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COVID-19 疫苗接种在真实环境下的自身免疫性炎症性风湿病患者中的体液和细胞反应。

Humoral and cellular response to COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases under real-life conditions.

机构信息

Rheumatology Unit, Clinic for Endocrinology, Nephrology and Rheumatology, Department of Internal Medicine, Neurology and Dermatology.

Institute of Medical Microbiology and Virology.

出版信息

Rheumatology (Oxford). 2022 Jun 28;61(SI2):SI180-SI188. doi: 10.1093/rheumatology/keac089.

Abstract

OBJECTIVES

Successful vaccination is key to overcoming the COVID-19 pandemic. Immunosuppressive medication is known to potentially compromise vaccination responses, and expansion of our knowledge on vaccination efficacy in patients with autoimmune inflammatory rheumatic diseases (AIIRD) is therefore of utmost importance.

METHODS

We conducted a single-centre observational study and evaluated the efficacy of approved COVID-19 vaccines in 303 adult AIIRD patients. Serum levels of IgG antibodies against the S1 subunit of SARS-CoV-2 spike proteins (anti-S IgG) were measured at least two weeks after vaccination. In a subgroup of patients without humoral response, T-cell responses were determined using an interferon-γ gamma release assay.

RESULTS

Overall seropositivity rate was 78.5% and was significantly lower in patients under immunosuppressive therapy (75.7 vs 93.2%, P = 0.009). No difference regarding the vaccination type was observed. Glucocorticoids, mycophenolate-mofetil, TNF inhibitors, tocilizumab, abatacept and rituximab were all associated with non-response after proper vaccination. The risk was highest under RTX therapy (OR 0.004, 95% CI 0.001, 0.023, P < 0.0001). A strong negative correlation was observed between time since vaccination with an mRNA vaccine and anti-S antibody levels (r=-0.6149, P < 0.0001). In patients without humoral response, a T-cell response was found in 50%.

CONCLUSIONS

COVID-19 vaccination in patients with AIIRD is effective using any approved vaccine. Humoral response might be impaired depending on the individual immunosuppressive medication. The risk of non-response is highest under rituximab therapy. Anti-S IgG antibody levels wane over time after mRNA vaccination. Importantly, 50% of humoral non-responders showed a T-cellular response, suggesting T-cell-mediated protection to a certain extent.

摘要

目的

成功接种疫苗是克服 COVID-19 大流行的关键。已知免疫抑制药物可能会影响疫苗接种反应,因此扩大我们对自身免疫性炎症性风湿病(AIIRD)患者疫苗接种效果的认识至关重要。

方法

我们进行了一项单中心观察性研究,评估了 303 例成年 AIIRD 患者中已批准的 COVID-19 疫苗的疗效。在接种疫苗至少两周后,测量针对 SARS-CoV-2 刺突蛋白 S1 亚单位的 IgG 抗体(抗-S IgG)的血清水平。在无体液反应的患者亚组中,使用干扰素-γ释放试验测定 T 细胞反应。

结果

总体血清阳性率为 78.5%,接受免疫抑制治疗的患者明显较低(75.7%比 93.2%,P=0.009)。未观察到疫苗类型的差异。糖皮质激素、霉酚酸酯、TNF 抑制剂、托珠单抗、阿巴西普和利妥昔单抗在适当接种疫苗后均与无反应相关。RTX 治疗的风险最高(OR 0.004,95%CI 0.001,0.023,P<0.0001)。在接受 mRNA 疫苗接种的患者中,疫苗接种时间与抗-S 抗体水平呈强烈负相关(r=-0.6149,P<0.0001)。在无体液反应的患者中,发现有 50%的患者存在 T 细胞反应。

结论

在 AIIRD 患者中,任何已批准的疫苗接种 COVID-19 都是有效的。根据个体免疫抑制药物的不同,体液反应可能会受损。在利妥昔单抗治疗下,无反应的风险最高。mRNA 疫苗接种后,抗-S IgG 抗体水平随时间推移而下降。重要的是,50%的体液无反应者表现出 T 细胞反应,这表明在一定程度上存在 T 细胞介导的保护。

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