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

英国50万免疫抑制人群中SARS-CoV-2感染的有效保护和管理策略具有广泛的意义。有证据表明，即使接种了两剂SARS-CoV-2疫苗，他们更有可能发生严重感染，发病率和死亡率也会增加。他们也更有可能有长时间的感染和病毒脱落，这增加了感染更多人的可能性，并有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人群来说是个好消息。然而，很大一部分免疫系统较弱的人即使注射了三剂也不会产生免疫反应。现在需要更加重视了解他们健康保护需求的研究。新出现的数据表明，以下患者群体将面临最大的风险：实体器官移植受者、接受抗体定向免疫抑制的自身免疫性疾病患者和接受治疗的血癌患者。这些人可能仍然无法完全免受严重形式的SARS-CoV-2感染，因此需要采取其他保护策略。事实上，其他机制，如通过使用单克隆抗体（MAb）使用被动免疫，已被证明可以保护血清阴性的人，无论是作为暴露前预防还是暴露后预防。REACT2研究在英国人群中使用自我给予的侧流免疫测定法（LFIAs）监测SARS-CoV-2抗体。尽管它们的敏感性和特异性低于在实验室环境中使用静脉血的免疫测定，但它们的性能足以用于人群水平的研究，并且它们的使用可能是一种实用的方法，有助于在“高危”患者群体中筛查和计划SARS-CoV-2干预措施。REACT2研究中使用的LFIA试剂盒将用于MELODY研究，并已在移植受者中进行了评估。采用与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在使用LFIAs的免疫抑制患者中研究抗体检测的使用。符合条件的人将通过患者登记、英国移植登记和英国公共卫生国家疾病登记服务（NDRS）随机确定，NDRS包括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）。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）将由Ipsos MORI通过私人信件邀请参加该研究。移植患者（n=12,000）将能够通过Ipsos MORI托管的研究门户网站选择加入。在门户网站上注册后，参与者将收到LFIA测试，并提供详细的指导手册和指导视频链接。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，包括免疫抑制史、社会人口统计学变量、屏蔽史和测试结果等信息。如果可能的话，他们会被要求上传考试照片。问卷中的所有数据将被输入数据库，并与上传的LFIA结果相关联。将设立热线电话，处理可能出现的任何疑问。一旦数据完成，研究数据库的副本将由Ipsos MORI安全地发送给NHS血液和移植和NDRS进行数据分析。初步数据将能够估计具有可检测到的SARS-CoV-2抗体的免疫抑制人群的比例，并将抗体状况与临床和社会人口因素联系起来。所使用的登记处已与感染数据相关联，因此在6个月的研究随访期间，也能够将这些患者感染后的抗体状态与结果相关联。

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.