Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
Department of Clinical Laboratory, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, 050021, China.
Virol Sin. 2023 Oct;38(5):723-734. doi: 10.1016/j.virs.2023.07.005. Epub 2023 Jul 22.
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.
慢性肝病（CLD）使 COVID-19 严重程度和死亡率的风险升高。在 CLD 患者中，灭活 SARS-CoV-2 疫苗加强针刺激抗体反应的效果尚不清楚。因此，我们进行了一项横断面研究，纳入了 237 例成年 CLD 患者和 170 例健康对照（HC），以分析针对 SARS-CoV-2 原型和 BA.4/5 变异株的中和抗体（NAb）、抗受体结合域（RBD）IgG 和总抗 SARS-CoV-2 抗体。与加强针前相比，加强针后 CLD 患者的总抗 SARS-CoV-2 抗体、抗 RBD IgG 和 NAb 的抑制效率均显著升高，但仍低于 HC。加强针接种后，诱导的体液免疫反应随时间逐渐下降。血清对 BA.4/5 的中和效率增加，但仍低于抑制阈值。在 CLD 患者中，所有四种 SARS-CoV-2 抗体（包括总抗 SARS-CoV-2 抗体、抗 RBD IgG 和针对原型和 BA.4/5 的 NAb）均低于非严重 CLD 患者。加强针后，年龄和上次接种疫苗后的时间是 CLD 患者对 BA.4/5 的 NAb 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，严重肝病是与总抗 SARS-CoV-2 抗体血清阳性相关的危险因素。总的来说，我们的数据揭示了 CLD 患者的抗体反应得到了改善，并在加强针后 120 天达到峰值。所有抗体（除总抗 SARS-CoV-2 抗体外）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 BA.4/5 的 NAb 减弱，这阻碍了加强针针对奥密克戎流行的保护作用。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。
