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.
SUMMARY:The regulatory mechanism of miRNA induction in response to Mycobacterium tuberculosis (MTB) infection has not been clearly established. Autophagy has recently been identified as an effective way to control intracellular survival of MTB. In the present study, we demonstrate a novel role of miR-30A in the negative regulation of the autophagy-mediated anti-MTB response. We found that overexpression of miR-30A suppresses the elimination of intracellular MTB through the inhibition of autophagy. Furthermore, there was a negative correlation between concentrations of miR-30A and beclin-1 in MTB positive patients and miR-30A expression decreased after anti-TB treatment. Our results indicate that miR-30A plays a key role in immune response against MTB and, therefore, may serve as a potential target for future treatments of tuberculosis infection.
Impulsive differential equations (hybrid dynamical systems) can provide a natural description of pulse-like actions such as when a pesticide kills a pest instantly. However, pesticides may have long-term residual effects, with some remaining active against pests for several weeks, months or years. Therefore, a more realistic method for modelling chemical control in such cases is to use continuous or piecewise-continuous periodic functions which affect growth rates. How to evaluate the effects of the duration of the pesticide residual effectiveness on successful pest control is key to the implementation of integrated pest management (IPM) in practice. To address these questions in detail, we have modelled IPM including residual effects of pesticides in terms of fixed pulse-type actions. The stability threshold conditions for pest eradication are given. Moreover, effects of the killing efficiency rate and the decay rate of the pesticide on the pest and on its natural enemies, the duration of residual effectiveness, the number of pesticide applications and the number of natural enemy releases on the threshold conditions are investigated with regard to the extent of depression or resurgence resulting from pulses of pesticide applications and predator releases. Latin Hypercube Sampling/Partial Rank Correlation uncertainty and sensitivity analysis techniques are employed to investigate the key control parameters which are most significantly related to threshold values. The findings combined with Volterra's principle confirm that when the pesticide has a strong effect on the natural enemies, repeated use of the same pesticide can result in target pest resurgence. The results also indicate that there exists an optimal number of pesticide applications which can suppress the pest most effectively, and this may help in the design of an optimal control strategy.
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.
stringent measures for controlling the novel coronavirus epidemic have been gradually enforced and strengthened in mainland China. The detection and diagnosis have been improved, as well. However, the daily reported cases remaining at a high level make the epidemic trend prediction difficult. Methods: Since the traditional SEIR model does not evaluate the effectiveness of control strategies, a novel model in line with the current epidemic's process and control measures was proposed, utilizing multisource datasets including the cumulative number of reported, deceased, quarantined and suspected cases.Results: Results show that the trend of the epidemic mainly depends on quarantined and suspected cases. The predicted cumulative numbers of quarantined and suspected cases nearly reached static states, and their inflection points have already been achieved, with the epidemic's peak coming soon. The estimated effective reproduction numbers using model-free and model-based methods are decreasing, as well as new infections, while newly reported cases are increasing. Most infected cases have been quarantined or put in the suspected class, which has been ignored in existing models. Conclusions: The uncertainty analyses reveal that the epidemic is still uncertain, and it is important to continue enhancing the quarantine and isolation strategy and improving the detection rate in mainland China.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.