Leston Meredith, Ordóñez-Mena José M, Joy Mark, Hobbs F D Richard, de Lusignan Simon, Teh Benjamin W, de Groot Ingrid, McInnes Iain, El Sahly Hana M, Isaacs John, Andersson Monique, Raffi Francois, Lim Wei Shen, Conway Richard, Siebert Stefan, Buchan Iain, Underwood Martin, Lowe David, Hoerger Michael, Griffiths Christopher E M, Alunno Alessia, Lee Lennard Y W
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Department of Infectious Diseases, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia.
EClinicalMedicine. 2025 May 5;83:103239. doi: 10.1016/j.eclinm.2025.103239. eCollection 2025 May.
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).
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.
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.
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.
This work was funded by the UK Medical Research Council and EMIS Health.
在免疫抑制的定义和分类方面缺乏国际共识，这对疾病监测和患者护理造成了不利影响，尤其是在新冠疫情期间。为解决这一问题，一个全球专家小组被招募加入电子德尔菲研究，以全面定义免疫抑制并对新冠风险进行分层（DESTINIES），并为“成人免疫抑制”开发一种新冠风险分层数字表型（DESTINIES表型）。
向专家小组成员展示了现行免疫抑制定义中引用的所有医学诊断和程序；他们通过匿名在线问卷和讨论，评估这些诊断和程序对DESTINIES表型的适用性以及发生严重新冠病毒疾病结局的风险。还评估了专家小组对一系列临床陈述的共识情况；这些陈述纳入了长期存在的争议，包括可能逆转免疫抑制的变量。每一轮数据收集都为表型草案提供信息并对其进行完善，直至最终批准。本研究于2024年5月至9月期间开展。
来自四大洲和12个国际机构的64位专家完成了两轮共识问卷、一个讨论组和批准投票。专家小组成员确定了新冠病毒疾病风险较高的情况（如移植、原发性免疫缺陷）和风险较低的情况（如神经性厌食症、脑脊液漏），但对其他情况（如无脾症、免疫介导的炎症性疾病）的分类存在分歧。就十项临床陈述达成了共识，特别是不再将药物治疗的人类免疫缺陷病毒感染和癌症缓解视为免疫抑制情况。DESTINIES表型以近乎一致的支持率（94%）获得批准，可用于监测。
在等待验证的情况下，DESTINIES表型为在医疗数据中识别成人免疫抑制患者并对其进行新冠病毒疾病风险分层提供了一种具有临床意义、国际认可且数字实用的方法。
本研究由英国医学研究理事会和EMIS Health资助。
