Deepak Parakkal, Kim Wooseob, Paley Michael A, Yang Monica, Carvidi Alexander B, Demissie Emanuel G, El-Qunni Alia A, Haile Alem, Huang Katherine, Kinnett Baylee, Liebeskind Mariel J, Liu Zhuoming, McMorrow Lily E, Paez Diana, Pawar Niti, Perantie Dana C, Schriefer Rebecca E, Sides Shannon E, Thapa Mahima, Gergely Maté, Abushamma Suha, Akuse Sewuese, Klebert Michael, Mitchell Lynne, Nix Darren, Graf Jonathan, Taylor Kimberly E, Chahin Salim, Ciorba Matthew A, Katz Patricia, Matloubian Mehrdad, O'Halloran Jane A, Presti Rachel M, Wu Gregory F, Whelan Sean P J, Buchser William J, Gensler Lianne S, Nakamura Mary C, Ellebedy Ali H, Kim Alfred H J
Washington University School of Medicine, St. Louis, Missouri (P.D., W.K., M.A.P., A.A.E., A.H., K.H., B.K., M.J.L., Z.L., L.E.M., D.C.P., R.E.S., S.E.S., M.T., M.G., S.A., S.A., M.K., L.M., D.N., S.C., M.A.C., J.A.O., R.M.P., G.F.W., S.P.W., W.J.B., A.H.E., A.H.K.).
University of California San Francisco, San Francisco, California (M.Y., A.B.C., E.G.D., D.P., N.P., J.G., K.E.T., P.K., M.M.).
Ann Intern Med. 2021 Nov;174(11):1572-1585. doi: 10.7326/M21-1757. Epub 2021 Aug 31.
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.
To determine the immunogenicity of mRNA-based SARS-CoV-2 vaccines in patients with CID.
Prospective observational cohort study.
Two U.S. CID referral centers.
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.
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.
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 ( = 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) ( = 10). Measures of immunogenicity differed numerically between those who were and those who were not receiving antimetabolites ( = 48), tumor necrosis factor inhibitors ( = 39), and Janus kinase inhibitors ( = 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.
Small sample that lacked demographic diversity, and residual confounding.
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.
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.
接受免疫抑制药物治疗的慢性炎症性疾病（CID）患者感染重症 COVID-19 的风险增加。尽管基于 mRNA 的 SARS-CoV-2 疫苗可在免疫功能正常的人群中提供保护，但在免疫抑制的 CID 患者中的免疫原性尚不清楚。
确定基于 mRNA 的 SARS-CoV-2 疫苗在 CID 患者中的免疫原性。
前瞻性观察队列研究。
两个美国 CID 转诊中心。
确诊 CID 且有资格早期接种 COVID-19 疫苗的成年志愿者样本，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从医院员工中单独招募。所有参与者在 2020 年 12 月 10 日至 2021 年 3 月 20 日期间接受 2 剂针对 SARS-CoV-2 的 mRNA 疫苗。在接种疫苗前 2 周内和最后一剂疫苗接种后 20 天对参与者进行评估。
所有参与者的抗 SARS-CoV-2 刺突（S）IgG 结合情况，以及一部分参与者的中和抗体滴度和循环 S 特异性浆母细胞，以评估接种疫苗后的体液反应。
133 名 CID 参与者中的大多数（88.7%）和所有 53 名免疫功能正常的参与者在接种基于 mRNA 的 SARS-CoV-2 疫苗后产生了抗体，尽管一些 CID 患者产生的抗 S IgG 滴度在数值上较低。接受糖皮质激素治疗的 CID 参与者（n = 17）接种疫苗后的抗 S IgG 抗体滴度低于未接受糖皮质激素治疗的参与者；接受泼尼松治疗的参与者抗 S IgG 抗体的几何平均值为 357（95%CI，96 至 1324），而未接受治疗的参与者为 2190（CI，1598 至 3002）。接受 B 细胞清除疗法（BCDT）的参与者（n = 10）的抗 S IgG 抗体滴度也较低。接受抗代谢药物（n = 48）、肿瘤坏死因子抑制剂（n = 39）和 Janus 激酶抑制剂（n = 11）的参与者与未接受这些药物的参与者在免疫原性测量值上在数值上有所不同；然而，95%CI 范围较宽且有重叠。中和滴度似乎总体上与抗 S IgG 结果一致。结果未针对基线临床因素（包括其他免疫抑制疗法）的差异进行调整。
样本量小且缺乏人口统计学多样性，存在残余混杂因素。
与未使用者相比，接受糖皮质激素和 BCDT 治疗的 CID 患者似乎对 SARS-CoV-2 疫苗诱导的抗体反应较低。这些初步发现需要在更大规模的研究中得到证实。
利昂娜·M. 和哈里·B. 赫尔姆斯利慈善信托基金、精准医学创新马库斯项目、国家推进转化科学中心以及国家关节炎、肌肉骨骼和皮肤病研究所。
