Background & Aims

Detailed information on the immune response after second vaccination of cirrhotic patients and liver transplant (LT) recipients against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is largely missing. We aimed at comparing the vaccine-induced humoral and T-cell responses of these vulnerable patient groups.

Methods

In this prospective cohort study, anti-SARS-CoV-2 spike-protein titers were determined using the DiaSorin LIAISON (anti-S trimer) and Roche Elecsys (anti-S RBD) immunoassays in 194 patients (141 LT, 53 cirrhosis Child-Pugh A-C) and 56 healthy controls before and 10 to 84 days after second vaccination. The spike-specific T-cell response was assessed using an interferon-gamma release assay (EUROIMMUN). A logistic regression analysis was performed to identify predictors of low response.

Results

After the second vaccination, seroconversion was achieved in 63% of LT recipients and 100% of cirrhotic patients and controls using the anti-S trimer assay. Median anti-SARS-CoV-2 titers of responding LT recipients were lower compared with cirrhotic patients and controls (P < .001). Spike-specific T-cell response rates were 36.6%, 65.4%, and 100% in LT, cirrhosis, and controls, respectively. Altogether, 28% of LT recipients did neither develop a humoral nor a T-cell response after second vaccination. In LT recipients, significant predictors of absent or low humoral response were age >65 years (odds ratio [OR], 4.57; 95% confidence interval [CI], 1.48-14.05) and arterial hypertension (OR, 2.50; 95% CI, 1.10-5.68), whereas vaccination failure was less likely with calcineurin inhibitor monotherapy than with other immunosuppressive regimens (OR, 0.36; 95% CI, 0.13-0.99).

Conclusion

Routine serological testing of the vaccination response and a third vaccination in patients with low or absent response seem advisable. These vulnerable cohorts need further research on the effects of heterologous vaccination and intermittent reduction of immunosuppression before booster vaccinations.

中文翻译：

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肝硬化和移植患者第二次接种后 SARS-CoV2 特异性体液和 T 细胞免疫反应

背景与目标

严重急性呼吸综合征冠状病毒 2 型 (SARS-CoV-2) 的肝硬化患者和肝移植 (LT) 接受者第二次接种疫苗后免疫反应的详细信息在很大程度上缺失。我们旨在比较这些易受攻击的患者群体的疫苗诱导的体液和 T 细胞反应。

方法

在这项前瞻性队列研究中，使用 DiaSorin LIAISON（抗 S 三聚体）和 Roche Elecsys（抗 S RBD）免疫测定法对 194 名患者（141 名 LT，53 名肝硬化儿童- Pugh AC) 和 56 名健康对照者在第二次接种疫苗之前和之后 10 至 84 天。使用干扰素-γ 释放测定 (EUROMMUN) 评估尖峰特异性 T 细胞反应。进行逻辑回归分析以确定低反应的预测因子。

结果

在第二次疫苗接种后，63% 的 LT 接受者和 100% 的肝硬化患者和对照使用抗 S 三聚体测定实现了血清转化。与肝硬化患者和对照组相比，有反应的 LT 接受者的中位抗 SARS-CoV-2 滴度较低（P< .001)。在 LT、肝硬化和对照组中，尖峰特异性 T 细胞反应率分别为 36.6%、65.4% 和 100%。总共有 28% 的 LT 接受者在第二次接种后既没有出现体液反应也没有出现 T 细胞反应。在 LT 受者中，体液反应缺失或低的显着预测因素是年龄 >65 岁（优势比 [OR]，4.57；95% 置信区间 [CI]，1.48-14.05）和动脉高血压（OR，2.50；95% CI， 1.10-5.68），而与其他免疫抑制方案相比，钙调神经磷酸酶抑制剂单药治疗的疫苗接种失败率较低（OR，0.36；95% CI，0.13-0.99）。

结论

对免疫反应低或无反应的患者进行常规血清学检测和第三次疫苗接种似乎是可取的。这些易受伤害的人群需要进一步研究异种疫苗接种的效果和加强疫苗接种前免疫抑制的间歇性降低。