Interferon-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients: a preliminary matched case-control study / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

BACKGROUND@#Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development.@*METHODS@#Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors.@*RESULTS@#A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206).@*CONCLUSIONS@#IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.

Comparison of epidemiological and clinical characteristics of COVID-19 patients with and without Wuhan exposure history in Zhejiang Province, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

BACKGROUND@#A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure.@*METHODS@#We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan.@*RESULTS@#Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups.@*CONCLUSIONS@#From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.

Efficacy comparison of lamivudine combined with adefovir dipivoxil de novo and entecavir monotherapy in treatment of patients with hepatitis B virus-related decompensated cirrhosis / 中国药学杂志

OBJECTIVE: To compare the efficacy of lamivudine (LAM) combined with adefovir dipivoxil (ADV) de novo and entecavir(LTV) monotherapy in treatment of patients with hepatitis B virus (HBV)-related decompensated cirrhosis for one year. METHODS: Sixty HBV-infected patients with decompensated cirrhosis treated with LAM combined with ADV de novo and 40 patients treated with ETV were enrolled. Liver and kidney function, HBVDNA, HBVM, AFP, US or CT scan of liver were tested every 1-3 month. The treatment efficacy was evaluated at month 12. RESULTS: By month 12, the HBV DNA negative rates in LAM combined with ADV de novo group (45 cases) and ETV monotherapy group (30 cases) were 51.1% and 60.0% respectively. There was no significant difference(P>0.05). The HBeAg negative rates in LAM + ADV group and ETV group were 30.4% and 26.7% respectively. There was no significant difference (P>0.05). The ALT normalization rates in two groups were similar. Viral breakthrough happened in 2 cases (4.4%) by month 12 in LAM + ADV group, and no viral resistance was observed, while viral breakthrough happened in 1 case (3.3%) by month 12 in ETV group. Improvement of liver function was obvious in both groups, for CTP and MELD scores decreased distinctly. The accumulative total mortality or liver transplantation rates were 9.4% and 8.7% respectively in LAM + ADV group and ETV group. No increase in blood creatinine above the upper normal limit was observed in both groups. CONCLUSION: Both of LAM combined with ADV de novo and ETV monotherapy are best choice in treatment of patients with HBV-related decompensated cirrhosis. They can inhibit HBV replication obviously, improve liver function and decrease mortality.

Efficacy of lamivudine monotherapy and combination therapy with adefovir dipivoxil for patients with hepatitis B virus-related decompensated cirrhosis / 中华肝脏病杂志

To compare the efficacy of Lamivudine (LAM) monotherapy and combination therapy with Adefovir Dipivoxil (ADV) for patients with hepatitis B virus (HBV) -related decompensated cirrhosis for 2 years. A total of 115 patients with HBV-related decompensated cirrhosis were erolled in this study, among 60 patients were treated with LAM combined with ADV and 55 were treated with LAM. The liver and kidney functions, HBV DNA, HBV-M, AFP, Ultrasond or CT scan of liver were tested every 1-3months. the treatment efficacy was evaluated by month 12 and 24. By month 12, the HBV DNA negative rates of combination therapy group and LAM monotherapy group were 51.1% (45 cases) and 47.5% (40 cases) respectively, by month 24 the rates were 86.7% and 60.0% respectively. By month 24 the HBeAg negative rates of combination therapy group and LAM monotherapy group were 43.5% and 30.0% respectively, with significant difference existed between the two therapy groups (P values is less than 0.05). By month 24, the ALT normalization rates of the two groups were 88.9% and 72.5% respectively. Viral breakthrough happened in 2 cases (4.4%) by month 12 and 3 cases (6.7%) by month 24 in LAM and ADV combination group, but no viral resistance observed. Viral breakthrough happened in 9 cases (22.5%) by month 12 and 15 cases (37.5%) by month 24 in LAM monotherapy group with viral resistance observed in 7 cases (17.5%) by month 12 and 13 cases (32.5) by month 24. Significant difference existed between the two groups (P is less than 0.05). Improvement of liver function was more obviously in the combination group. The accumulative total mortality or liver transplantation rate were 16.7% and 20.0% respectively in combination therapy group and LAM monotheapy group. No renal dysfunction observed in both groups. LAM combined with ADV is better choice for patients with HBV-related decompensated cirrhosis as compared to LAM monotherapy.

Adjuvant effect of co-stimulatory molecule CD137L on cellular responses to HBsAg DNA vaccination in mice / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the adjuvant effect of co-stimulatory molecule CD137L on cellular responses to HBsAg DNA vaccination in mice.</p><p><b>METHODS</b>Eukaryotic expression vector containing the full length of mouse CD137L cDNA sequence (pcD137L) was transfected into NIH3T3 cells, and then the expression of CD137L mRNA and protein in the transfected cells were detected by RT-PCR, flow cytometry and immunofluorescence method, respectively. The BALB/c mice were co-immunized with pcD137L and HBsAg DNA vaccine (pcDS) by intramuscular injection. HBsAg-specific activity of splenic cytotoxic T lymphocyte (CTL) in the immunized mice was measured by LDH release assay. The splenic memory CD8+ T cells, and intracellular IFN-gamma and IL-4 of splenic lymphocytes and CD8+ T cells after immunization were detected by flow cytometry.</p><p><b>RESULTS</b>The NIH3T3 cells transfected with pcD137L efficiently expressed mouse CD137L mRNA and protein. HBsAg-specific CTL responses induced by the pcDS plus pcD137L group were much stronger than those induced by pcDS alone at a week after immunization (P<0.05). Compared to mice immunized with pcDS alone, CD44high and CD127(IL-7R) were all significantly up-regulated in memory CD8+ T cells from the mice immunized with pcDS combined CD137L both at a week and 12 weeks after immunization (P<0.05 and P<0.01). The pcDS plus CD137L group also elicited higher levels of IFN-gamma secreted by CD8+ T cells and splenic lymphocytes than pcDS alone at a week, 12 and 13 weeks after immunization, respectively (all P<0.01).</p><p><b>CONCLUSION</b>DNA, viral/immunol; Co-stimulatory molecule CD137L can enhance the Tc1 (type I) cell-mediated immunity, HBsAg-specific CTL and memory responses induced by HBsAg DNA vaccine, and may be an efficient adjuvant in priming HBV-specific T cell response.</p>

Inhibition of binding peptides on replication of duck hepatitis B virus / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the inhibitory effect of binding peptides on duck hepatitis B virus (DHBV) replication in duck hepatocytes.</p><p><b>METHODS</b>Specific binding peptides to duck hepatitis B virus polymerase (DHBVP) were screened by phage display technology (PDT), then were sequenced and synthesized. Binding peptides were added into primary culture of duck hepatocytes infected with DHBV in vitro. DHBV-DNA in the cytoplasm, cell nucleus and medium supernatant was assayed over time.</p><p><b>RESULTS</b>Seven binding peptides were obtained after 3-round screening by PDT. Duck primary hepatocytes infected by DHBV were treated with above obtained binding peptides. The DHBV-DNA levels in medium supernatant and cytoplasm of duck hepatocytes treated with synthesized peptides (the 3rd and the 6th peptide) were significantly lower than those of control cells (P<0.05).</p><p><b>CONCLUSION</b>Specific binding peptides to DHBVP could inhibit the replication of DHBV.</p>