Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2 A Prospective Cohort Study
Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2 A Prospective Cohort Study
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DOI：
10.7326/m21-1757
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发表时间：
2021-11-01
影响因子：
39.2
通讯作者：
Kim, Alfred H. J.
中科院分区：
文献类型：
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作者：
Deepak, Parakkal;Kim, Wooseob;Kim, Alfred H. J.
背景：接受免疫抑制药物治疗的慢性炎症性疾病（CID）患者患严重COVID-19的风险增加。虽然基于mRNA的SARS-CoV-2疫苗接种在免疫功能正常的人中提供保护，但免疫抑制CID患者的免疫原性尚不清楚。目的：确定基于mRNA的SARS-CoV-2疫苗在CID患者中的免疫原性。设计：前瞻性观察性队列研究。设置：两个美国CID转诊中心。参与者：符合早期COVID-19疫苗接种资格的确诊CID成人志愿者样本，包括任何年龄的医院员工和65岁以上的患者。免疫功能正常的参与者是从医院员工中单独招募的。所有参与者在2020年12月10日至2021年3月20日期间接受了2剂针对SARS-CoV-2的mRNA疫苗。参与者在接种疫苗前2周内和最后一次接种疫苗后20天内进行评估。测量：所有参与者的抗SARS-CoV-2刺突（S）IgG+结合，中和抗体滴度和循环S特异性浆母细胞亚群，以评估接种疫苗后的体液反应。在133名CID参与者中，（88.7%），所有53名免疫功能正常的参与者对基于mRNA的SARS-CoV-2疫苗接种产生了抗体，尽管一些CID患者的抗-S IgG滴度在数值上较低。接种疫苗后，接受糖皮质激素治疗的CID参与者（n= 17）的抗S IgG抗体滴度低于未接受糖皮质激素治疗的参与者;抗-S IgG抗体的几何平均数为357（95% CI，96 - 1324），接受泼尼松的受试者vs 2190在接受B细胞耗竭疗法（BCDT）的那些（n= 10）中，抗S IgG抗体滴度也较低。接受和未接受抗代谢药（n= 48）、肿瘤坏死因子抑制剂（n= 39）和Janus激酶抑制剂（n= 11）的受试者之间的免疫原性指标在数值上存在差异;然而，95% CI较宽且重叠。中和滴度似乎与抗S IgG结果基本一致。结果未调整基线临床因素的差异，包括其他免疫抑制剂therapy.Limitations：小样本，缺乏人口统计学多样性，和残留confounding.Conclusion：与非使用者相比，用糖皮质激素和BCDT治疗的CID患者似乎有较低的SARS-CoV-2疫苗诱导的抗体应答。这些初步的发现需要在一个更大的研究中得到证实。还有哈利B赫尔姆斯利慈善信托基金、马库斯精准医学创新计划、国家推进转化科学中心和国家关节炎、肌肉骨骼和皮肤病研究所。
Background: Patients with chronic inflammatory disease (CID) treated with immunosuppressive medications have increased risk for severe COVID-19. Although mRNA-based SARS-CoV-2 vaccination provides protection in immunocompetent persons, immunogenicity in immunosuppressed patients with CID is unclear.Objective: To determine the immunogenicity of mRNAbased SARS-CoV-2 vaccines in patients with CID.Design: Prospective observational cohort study.Setting: Two U.S. CID referral centers.Participants: Volunteer sample of adults with confirmed CID eligible for early COVID-19 vaccination, including hospital employees of any age and patients older than 65 years. Immunocompetent participants were recruited separately from hospital employees. All participants received 2 doses of mRNA vaccine against SARS-CoV-2 between 10 December 2020 and 20 March 2021. Participants were assessed within 2 weeks before vaccination and 20 days after final vaccination.Measurements: Anti-SARS-CoV-2 spike (S) IgG+ binding in all participants, and neutralizing antibody titers and circulating S-specific plasmablasts in a subset to assess humoral response after vaccination.Results: Most of the 133 participants with CID (88.7%) and all 53 immunocompetent participants developed antibodies in response to mRNA-based SARS-CoV-2 vaccination, although some with CID developed numerically lower titers of anti-S IgG. Anti-S IgG antibody titers after vaccination were lower in participants with CID receiving glucocorticoids (n= 17) than in those not receiving them; the geometric mean of anti-S IgG antibodies was 357 (95% CI, 96 to 1324) for participants receiving prednisone versus 2190 (CI, 1598 to 3002) for those not receiving it. Anti-S IgG antibody titers were also lower in those receiving B-cell depletion therapy (BCDT) (n= 10). Measures of immunogenicity differed numerically between those who were and those who were not receiving antimetabolites (n= 48), tumor necrosis factor inhibitors (n= 39), and Janus kinase inhibitors (n= 11); however, 95% CIs were wide and overlapped. Neutralization titers seemed generally consistent with anti-S IgG results.Results were not adjusted for differences in baseline clinical factors, including other immunosuppressant therapies.Limitations: Small sample that lacked demographic diversity, and residual confounding.Conclusion: Compared with nonusers, patients with CID treated with glucocorticoids and BCDT seem to have lower SARS-CoV-2 vaccine-induced antibody responses. These preliminary findings require confirmation in a larger study.Primary Funding Source: The Leona M. and Harry B. Helmsley Charitable Trust, Marcus Program in Precision Medicine Innovation, National Center for Advancing Translational Sciences, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.