通过无监督机器学习在感染 SARS-CoV-2 的儿童和青少年中识别出六种具有预后意义的临床表型:来自德国全国范围登记的结果。

IF 5.8 2区 医学 Q1 Medicine Respiratory Research Pub Date : 2024-10-30 DOI:10.1186/s12931-024-03018-3
Yanyan Shi, Ralf Strobl, Reinhard Berner, Jakob Armann, Simone Scheithauer, Eva Grill
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引用次数: 0

摘要

目的:表型对于患者分类、疾病预后和定制治疗非常重要。我们旨在确定感染 SARS-CoV-2 住院儿童和青少年的不同临床表型,并评估其预后差异:方法:德国儿科传染病学会(DGPI)登记处是一个全国性的前瞻性登记处,登记对象为德国因感染 SARS-CoV-2 而住院的儿童和青少年。我们采用分层聚类的方法进行表型识别,变量包括性别、入院时的 SARS-CoV-2 相关症状、入院前的合并症、临床相关的合并感染以及 SARS-CoV-2 风险因素。本研究的结果包括:出院情况和入住重症监护室情况。出院状态分为:完全康复、残留症状和预后不良(包括出院时已被确定为潜在不可逆的后遗症和与 SARS-CoV-2 相关的死亡)。获得表型后,我们通过多项式逻辑回归模型评估了它们与出院状态的相关性,并通过二元逻辑回归模型评估了它们与入住重症监护室的相关性。我们还对年龄较大的患者进行了类似的亚组分析:DGPI 登记了 6983 名患者,通过这些患者,我们确定了儿童和青少年 SARS-CoV-2 患者的六种不同表型,这些表型可根据症状模式来描述:表型 A 患者有一系列症状,而其他表型患者的主要症状是胃肠道症状(95.9%,B)、无症状(95.9%,C)、下呼吸道(49.8%,D)、下呼吸道和耳鼻喉(86.2%和 41.7%,E)以及神经系统(99.2%,F)。在出院状态方面,表型为 D 和 E 的患者出现残留症状的几率最高(OR:分别为 1.33 [1.11, 1.59] 和 1.91 [1.65, 2.21]),表型为 D 的患者预后不良的几率明显更高(OR:4.00 [1.95, 8.19])。在重症监护室方面,与表型为 A 的患者相比,表型为 D 的患者入住重症监护室的可能性高于普通病房(OR:4.26 [3.06,5.98])。除了婴儿没有表现出典型的神经/神经肌肉表型外,在婴儿和非婴儿中观察到的结果与所有登记人群的结果非常相似:表型有助于根据风险对儿科病人进行分层,从而帮助对病人进行个性化治疗。我们在 SARS-CoV-2 感染人群中的发现也可用于其他传染病。
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Six clinical phenotypes with prognostic implications were identified by unsupervised machine learning in children and adolescents with SARS-CoV-2 infection: results from a German nationwide registry.

Objective: Phenotypes are important for patient classification, disease prognostication, and treatment customization. We aimed to identify distinct clinical phenotypes of children and adolescents hospitalized with SARS-CoV-2 infection, and to evaluate their prognostic differences.

Methods: The German Society of Pediatric Infectious Diseases (DGPI) registry is a nationwide, prospective registry for children and adolescents hospitalized with a SARS-CoV-2 infection in Germany. We applied hierarchical clustering for phenotype identification with variables including sex, SARS-CoV-2-related symptoms on admission, pre-existing comorbidities, clinically relevant coinfection, and SARS-CoV-2 risk factors. Outcomes of this study were: discharge status and ICU admission. Discharge status was categorized as: full recovery, residual symptoms, and unfavorable prognosis (including consequential damage that has already been identified as potentially irreversible at the time of discharge and SARS-CoV-2-related death). After acquiring the phenotypes, we evaluated their correlation with discharge status by multinomial logistic regression model, and correlation with ICU admission by binary logistic regression model. We conducted an analogous subgroup analysis for those aged < 1 year (infants) and those aged ⩾ 1 year (non-infants).

Results: The DGPI registry enrolled 6983 patients, through which we identified six distinct phenotypes for children and adolescents with SARS-CoV-2 which can be characterized by their symptom pattern: phenotype A had a range of symptoms, while predominant symptoms of patients with other phenotypes were gastrointestinal (95.9%, B), asymptomatic (95.9%, C), lower respiratory tract (49.8%, D), lower respiratory tract and ear, nose and throat (86.2% and 41.7%, E), and neurological (99.2%, F). Regarding discharge status, patients with D and E phenotype had the highest odds of having residual symptoms (OR: 1.33 [1.11, 1.59] and 1.91 [1.65, 2.21], respectively) and patients with phenotype D were significantly more likely (OR: 4.00 [1.95, 8.19]) to have an unfavorable prognosis. Regarding ICU, patients with phenotype D had higher possibility of ICU admission than staying in normal ward (OR: 4.26 [3.06, 5.98]), compared to patients with phenotype A. The outcomes observed in the infants and non-infants closely resembled those of the entire registered population, except infants did not exhibit typical neurological/neuromuscular phenotypes.

Conclusions: Phenotypes enable pediatric patient stratification by risk and thus assist in personalized patient care. Our findings in SARS-CoV-2-infected population might also be transferable to other infectious diseases.

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来源期刊
Respiratory Research
Respiratory Research RESPIRATORY SYSTEM-
CiteScore
9.70
自引率
1.70%
发文量
314
审稿时长
4-8 weeks
期刊介绍: Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.
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