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

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.

The MELODY Study aims to assess:
1. The proportion of immunosuppressed patients who have detectable SARS-CoV-2 antibodies following a primary vaccine course (3 doses), and the demographic, disease, and treatment characteristics that influence antibody status.
2. If the detection of antibodies inversely correlates with subsequent risk of SARS-CoV2 infection and/or severity of disease.

Building on the successful methodology used in the REACT2 Study (community assessment of SARS-CoV-2 antibody tests), the study will assess self-administered LFIAs in 36,000 patients, who have completed their primary COVID-19 vaccination course. The study will recruit; a) solid organ transplant recipients, b) patients with autoimmune diseases receiving immunosuppression, c) patients with haematological malignancies.

The study will utilise the digital web platform and research expertise of Ipsos MORI linked with the patient registries, UK Transplant Registry and 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).
Patients will be recruited following a letter of invitation or via an 'opt-in' option on the study web portal. Once consent is registered via the portal, a LFIA kit will be sent to the participant together with instructions to use. Participants will be required to fill in a brief questionnaire and to upload the results of their tests, together with a photograph of the test using a mobile phone, if possible. Once all the data is returned, Ipsos MORI will collate and send the data back to the registries for analysis. The registries will subsequently capture all RT-qPCR proven infection episodes and outcomes over the course of the 6 month study period, and compare outcomes by antibody status.