MELODY Study (Mass evaluation of lateral flow immunoassays for the detection of SARS-CoV-2 antibody responses in immunosuppressed people) - COVID-19 related hospitalisations in solid transplant patients

Imperial College London and NHS Blood & Transplant (NHSBT) require access to NHS England Data for the purpose of the following research project: “MELODY Study - Mass evaluation of lateral flow immunoassays for the detection of SARS-CoV-2 antibody responses in immunosuppressed people”

The following is a summary of the aims of the research project provided by Imperial College London and NHSBT:

"The study aims to estimate how many immunosuppressed people in the UK have antibodies that may provide protection against COVID-19 after at least 3 vaccines and then assess whether people with antibodies have lower rates of infection and severe outcomes of infection than people without antibodies. The results of this study may help assess the impact of the vaccines on the level of antibody response to COVID-19 across the UK and help guide public health policy towards vulnerable groups."

“The study aims to determine:

1. The proportion of immunosuppressed people who have detectable SARS-CoV-2 antibodies following a primary vaccine course (at least 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 severe acute respiratory syndrome coronavirus-2 infection and/or severity of disease in immunosuppressed people.”

This Data Sharing Agreement (DSA) relates to the following outcome measure:

“The incidence of participants hospitalised due to COVID-19 and deaths due to COVID-19 by 6 months will be presented for those with and without antibodies to SARS-CoV-2 following 3rd or 4th vaccine, and compared as described above if there are sufficient events.”

The following NHS England Data will be accessed:

• Hospital Episode Statistics Admitted Patient Care and Critical Care – necessary to evaluate vaccine effectiveness in solid organ transplant recipients in relation to incidence and severity of hospitalisation

• COVID-19 Therapeutics (Blueteq) - necessary to compare outcomes between solid organ transplant patients who did and did not receive treatment with COVID-19 therapeutics, and the effectiveness of such treatments in preventing severe COVID-19 illness in this group of patients

The level of the Data will be pseudonymised, however NHSBT separately hold the identifiable information of all study participants relating to this DSA on their transplant registry.

The Data will be minimised as follows:

• Limited to Data for a consented study cohort of solid organ transplant recipients held by NHSBT (~10,000 individuals)

• Limited to Data between December 2021 and January 2023

• Excluding one-off day case inpatient and elective admissions

Imperial College London as the research sponsor, and NHSBT as the main collaborator, are joint controllers as the organisations responsible for ensuring that the Data will only be processed for the purpose described above.

Imperial College London’s and NHSBT’s lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.

Imperial College London’s and NHSBT’s lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research and aims to produce publicly available information to inform future decisions over patients’ treatments or care.

The funding is provided by the Medical Research Council. The funding is specifically for the study described. Funding is in place until April 2023.

The MELODY study protocol and acceptability was designed and adapted with patient representatives from several different health charities (Kidney Research UK, Blood Cancer UK, Vasculitis UK, Lupus UK, the Cystic Fibrosis Trust and Kidney Care UK) as well as the NHSBT patient advisory groups.

NHS Blood & Transplant (NHSBT) will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, date of birth and a unique person ID) for the cohort to be linked with NHS England Data.

NHS England will provide the relevant records from the HES Admitted Patient Care and Critical Care datasets, and the COVID-19 Therapeutics (Blueteq) dataset to NHSBT. The Data will contain no direct identifying data items but will contain a unique person ID which can be used to link the Data with other record level data already held by the recipient.

The Data will be linked at person record level with questionnaire results obtained directly from study participants; NHSBT transplant registry clinical data; and information about vaccinations, subsequent COVID-19 infections or details of any deaths which have been provided by the UK Health Security Agency.

Identifying details of all participants are stored separately in NHSBT’s transplant registry. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

The Data will not be transferred to any other location.

The Data will be stored on servers at NHSBT.

The Data will be accessed onsite at the premises of NHSBT only or the data will be accessed by authorised personnel via remote access. The Data will remain on the servers at NHSBT at all times.

Personnel are prohibited from downloading or copying Data to local devices.

The Data will not leave England at any time.

Access is restricted to employees of the statistics team within NHSBT. All such individuals are substantive employees of NHSBT and have been granted approval by the Information Asset Owner.

Employees or agents of Imperial College London are only permitted to access anonymised data including information derived from NHS England Data. Such datasets will adhere to the relevant suppression rules.

All personnel accessing the Data have been appropriately trained in data protection and confidentiality.

Analysts from NHSBT will analyse the Data for the purposes described in ‘Objectives for Processing’. The NHS England Data will not be used for any other purposes or combined with any other datasets other than those detailed in this Data Sharing Agreement.

The expected outputs of the processing will be:

• A report of findings to the Department of Health and Social Care (DHSC)

• Submissions to peer reviewed journals

The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Public reports

• Press/media engagement

• Public promotion of the research via social media sites (Facebook & Twitter)

• Participant newsletters

The target dates for production and dissemination of the outputs are late 2023 – early 2024.

The findings of this research study are expected to describe the real-world effectiveness of at least three COVID-19 vaccinations against COVID-19 infection, hospitalisation and death in immunosuppressed individuals.

The use of the Data could:

• advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations such as organ transplant recipients

• inform planning health services and programmes, for example to improve experience and outcomes

• support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work)

The results are intended to be used to help provide stratified advice to specific patient groups, rather than classify all immunosuppressed patients at risk. Understanding if and how the detection of antibodies relates to the subsequent risk of SARS-CoV2 infection and/or severity of disease in immunosuppressed individuals could help estimate and/or identify the number of patients who may benefit from additional or alternative treatments given or actions taken to prevent disease. This is hoped to lead to implementation of additional measures targeted towards these individuals, to reduce their future risk of severe disease.

It is hoped that through publication of findings in appropriate media, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients.

The findings will also be shared with participants through direct contact and via relevant charities. Findings will also be publicised on social media sites through Facebook and Twitter accounts.

The MELODY study included 21,155 people, and COVID-19 antibodies were detected in the majority of study participants: 77% of those with solid organ transplants, 85.9% of those with rare autoimmune rheumatic diseases, and 79.3% of those with lymphoid cancers. Around 1 in 5 people taking part in the study did not have detectable antibodies.

COVID-19 infection was recorded in 3,907 people, with 556 needing hospital care and 20 dying within 28 days of infection (less than 1 in 1000 of the study population).

Rates of COVID infection varied between people and were higher among those who were younger or living with children. Rates of hospitalisation with COVID-19 increased with age and with the number of other illnesses.

In all groups, having COVID-19 antibodies protected against infection and hospitalisation. As fortunately the numbers of people in the study who died were small, we couldn’t comment on whether having COVID-19 antibodies reduced the chance of death due to COVID.

The chance of having a COVID-19 infection was reduced in people with COVID-19 antibodies compared to those without measurable antibodies. This reduction was 31% in those with solid organ transplants, 43% in those with rare autoimmune rheumatic diseases, and 38% in those with lymphoid cancers.

People with COVID-19 antibodies were much less likely to be hospitalised due to COVID-19 compared to those without measurable antibodies. Hospitalisation was reduced by 60% in those with solid organ transplants, 68% in those with rare autoimmune rheumatic diseases, and 59% in those with lymphoid cancers. Overall, the likelihood of being hospitalised due to COVID-19 was reduced by two-thirds for those people with antibodies.

This was published in the paper: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02560-1/fulltext

We hope to further analyse this data to investigate variation in immunosuppression practices and explore how different immunosuppression impacts on transplant recipient outcomes including hospitalisation.