The DESTINIES Study: an online Delphi study to build international consensus on the medical conditions and procedures that confer immunosuppression and their respective COVID-19 risk profiles.

Background: The lack of international consensus on defining and categorising immunosuppression has undermined disease surveillance and patient care, particularly during the COVID-19 pandemic. To address this, a global expert panel was recruited to join the eDElphi STudy to fully defiINe and COVID-risk stratify ImmunosupprESsion (DESTINIES) and develop a COVID risk-stratified digital phenotype for 'adult immunosuppression' (the DESTINIES phenotype).

Methods: Panellists were presented with all medical diagnoses and procedures cited in prevailing immunosuppressed definitions; they evaluated their appropriateness for the DESTINIES phenotype and their risks for severe COVID-19 outcomes through anonymous online questionnaires and discussion. Panel agreement with a series of clinical statements were also assessed; statements incorporated longstanding disputes, including variables that could reverse immunosuppression. Each round of data collection informed and refined a draft phenotype until final ratification. This study was active between May and September 2024.

Findings: Sixty-four experts from four continents and 12 international agencies completed two rounds of consensus questionnaire, a discussion group and ratifying vote. Panellists identified candidates posing higher (e.g. Transplantation, Primary Immunodeficiency) and lower COVID-19 risk (e.g. Anorexia nervosa, Cerebral spinal fluid leak) but disagreed on the categorisation of others (e.g. Asplenia, Immune-mediated Inflammatory Disease). Consensus was reached on ten clinical statements, notably removing Drug-managed HIV and Cancer remission from consideration as immunosuppressed. The DESTINIES phenotype was ratified with near unanimous support (94%) for implementation in surveillance.

Interpretation: Pending validation, the DESTINIES phenotype provides a clinically meaningful, internationally ratified and digitally practical method for identifying and COVID-19 risk-stratifying adult immunosuppressed patients in healthcare data.

Funding: This work was funded by the UK Medical Research Council and EMIS Health.