Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
State Key Laboratory of Brain & Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
J Med Virol. 2023 Jul;95(7):e28895. doi: 10.1002/jmv.28895.
Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron-related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro-COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron-related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1-13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike-and-wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron-related neurological manifestations had significantly higher blood levels of IL-6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL-6 (p = 0.002) than children with non-COVID-19-related febrile illnesses. Higher CSF-to-blood ratios of IL-8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL-6 and IL-8 were associated with higher blood tau level. The role of CSF:blood ratio of IL-6, IL-8, and CHI3L1 as prognostic markers for neuro-COVID should be further evaluated.
奥密克戎通常比以前的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）菌株引起的疾病更轻，特别是在完全接种疫苗的个体中。然而，未完全接种疫苗的儿童可能会出现与奥密克戎相关的并发症，例如影响中枢神经系统的并发症。为了描述神经 COVID 的临床表现谱，并确定与临床结果相关的潜在生物标志物，我们在香港的三家医院招募了 15 名因奥密克戎相关神经系统表现住院的儿童（9 名男孩和 6 名女孩，年龄 1-13 岁）。所有患儿均未接种疫苗或未完全接种疫苗。14 名（93.3%）患儿因惊厥入院，包括热性惊厥（n=7）、复杂性热性惊厥（n=2）、发热伴惊厥（n=3）和复发性突破发作（n=2），而另一名非惊厥患儿出现意识障碍的脑病状态。在 9 个月的随访中，7 名热性惊厥患儿中无 1 名患儿和 8 名其他神经系统表现患儿中有 6 名患儿有残留缺陷。接受腰椎穿刺的 7 名患者的脑脊液（CSF）标本中均未检测到 SARS-CoV-2 RNA。7 名患者中有 4 名（57.1%）进行了脑电图，显示影响额叶的棘波和尖波。与健康对照组相比，奥密克戎相关神经系统表现的患儿血液中白细胞介素 6（IL-6）（p<0.001）和 CHI3L1（p=0.022）水平显著升高，与非 COVID-19 相关发热性疾病患儿相比，脑脊液中白细胞介素 6（IL-6）水平显著升高。脑脊液中白细胞介素 8 和 CHI3L1 的脑脊液与血液比值较高与住院时间较长有关，而白细胞介素 6 和白细胞介素 8 的比值较高与血液 tau 水平较高有关。IL-6、IL-8 和 CHI3L1 的 CSF：血液比值作为神经 COVID 的预后标志物的作用需要进一步评估。
