Mass evaluation of lateral flow immunoassays for the detection of SARS-CoV-2 antibody responses in immunosuppressed people (MELODY Study)

用于检测免疫抑制人群中 SARS-CoV-2 抗体反应的侧流免疫分析的大规模评估（MELODY 研究）

• 批准号: MR/W029200/1
• 负责人: Michelle Willicombe
• 金额: $ 125.47万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW029200%2F1
• 关键词: Mass; evaluation; lateral; flow; immunoassays

Effective protection and management strategies of SARS-CoV-2 infection in the 500,000 immunosuppressed people in the UK have wide-reaching implications. Evidence has shown they are more likely to have severe infection with increased morbidity and mortality, even following 2 doses of SARS-CoV-2 vaccines. They are also more likely to have prolonged infection and viral shedding which enhances the potential to infect more people, and is a risk for promoting viral evolution and mutations.The 3rd vaccine dose roll out was welcome news for immunosuppressed people. However, a significant proportion of people with weakened immune systems will still not mount an immune response even after 3 doses. Research to understand their health protection needs now requires greater prioritisation. Emerging data suggest the following patient groups will be most at risk: solid organ transplant recipients, people with autoimmune disease receiving antibody directed immunosuppression, and people with blood cancer receiving treatment. Such people are likely to remain incompletely protected from severe forms of SARS-CoV-2 infection, and other strategies to protect them are required. Indeed, other mechanisms such as the use of passive immunity, via monoclonal antibody (MAb) use, have been shown to protect seronegative people whether used as pre-exposure or post-exposure prophylaxis. The REACT2 study monitored SARS-CoV-2 antibodies in the UK population using self-administered lateral flow immunoassays (LFIAs) at home. Although their sensitivity and specificity is lower than immunoassays using venous blood in the laboratory setting, their performance is sufficient for population level studies, and their use may be a pragmatic way to help screen and plan SARS-CoV-2 interventions in 'at risk' patient groups. The LFIA kits used in the REACT2 study will be used in the MELODY study, and have been evaluated in transplant recipients. Using the same methodology as the REACT2 study, this proposal, sponsored by Imperial College London plans to investigate the use of antibody detection in immunosuppressed people using LFIAs. Eligible people will be randomly identified using patient registries, the UK Transplant Registry and the National Disease Registration Service (NDRS) at Public Health England, which comprises the National Cancer Registration and Analysis Service (NCRAS) and the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS). Eligible patients with cancer (n=12,000) and autoimmune disease (n=12,000 ), will be invited by personal letter to join the study by Ipsos MORI. Transplant patients (n=12,000) will be able to opt-in via the study web portal hosted by Ipsos MORI. Following registration on the web portal, participants will be sent a LFIA test, which is provided with a detailed instruction booklet and link to an instruction video. Participants will be asked to carry out the test and follow the instructions to read the result. They will then complete a short online questionnaire including information on immunosuppression history, socio-demographic variables, shielding history and the test result. They will be asked to upload the photo of the test if possible. All the data from the questionnaires will be entered into a database and linked to the uploaded LFIA results. A telephone helpline will be established to deal with any queries that may arise. Once data is complete, a copy of the study database will be sent securely from Ipsos MORI to NHS Blood and Transplant and NDRS for data analysis. The initial data will enable an estimate of the proportion of immunosuppressed people who have detectable SARS-CoV-2 antibodies, and correlate antibody status with clinical and socio-demographic factors. The registries utilised have been linked with infection data, so will also be able to correlate antibody status with outcome following infection in these patients during the study follow up of 6 months.

在英国500,000人中，SARS-COV-2感染的有效保护和管理策略具有广泛的影响。证据表明，即使在2剂SARS-COV-2疫苗之后，它们也更有可能患有严重的发病率和死亡率。他们也更有可能长时间感染和病毒脱落，从而增强了感染更多人的潜力，并且是促进病毒进化和突变的风险。第三疫苗剂量引起了免疫抑制的人的欢迎消息。但是，即使在3剂后，很大一部分患有免疫系统弱的人仍然不会产生免疫反应。现在了解他们的健康保护需求的研究需要更高的优先级。新兴数据表明，以下患者组将处于最大风险：固体器官移植受者，接受抗体的自身免疫性疾病的患者定向免疫抑制，以及接受血液癌的患者接受治疗。这样的人可能不完全保护SARS-COV-2感染的严重形式，并且需要保护他们的其他策略。实际上，已证明其他机制，例如通过单克隆抗体（MAB）使用诸如使用被用作静态抗体的人（MAB）的使用，无论是用作静脉内的人，无论是用作暴露前还是暴露后预防。这项React2研究使用自我管理的侧向流免疫测定（LFIAS）在家中监测了英国种群中的SARS-COV-2抗体。尽管它们的敏感性和特异性低于在实验室中使用静脉血的免疫测定，但它们的表现足以进行人口水平的研究，并且它们的使用可能是一种实用的方式，可以帮助筛查和计划“处于风险”患者组中的SARS-COV-2干预措施。 React2研究中使用的LFIA试剂盒将用于旋律研究，并已在移植受者中进行了评估。使用与React2研究相同的方法，该提案由伦敦帝国学院（Imperial College）赞助，计划调查使用LFIA的免疫抑制人群中使用抗体检测的。符合条件的人将使用患者登记处，英国公共卫生登记局（NDRS）随机识别，该注册表（NDRS）包括国家癌症注册和分析服务（NCRAS）和国民先天性异常和罕见疾病登记局（NCARDRS）。合格的癌症患者（n = 12,000）和自身免疫性疾病（n = 12,000），将由个人信件邀请IPSOS Mori加入研究。移植患者（n = 12,000）将能够通过IPSOS MORI托管的研究网站选择加入。在Web门户网站上注册后，将向参与者发送LFIA测试，其中提供了详细的说明手册和指导视频链接。将要求参与者进行测试，并按照说明阅读结果。然后，他们将完成一份简短的在线问卷，包括有关免疫抑制历史，社会人口统计学变量，屏蔽历史和测试结果的信息。如果可能的话，将要求他们上传测试照片。来自问卷的所有数据都将输入到数据库中，并链接到上传的LFIA结果。将建立电话求助热线，以处理可能出现的任何查询。数据完成后，研究数据库的副本将从IPSOS MORI牢固地发送到NHS血液和移植和NDR，以进行数据分析。初始数据将估算具有可检测到的SARS-COV-2抗体的免疫抑制人群的比例，并将抗​​体状态与临床和社会人口统计学因素相关联。所用的注册表与感染数据有关，因此在研究期间，这些患者在6个月后的感染后也能够将抗体状态与感染后的结局相关联。

项目成果

Antibody prevalence after 3 or more COVID-19 vaccine doses in 23,000 immunosuppressed individuals: a cross-sectional study from MELODY

23,000 名免疫抑制个体接种 3 剂或以上 COVID-19 疫苗后的抗体流行率：MELODY 的一项横断面研究

• DOI: 10.1101/2023.02.09.23285649
• 发表时间: 2023
• 作者: Pearce F

Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODY

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
• 发表时间: 2023
• 期刊: The Lancet Rheumatology
• 作者: Pearce F