Risk factors of Omicron variant associated acute encephalitis/encephalopathy in children

Chong-Wei Huang; Jainn-Jim Lin; Chen-Yen Kuo; Kuang-Lin Lin; Yhu-Chering Huang; Cheng-Hsun Chiu; Yi-Ching Chen; Chih-Ho Chen; Yu-Chia Hsieh

doi:10.1016/j.jmii.2023.08.010

Risk factors of Omicron variant associated acute encephalitis/encephalopathy in children

J Microbiol Immunol Infect. 2023 Dec;56(6):1169-1177. doi: 10.1016/j.jmii.2023.08.010. Epub 2023 Sep 4.

Authors

Chong-Wei Huang¹, Jainn-Jim Lin², Chen-Yen Kuo¹, Kuang-Lin Lin³, Yhu-Chering Huang¹, Cheng-Hsun Chiu⁴, Yi-Ching Chen¹, Chih-Ho Chen⁵, Yu-Chia Hsieh⁶

Affiliations

¹ Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan; Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
² Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan; Division of Pediatric Critical Care, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Division of Pediatric Neurology, Department of Pediatrics, Chang Gung Children's Hospital and Chang Gung Memorial Hospital, Taoyuan, Taiwan.
³ Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan; Division of Pediatric Neurology, Department of Pediatrics, Chang Gung Children's Hospital and Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁴ Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan; Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁵ Division of Pediatric Infectious Diseases, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁶ Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan; Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: ychsieh@cgmh.org.tw.

PMID: 37709632
DOI: 10.1016/j.jmii.2023.08.010

Abstract

Background: Outbreak of Omicron BA.2 in Taiwan led to an increased number of acute encephalitis/encephalopathy cases in children and several fatal cases drew public attention. In pre-Omicron period, pediatric cases of COVID-19-associated acute encephalitis have been reported and during Omicron epidemic, febrile convulsions, encephalitis were mentioned more frequently. The outcome of patients with neurological complications was worse. However, few studies investigated the risk factors, pathophysiology and prognosis of COVID-19-associated encephalitis/encephalopathy. Here, we describe the presentation of pediatric cases of COVID-19-associated acute encephalitis/encephalopathy and explore the associated risk factors.

Methods: Pediatric patients with confirmed SARS-CoV-2 infections were prospectively enrolled at admission at Chang Gung Memorial Hospital between April and August 2022. Patients were categorized into groups of acute encephalitis/encephalopathy, febrile convulsions or mild disease. Demographic descriptions, clinical manifestations and laboratory data were collected.

Results: Of 288 acute COVID-19 patients, there were 38 (13.2%) acute encephalitis/encephalopathy, 40 (13.9%) febrile convulsions, and 210 (72.9%) mild disease. Among acute encephalitis/encephalopathy group, the mean age was 68.3 ± 45.0 months. The common neurological symptoms were lethargy (65.8%), seizures (52.6%), and impaired consciousness (34.2%). Over 3 years old (adjusted odds ratio [aOR]: 7.57, p < 0.001), absolute neutrophil count ≥3150/μL (aOR: 5.46, p = 0.008), and procalcitonin ≥0.5 ng/mL (aOR: 4.32, p = 0.021) were independent factors for acute encephalitis/encephalopathy.

Conclusions: Most cases of COVID-19-associated acute encephalitis/encephalopathy showed no evidence of direct viral invasion but associations with older age, increased peripheral neutrophil, and serum procalcitonin. These findings may imply the neutrophil-mediated systemic inflammatory response plays an important role on central nerve system, leading to cerebral dysfunction.

Keywords: COVID-19; Encephalitis; Encephalopathy; Omicron.

MeSH terms

Brain Diseases* / complications
Brain Diseases* / epidemiology
COVID-19* / complications
COVID-19* / epidemiology
Child
Child, Preschool
Encephalitis* / epidemiology
Humans
Infant
Procalcitonin
Risk Factors
Seizures, Febrile* / complications
Seizures, Febrile* / epidemiology

Substances

Procalcitonin