Proteomic and metabolomic investigation of serum lactate dehydrogenase elevation in COVID-19 patients.

Serum lactate dehydrogenase (LDH) has been established as a prognostic indicator given its differential expression in COVID-19 patients. However, the molecular mechanisms underneath remain poorly understood. In this study, 144 COVID-19 patients were enrolled to monitor the clinical and laboratory parameters over 3 weeks. Serum LDH was shown elevated in the COVID-19 patients on admission and declined throughout disease course, and its ability to classify patient severity outperformed other biochemical indicators. A threshold of 247 U/L serum LDH on admission was determined for severity prognosis. Next, we classified a subset of 14 patients into high- and low-risk groups based on serum LDH expression and compared their quantitative serum proteomic and metabolomic differences. The results showed that COVID-19 patients with high serum LDH exhibited differentially expressed blood coagulation and immune responses including acute inflammatory responses, platelet degranulation, complement cascade, as well as multiple different metabolic responses including lipid metabolism, protein ubiquitination and pyruvate fermentation. Specifically, activation of hypoxia responses was highlighted in patients with high LDH expressions. Taken together, our data showed that serum LDH levels are associated with COVID-19 severity, and that elevated serum LDH might be consequences of hypoxia and tissue injuries induced by inflammation.

Clinical characteristics of 60 discharged cases of 2019 novel coronavirus-infected pneumonia in Taizhou, China.

BACKGROUND: The number of patients with pneumonia stemming from the 2019 novel coronavirus (COVID-19) infection has increased rapidly. However, the clinical characteristics of discharged patients remain little known. Here, we attempt to describe the clinical characteristics and treatment experiences of discharged cases from Taizhou, China. METHODS: A total of 60 patients with COVID-19-infected pneumonia who were discharged from Taizhou Enze Medical Center (Group), from January 31, 2020, to February 16, 2020, were included in the analysis. The discharge criteria were based on the New Coronavirus Pneumonia Prevention and Control Program (Fifth Edition, China). RESULTS: Of the 60 patients, the median age was 41 years, and 58.3% were male. Only 13.3% of patients were identified as having severe novel coronavirus pneumonia. All patients received combined antiviral treatment on admission, including ß-interferon, lopinavir/tonavir, Abidol and oseltamivir. All patients with severe conditions received gamma globulin and hormone therapy. No patients had endotracheal intubation or died. The median duration from symptom onset to hospitalization was 3 (range, 0-15) days. The median duration of COVID-19 shedding was 14 (range, 5-26) days, and the median duration of hospital stay was 15 (range, 7-23) days. CONCLUSIONS: Early therapy and comprehensive therapy are key to the outcome for patients with COVID-19-infected pneumonia, especially for those with severe pneumonia. TRIAL REGISTRATION NUMBER: ChiCTR2000029866.

Randomized trial of lamivudine, adefovir, and the combination in HBeAg-positive chronic hepatitis B.

The aim of this study was to compare the efficacy of lamivudine or adefovir alone for 96 weeks versus initial treatment with the combination of lamivudine and adefovir for 12 to 24 weeks followed by adefovir alone. One hundred and fifty patients with HBeAg-positive chronic hepatitis B were randomized equally to lamivudine and adefovir diprivoxil combination therapy (LA), lamivudine alone (L), or adefovir dipivoxil alone (A) in a multicenter randomized clinical trial. In the LA group, the earliest time for lamivudine discontinuation was 12 weeks and adefovir monotherapy was continued until 96 weeks. Groups L and A received monotherapies for 96 weeks. At 12 weeks, the decrease in HBV DNA, percentage of patients with negative HBV DNA, and ALT normalization rate for the LA group were comparable to those of group L, but superior to those of group A. At 24 weeks, the rates of negative HBV DNA and HBeAg seroconversion of group LA were significantly higher than the monotherapy groups. This superiority was subsequently preserved during the maintenance phase with adefovir monotherapy. Starting at 48 weeks, the mean HBV DNA level of group L increased over the 24-week level. In contrast, the A group's rates of virological response, biochemical response, and HBeAg seroconversion continued to improve. At week 96, the percentage of patients with undetectable DNA and HBe seroconversion of LA group (100%, 51%) was higher than that of L (66%, 21%) and A group (49%, 33%), while no significant difference was observed between the L and A groups. During the course of therapy, no lamivudine- or adefovir-resistance mutations were discovered in the LA group. Rates of adverse reactions were comparable between the three groups. Combination therapy with lamivudine and adefovir for 12 to 24 weeks followed by adefovir monotherapy significantly improved antiviral efficacy and reduced drug resistance without compromising safety and tolerability compared to either drug alone in HBeAg-positive chronic hepatitis B.