PDF(Pubmed)
Abstract：
Chronic liver disease (CLD) entails elevated risk of COVID-19 severity and mortality. The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear. Therefore, we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls (HC) to analyze neutralizing antibodies (NAbs) against SARS-CoV-2 prototype and BA.4/5 variant, anti-receptor binding domain (RBD) IgG, and total anti-SARS-CoV-2 antibodies. Serum levels of the total anti-SARS-CoV-2 antibodies, anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose, but were relatively lower than those of HCs. Induced humoral responses decreased over time after booster vaccination. The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold. All four SARS-CoV-2 antibodies, including total anti-SARS-CoV-2 antibodies, anti-RBD IgG and NAbs against prototype and BA.4/5, were lower in patients with severe CLD than those with non-severe CLD. After booster shot, age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients. Additionally, white blood cell counts and hepatitis B core antibodies were the protective factors, and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies. Overall, our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines. All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak. CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5, which hindered the protective effect of the booster shot against Omicron prevalence. Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.
摘要：
慢性肝病（CLD）导致COVID-19严重程度和死亡率的风险升高。灭活SARS-CoV-2疫苗的加强剂量在CLD患者中刺激抗体反应的有效性尚不清楚。因此,我们进行了一项横断面研究，包括237名成年CLD患者和170名健康对照（HC），以分析针对SARS-CoV-2原型和BA4/5变体的中和抗体（NAb）。抗受体结合域（RBD）IgG，和总的抗SARS-CoV-2抗体。血清总的抗SARS-CoV-2抗体水平,与加强前剂量相比，加强剂量后CLD患者的抗RBDIgG和NAb的抑制功效显着升高，但相对低于HC。增强疫苗接种后，诱导的体液反应随时间减少。血清对BA.4/5的中和效率增加，但仍低于抑制阈值。所有四种SARS-CoV-2抗体,包括总的抗SARS-CoV-2抗体,重度CLD患者的抗RBDIgG和针对原型和BA4/5的NAb低于非重度CLD患者。加强注射后，年龄和最后一次疫苗接种后的时间是CLD患者NAb对BA4/5血清阳性的危险因素.此外,白细胞计数和乙型肝炎核心抗体是保护因素，严重的肝脏疾病是与总的抗SARS-CoV-2抗体阳性相关的危险因素。总的来说,我们的数据发现,CLD患者的抗体应答得到改善,并在强化疫苗接种后120天达到峰值.除总的抗SARS-CoV-2抗体外，所有抗体在达到峰值后均下降。CLD患者对疫苗接种的免疫反应受损，对BA4/5的NAb减弱，这阻碍了加强注射对Omicron患病率的保护作用。应进一步评估细胞免疫反应，以确定CLD患者的最佳疫苗方案。
