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.

有效预防和管理英国50万免疫抑制人群中的SARS-CoV-2感染具有广泛的意义。有证据表明，即使在接种了两剂SARS-CoV-2疫苗后，他们也更有可能患上严重感染，发病率和死亡率增加。他们也更有可能长期感染和病毒脱落，这增加了感染更多人的可能性，也是促进病毒进化和突变的风险。第三剂疫苗的推出对免疫抑制的人来说是个好消息。然而，相当大比例的免疫系统减弱的人即使在接种了3剂疫苗后仍不会产生免疫反应。为了了解他们的健康保护需求，研究现在需要更优先考虑。新出现的数据表明，以下患者群体面临的风险最大：实体器官移植接受者，接受抗体导向免疫抑制的自身免疫性疾病患者，以及接受治疗的血癌患者。这些人很可能仍然不能完全免受严重形式的SARS-CoV-2感染，因此需要采取其他战略来保护他们。事实上，其他机制，如使用被动免疫，通过使用单抗(MAb)，已被证明可以保护血清阴性者，无论是作为暴露前预防还是暴露后预防。REACT2研究使用在家中自我管理的横向流动免疫分析(LFIA)来监测英国人群中的SARS-CoV-2抗体。尽管它们的灵敏度和特异度低于实验室中使用静脉血液的免疫分析，但它们的性能足以进行人群水平的研究，而且它们的使用可能是一种实用的方法，有助于在“高危”患者群体中筛选和计划SARS-CoV-2干预措施。REACT2研究中使用的LFIA试剂盒将用于Melody研究，并已在移植接受者中进行评估。使用与REACT2研究相同的方法，这项由伦敦帝国理工学院赞助的提案计划调查在使用LFIA的免疫抑制患者中使用抗体检测的情况。符合条件的人将通过患者登记、英国移植登记和英格兰公共卫生的国家疾病登记服务(NDRS)随机确定，该服务由国家癌症登记和分析服务(NCRAS)和国家先天性异常和罕见疾病登记服务(NCARDRS)组成。符合条件的癌症患者(n=12,000)和自身免疫性疾病患者(n=12,000)将通过私人信件邀请加入Ipsos MORI的研究。移植患者(n=12,000)将能够通过Ipsos MORI主办的研究门户网站选择加入。在门户网站上注册后，将向参与者发送LFIA测试，其中提供了详细的指导手册并链接到指导视频。参与者将被要求进行测试，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，其中包括免疫抑制史、社会人口变量、屏蔽史和测试结果等信息。如果可能，他们将被要求上传测试的照片。调查问卷的所有数据将被输入数据库，并与上传的LFIA结果相关联。当局将设立电话求助热线，处理可能出现的任何查询。一旦数据完成，研究数据库的副本将从益普索MORI安全地发送到NHS血液与移植和NDRS进行数据分析。最初的数据将使人们能够估计免疫抑制人群中可检测到SARS-CoV-2抗体的比例，并将抗体状况与临床和社会人口因素联系起来。使用的登记已与感染数据相联系，因此在6个月的研究跟踪期间，还将能够将这些患者的抗体状况与感染后的结果联系起来。

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