Background and aims We aim to assess the safety and immunogenicity of inactivated whole-virion SARS-CoV-2 vaccines in patients with chronic liver diseases (CLD) in this study. Methods This was a prospective, multi-center, open-label study. Participants aged over 18 years with confirmed CLD and healthy volunteers were enrolled. All participants received 2 doses of inactivated whole-virion SARS-CoV-2 vaccines. Adverse reactions were recorded within 14 days after any dose of SARS-CoV-2 vaccine, laboratory testing results were collected after the second dose, and serum samples of enrolled subjects were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Results A total of 581 participants (437 patients with CLD and 144 healthy volunteers) were enrolled from 15 sites in China. Most adverse reactions were mild and transient, and injection site pain (36 [8.2%]) was the most frequently reported adverse event. Three participants had Grade 3 aminopherase elevation (defined as alanine aminopherase>5 upper limits of normal) after the second dose of inactivated whole-virion SARS-CoV-2 vaccination, and only one of them was judged as severe adverse event potentially related to SARS-CoV-2 vaccination. The positive rates of SARS-CoV-2 neutralizing antibodies were 76.8% in non-cirrhotic CLD group, 78.9% in compensated cirrhotic group, 76.7% in decompensated cirrhotic group (P=0.894 among CLD subgroups) and 90.3% in healthy controls (P=0.008 versus CLD group). Conclusion Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with CLD. Patients with CLD had lower immunological response to SARS-CoV-2 vaccines than healthy population. The immunogenicity is similarly low in non-cirrhotic CLD, compensated cirrhosis and decompensated cirrhosis.

Background & Aims The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. Methods This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. Results A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0–48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m 2 (IQR 23.8–28.1 kg/m 2 ). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. Conclusions The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. Lay summary The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

Background Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with compensated (C-cirrhosis) and decompensated cirrhosis (D-cirrhosis) are limited. Methods In this prospective multicenter study, adult participants with C-cirrhosis and D-cirrhosis were enrolled and received two doses of inactivated whole-virion COVID-19 vaccines. Adverse events were recorded within 14 days after any dose of vaccination, and serum samples of enrolled patients were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Risk factors for negative neutralizing antibody were analyzed. Results In total, 553 patients were enrolled from 15 centers in China, including 388 and 165 patients with C-cirrhosis and D-cirrhosis. The vaccines were well tolerated, most adverse reactions were mild and transient, and injection site pain (23/388 [5.9%] vs 9/165 [5.5%]) and fatigue (5/388 [1.3%] vs 3/165 [1.8%]) were the most frequently local and systemic adverse events in both the C-cirrhosis and D-cirrhosis groups. Overall, 4.4% (16/363) and 0.3% (1/363) of patients were reported Grades 2 and 3 alanine aminotransferase (ALT) elevations (defined as ALT > 2 upper limit of normal [ULN] but ≤ 5 ULN, and ALT > 5 ULN, respectively). The positive rates of COVID-19 neutralizing antibodies were 71.6% (278/388) and 66.1% (109/165) in C-cirrhosis and D-cirrhosis groups. Notably, Child–Pugh score of B and C levels was an independent risk factor of negative neutralizing antibody. Conclusions Inactivated COVID-19 vaccinations are safe with acceptable immunogenicity in cirrhotic patients, and Child–Pugh score of B and C levels is associated with hyporesponsive to COVID-19 vaccination.

No abstract

Background The present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)/NF-κB signaling pathway. Methods A total of 40 male Sprague-Dawley rats were randomly divided into five groups: The healthy, diabetic, 50 mg/kg ART (ig) treatment diabetic, 100 mg/kg ART (ig) treatment diabetic, and 6 U/kg insulin (iH) treatment diabetic groups. The treatment lasted 4 weeks after the diabetic model was established via intraperitoneal injection of streptozotocin. Blood samples were collected, and cardiovascular tissues were harvested and processed to measure various parameters after the animals were sacrificed. The myocardium and aortic arch tissues were evaluated using hematoxylin-eosin and Masson staining. Expression levels of RAGE, NF-κB, matrix metalloproteinase MMP9, MMP1 and CD68 in the myocardium and aortic arch tissues were detected using immunohistochemistry, and mRNA expression was determined using reverse transcription-quantitative PCR. Results The results of the present study demonstrated that ART treatment may restrain diabetes-induced cardiovascular complications by maintaining heart and body weight while reducing blood glucose, as well as regulating blood lipid indicators to normal level (P < 0.05). The expression levels of NF-κB, CD68, MMP1, MMP9 and RAGE were decreased in the ART-treated diabetic rats (P < 0.05). Conclusions ART treatment may have a protective role against diabetes-associated cardiovascular complications in diabetic rats by inhibiting the expression of proteins in the RAGE/NF-κB signaling pathway and downstream inflammatory factors. High concentrations of ART had a hypoglycemic effect, while a low concentration of ART prevented cardiovascular complications.