Dailey Joelynn, Kozhaya Lina, Dogan Mikail, Hopkins Dena, Lapin Blaine, Herbst Katherine, Brimacombe Michael, Grandonico Kristen, Karabacak Faith, Schreiber John, Liang Bruce Tsan-Liang, Salazar Juan C, Unutmaz Derya, Hyams Jeffrey S
medRxiv. 2021 Jun 15:2021.06.12.21258810. doi: 10.1101/2021.06.12.21258810.
Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial.
e performed a prospective longitudinal cohort study evaluating SARS-CoV-2 Spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines. IgG antibody to the spike protein binding domain of SARS-CoV-2 was assayed with a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. A sensitive and high-throughput neutralization assay that incorporates SARS-CoV-2 Spike protein onto a lentivirus and measures pseudoviral entry into ACE2 expressing HEK-293 cells was used.
436 patients were enrolled (mean age 17 years, range 2-26 years, 58% male, 71% Crohn’s disease, 29% ulcerative colitis, IBD-unspecified). 44 (10%) of enrolled subjects had SARS-CoV-2 S-RBD IgG antibodies. Compared to non-IBD adults (ambulatory) and hospitalized pediatric patients with PCR documented SARS-CoV-2 infection, S-RBD IgG antibody levels were significantly lower in the IBD cohort and by 6 months post infection most patients lacked neutralizing antibody. Following vaccination (n=33) patients had a 15-fold higher S-RBD antibody response in comparison to natural infection, and all developed neutralizing antibodies to both wild type and variant SARS-CoV-2.
The lower and less durable SARS-CoV-2 S-RBD IgG response to natural infection in IBD patients receiving biologics puts them at risk of reinfection. The robust response to immunization is likely protective.
Our study showed a low and poorly durable SARS-CoV-2 S-RBD neutralizing IgG response to natural infection in IBD patients receiving biologics potentially putting them at risk of reinfection. However, they also had a robust response to immunization that is likely protective.
对于接受生物疗法的炎症性肠病（IBD）儿童和青年，其针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染或疫苗接种的中和抗体特征至关重要。
我们开展了一项前瞻性纵向队列研究，评估接受英夫利昔单抗或维多珠单抗治疗的IBD患者中SARS-CoV-2刺突蛋白受体结合域（S-RBD）IgG阳性情况以及一致的临床症状。在患者接种获批疫苗后也采集了血清。采用基于荧光微球的免疫测定法检测针对SARS-CoV-2刺突蛋白结合域的IgG抗体，该方法利用流式细胞术检测荧光分子的高动态范围。使用一种灵敏且高通量的中和测定法，该方法将SARS-CoV-2刺突蛋白整合到慢病毒上，并检测假病毒进入表达血管紧张素转换酶2（ACE2）的人胚肾293（HEK-293）细胞的情况。
共纳入436例患者（平均年龄17岁，范围2至26岁，58%为男性，71%为克罗恩病，29%为溃疡性结肠炎，未明确类型的IBD）。44例（10%）纳入研究的受试者具有SARS-CoV-2 S-RBD IgG抗体。与非IBD成年人（门诊患者）以及经聚合酶链反应（PCR）确诊感染SARS-CoV-2的住院儿科患者相比，IBD队列中的S-RBD IgG抗体水平显著更低，且感染后6个月时大多数患者缺乏中和抗体。接种疫苗后（n = 33），患者的S-RBD抗体反应比自然感染高15倍，并且所有患者均产生了针对野生型和变异型SARS-CoV-2的中和抗体。
接受生物制剂治疗的IBD患者对自然感染的SARS-CoV-2 S-RBD IgG反应较低且持续时间较短，这使他们面临再次感染的风险。对疫苗接种的强烈反应可能具有保护作用。
我们的研究表明，接受生物制剂治疗的IBD患者对自然感染的SARS-CoV-2 S-RBD中和IgG反应较低且持续时间较短，这可能使他们面临再次感染的风险。然而，他们对疫苗接种也有强烈反应，这可能具有保护作用。
