Plasencia-Rodríguez Chamaida, Martínez-Feito Ana, Hernández Marta, Del Pino-Molina Lucia, Novella-Navarro Marta, Serrano Yolanda, González-Muñoz Miguel, Peiteado Diana, Bonilla Gema, Monjo Irene, Nuño Laura, Tornero Carolina, López-Granados Eduardo, Balsa Alejandro, Nozal Pilar
Rheumatology Unit, La Paz University Hospital, Paseo de la Castellana 261, 28046, Madrid, Spain.
Immunology, La Paz University Hospital, Madrid, Spain.
Allergy Asthma Clin Immunol. 2023 Aug 19;19(1):71. doi: 10.1186/s13223-023-00832-0.
Real world data on the response to the SARS-CoV-2 vaccine in patients with immunomediated diseases (IMIDs) treated with immunesuppressants is of great interest because vaccine response may be impaired. The main aim was to study the humoral and cellular immune response after SARS-CoV-2 vaccination in patients with IMIDs treated with immunosuppressants. The secondary aim was to describe the frequency of SARS-CoV-2 infections after vaccination in these patients.
This is an observational study including 86 patients with IMIDs. All patients were treated with biologic or targeted synthetic disease-modifying antirheumatic drugs [b/tsDMARDs: TNF inhibitors (TNFi), rituximab, anti-interleukin 6 receptor (anti-IL6R) or JAK inhibitors (JAKi)]. Demographic and clinical information were collected. After 4-6 weeks of 2nd and 3rd vaccine doses, humoral response was assessed using the Thermo Scientific ELiA SARS-CoV-2-Sp1 IgG Test. Also, in patients with serum SARS-CoV-2 antibody levels under 100UI/ml, cellular response was analyzed using the QuantiFERON SARS-CoV-2 Starter Pack.
A total of 86 patients under b/tsDMARDs and 38 healthy controls were included. Most patients received TNFi (45 with TNFi, 31 with rituximab, 5 with anti-IL6R and 5 with JAKi). SARS-CoV-2 antibodies (Ab) were present in an 86% of patients with IMIDs and in 100% healthy controls (p = 0.017). However, 12 (14%) patients had undetectable SARS-CoV-2 Ab levels, all treated with rituximab. In addition, SARS-CoV-2 Ab (IU/ml) were statistically lower in patients (Mdn (IQR): 59.5 (17-163) in patients vs 625 (405-932) in controls, p < 0.001). Patients treated with rituximab had lower Ab levels than those treated with TNFi and controls (p < 0.001). The cellular response to SARS-CoV-2 vaccine was evaluated in 30 patients. Eleven patients had a positive cellular response, being more frequent in patients treated with rituximab (p = 0.03). SARS-CoV-2 infection was reported in 43% of patients and 34% of controls after vaccination. Only 6 (7%) patients required hospitalization, most of whom treated with rituximab (67%).
SARS-CoV-2 antibody levels were lower in patients than in controls, especially in patients treated with rituximab. A cellular response can be detected despite having a poor humoral response. Severe infections in vaccinated patients with IMIDs are rare, and are observed mainly in patients treated with rituximab.
免疫介导疾病（IMIDs）患者使用免疫抑制剂治疗后对SARS-CoV-2疫苗的反应的真实世界数据备受关注，因为疫苗反应可能受损。主要目的是研究使用免疫抑制剂治疗的IMIDs患者接种SARS-CoV-2疫苗后的体液和细胞免疫反应。次要目的是描述这些患者接种疫苗后SARS-CoV-2感染的频率。
这是一项观察性研究，纳入了86例IMIDs患者。所有患者均接受生物制剂或靶向合成的改善病情抗风湿药物[b/tsDMARDs：肿瘤坏死因子抑制剂（TNFi）、利妥昔单抗、抗白细胞介素6受体（抗IL6R）或JAK抑制剂（JAKi）]治疗。收集了人口统计学和临床信息。在第2剂和第3剂疫苗接种4 - 6周后，使用赛默飞世尔科技的酶联免疫吸附测定（ELiA）SARS-CoV-2-Sp1 IgG检测试剂盒评估体液反应。此外，对于血清SARS-CoV-2抗体水平低于100 UI/ml的患者，使用定量干扰素γ释放试验（QuantiFERON）SARS-CoV-2起始试剂盒分析细胞反应。
共纳入86例接受b/tsDMARDs治疗的患者和38例健康对照。大多数患者接受TNFi治疗（45例接受TNFi，31例接受利妥昔单抗，5例接受抗IL6R，5例接受JAKi）。86%的IMIDs患者和100%的健康对照中存在SARS-CoV-2抗体（Ab）（p = 0.017）。然而，12例（14%）患者的SARS-CoV-2 Ab水平检测不到，所有这些患者均接受利妥昔单抗治疗。此外，患者的SARS-CoV-2 Ab（IU/ml）在统计学上低于对照组（患者中位数（四分位间距）：59.5（17 - 163），对照组为625（405 - 932），p < 0.001）。接受利妥昔单抗治疗的患者的Ab水平低于接受TNFi治疗的患者和对照组（p < 0.001）。对30例患者评估了对SARS-CoV-2疫苗的细胞反应。11例患者细胞反应呈阳性，在接受利妥昔单抗治疗的患者中更常见（p = 0.03）。接种疫苗后，43%的患者和34%的对照报告发生SARS-CoV-2感染。只有6例（7%）患者需要住院治疗，其中大多数接受利妥昔单抗治疗（67%）。
患者的SARS-CoV-2抗体水平低于对照组，尤其是接受利妥昔单抗治疗的患者。尽管体液反应不佳，但仍可检测到细胞反应。接种疫苗的IMIDs患者中严重感染很少见，主要见于接受利妥昔单抗治疗的患者。
