Leston Meredith, Kar Debasish, Forbes Anna, Jamie Gavin, Wimalaratna Rashmi, Jiwani Gunjan, Ordóñez-Mena José M, Stewart Daniel E, Whitaker Heather, Joy Mark, Lee Lennard Y W, Hobbs F D Richard, de Lusignan Simon
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Immunisation and Vaccine Preventable Diseases Division, UK Health Security Agency, London, United Kingdom.
Front Immunol. 2024 Dec 4;15:1491565. doi: 10.3389/fimmu.2024.1491565. eCollection 2024.
Adults classified as immunosuppressed have been disproportionately affected by the COVID-19 pandemic. Compared to the immunocompetent, certain patients are at increased risk of suboptimal vaccine response and adverse health outcomes if infected. However, there has been insufficient work to pinpoint where these risks concentrate within the immunosuppressed spectrum; surveillance efforts typically treat the immunosuppressed as a single entity, leading to wide confidence intervals. A clinically meaningful and computerised medical record (CMR) compatible method to subdivide immunosuppressed COVID-19 data is urgently needed.
We conducted a rapid scoping review into COVID-19 mortality across UK immunosuppressed categories to assess if differential mortality risk was a viable means of subdivision. We converted the risk hierarchy that surfaced into a pilot digital phenotype-a valueset and series of ontological rules ready to extract immunosuppressed patients from CMR data and stratify outcomes of interest in COVID-19 surveillance dataflows.
The rapid scoping review returned COVID-19 mortality data for all immunosuppressed subgroups assessed and revealed significant heterogeneity across the spectrum. There was a clear distinction between heightened COVID-19 mortality in haematological malignancy and transplant patients and mortality that approached the immunocompetent baseline amongst cancer therapy recipients, autoimmune patients, and those with HIV. This process, complemented by expert clinical input, informed the curation of the five-part digital phenotype now ready for testing in real-world data; its ontological rules will enable mutually exclusive, hierarchical extraction with nuanced time and treatment conditions. Unique categorisations have been introduced, including 'Bone Marrow Compromised' and those dedicated to differentiating prescriptions related and unrelated to cancer. Codification was supported by existing reference sets of medical codes; absent or redundant codes had to be resolved manually.
Although this work is in its earliest phases, the development process we report has been highly informative. Systematic review, clinical consensus building, and implementation studies will test the validity of our results and address criticisms of the rapid scoping exercise they are predicated on.
Comprehensive testing for COVID-19 has differentiated mortality risks across the immunosuppressed spectrum. This risk hierarchy has been codified into a digital phenotype for differentiated COVID-19 surveillance; this marks a step towards the needs-based management of these patients that is urgently required.
被归类为免疫抑制的成年人在新冠疫情中受到的影响尤为严重。与免疫功能正常的人相比，某些患者如果感染，疫苗反应欠佳和健康不良后果的风险会增加。然而，目前尚无足够的研究来确定这些风险在免疫抑制范围内的集中点；监测工作通常将免疫抑制人群视为一个整体，导致置信区间较宽。迫切需要一种具有临床意义且与计算机化病历（CMR）兼容的方法来细分免疫抑制的新冠数据。
我们对英国免疫抑制类别中的新冠死亡率进行了快速范围审查，以评估差异死亡率风险是否是一种可行的细分方法。我们将浮现出的风险等级转化为一个试点数字表型——一个值集和一系列本体规则，准备从CMR数据中提取免疫抑制患者，并对新冠监测数据流中感兴趣的结果进行分层。
快速范围审查返回了所有评估的免疫抑制亚组的新冠死亡率数据，并揭示了整个范围内的显著异质性。血液系统恶性肿瘤患者和移植患者的新冠死亡率升高与癌症治疗接受者、自身免疫性疾病患者和艾滋病毒感染者中接近免疫功能正常基线的死亡率之间存在明显区别。这一过程在专家临床意见的补充下，为现在准备在真实世界数据中进行测试的五部分数字表型的策划提供了信息；其本体规则将实现互斥、分层提取，并带有细微的时间和治疗条件。引入了独特的分类，包括“骨髓受损”以及专门用于区分与癌症相关和无关处方的分类。编码得到了现有医学代码参考集的支持；缺失或冗余的代码必须手动解决。
尽管这项工作尚处于早期阶段，但我们报告的开发过程提供了很多信息。系统评价、临床共识建立和实施研究将检验我们结果的有效性，并回应基于快速范围审查提出的批评。
针对新冠的全面检测已经区分了免疫抑制范围内的死亡风险。这一风险等级已被编码为用于差异化新冠监测的数字表型；这标志着朝着迫切需要的基于需求的这些患者管理迈出了一步。
