Severe central nervous system injury in children caused by COVID-19

Severe central nervous system injury in children caused by COVID-19 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Severe central nervous system injury in children caused by COVID-19 Peipei zhang, Meiyun xin, Yingge bai, Xueyun ren, Na Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3669572/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Jan, 2025 Read the published version in BMC Pediatrics → Version 1 posted 12 You are reading this latest preprint version Abstract Purpose To investigate the clinical features and prognosis of severe central nervous system (CNS) injury in children caused by coronavirus disease 2019 (COVID-19). Method We retrospectively studied confirmed pediatric cases of COVID-19 complicated with CNS injury. Results Nine patients diagnosed with COVID-19 complicated with severe CNS injury were admitted to the pediatric intensive care unit of the Affiliated Hospital of Jining University from December 1, 2022 to January 12, 2023. Of the nine patients, seven were male (77.78%). Five children were aged ≥ 10 years, and the others were 1–2 years old. All children had fever, eight had convulsions, seven had progressed to multiple organ failure, and all suffered varying degrees of coma. Most of the children had elevated interleukin-6 (100%), lactic acid (100%), alanine transaminase (87.5%), aspartate transaminase (87.5%), creatine kinase MB (87.5%), and lactate dehydrogenase (85.7%) levels. Four children had cerebrospinal fluid protein-cell separation. The cranial imaging results of five children were abnormal. One child had lost his vital signs when admitted to hospital, and the remaining eight received hormonal shock, human immunoglobulin transfusion, anti-infection, cranial pressure reduction, and mechanical ventilation treatments, among others, during hospitalization. Ultimately, eight children died, and the remaining child has serious neurological sequelae and is undergoing rehabilitation. Conclusions Severe CNS injury caused by COVID-19 has an acute onset, rapid progression, high disability rate, and high fatality rate. A low cerebrospinal fluid protein level may be a protective factor for children with severe nervous system injury caused by COVID-19. COVID-19 Severe central nervous system injury Children Figures Figure 1 Introduction The novel coronavirus disease 2019 (COVID-19) pandemic has brought great clinical challenges worldwide. Since the beginning of the pandemic, neurologic manifestations in patients with COVID-19 have been extensively described [ 1 – 2 ]. More serious neurological disorders, such as encephalitis (inflammation of the brain) and encephalopathy (a brain disease characterized by altered consciousness), are rare complications of COVID-19 and are often fatal [ 3 – 4 ]. For example, a study that included 3,707 children reported that only 1% developed encephalopathy [ 5 ], but this was associated with increased mortality [ 6 ]. Encephalitis/encephalopathy may occur via different mechanisms, including direct infection, systemic inflammation caused by cytokine storms, and autoimmunity [ 7 ]. Since the epidemic prevention policy for COVID-19 in China was lifted in December 2022, the number of cases of COVID-19 has rapidly increased. In light of the growing number of cases, familiarizing physicians with various neurological features that may be observed in these patients is extremely important. This paper reports the condition and prognoses of nine pediatric patients complicated with central nervous system (CNS) injury. Our aim is to make clinicians aware of the severity of CNS injury in children with COVID-19 and to help them identify severe cases as soon as possible. Material and methods From December 1, 2022 to January 12, 2023, a retrospective review was conducted of the clinical, laboratory, and magnetic resonance imaging (MRI)/computed tomography (CT) findings of nine children admitted to the pediatric intensive care unit (PICU) of the Affiliated Hospital of Jining Medical University. The children were determined to be nucleic acid-positive for SARS-CoV-2 by oropharyngeal swabs. Sample collection and pathogen identification were performed after admission to the hospital. The basic information of the children was recorded, including their age, sex, symptoms, underlying diseases, and vaccination records. All laboratory tests were carried out in accordance with the health standards of the People's Republic of China. Results General information From December 1, 2022 to January 12, 2023, we encountered nine pediatric cases of COVID-19 with severe CNS injury. Of the nine patients, seven were male (77.78%) and two were female (22.22%). Five children were aged ≥ 10 years, and the other four were 1–2 years old. The latter children were not vaccinated, and six children were previously healthy. One child (10 years old at the time of admission) had a history of asthma before the age of 3 years, one child was diagnosed with acute disseminated encephalomyelitis 1 year earlier, and one child with abnormal genetic test results was diagnosed with severe encephalitis 6 months earlier and treated with oral antiepileptic drugs as maintenance therapy (Table 1 ). Table 1 General information of the 9 children with CNS consequences of COVID-19 No. Gender Age Admit date Survival time Vaccination Underlying disease Max body temp. (°C) Convulsions DIC stroke Gastrointestinal bleeding Pneumonia 1 M 10years 2022/12/23 22 hours 55 minutes Yes No 40.0℃ Yes No Yes No Yes 2 F 1year 2022/12/24 120 hours 20 minutes No ADEM 38.6℃ Yes No No No Yes 3 M 10years 2022/12/24 23 hours 5 minutes Yes asthma 41.0℃ Yes Yes Yes Yes Yes 4 M 1year 2022/12/26 98 hours 11 minutes No RANBP2NM- 006767.4 39.5℃ Yes No No No Yes 5 M 10years 2022/12/25 73 hours 33 minutes Yes No 38.6℃ No No No No No 6 M 10years 2022/12/24 84 hours 9 minutes Yes No 39.0℃ Yes Yes No Yes Yes 7 M 2years 2022/12/25 40 hours 1 minutes No No 41.3℃ Yes No No Yes Yes 8 M 1year 2022/12/26 Alive No No 41.0℃ Yes No No No Yes 9 F 11years 2022/12/28 40 minutes Yes No 40.0℃ Yes No No No - ADEM,acute disseminated encephalomyelitis;Survival time,Time of presentation to death Clinical manifestations All nine pediatric patients had fever, and five had a body temperature of ≥ 40°C and difficulty during defervescence. Eight patients developed fever and convulsions, and the remaining child developed fever and headache. Seven patients had generalized tonic-clonic seizures, one had an unknown form of convulsions, and four had status convulsivus. All patients experienced varying degrees of coma, ranging from fever to coma between 2 hours and 3 days in duration. Eight patients died, and the length of hospital stay ranged from 30 minutes to 5 days. The only survivor has severe neurological sequelae and is currently undergoing rehabilitation. In addition to neurological symptoms, two patients developed shock, and two others developed diffuse intravascular coagulation. Three patients developed gastrointestinal bleeding, and seven progressed to multiple organ failure involving the nervous, respiratory, circulatory, digestive, and coagulation systems. Laboratory tests and imaging examinations One child (case 9) did not undergo any examinations because his vital signs had disappeared at the time of admission. Another child (case 1) died within half a day of admission. On admission, white blood cell counts were normal or low (62.5%). All patients had reduced lymphocyte counts and lymphocyte rates. Most patients had a high neutrophil-to-lymphocyte ratio of > 5.0 (75%). Platelet and hemoglobin levels were decreased in 62.5% of patients. All patients had elevated procalcitonin, and 50% had elevated C-reactive protein. Moreover, all patients tested exhibited elevated lactic acid (n = 8/8), interleukin-6 (n = 7/7), D-dimer (n = 8/8) and myoglobin (n = 3/3). Most patients had high creatine kinase-MB (n = 7/8, 87.5%), cardiac troponin I (n = 6/7, 85.7%), creatine kinase (n = 5/7, 71.4%), lactate dehydrogenase (n = 6/7, 85.7%), alanine aminotransferase (n = 7/8, 87.5%), aspartate aminotransferase (n = 7/8, 87.5%), and immunoglobulin E (n = 3/4, 75%) levels. We observed a decrease in albumin levels in seven of eight patients (87.5%). The plasma ammonia levels of most children were within the normal range (n = 5/6, 83.33%) (Table 2 ). Table 2 Abnormal laboratory data categorized from the normal range Normal range available laboratory measurement，n abnormal laboratory value，n (%) Elevated white blood cell, ×10 9 / L 1～<2years，5.1～14.1 2～<6years，4.4～11.9 6～<13years，4.3～11.3 8 3（37.5） Elevated Neutrophil count, ×10 9 /L 1～<2years，0.8～5.8 2～<6years，1.2～7.0 6～<13years，1.6～7.8 8 4（50） Elevated Neutrophil count, % 1～<2years，13～54 2～<6years，22～65 6～<13years，31～70 8 8（100） Low Lymphocyte count, × 10 9 /L 1～<2years，2.7～9.1 2～<6years，1.8～6.3 6～<13years，1.5～4.6 8 8（100） Low Lymphocyte count, % 1～<2years，33～77 2～<6years，23～69 6～<13years，23～59 8 8（100） Elevated Neutrophil-to-lymphocyte ratio, % ≤5 8 6（75） Low Platelet count,×10 9 / L 1～<2years，190～524 2～<6years，188～472 6～<12years，167～453 8 5（62.5） Low hemoglobin,g/L 1～<2years，107～141 2～<6years，112～149 6～<13years，118～156 8 5（62.5） Elevated C-reactive protein level, U/L 0-6 8 4（50.0） Elevated Procalcitonin, ng/ml 0-0.05 7 7（100） Elevated D-dimer, mg/L 0-0.5 8 8（100） Elevated Creatine kinase-MB, ng/ml 0-5 8 7（87.5） Elevated Cardiac troponin I, pg/ml 0-0.175 7 6（85.7） Elevated Myoglobin, μg/L 1.5-70 3 3（100） Elevated Creatine kinase, U/L 50-310 7 5（71.4） Elevated Lactate dehydrogenase, U/L 120-250 7 6（85.7） Elevated Creatinine, μmol/L 28days～＜2years,13～33 2～＜6years，19～44 6～＜13years，27～66 8 5（62.5） Elevated Blood urea nitrogen, mmol/L 1～＜2years,2.3～6.7 2～18years 2.7～7.0（male） 2.5～6.5（female） 8 2（25） Elevated Alanine aminotransferase, U/L 1～＜2years，8～42 2～＜13years，7～30 8 7（87.5） Elevated Aspartate aminotransferase, U/L 1～＜2years，11～47 2～＜13years，8～30 8 7（87.5） Low Albumin, g/L 6months～＜13years, 39～54 8 7（87.5） Elevated NT-pro B-type natriuretic peptide, pg/ml 0-100 7 3（42.9） Elevated lactic acid, mmol/L 0.5-1.8 8 8（100） Elevated ferritin, ng/mL Male，21.81 - 274.66 Famale，4.63 - 204.00 3 1（33.3） Elevated，plasma ammonia, umol/L 9-33 6 1（16.7） Elevated Interleukin-6, pg/ml 0-3.4 7 7（100） Elevated Immunoglobulin E, IU/mL 1~5years，< 60 10~15years，< 200 4 3（75） Low Immunoglobulin A, g/L 0.7-4 6 3（50） Low Immunoglobulin M, g/L 0.4-2.3 6 0（0） Low Immunoglobulin G, g/L 7-16 6 2（33.3） Chest imaging showed that seven patients were complicated with pneumonia. However, the imaging also showed that it was not typical viral pneumonia; rather, it was considered to be hypostatic pneumonia caused by convulsive coma. Moreover, one child had bronchitis. Six patients underwent cardiac ultrasound, two of whom had decreased left heart function (ejection fraction < 40%). Two patients were complicated with myocarditis, and one child had arrhythmia. Five patients underwent lumbar puncture, and the cerebrospinal fluid (CSF) white blood cell count was in the normal range. Four patients exhibited CSF protein-cell separation, with the CSF protein content being increased by 80%. The lactate dehydrogenase level in the CSF of three patients was increased by 60%. The protein and lactate dehydrogenase levels in the CSF of the surviving child were normal (Table 3 ). Table 3 The CSF and neuroimaging results of children No. CSF protein, g/L CSF white blood cells, × 10 6 / L CSF Lactate dehydrogenase, U/L CT of the brain MRI of the brain encephlogram 1 1.84 10 657 plain scanning, no obvious abnormalities - - 2 1.52 3 157 - multiple abnormal signals in the brain, infectious disease likely, acute disseminated encephalomyelitis possible Broad persistent low voltage pattern 3 - - - 1. Subarachnoid hemorrhage, diffuse cerebral edema, 2. Bilateral globus pallidus, caudate nucleus head symmetrical high-density shadow - - 4 2.18 12 37 - multiple symmetric abnormal signals in bilateral basal ganglia-thalamus, corpus callosum, pons, and cerebral cortex Broad persistent low voltage pattern 5 - - - Plain scanning, no obvious abnormalities - - 6 - - - 1. Bilateral thalamic-midbrain and pontine swelling, ring cistern and fourth ventricle unclear 2. Minor subarachnoid hemorrhage. - - 7 6.25 2 188 - - - 8 0.27 6 28 - Abnormal signal foci on the left side of the corpus callosum pressure A small amount of multi-focal discharge in waking period, slow background rhythm;Sleep is highly arrhythmic CSF protein, Normal range 0-0.4g/L.CSF white blood cells, Normal range 0–15 ×10 6 / L.CSF Lactate dehydrogenase, Normal range 3-40U/L. Seven patients underwent cranial imaging, two of whom had no obvious abnormalities on cranial CT examination. One child (case 6) had a bilateral thalamus lesion on cranial CT on the second day after illness, along with swelling of the midbrain and pons (Fig. 1 ). One child (case 8) showed abnormal MRI signals in the corpus callosum, and the encephalogram showed a small amount of multifocal discharge during waking hours and a slow background rhythm; sleep was highly arrhythmic. Cranial MRI of one child (case 2) showed multiple abnormal signals in the brain, considered indicative of infectious lesions, and the encephalogram showed persistent and widespread low voltage. Another child (case 4) showed abnormal signals in the bilateral basal ganglia, thalamus, corpus callosum, pons, and multiple areas under the cerebral cortex, and encephalogram showed persistent and widespread low voltage. Finally, diffuse cerebral edema was seen in one child (case 3). Treatment regimen and prognosis One child who presented to the emergency department with respiratory and cardiac arrest died despite treatment with active chest compression, positive pressure ventilation, and vasoactive drugs. The remaining eight patients were admitted to the PICU and received comprehensive anti-infection, intracranial pressure reduction, and mechanical ventilation treatments. In the PICU, all eight of these patients were given glucocorticoids (pulse methylprednisolone, 20 mg/kg/day [maximum = 1 g/day]) and intravenous human immunoglobulin (2 g/kg [maximum dose = 80 g). To address inflammatory factors, two patients underwent plasmapheresis and three underwent hemodialysis. Because of abnormal coagulation function, plasma transfusion was given to seven patients and cryoprecipitate was given to three patients. Because of varying degrees of anemia, three patients underwent “suspended” red blood cell infusion to enhance blood oxygen carrying capacity. Because of severe shock or multiorgan failure, seven patients died 12 hours to 5 days after onset, and no cases were autopsied. We followed one child (case 8) receiving antiepileptic and rehabilitation therapy for 6 months and noted frequent nodding spasms after startle and infection. This patient had severe motor and neurodevelopmental delay; now aged 2 years and 7 months, the child is still unable to sit or stand. Discussion The COVID-19 virus has undergone several mutations since its discovery in 2020. The Omicron variant was first identified in South Africa in November 2021 [ 8 – 9 ]. This variant spreads more rapidly and has a greater ability to evade immunity than other variants [ 10 ], and it has been the dominant strain globally since February 2022 [ 11 ]. Approximately 1 week after the adjustment of epidemic prevention policies, an Omicron infection broke out in mid-December 2022 in eastern China, which reached a peak in around 2 weeks and declined rapidly 3 weeks thereafter. During this period, monitoring by the local Center for Disease Control and Prevention showed that the circulating strains were BA.5.2 and BF.7; no other strains were found. The local Omicron variant spread rapidly, with a short incubation period (typically 2–4 days). The main symptoms of infection in pediatric patients include fever of varying severity (typically moderate-to-high fever) and febrile seizures. However, the prognosis is good. In the majority of patients, the fever lasted 1–3 days and rarely persisted for > 5 days. A small number of patients suffered coughs, sore throats, headaches, and fatigue, and pneumonia developed in a very small number of cases. Within 43 days after the lifting of lockdown, a total of 9,500 children presented to the center with fever. Among these children, we identified nine with severe CNS injury caused by COVID-19 (morbidity rate = 0.09%). Many pediatric cases of multisystem inflammatory response syndrome induced by COVID-19 have been reported in Europe, the United States, and other parts of China [ 12 , 13 ]. Moreover, the locally endemic Omicron variant caused more severe neurological lesions in pediatric patients than severe lower respiratory pathologies. At present, our understanding of CNS injury caused by COVID-19 is insufficient, and no clear conclusion on the pathogenesis has been drawn. Following infection, COVID-19 enters the CNS through a variety of pathways, such as the blood circulation, sieve plates, and synaptic pathways [ 14 – 16 ]. Viruses can cause nerve damage by directly invading the nervous system, leading to tissue hypoxia, inflammatory mediators producing cytokine storms [ 17 – 18 ], anosmia, taste disorders, viral encephalitis [ 19 – 20 ], demyelinating lesions [ 21 ], toxic encephalopathy [ 22 ], and necrotizing encephalopathy, etcetera. At the beginning of the pandemic in 2020, necrotizing encephalopathy in adults caused by COVID-19 infection was reported both in China and elsewhere [ 23 ]. In May 2021, Lazarte-Rantes et al. reported the first pediatric cases of acute necrotizing encephalopathy associated with COVID-19 [ 24 ]. The patients in the above reports all exhibited rapid progression, poor prognosis, and a requirement for mechanical ventilation during treatment. The first reported pediatric case with necrotizing encephalopathy was discharged with severe neurological sequelae [ 24 ]. This study reported cases of severe CNS injury in children infected with COVID-19 who presented to our center during the pandemic. We analyzed the incidence, clinical manifestations, imaging examination and laboratory results, and prognoses. All patients had severe CNS injury, and eight pediatric patients developed fever and convulsions. All patients experienced varying degrees of coma, ranging from fever to coma between 2 hours and 3 days in duration. Three children were diagnosed with necrotizing encephalopathy. CSF and brain imaging examinations were not performed in two patients because of rapid disease progression, but necrotizing encephalopathy was highly suspected clinically.In this study, there were more male than female patients, which is inconsistent with previous studies and may be related to the small sample size [ 25 ]. Most patients exhibited inflammatory cytokine storm, ultrahigh fever, cranial imaging abnormalities, and symmetric multifocal brain damage. We also found that most of the children had abnormal liver, heart, coagulation, and hematopoietic function. This finding is suggestive of multiorgan failure. Their disease progressed rapidly, which is apt to give rise to multiple organ dysfunction and a poor prognosis, especially in older children. Even if they survive, such patients are likely to suffer serious neurological sequelae. Importantly, of the nine children in this study, five underwent a complete CSF examination, and four had significantly higher CSF protein levels than normal; all of the latter patients died. The CSF protein levels of the surviving child were normal. In a previous report, all seven children with COVID-19 complicated with neurological manifestations who died had elevated CSF protein levels [ 26 ]. In another study, the CSF protein levels of five children who died of COVID-19 complicated with necrotizing encephalopathy were higher than those of the surviving children [ 25 ]. Finally, the CSF protein levels of surviving children with severe encephalopathy were found to be normal [ 27 ]. We speculate that decreased CSF protein levels may be a protective factor for severe neurological impairment or death in children with necrotizing encephalopathy caused by COVID-19. Limitations This study had two limitations. First, the sample size was small. Second, this retrospective study enrolled hospitalized children from a single center. Multicenter studies with larger sample sizes are needed. Conclusions COVID-19 can cause severe damage to the CNS in pediatric patients. A low level of CSF protein may be a protective factor for death in children with severe neurological damage caused by COVID-19. In view of the high mortality and disability rates of COVID-19-related severe CNS injury, the clinical symptoms of pediatric patients need to be studied in greater depth. It is hoped that this article will serve as a reference for the diagnosis, treatment and management of severe CNS injury associated with COVID-19 in children. Declarations Ethics approval and consent to participate The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This study was approved by the Ethics Committee of Affiliated Hospital of Jining Medical University.Ethical number:2022C253.All methods were carried out in accordance with relevant guidelines and regulations.Confirm that the informed consent of all subjects' legal guardians has been obtained for this study. Consent for publication Not applicable. Availability of Data and Materials The raw data supporting the conclusions of this article will be made available by the corresponding author, without undue reservation. Competing interests The authors declare no competing interests. Funding This work was supported by the Affiliated Hospital of Jining Medical University (grant number 2020-BS-010). Author c ontributions PPZ, NL contributed to primary manuscript writing and editing.MYX has made outstanding contributions to the preparation, planning and revision of it, and put forward some valuable ideas. YGB was responsible for the collection and interpretation of data. XYR was responsible for the quality control and supervision of medical records.All authors contributed to the paper and approved the submitted version.All authors contributed to study conceptualization and design. Acknowledgements We would like to thank all the pediatric staff of the Affiliated Hospital of Jining Medical University for their support and help. Authors' information 1 Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272007,China. 2 Surrey College，Dongbei University of Finance and Economics, Dalian, Liaoning, 116025，China. 3 Postdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, China. 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Supplementary Files rawdata.xlsx Cite Share Download PDF Status: Published Journal Publication published 27 Jan, 2025 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 10 Jun, 2024 Reviews received at journal 03 Jun, 2024 Reviews received at journal 31 May, 2024 Reviewers agreed at journal 25 May, 2024 Reviewers agreed at journal 24 May, 2024 Reviewers agreed at journal 08 Mar, 2024 Reviewers agreed at journal 07 Mar, 2024 Reviewers invited by journal 07 Mar, 2024 Editor assigned by journal 07 Mar, 2024 Editor invited by journal 26 Dec, 2023 Submission checks completed at journal 26 Dec, 2023 First submitted to journal 26 Nov, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3669572","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":263341461,"identity":"eae7c6be-f24f-4da9-b10f-cc0e7624d1de","order_by":0,"name":"Peipei zhang","email":"","orcid":"","institution":"Affiliated Hospital of Jining Medical University","correspondingAuthor":false,"prefix":"","firstName":"Peipei","middleName":"","lastName":"zhang","suffix":""},{"id":263341462,"identity":"a39e96f1-1a02-44c0-88ac-74370d0ffd31","order_by":1,"name":"Meiyun xin","email":"","orcid":"","institution":"Affiliated Hospital of Jining Medical University","correspondingAuthor":false,"prefix":"","firstName":"Meiyun","middleName":"","lastName":"xin","suffix":""},{"id":263341463,"identity":"1e46188c-b86d-48fd-aab5-8392d4b45a35","order_by":2,"name":"Yingge bai","email":"","orcid":"","institution":"Dongbei University of Finance and Economics","correspondingAuthor":false,"prefix":"","firstName":"Yingge","middleName":"","lastName":"bai","suffix":""},{"id":263341464,"identity":"d13b4ee3-6825-49e2-a7a0-ba6b69bb8b66","order_by":3,"name":"Xueyun ren","email":"","orcid":"","institution":"Affiliated Hospital of Jining Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xueyun","middleName":"","lastName":"ren","suffix":""},{"id":263341465,"identity":"854b9661-a607-4946-81ea-128d5427fcbe","order_by":4,"name":"Na Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYBACPhDB+E+ino29sfHhB2K0sEFImwR+nsPNxhIkaElLkJyR3ibAQ5QW6R7jlz94DucZ3HzYxiDBYCen20BIi8wZMwsJicPFBrcT2x4UMCQbmx0gpEUix8zAwOAw44bbie0GEgwHErcRpSUhAajl5sE2CR4itRg/OHAgLXHmDEaitaSVMTY22Bjz8yQCA9mACL/wSyRv/vizQUKOjf34w4cfKuzkCGphYOAwQ4pAA4LKQYD9MVHJZBSMglEwCkYwAAAiZkE+PWC3LAAAAABJRU5ErkJggg==","orcid":"","institution":"Affiliated Hospital of Jining Medical University","correspondingAuthor":true,"prefix":"","firstName":"Na","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2023-11-27 00:59:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3669572/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3669572/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-025-05436-8","type":"published","date":"2025-01-27T15:57:26+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":49076488,"identity":"9bde919c-786d-4b7f-ade5-79ad44d84a48","added_by":"auto","created_at":"2024-01-02 18:40:44","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":242965,"visible":true,"origin":"","legend":"\u003cp\u003eA and B, cranial CT, images of case 3 and case 6; C, D and E, cranial MRI, images of case 2, case 4 and case 8 respectively.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3669572/v1/b23fc565500095b764d508d7.jpeg"},{"id":75351416,"identity":"7d74fff9-03da-44aa-8890-130499620406","added_by":"auto","created_at":"2025-02-03 16:11:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":980331,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3669572/v1/032937cb-7a8e-4438-9f7b-d06a01c05b05.pdf"},{"id":49076489,"identity":"39ec4f28-5e2d-4894-a883-b3956b0c0323","added_by":"auto","created_at":"2024-01-02 18:40:44","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":40314,"visible":true,"origin":"","legend":"","description":"","filename":"rawdata.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3669572/v1/ac866199020c341f345c859e.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Severe central nervous system injury in children caused by COVID-19","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe novel coronavirus disease 2019 (COVID-19) pandemic has brought great clinical challenges worldwide. Since the beginning of the pandemic, neurologic manifestations in patients with COVID-19 have been extensively described [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMore serious neurological disorders, such as encephalitis (inflammation of the brain) and encephalopathy (a brain disease characterized by altered consciousness), are rare complications of COVID-19 and are often fatal [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. For example, a study that included 3,707 children reported that only 1% developed encephalopathy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], but this was associated with increased mortality [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Encephalitis/encephalopathy may occur via different mechanisms, including direct infection, systemic inflammation caused by cytokine storms, and autoimmunity [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSince the epidemic prevention policy for COVID-19 in China was lifted in December 2022, the number of cases of COVID-19 has rapidly increased. In light of the growing number of cases, familiarizing physicians with various neurological features that may be observed in these patients is extremely important. This paper reports the condition and prognoses of nine pediatric patients complicated with central nervous system (CNS) injury. Our aim is to make clinicians aware of the severity of CNS injury in children with COVID-19 and to help them identify severe cases as soon as possible.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cp\u003eFrom December 1, 2022 to January 12, 2023, a retrospective review was conducted of the clinical, laboratory, and magnetic resonance imaging (MRI)/computed tomography (CT) findings of nine children admitted to the pediatric intensive care unit (PICU) of the Affiliated Hospital of Jining Medical University. The children were determined to be nucleic acid-positive for SARS-CoV-2 by oropharyngeal swabs. Sample collection and pathogen identification were performed after admission to the hospital. The basic information of the children was recorded, including their age, sex, symptoms, underlying diseases, and vaccination records. All laboratory tests were carried out in accordance with the health standards of the People's Republic of China.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eGeneral information\u003c/p\u003e \u003cp\u003eFrom December 1, 2022 to January 12, 2023, we encountered nine pediatric cases of COVID-19 with severe CNS injury. Of the nine patients, seven were male (77.78%) and two were female (22.22%). Five children were aged\u0026thinsp;\u0026ge;\u0026thinsp;10 years, and the other four were 1\u0026ndash;2 years old. The latter children were not vaccinated, and six children were previously healthy. One child (10 years old at the time of admission) had a history of asthma before the age of 3 years, one child was diagnosed with acute disseminated encephalomyelitis 1 year earlier, and one child with abnormal genetic test results was diagnosed with severe encephalitis 6 months earlier and treated with oral antiepileptic drugs as maintenance therapy (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral information of the 9 children with CNS consequences of COVID-19\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdmit date\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurvival time\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVaccination\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnderlying disease\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMax body temp. (\u0026deg;C)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eConvulsions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eDIC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003estroke\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eGastrointestinal bleeding\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2022/12/23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22 hours\u003c/p\u003e \u003cp\u003e55 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e40.0℃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2022/12/24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e120 hours\u003c/p\u003e \u003cp\u003e20 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eADEM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e38.6℃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2022/12/24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23 hours\u003c/p\u003e \u003cp\u003e5 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003easthma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e41.0℃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2022/12/26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e98 hours\u003c/p\u003e \u003cp\u003e11 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRANBP2NM-\u003c/p\u003e \u003cp\u003e006767.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e39.5℃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2022/12/25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e73 hours\u003c/p\u003e \u003cp\u003e33 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e38.6℃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2022/12/24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e84 hours\u003c/p\u003e \u003cp\u003e9 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e39.0℃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2022/12/25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40 hours\u003c/p\u003e \u003cp\u003e1 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e41.3℃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2022/12/26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e41.0℃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2022/12/28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e40.0℃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"13\"\u003eADEM,acute disseminated encephalomyelitis;Survival time,Time of presentation to death\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eClinical manifestations\u003c/p\u003e \u003cp\u003eAll nine pediatric patients had fever, and five had a body temperature of \u0026ge;\u0026thinsp;40\u0026deg;C and difficulty during defervescence. Eight patients developed fever and convulsions, and the remaining child developed fever and headache. Seven patients had generalized tonic-clonic seizures, one had an unknown form of convulsions, and four had status convulsivus. All patients experienced varying degrees of coma, ranging from fever to coma between 2 hours and 3 days in duration. Eight patients died, and the length of hospital stay ranged from 30 minutes to 5 days. The only survivor has severe neurological sequelae and is currently undergoing rehabilitation. In addition to neurological symptoms, two patients developed shock, and two others developed diffuse intravascular coagulation. Three patients developed gastrointestinal bleeding, and seven progressed to multiple organ failure involving the nervous, respiratory, circulatory, digestive, and coagulation systems.\u003c/p\u003e \u003cp\u003eLaboratory tests and imaging examinations\u003c/p\u003e \u003cp\u003eOne child (case 9) did not undergo any examinations because his vital signs had disappeared at the time of admission. Another child (case 1) died within half a day of admission. On admission, white blood cell counts were normal or low (62.5%). All patients had reduced lymphocyte counts and lymphocyte rates. Most patients had a high neutrophil-to-lymphocyte ratio of \u0026gt;\u0026thinsp;5.0 (75%). Platelet and hemoglobin levels were decreased in 62.5% of patients. All patients had elevated procalcitonin, and 50% had elevated C-reactive protein. Moreover, all patients tested exhibited elevated lactic acid (n\u0026thinsp;=\u0026thinsp;8/8), interleukin-6 (n\u0026thinsp;=\u0026thinsp;7/7), D-dimer (n\u0026thinsp;=\u0026thinsp;8/8) and myoglobin (n\u0026thinsp;=\u0026thinsp;3/3). Most patients had high creatine kinase-MB (n\u0026thinsp;=\u0026thinsp;7/8, 87.5%), cardiac troponin I (n\u0026thinsp;=\u0026thinsp;6/7, 85.7%), creatine kinase (n\u0026thinsp;=\u0026thinsp;5/7, 71.4%), lactate dehydrogenase (n\u0026thinsp;=\u0026thinsp;6/7, 85.7%), alanine aminotransferase (n\u0026thinsp;=\u0026thinsp;7/8, 87.5%), aspartate aminotransferase (n\u0026thinsp;=\u0026thinsp;7/8, 87.5%), and immunoglobulin E (n\u0026thinsp;=\u0026thinsp;3/4, 75%) levels. We observed a decrease in albumin levels in seven of eight patients (87.5%). The plasma ammonia levels of most children were within the normal range (n\u0026thinsp;=\u0026thinsp;5/6, 83.33%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Abnormal laboratory data categorized from the normal range\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"609\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003eNormal range\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003eavailable laboratory measurement，n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003eabnormal laboratory value，n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated white blood cell, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/ L\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e1～\u0026lt;2years，5.1～14.1\u003c/p\u003e\n \u003cp\u003e2～\u0026lt;6years，4.4～11.9\u003c/p\u003e\n \u003cp\u003e6～\u0026lt;13years，4.3～11.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e3（37.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Neutrophil count, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e1～\u0026lt;2years，0.8～5.8\u003c/p\u003e\n \u003cp\u003e2～\u0026lt;6years，1.2～7.0\u003c/p\u003e\n \u003cp\u003e6～\u0026lt;13years，1.6～7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e4（50）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Neutrophil count, %\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e1～\u0026lt;2years，13～54\u003c/p\u003e\n \u003cp\u003e2～\u0026lt;6years，22～65\u003c/p\u003e\n \u003cp\u003e6～\u0026lt;13years，31～70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e8（100）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eLow Lymphocyte count, \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e1～\u0026lt;2years，2.7～9.1\u003c/p\u003e\n \u003cp\u003e2～\u0026lt;6years，1.8～6.3\u003c/p\u003e\n \u003cp\u003e6～\u0026lt;13years，1.5～4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e8（100）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eLow Lymphocyte count, %\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e1～\u0026lt;2years，33～77\u003c/p\u003e\n \u003cp\u003e2～\u0026lt;6years，23～69\u003c/p\u003e\n \u003cp\u003e6～\u0026lt;13years，23～59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e8（100）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Neutrophil-to-lymphocyte ratio, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026le;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e6（75）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eLow Platelet count,\u0026times;10\u003csup\u003e9\u003c/sup\u003e/ L\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e1～\u0026lt;2years，190～524\u003c/p\u003e\n \u003cp\u003e2～\u0026lt;6years，188～472\u003c/p\u003e\n \u003cp\u003e6～\u0026lt;12years，167～453\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e5（62.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eLow hemoglobin,g/L\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e1～\u0026lt;2years，107～141\u003c/p\u003e\n \u003cp\u003e2～\u0026lt;6years，112～149\u003c/p\u003e\n \u003cp\u003e6～\u0026lt;13years，118～156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e5（62.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated C-reactive protein level, U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e0-6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e4（50.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Procalcitonin, ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e0-0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e7（100）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated D-dimer, mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e0-0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e8（100）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Creatine kinase-MB, ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e0-5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e7（87.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Cardiac troponin I, pg/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e0-0.175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e6（85.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Myoglobin, \u0026mu;g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e1.5-70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e3（100）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Creatine kinase, U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e50-310\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e5（71.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Lactate dehydrogenase, U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e120-250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e6（85.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Creatinine, \u0026mu;mol/L\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e28days～＜2years,13～33\u003c/p\u003e\n \u003cp\u003e2～＜6years，19～44\u003c/p\u003e\n \u003cp\u003e6～＜13years，27～66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e5（62.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Blood urea nitrogen, mmol/L\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e1～＜2years,2.3～6.7\u003c/p\u003e\n \u003cp\u003e2～18years\u003c/p\u003e\n \u003cp\u003e2.7～7.0（male）\u003c/p\u003e\n \u003cp\u003e2.5～6.5（female）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e2（25）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Alanine aminotransferase, U/L\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e1～＜2years，8～42\u003c/p\u003e\n \u003cp\u003e2～＜13years，7～30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e7（87.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Aspartate aminotransferase, U/L\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e1～＜2years，11～47\u003c/p\u003e\n \u003cp\u003e2～＜13years，8～30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e7（87.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eLow Albumin, g/L\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e6months～＜13years,\u003c/p\u003e\n \u003cp\u003e39～54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e7（87.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated NT-pro B-type natriuretic peptide, pg/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e0-100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e3（42.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated lactic acid, mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e0.5-1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e8（100）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated ferritin, ng/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003eMale，21.81 - 274.66\u003c/p\u003e\n \u003cp\u003eFamale，4.63 - 204.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e1（33.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated，plasma ammonia, umol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e9-33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e1（16.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Interleukin-6, pg/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e0-3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e7（100）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eElevated Immunoglobulin E, IU/mL\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e1~5years，\u0026lt; 60\u003c/p\u003e\n \u003cp\u003e10~15years，\u0026lt; 200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e3（75）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eLow Immunoglobulin A, g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e0.7-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e3（50）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eLow Immunoglobulin M, g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e0.4-2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e0（0）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.960591133004925%\" valign=\"bottom\"\u003e\n \u003cp\u003eLow Immunoglobulin G, g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.794745484400657%\" valign=\"top\"\u003e\n \u003cp\u003e7-16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.211822660098523%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.032840722495894%\" valign=\"top\"\u003e\n \u003cp\u003e2（33.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n \u003cp\u003eChest imaging showed that seven patients were complicated with pneumonia. However, the imaging also showed that it was not typical viral pneumonia; rather, it was considered to be hypostatic pneumonia caused by convulsive coma. Moreover, one child had bronchitis. Six patients underwent cardiac ultrasound, two of whom had decreased left heart function (ejection fraction\u0026thinsp;\u0026lt;\u0026thinsp;40%). Two patients were complicated with myocarditis, and one child had arrhythmia.\u003c/p\u003e \u003cp\u003eFive patients underwent lumbar puncture, and the cerebrospinal fluid (CSF) white blood cell count was in the normal range. Four patients exhibited CSF protein-cell separation, with the CSF protein content being increased by 80%. The lactate dehydrogenase level in the CSF of three patients was increased by 60%. The protein and lactate dehydrogenase levels in the CSF of the surviving child were normal (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe CSF and neuroimaging results of children\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCSF protein, g/L\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCSF white blood cells, \u0026times; 10\u003csup\u003e6\u003c/sup\u003e/ L\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCSF Lactate dehydrogenase, U/L\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCT of the brain\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMRI of the brain\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eencephlogram\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e657\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eplain scanning, no obvious abnormalities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003emultiple abnormal signals in the brain, infectious disease likely, acute disseminated encephalomyelitis possible\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBroad persistent low voltage pattern\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1. Subarachnoid hemorrhage, diffuse cerebral edema,\u003c/p\u003e \u003cp\u003e2. Bilateral globus pallidus, caudate nucleus head symmetrical high-density shadow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003emultiple symmetric abnormal signals in bilateral basal ganglia-thalamus, corpus callosum, pons, and cerebral cortex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBroad persistent low voltage pattern\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePlain scanning, no obvious abnormalities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1. Bilateral thalamic-midbrain and pontine swelling, ring cistern and fourth ventricle unclear\u003c/p\u003e \u003cp\u003e2. Minor subarachnoid hemorrhage.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAbnormal signal foci on the left side of the corpus callosum pressure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eA small amount of multi-focal discharge in waking period, slow background rhythm;Sleep is highly arrhythmic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eCSF protein, Normal range 0-0.4g/L.CSF white blood cells, Normal range 0\u0026ndash;15 \u0026times;10\u003csup\u003e6\u003c/sup\u003e/ L.CSF Lactate dehydrogenase, Normal range 3-40U/L.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSeven patients underwent cranial imaging, two of whom had no obvious abnormalities on cranial CT examination. One child (case 6) had a bilateral thalamus lesion on cranial CT on the second day after illness, along with swelling of the midbrain and pons (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). One child (case 8) showed abnormal MRI signals in the corpus callosum, and the encephalogram showed a small amount of multifocal discharge during waking hours and a slow background rhythm; sleep was highly arrhythmic. Cranial MRI of one child (case 2) showed multiple abnormal signals in the brain, considered indicative of infectious lesions, and the encephalogram showed persistent and widespread low voltage. Another child (case 4) showed abnormal signals in the bilateral basal ganglia, thalamus, corpus callosum, pons, and multiple areas under the cerebral cortex, and encephalogram showed persistent and widespread low voltage. Finally, diffuse cerebral edema was seen in one child (case 3).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTreatment regimen and prognosis\u003c/p\u003e \u003cp\u003eOne child who presented to the emergency department with respiratory and cardiac arrest died despite treatment with active chest compression, positive pressure ventilation, and vasoactive drugs. The remaining eight patients were admitted to the PICU and received comprehensive anti-infection, intracranial pressure reduction, and mechanical ventilation treatments. In the PICU, all eight of these patients were given glucocorticoids (pulse methylprednisolone, 20 mg/kg/day [maximum\u0026thinsp;=\u0026thinsp;1 g/day]) and intravenous human immunoglobulin (2 g/kg [maximum dose\u0026thinsp;=\u0026thinsp;80 g). To address inflammatory factors, two patients underwent plasmapheresis and three underwent hemodialysis. Because of abnormal coagulation function, plasma transfusion was given to seven patients and cryoprecipitate was given to three patients. Because of varying degrees of anemia, three patients underwent \u0026ldquo;suspended\u0026rdquo; red blood cell infusion to enhance blood oxygen carrying capacity. Because of severe shock or multiorgan failure, seven patients died 12 hours to 5 days after onset, and no cases were autopsied. We followed one child (case 8) receiving antiepileptic and rehabilitation therapy for 6 months and noted frequent nodding spasms after startle and infection. This patient had severe motor and neurodevelopmental delay; now aged 2 years and 7 months, the child is still unable to sit or stand.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe COVID-19 virus has undergone several mutations since its discovery in 2020. The Omicron variant was first identified in South Africa in November 2021 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This variant spreads more rapidly and has a greater ability to evade immunity than other variants [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and it has been the dominant strain globally since February 2022 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Approximately 1 week after the adjustment of epidemic prevention policies, an Omicron infection broke out in mid-December 2022 in eastern China, which reached a peak in around 2 weeks and declined rapidly 3 weeks thereafter. During this period, monitoring by the local Center for Disease Control and Prevention showed that the circulating strains were BA.5.2 and BF.7; no other strains were found. The local Omicron variant spread rapidly, with a short incubation period (typically 2\u0026ndash;4 days). The main symptoms of infection in pediatric patients include fever of varying severity (typically moderate-to-high fever) and febrile seizures. However, the prognosis is good. In the majority of patients, the fever lasted 1\u0026ndash;3 days and rarely persisted for \u0026gt;\u0026thinsp;5 days. A small number of patients suffered coughs, sore throats, headaches, and fatigue, and pneumonia developed in a very small number of cases. Within 43 days after the lifting of lockdown, a total of 9,500 children presented to the center with fever. Among these children, we identified nine with severe CNS injury caused by COVID-19 (morbidity rate\u0026thinsp;=\u0026thinsp;0.09%). Many pediatric cases of multisystem inflammatory response syndrome induced by COVID-19 have been reported in Europe, the United States, and other parts of China [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Moreover, the locally endemic Omicron variant caused more severe neurological lesions in pediatric patients than severe lower respiratory pathologies.\u003c/p\u003e \u003cp\u003eAt present, our understanding of CNS injury caused by COVID-19 is insufficient, and no clear conclusion on the pathogenesis has been drawn. Following infection, COVID-19 enters the CNS through a variety of pathways, such as the blood circulation, sieve plates, and synaptic pathways [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Viruses can cause nerve damage by directly invading the nervous system, leading to tissue hypoxia, inflammatory mediators producing cytokine storms [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], anosmia, taste disorders, viral encephalitis [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], demyelinating lesions [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], toxic encephalopathy [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], and necrotizing encephalopathy, etcetera. At the beginning of the pandemic in 2020, necrotizing encephalopathy in adults caused by COVID-19 infection was reported both in China and elsewhere [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In May 2021, Lazarte-Rantes et al. reported the first pediatric cases of acute necrotizing encephalopathy associated with COVID-19 [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The patients in the above reports all exhibited rapid progression, poor prognosis, and a requirement for mechanical ventilation during treatment. The first reported pediatric case with necrotizing encephalopathy was discharged with severe neurological sequelae [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study reported cases of severe CNS injury in children infected with COVID-19 who presented to our center during the pandemic. We analyzed the incidence, clinical manifestations, imaging examination and laboratory results, and prognoses. All patients had severe CNS injury, and eight pediatric patients developed fever and convulsions. All patients experienced varying degrees of coma, ranging from fever to coma between 2 hours and 3 days in duration. Three children were diagnosed with necrotizing encephalopathy. CSF and brain imaging examinations were not performed in two patients because of rapid disease progression, but necrotizing encephalopathy was highly suspected clinically.In this study, there were more male than female patients, which is inconsistent with previous studies and may be related to the small sample size [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Most patients exhibited inflammatory cytokine storm, ultrahigh fever, cranial imaging abnormalities, and symmetric multifocal brain damage. We also found that most of the children had abnormal liver, heart, coagulation, and hematopoietic function. This finding is suggestive of multiorgan failure. Their disease progressed rapidly, which is apt to give rise to multiple organ dysfunction and a poor prognosis, especially in older children. Even if they survive, such patients are likely to suffer serious neurological sequelae.\u003c/p\u003e \u003cp\u003eImportantly, of the nine children in this study, five underwent a complete CSF examination, and four had significantly higher CSF protein levels than normal; all of the latter patients died. The CSF protein levels of the surviving child were normal. In a previous report, all seven children with COVID-19 complicated with neurological manifestations who died had elevated CSF protein levels [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In another study, the CSF protein levels of five children who died of COVID-19 complicated with necrotizing encephalopathy were higher than those of the surviving children [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Finally, the CSF protein levels of surviving children with severe encephalopathy were found to be normal [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. We speculate that decreased CSF protein levels may be a protective factor for severe neurological impairment or death in children with necrotizing encephalopathy caused by COVID-19.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis study had two limitations. First, the sample size was small. Second, this retrospective study enrolled hospitalized children from a single center. Multicenter studies with larger sample sizes are needed.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eCOVID-19 can cause severe damage to the CNS in pediatric patients. A low level of CSF protein may be a protective factor for death in children with severe neurological damage caused by COVID-19. In view of the high mortality and disability rates of COVID-19-related severe CNS injury, the clinical symptoms of pediatric patients need to be studied in greater depth. It is hoped that this article will serve as a reference for the diagnosis, treatment and management of severe CNS injury associated with COVID-19 in children.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are accountable for all aspects of the work in ensuring that \u0026nbsp; questions related to the accuracy or integrity of any part of the work are \u0026nbsp; appropriately investigated and resolved. \u0026nbsp;The study was conducted in \u0026nbsp; accordance with the Declaration of Helsinki (as revised in 2013). This study was approved by the Ethics Committee of Affiliated Hospital of Jining Medical University.Ethical number:2022C253.All methods were carried out in accordance with relevant guidelines and regulations.Confirm that the informed consent of all subjects\u0026apos; legal guardians has been obtained for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw data supporting the conclusions of this article will be made available by the corresponding author, without undue reservation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Affiliated Hospital of Jining Medical University\u003c/p\u003e\n\u003cp\u003e(grant number 2020-BS-010).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ec\u003c/strong\u003e\u003cstrong\u003eontributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePPZ, NL\u0026nbsp;contributed to primary manuscript writing and editing.MYX has made outstanding contributions to the preparation, planning and revision of it, and put forward some valuable ideas. YGB was responsible for the collection and interpretation of data. XYR was responsible for the quality control and supervision of medical records.All authors contributed to the paper and approved the submitted version.All authors contributed to study conceptualization and design.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank all the pediatric staff of the Affiliated Hospital of Jining Medical University for their support and help.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272007,China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eSurrey College，Dongbei University of Finance and Economics, Dalian, Liaoning, 116025，China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3\u003c/sup\u003ePostdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLi YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol 2020;92(6):552-5.doi: 10.1002/jmv.25728\u003c/li\u003e\n\u003cli\u003eHuang Chaolin,Wang Yeming,Li Xingwang et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395(10223), 497-506. doi:10.1016/S0140-6736(20)30183-5.\u003c/li\u003e\n\u003cli\u003eSiow I, Lee KS, Zhang JJY, et al. Encephalitis as a neurological complication of COVID-19: A systematic review and meta-analysis of incidence, outcomes, and predictors. Eur J Neurol. 2021;28:3491\u0026ndash;3502.doi:10.1111/ene.14913\u003c/li\u003e\n\u003cli\u003eShimohata T. Neuro-COVID-19. Clin Exp Neuroimmunol. 2022;13(1):17-23.doi:10.1111/cen3.12676\u003c/li\u003e\n\u003cli\u003ePanda PK, Sharawat IK, Panda P, et al. Neurological complications of SARS-CoV-2 infection in children: A systematic review and meta-analysis. J Trop Pediatr. 2021;67(3). doi:10.1093/tropej/fmaa070\u003c/li\u003e\n\u003cli\u003eValderas C, M\u0026eacute;ndez G, Echeverr\u0026iacute;a A, et al. COVID-19 and neurologic manifestations: a synthesis from the child neurologist\u0026rsquo;s corner.World J Pediatr. 2022;18(6):373\u0026ndash;382. doi:10.1007/s12519-022-00550-4\u003c/li\u003e\n\u003cli\u003eUmapathi T, Quek WMJ, Yen JM, et al. Encephalopathy in COVID-19 patients; viral, parainfectious, or both? eNeurologicalsci.2020;21:100275.doi:10.1016/j.ensci.2020.100275\u003c/li\u003e\n\u003cli\u003eKarim S, Karim QA. Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic. Lancet, 2021,398(10317): 2126-2128. doi: 10.1016/S0140-6736(21)02758-6\u003c/li\u003e\n\u003cli\u003eCallaway E. Heavily mutated Omicron variant puts scientists on alert[J]. Nature, 2021, 600(7887): 21.doi: 10.1038/d41586-021-03552-w\u003c/li\u003e\n\u003cli\u003eViana R, Moyo S, Amoako DG, et al. Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa.Nature, 2022, 603(7902): 679-686.doi: 10.1038/s41586-022-04411-y\u003c/li\u003e\n\u003cli\u003eJiao FY, Ma L. Strengthening the prevention and treatment of Omicron infection in children. Chinese Journal of Contemporary Pediatric,2022,24(4):345-349.doi: 10.7499/j.issn.1008-8830.2201001\u003c/li\u003e\n\u003cli\u003eZhi GF,Yan MB,Yong HY,et al.Severe acute respiratory syndrome coronavirus 2-induced multisystem inflammatory syndrome in children.Pediatr Investig.2020 Dec 28;4(4):257-262.doi: 10.1002/ped4.12225. \u003c/li\u003e\n\u003cli\u003eWaseem M, MS M , Shariff MA et al.Multisystem Inflammatory Syndrome in Children. The Journal of Emergency Medicine 2022,62:28\u0026ndash;37.doi:10.1016/j.jemer-med.2021.07.070.\u003c/li\u003e\n\u003cli\u003eBaigAM,KhaleeqA,AliU,et al.Evidence of the COVID-19 virus targeting the cns: tissue distribution, host-virus interaction,and proposed neurotropic mechanisms.ACS Chem Neurosci,2020,11(7):995-998.doi: 10.1021/acschemneuro.0c00122\u003c/li\u003e\n\u003cli\u003eBaigAM.Neurological manifestations in COVID-19 caused by SARS-CoV-2.CNS Neurosci Ther,2020,26(5):499-501.doi: 10.1111/cns.13372.\u003c/li\u003e\n\u003cli\u003eLiYC,BaiWZ,HashikawaT.The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients.J Med Virol,2020,92(6):552-555.doi: 10.1002/jmv.25728\u003c/li\u003e\n\u003cli\u003eChenC,ZhangXR,JuZY,et al.Advances in the research of mechanism and related immunotherapy on the cytokine storm induced by coronavirus disease 2019.Chin J Burns,2020,36(6):471-475.doi: 10.3760/cma.j.cn501120-20200224-00088\u003c/li\u003e\n\u003cli\u003eMehtaP,McAuleyDF,BrownM,etal.COVID-19:consider cytokine storm syndro-mes and immunosuppression.Lancet,2020,395(10229):1033-1034.doi:10.1016/S0140-6736(20)30628-0\u003c/li\u003e\n\u003cli\u003eMoriguchiT,HariiN,GotoJ,et al.A first case of meningitis/encephalitis associated with SARS-Coronavirus-2.Int J Infect Dis,2020,94:55-58.doi: 10.1016/j.ijid.2020.03.062\u003c/li\u003e\n\u003cli\u003eYeM,RenY,LvT.Encephalitis as a clinical manifestation of COVID-19.Brain Behav Immun,2020,88:945-946.doi: 10.1016/j.bbi.2020.04.017\u003c/li\u003e\n\u003cli\u003eSedaghatZ,KarimiN.Guillain Barre syndrome associated with COVID-19 infection:A case report.J Clin Neurosci,2020,76:233-235.doi: 10.1016/j.jocn.2020.04.062\u003c/li\u003e\n\u003cli\u003eGuoYR,CaoQD,HongZS,et al.The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak-an update on the status.Mil Med Res,2020,7(1):11.doi: 10.1186/s40779-020-00240-0\u003c/li\u003e\n\u003cli\u003eDixon L,VarleyJ,Gontsarova A,et al.COVID-19-related acute necrotizing encephalopathy with brain stem involvement in a patient with aplastic anemia.Nurol Neuroimmunol Neuroinflamm,2020,7(5):e789.doi: 10.1212/NXI.0000000000000789\u003c/li\u003e\n\u003cli\u003eLazarte-Rantes C, Guevara-Casta\u0026ntilde;\u0026oacute;n J, Romero L, Guill\u0026eacute;n-Pinto D. Acute Necrotizing Encephalopathy Associated With SARS-CoV-2 Exposure in a Pediatric Patient. Cureus. 2021 May 13;13(5):e15018. doi: 10.7759/cureus.15018\u003c/li\u003e\n\u003cli\u003eLin Xia,Wang Ying,Li Xiaoying et al. Acute necrotizing encephalopathy in children with COVID-19: a retrospective study of 12 cases.Front Neurol, 2023, 14: 1184864.doi: 10.3389/fneur.2023.1184864\u003c/li\u003e\n\u003cli\u003eTandon Medha,Kataria Saurabh,Patel Jenil et al. A Comprehensive Systematic Review of CSF analysis that defines Neurological Manifestations of COVID-19.Int J Infect Dis, 2021, 104: 390-397.doi: 10.1016/j.ijid.2021.01.002\u003c/li\u003e\n\u003cli\u003eZhang Tao, WANG Li-jie, XU Wei et al.Clinical features of three children with severe COVID-19 encephalopathy and literature review[J].Chinese Pediatric Emergency Medicine,2023,30(3):E001.DOI:10.3760/cma.j.issn.1673-4912.2023.03.002\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, Severe central nervous system injury, Children","lastPublishedDoi":"10.21203/rs.3.rs-3669572/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3669572/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo investigate the clinical features and prognosis of severe central nervous system (CNS) injury in children caused by coronavirus disease 2019 (COVID-19).\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eWe retrospectively studied confirmed pediatric cases of COVID-19 complicated with CNS injury.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eNine patients diagnosed with COVID-19 complicated with severe CNS injury were admitted to the pediatric intensive care unit of the Affiliated Hospital of Jining University from December 1, 2022 to January 12, 2023. Of the nine patients, seven were male (77.78%). Five children were aged\u0026thinsp;\u0026ge;\u0026thinsp;10 years, and the others were 1\u0026ndash;2 years old. All children had fever, eight had convulsions, seven had progressed to multiple organ failure, and all suffered varying degrees of coma. Most of the children had elevated interleukin-6 (100%), lactic acid (100%), alanine transaminase (87.5%), aspartate transaminase (87.5%), creatine kinase MB (87.5%), and lactate dehydrogenase (85.7%) levels. Four children had cerebrospinal fluid protein-cell separation. The cranial imaging results of five children were abnormal. One child had lost his vital signs when admitted to hospital, and the remaining eight received hormonal shock, human immunoglobulin transfusion, anti-infection, cranial pressure reduction, and mechanical ventilation treatments, among others, during hospitalization. Ultimately, eight children died, and the remaining child has serious neurological sequelae and is undergoing rehabilitation.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eSevere CNS injury caused by COVID-19 has an acute onset, rapid progression, high disability rate, and high fatality rate. A low cerebrospinal fluid protein level may be a protective factor for children with severe nervous system injury caused by COVID-19.\u003c/p\u003e","manuscriptTitle":"Severe central nervous system injury in children caused by COVID-19","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-02 18:40:39","doi":"10.21203/rs.3.rs-3669572/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-10T10:56:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-03T21:31:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-31T10:03:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"89613184905386546143771375199033810934","date":"2024-05-25T04:58:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"165231826764006183970278426204580785328","date":"2024-05-24T16:55:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"f5e945c1-04d5-44d7-8b6b-f40e0933c7fe","date":"2024-03-08T05:01:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"5842f01f-5c13-4b4e-9ccc-a54a583b9f31","date":"2024-03-08T03:52:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-07T20:09:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-07T20:07:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2023-12-26T10:14:41+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-12-26T10:12:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2023-11-27T00:47:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2b6849c1-ff26-481e-998b-ade35c94725a","owner":[],"postedDate":"January 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-03T16:05:45+00:00","versionOfRecord":{"articleIdentity":"rs-3669572","link":"https://doi.org/10.1186/s12887-025-05436-8","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2025-01-27 15:57:26","publishedOnDateReadable":"January 27th, 2025"},"versionCreatedAt":"2024-01-02 18:40:39","video":"","vorDoi":"10.1186/s12887-025-05436-8","vorDoiUrl":"https://doi.org/10.1186/s12887-025-05436-8","workflowStages":[]},"version":"v1","identity":"rs-3669572","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3669572","identity":"rs-3669572","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}