mRNA新冠疫苗接种后肝硬化患者中严重急性呼吸综合征冠状病毒2特异性T细胞反应受损。
Impaired SARS-CoV-2-specific T-cell reactivity in patients with cirrhosis following mRNA COVID-19 vaccination.
作者信息
Al-Dury Samer, Waern Johan, Waldenström Jesper, Alavanja Marko, Saed Hevar Hamah, Törnell Andreas, Arabpour Mohammad, Wiktorin Hanna Grauers, Einarsdottir Sigrun, Ringlander Johan, Ringström Gisela, Hellstrand Kristoffer, Martner Anna, Lagging Martin
机构信息
Department of Medicine, Gastroenterology and Hepatology Unit, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
出版信息
JHEP Rep. 2022 Jul;4(7):100496. doi: 10.1016/j.jhepr.2022.100496. Epub 2022 Apr 27.
BACKGROUND & AIMS: Cirrhosis entails elevated risk of COVID-19-associated mortality. This study determined T cell-mediated and antibody reactivity against the spike 1 (S1) protein of SARS-CoV-2 among 48 patients with cirrhosis and 39 healthy controls after mRNA COVID-19 vaccination.
METHODS
SARS-CoV-2-specific T-cell reactivity was measured by induced level of T cell-derived interferon-γ (IFN-γ) in blood cells stimulated with multimeric peptides spanning the N-terminal portion of S1. S1-induced IFN-γ was quantified before and after the 1 and 2 vaccination (BNT162b2, Pfizer-BioNTech or mRNA-1273, Moderna) alongside serum IgG against the receptor-binding domain (RBD) within S1 (anti-RBD-S1 IgG).
RESULTS
T-cell reactivity against S1 was reduced in patients with cirrhosis after the 1 (0.001 controls) and 2 (0.001) vaccination. Sixty-eight percent of patients lacked detectable S1-specific T-cell reactivity after the 1 vaccination 19% in controls (odds ratio 0.11, 95% CI 0.03-0.48, 0.003) and 36% remained devoid of reactivity after the 2 vaccination 6% in controls (odds ratio 0.12, 95% CI 0.03-0.59, 0.009). T-cell reactivity in cirrhosis remained significantly impaired after correction for potential confounders in multivariable analysis. Advanced cirrhosis (Child-Pugh class B) was associated with absent or lower T-cell responses (0.05 Child-Pugh class A). The deficiency of T-cell reactivity was paralleled by lower levels of anti-RBD-S1 IgG after the 1 (0.001 controls) and 2 (0.05) vaccination.
CONCLUSIONS
Patients with cirrhosis show deficient T-cell reactivity against SARS-CoV-2 antigens along with diminished levels of anti-RBD-S1 IgG after dual COVID-19 vaccination, highlighting the need for vigilance and additional preventative measures.
CLINICAL TRIAL REGISTRATION
EudraCT 2021-000349-42.
LAY SUMMARY
T cells are a pivotal component in the defence against viruses. We show that patients with cirrhosis have impaired SARS-CoV-2-specific T-cell responses and lower antibody levels after mRNA vaccination against COVID-19 compared with healthy controls. Patients with more advanced liver disease exhibited particularly inferior vaccine responses. These results call for additional preventative measures in these patients.
背景与目的
肝硬化会增加新冠病毒 2019 相关死亡风险。本研究测定了 48 例肝硬化患者和 39 例健康对照在接种新冠 mRNA 疫苗后针对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）刺突 1（S1）蛋白的 T 细胞介导反应和抗体反应性。
方法
通过用跨越 S1 蛋白 N 端部分的多聚体肽刺激血细胞后诱导产生的 T 细胞衍生干扰素-γ（IFN-γ）水平来测量 SARS-CoV-2 特异性 T 细胞反应性。在第 1 剂和第 2 剂疫苗接种（BNT162b2，辉瑞 - 生物科技公司或 mRNA-1273，莫德纳公司）前后，对 S1 诱导的 IFN-γ 以及针对 S1 内受体结合域（RBD）的血清 IgG（抗 RBD-S1 IgG）进行定量。
结果
在接种第 1 剂（P = 0.001，与对照组相比）和第 2 剂（P = 0.001）疫苗后，肝硬化患者对 S1 的 T 细胞反应性降低。68%的患者在接种第 1 剂疫苗后缺乏可检测到的 S1 特异性 T 细胞反应性，而对照组为 19%（优势比 0.11，95%置信区间 0.03 - 0.48，P = 0.003）；36%的患者在接种第 2 剂疫苗后仍无反应性，而对照组为 6%（优势比 0.12，95%置信区间 0.03 - 0.59，P = 0.009）。在多变量分析中校正潜在混杂因素后，肝硬化患者的 T 细胞反应性仍显著受损。晚期肝硬化（Child-Pugh B 级）与无或较低的 T 细胞反应相关（P = 0.05，与 Child-Pugh A 级相比）。T 细胞反应性不足与接种第 1 剂（P = 0.001，与对照组相比）和第 2 剂（P = 0.05）疫苗后抗 RBD-S1 IgG 水平较低相平行。
结论
肝硬化患者在接种两剂新冠疫苗后，对 SARS-CoV-2 抗原的 T 细胞反应性不足，同时抗 RBD-S1 IgG 水平降低，这凸显了保持警惕和采取额外预防措施的必要性。
临床试验注册号
EudraCT 2021-000349-42。
简要概述
T 细胞是抵御病毒的关键组成部分。我们发现，与健康对照相比，肝硬化患者在接种新冠 mRNA 疫苗后，针对 SARS-CoV-2 的特异性 T 细胞反应受损，抗体水平较低。肝病更严重的患者疫苗反应尤其较差。这些结果呼吁对这些患者采取额外的预防措施。
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