of Novaferon, Novaferon plus Lopinavir/Ritonavir, or Lopinavir/Ritonavir. The primary endpoint was the SARS-CoV-2 clearance rates on day 6 of treatment, and the secondary endpoint was the time to the SARS-CoV-2 clearance in COVID-19 patients ResultsNovaferon inhibited the viral replication in infected cells (EC50=1.02 ng/ml), and protected healthy cells from SARS-CoV-2 infection (EC50=0.1 ng/ml). Results from the 89 enrolled COVID-19 patients showed that both Novaferon and Novaferon plus Lopinavir/Ritonavir groups had significantly higher SARS-CoV-2 clearance rates on day 6 than the Lopinavir/Ritonavir group (50.0% vs.24.1%, p = 0.0400, and 60.0% vs.24.1%, p = 0.0053). Median time to SARS-CoV-2 clearance were 6 days, 6 days, and 9 days for three groups respectively, suggesting a 3-dayreduction of time to SARS-CoV-2 clearance in both Novaferon and Novaferon plus Lopinavir/Ritonavir groups compared with Lopinavir/Ritonavir group. ConclusionsNovaferon exhibited anti-SARS-CoV-2 effects in vitro and in COVID-19 patients. These data justified the further evaluation of Novaferon.

Epidemiological and clinical features of 291 cases with coronavirus disease 2019 in areas adjacent to Hubei, China: a double-center observational study

BackgroundThe clinical outcomes of COVID-19 patients in Hubei and other areas are different. We aim to investigate the epidemiological and clinical characteristics of patient with COVID-19 in Hunan which is adjacent to Hubei. MethodsIn this double-center, observational study, we recruited all consecutive patients with laboratory confirmed COVID-19 from January 23 to February 14, 2020 in two designated hospitals in Hunan province, China. Epidemiological and clinical data from patients electronic medical records were collected and compared between mild, moderate and severe/critical group in detail. Clinical outcomes were followed up to February 20, 2020. Findings291 patients with COVID-19 were categorized into mild group (10.0%), moderate group (72.8%) and severe/critical group (17.2%). The median age of all patients was 46 years (49.8% were male). 86.6% patients had an indirect exposure history. The proportion of patients that had been to Wuhan in severe/critical group (48.0% vs 17.2%, p=0.006) and moderate group (43.4% vs 17.2%, p=0.007) were higher than mild group. Fever (68.7%), cough (60.5%), and fatigue (31.6%) were common symptoms especially for severe and critical patients. Typical lung imaging finding were bilateral and unilateral ground glass opacity or consolidation. Leukopenia, lymphopenia and eosinopenia occurred in 36.1%, 22.7% and 50.2% patients respectively. Increased fibrinogen was detected in 45 of 58 (77.6%) patients with available results. 29 of 44 (65.9%) or 22 of 40 (55.0%) patients were positive in Mycoplasma pneumonia or Chlamydia pneumonia antibody test respectively. Compared with mild or moderate group, severe/critical group had a relative higher level of neutrophil, Neutrophil-to-Lymphocyte Ratio, h-CRP, ESR, CK, CK-MB, LDH, D-dimer, and a lower level of lymphocyte, eosinophils, platelet, HDL and sodium (all p<0.01). Most patients received antiviral therapy and Chinese Medicine therapy. As of February 20, 2020, 159 (54.6%) patients were discharged and 2 (0.7%) patients died during hospitalization. The median length of hospital stay in discharged patients was 12 days (IQR: 10-15). InterpretationThe epidemiological and clinical characteristics of COVID-19 patients in Hunan is different from patients in Wuhan. The proportion of patients that had been to Wuhan in severe/critical group and moderate group were higher than mild group. Laboratory and imaging examination can assist in the diagnosis and classification of COVID-19 patients.

Clinical characteristics of coronavirus disease 2019 patients complicated with liver injury / 中南大学学报(医学版)

OBJECTIVES@#To analyze the clinical characteristics in patients of coronavirus disease 2019 (COVID-19) complicated with liver injury, to explore the relationship between COVID-19 clinical classification and liver injury, and to elucidate whether COVID-19 complicated with hepatitis B virus can aggravate liver injury.@*METHODS@#The abnormal liver function in 110 patients in the First Hospital of Changsha, who were confirmed COVID-19 and admitted to the designated hospital from January 17, 2020 to February 20, 2020, wereretrospectively analyzed. The detection indexes included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBIL).@*RESULTS@#A total of 49.1% of the COVID-19 patients had liver injury. There were significant difference in the ALT, AST, ALB (all 0.05) between the severe (critical) patients and the general (light) patients. There was also no significant difference in the liver function injury between the HBsAg-positive COVID-19 patients and HBsAg-negative COVID-19 patients (>0.05). Acute liver injury was not found to be a direct cause of death in the patients.@*CONCLUSIONS@#In the COVID-19 patients, the incidence of liver injury is high with the increase of ALT and AST and the decrease of ALB. Severe and critical patients have obvious liver injury, and those patients complicated with hepatitis B virus infection don't show aggravated liver injury.

Analysis of the bone mineral density of 278 HIV-infected patients / 中国医师杂志

Objective To investigate the changes of bone mineral density (BMD) in human immunodeficiency virus (HIV)-infected patients in Changsha,and take intervention measures to prevent the occurrence of osteoporosis and fracture.Methods A total of 278 HIV-infected patients and 154 cases of healthy adults from March 2011 to May 2015 were selected.Dual energy X-ray absorptiometry (DXA) was used to detect BMD,T-score and Z-score of all the research objects,including the whole body,lumbar spine (L2～4),and left hip joint.The height and weight were measured at the same time.Results The HIV infection group had an average age of (31.53 ± 8.56) years old,and the healthy control group was (34.45 ± 8.22) years old.Height between two groups had no significant difference.The average weight of HIV infection group was 6.93 kg [95％ CI,-9.01,-4.97;P ＜0.001] lighter than that in the normal control group.BMD,T-score and Z-score of HIV infection group were significantly lower than those in norrmal control group (P ＜ 0.001).The occurrence rate of osteopenia (Z ≤-1.0)and osteoporosis (Z ≤-2.0)in HIV infection group were correspondingly 43.53％ ～ 54.68％ and 9.71％ ～23.74％,which is about 4 times of that in the healthy control group (14.28％ ～ 20.13％,0.65％ ～ 5.84％).Conclusions The average body weight of HIV-infected patients was significantly lower than that of normal control group,and the incidence of osteopenia and osteoporosis in HIV-infected group was significantly higher than that in normal control group.

Construction of recombinant plasmid siRNA of XIAP and its biological role / 中国医师杂志

Objective To construct siRNA expression vector of XIAP,and study its effect on XIAP expression in Hep3B cells. MethodsThree XIAP siRNA sequences were designed,synthesized,and cloned to pRNAT-U6.1/Neo.The successfully constructed recombinant plasmid was determined by sequence analysis,and will be transfected into Hep3B.The best interference plasmid were analyzed by RTPCR,Western blot,and immunohistochemistry.Results The plasmid of pRNAT-U6.1/Neo-XIAP was constructed successfully,the trans-fected with different plasmid of siRNA XIAP can lower significantly XIAP.Conclusions The siRNA vector of XIAP gene was constructed successfully.It will be a basis for the study of XIAP function in apoptosis regulation of the Hepatoma cells.