Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODY
Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODY
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英国免疫抑制个体接种三剂或三剂以上 COVID-19 疫苗后的抗体流行率：MELODY 的一项横断面研究
DOI：
10.1016/s2665-9913(23)00160-1
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Pearce F
中科院分区：
文献类型：
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作者：
Pearce F
背景在英国，向免疫抑制的人提供额外的 COVID-19 疫苗加强剂量和治疗，以预防严重的 COVID-19，但如何最好地选择接受这些疫苗加强剂量和治疗的个人尚不清楚。我们在三组免疫抑制人群中研究了至少三种 COVID-19 疫苗后，SARS-CoV-2 刺突蛋白血清阳性与人口统计学、疾病和治疗相关特征之间的关联。方法在一项使用英国国家疾病登记处的横断面研究中，我们确定、联系和招募了实体器官移植的接受者、患有罕见自身免疫性风湿病的参与者以及患有淋巴恶性肿瘤的 18 岁或以上的参与者，居住在英国，并且已接种至少三剂 COVID-19 疫苗。该研究于 2021 年 12 月 7 日至 2022 年 6 月 26 日期间开放招募。参与者在家中完成了 SARS-CoV-2 刺突抗体的侧流免疫测定测试，并收到了一份在线调查问卷。使用多变量逻辑回归来估计针对每个特征的血清阳性率的相互调整几率。结果在2022年2月14日至6月26日期间，我们筛查了101 972人（98 725人受邀，3247人自行登记）并招募了28 411人（27·9%）参与研究。 23 036 (81·1%) 招募的个体提供了血清学数据。其中，9927例（43·1%）接受实体器官移植，6516例（28·3%）患有罕见的自身免疫性风湿病，6593例（28·6%）患有淋巴恶性肿瘤。 10 485 (45·5%) 参与者为男性，12 535 (54·4%) 为女性（16 [<0·1%] 参与者未报告性别），21661 (94·0%) 参与者为白人。实体器官移植参与者的中位年龄为 60 岁 (SD 50-67)，罕见自身免疫性风湿病参与者的中位年龄为 65 岁 (54-73)，淋巴恶性肿瘤参与者的中位年龄为 69 岁 (61-75)。在有血清学数据的 23 036 名参与者中，6583 名 (28·6%) 接受了三剂疫苗，14 234 名 (61·8%) 接受了四剂疫苗，2219 名 (9·6%) 接受了五剂或更多疫苗。 9927 例实体器官移植患者中的 2310 例 (23·3%)、6516 例罕见自身免疫性风湿病患者中的 922 例 (14·1%) 以及 6593 例淋巴恶性肿瘤患者中的 1366 例 (20·7%) 未检测到 IgG 抗刺突抗体。在所有组中，血清阳性均与年龄较小、疫苗剂量较多（即五剂对三剂）以及既往感染过 COVID-19 相关。免疫抑制药物降低了血清阳性的可能性：接受抗增殖剂、钙调神经磷酸酶抑制剂和类固醇联合治疗的实体器官移植受者，以及患有罕见自身免疫性风湿病或接受抗 CD20 疗法治疗的淋巴恶性肿瘤的实体器官移植受者中，血清阳性的几率最低。解释 大约五分之一的实体器官移植受者患有罕见自身免疫性风湿病疾病和淋巴恶性肿瘤患者尽管接种了三剂或三剂以上疫苗，但仍没有可检测到的 IgG 抗尖峰抗体，但这一比例随着连续加强剂量的增加而降低。免疫抑制剂和疾病类型的选择与血清学反应密切相关。使用侧流免疫分析测试进行抗体测试可以快速识别最有可能从额外的 COVID-19 干预措施中受益的个体。FundingUK Research and Innovation、Kidney Research UK、Blood Cancer UK、Vasculitis UK 和 Cystic Fibrosis Trust。
BackgroundIn the UK, additional COVID-19 vaccine booster doses and treatments are offered to people who are immunosuppressed to protect against severe COVID-19, but how best to choose the individuals that receive these vaccine booster doses and treatments is unclear. We investigated the association between seropositivity to SARS-CoV-2 spike protein with demographic, disease, and treatment-related characteristics after at least three COVID-19 vaccines in three cohorts of people who are immunosuppressed.MethodsIn a cross-sectional study using UK national disease registries, we identified, contacted, and recruited recipients of solid organ transplants, participants with rare autoimmune rheumatic diseases, and participants with lymphoid malignancies who were 18 years or older, resident in the UK, and who had received at least three doses of a COVID-19 vaccine. The study was open to recruitment from Dec 7, 2021, to June 26, 2022. Participants received a lateral flow immunoassay test for SARS-CoV-2 spike antibodies to complete at home, and an online questionnaire. Multivariable logistic regression was used to estimate the mutually adjusted odds of seropositivity against each characteristic.FindingsBetween Feb 14 and June 26, 2022, we screened 101 972 people (98 725 invited, 3247 self-enrolled) and recruited 28 411 (27·9%) to the study. 23 036 (81·1%) recruited individuals provided serological data. Of these, 9927 (43·1%) were recipients of solid organ transplants, 6516 (28·3%) had rare autoimmune rheumatic diseases, and 6593 (28·6%) had lymphoid malignancies. 10 485 (45·5%) participants were men and 12 535 (54·4%) were women (gender was not reported for 16 [<0·1%] participants), and 21661 (94·0%) participants were of White ethnicity. The median age of participants with solid organ transplants was 60 years (SD 50–67), with rare autoimmune rheumatic diseases was 65 years (54–73), and with lymphoid malignancy was 69 years (61–75). Of the 23 036 participants with serological data, 6583 (28·6%) had received three vaccine doses, 14 234 (61·8%) had received four vaccine doses, and 2219 (9·6%) had received five or more vaccine doses. IgG anti-spike antibodies were undetectable in 2310 (23·3%) of 9927 patients with solid organ transplants, 922 (14·1%) of 6516 patients with rare autoimmune rheumatic diseases, and 1366 (20·7%) of 6593 patients with lymphoid malignancies. In all groups, seropositivity was associated with younger age, higher number of vaccine doses (ie, fivevsthree), and previous COVID-19. Immunosuppressive medication reduced the likelihood of seropositivity: the lowest odds of seropositivity were found in recipients of solid organ transplants receiving a combination of an anti-proliferative agent, a calcineurin inhibitor, and steroids, and those with rare autoimmune rheumatic diseases or lymphoid malignancies treated with anti-CD20 therapies.InterpretationApproximately one in five recipients of solid organ transplants, individuals with rare autoimmune rheumatic diseases, and individuals with lymphoid malignancies have no detectable IgG anti-spike antibodies despite three or more vaccine doses, but this proportion decreases with sequential booster doses. Choice of immunosuppressant and disease type is strongly associated with serological response. Antibody testing using lateral flow immunoassay tests could enable rapid identification of individuals who are most likely to benefit from additional COVID-19 interventions.FundingUK Research and Innovation, Kidney Research UK, Blood Cancer UK, Vasculitis UK and the Cystic Fibrosis Trust.