Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Clinical Research Article
  • Published:

Children with severe neurological symptoms associated with SARS-CoV-2 infection during Omicron pandemic in China

Pediatric Research volume 95, pages 1088–1094 (2024)Cite this article

Abstract

Background

To analyze the clinical characteristics and outcomes of children with severe neurological symptoms associated with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the Omicron pandemic in China.

Methods

This study used a questionnaire to obtain data from pediatric intensive care unit (PICU) centers in seven tertiary hospitals in Northeast China from December 1, 2022, to January 31, 2023.

Results

A total of 255 patients were confirmed to have SARS-CoV-2 infection, and 45 patients (17.65 %) were included in this study. Of these, seven (15.6%) patients died, and the median time from admission to death was 35 h (IQR, 14–120 h). Twenty (52.6%) survivors experienced neurological sequelae. Patients with platelet counts lower than 100 × 109/L had a higher incidence of complications such as multiple organ dysfunction, mechanical ventilation rate, and mortality. Cranial magnetic resonance imaging (MRI) always reveals cerebral tissue edema, with some severe lesions forming a softening site.

Conclusion

Children infected with SARS-CoV-2 often exhibit severe neurological symptoms, and in some cases, they may rapidly develop malignant cerebral edema or herniation, leading to a fatal outcome. An early decrease in platelet count may associated with an unfavorable prognosis.

Impact

  • Since early December 2022, China has gradually adjusted its prevention and control policy of SARS-CoV-2; Omicron outbreaks have occurred in some areas for a relatively short period. Due to the differences in ethnicity, endemic strains and vaccination status, there was a little difference from what has been reported about children with SARS-CoV-2 infection with severe neurological symptoms in abroad. This is the first multicenter clinical study in children with nervous system involvement after acute SARS-CoV-2 infection in China, and helpful for pediatricians to have a more comprehensive understanding of the clinical symptoms and prognosis of such disease.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Patient screening process.
Fig. 2: Neurological imaging of the patients.

Similar content being viewed by others

Data availability

All authors agreed that the data and materials mentioned in this article are true and availability. The datasets used and/or analyzed during the current study available from the appendix.

References

  1. Wang, L. et al. Comparison of outcomes from covid infection in pediatric and adult patients before and after the emergence of omicron. medRxiv https://doi.org/10.1101/2021.12.30.21268495 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Viana, R. et al. Rapid epidemic expansion of the SARS-cov-2 omicron variant in southern africa. Nature 603, 679–686 (2022).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lin, J. E. et al. Neurological issues in children with covid-19. Neurosci. Lett. 743, 135567 (2021).

    Article  CAS  PubMed  Google Scholar 

  4. Schober, M. E., Pavia, A. T. & Bohnsack, J. F. Neurologic manifestations of covid-19 in children: emerging pathophysiologic insights. Pediatr. Crit. Care Med. 22, 655–661 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lewis, A. et al. Cerebrospinal fluid in covid-19: a systematic review of the literature. J. Neurol. Sci. 421, 117316 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Stafstrom, C. E. & Jantzie, L. L. Covid-19: neurological considerations in neonates and children. Children 7. https://doi.org/10.3390/children7090133 (2020).

  7. Franke, C. et al. High frequency of cerebrospinal fluid autoantibodies in covid-19 patients with neurological symptoms. Brain Behav. Immun. 93, 415–419 (2021).

    Article  CAS  PubMed  Google Scholar 

  8. Nordvig, A. S. et al. Potential neurologic manifestations of covid-19. Neurol. Clin. Pract. 11, e135–e146 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Smadja, D. M. et al. Covid-19 is a systemic vascular hemopathy: insight for mechanistic and clinical aspects. Angiogenesis 24, 755–788 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Thakur, K. T. et al. Covid-19 neuropathology at columbia university irving medical center/new york presbyterian hospital. Brain 144, 2696–2708 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Mizuguchi, M. et al. Acute necrotising encephalopathy of childhood: a new syndrome presenting with multifocal, symmetric brain lesions. J. Neurol. Neurosurg. Psychiatry 58, 555–561 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Michael, B. D. et al. Consensus clinical guidance for diagnosis and management of adult COVID-19 encephalopathy patients. J. Neuropsychiatry Clin. Neurosci. 35, 12–27 (2023).

    Article  PubMed  Google Scholar 

  13. Garcia-Vera, C. et al. Covid-19 in children: clinical and epidemiological spectrum in the community. Eur J. Pediatr. 181, 1235–1242 (2022).

    Article  CAS  PubMed  Google Scholar 

  14. Cui, X. et al. A systematic review and meta-analysis of children with coronavirus disease 2019 (covid-19). J. Med. Virol. 93, 1057–1069 (2021).

    Article  CAS  PubMed  Google Scholar 

  15. Moreira, A. et al. Demographic predictors of hospitalization and mortality in us children with covid-19. Eur. J. Pediatr. 180, 1659–1663 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ranabothu, S. et al. Spectrum of covid-19 in children. Acta Paediatr. 109, 1899–1900 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lee, P. Y. et al. Distinct clinical and immunological features of SARS-cov-2-induced multisystem inflammatory syndrome in children. J. Clin. Investig. 130, 5942–5950 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Panda, P. K. et al. Neurological complications of SARS-cov-2 infection in children: a systematic review and meta-analysis. J. Trop. Pediatr. 67. https://doi.org/10.1093/tropej/fmaa070 (2021).

  19. Nepal, G. et al. Neurological manifestations of covid-19 associated multi-system inflammatory syndrome in children: a systematic review and meta-analysis. J. Nepal Health Res. Counc. 19, 10–18 (2021).

    Article  PubMed  Google Scholar 

  20. Abdel-Mannan, O. et al. Neurologic and radiographic findings associated with covid-19 infection in children. Jama Neurol. 77, 1440–1445 (2020).

    Article  PubMed  Google Scholar 

  21. Ray, S. T. J. et al. Neurological manifestations of SARS-cov-2 infection in hospitalised children and adolescents in the uk: a prospective national cohort study. Lancet Child Adolesc. Health 5, 631–641 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. LaRovere, K. L. et al. Neurologic involvement in children and adolescents hospitalized in the united states for covid-19 or multisystem inflammatory syndrome. Jama Neurol. 78, 536 (2021).

    Article  PubMed  Google Scholar 

  23. Xiao, L., Ran, X., Zhong, Y. & Li, S. Clinical value of blood markers to assess the severity of coronavirus disease 2019. BMC Infect. Dis. 21, 1471–2334 (2021).

    Article  Google Scholar 

  24. Zhao, X. et al. Early decrease in blood platelet count is associated with poor prognosis in COVID-19 patients-indications for predictive, preventive, and personalized medical approach. EPMA J. 11, 139–145 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Gorog, D. A. et al. Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium. Nat. Rev. Cardiol. 19, 475–495 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Overmyer, K. A. et al. Large-scale multi-omic analysis of COVID-19 severity. Cell Syst. 12, 23–40 (2021).

    Article  CAS  PubMed  Google Scholar 

  27. Liao, D. et al. Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study. Lancet Haematol. 7, e671–e678 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Henry, B. M., de Oliveira, M., Benoit, S., Plebani, M. & Lippi, G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin. Chem. Lab. Med. 58, 1021–1028 (2020).

    Article  CAS  PubMed  Google Scholar 

  29. COVID-19 Forecasting Team. Past SARS-cov-2 infection protection against re-infection: a systematic review and meta-analysis. Lancet 401, 833–842 (2023).

    Article  Google Scholar 

  30. Tenforde, M. W. et al. Vaccine effectiveness against influenza-associated urgent care, emergency department, and hospital encounters during the 2021-2022 season, vision network. J. Infect. Dis. https://doi.org/10.1093/infdis/jiad015 (2023).

    Article  PubMed  Google Scholar 

  31. Adams, K. et al. Prevalence of SARS-cov-2 and influenza coinfection and clinical characteristics among children and adolescents aged <18 years who were hospitalized or died with influenza - united states, 2021-22 influenza season. MMWR Morb. Mortal Wkly Rep. 71, 1589–1596 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the Major science and technology Project of Liaoning Province (No. 2020JH1/10300001 to Chun-Feng Liu); the Natural Science Foundation of Liaoning Province (No. 2023-MS-191 to T.Z.), and 345 Talent Project of Shengjing Hospital of China Medical University (C.-F.L. and T.Z.).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China

    Tao Zhang & Chun-Feng Liu

  2. Department of Pediatric Intensive Care Unit, Dalian Women and Children’s Medical Group, Dalian, China

    Qiao-Feng Zhang & Hong-Mei Yang

  3. Department of Pediatric Intensive Care Unit, Shenyang Children’s Hospital, Shenyang, China

    Pin Liu & Peng Sun

  4. Department of Pediatric Intensive Care Unit, The First Hospital of Jilin University, Changchun, China

    Yu-Mei Li & Zhen Zhang

  5. Changchun Children’s Hospital, Changchun, China

    Yan-Zhi Huang

  6. Department of Critical Medicine, Jiangnan Hospital of the Sixth Affiliated Hospital of Harbin Medical University (Harbin Children’s Hospital), Harbin, China

    Xin-Yan Yu

  7. Department of Intensive Care Unit, Inner Mongolia Medical University Affiliated Hospital, Hohhot, China

    Qi-Qi-Ge Chao-Lu-Men & Qin Su

Authors
  1. Tao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiao-Feng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hong-Mei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peng Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu-Mei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yan-Zhi Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xin-Yan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Qi-Qi-Ge Chao-Lu-Men
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Qin Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Chun-Feng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

T.Z., and C.F.L, conceived and designed the study. T.Z., Q.F.Z., H.M.Y., P.L., P.S., Y.M.L., Z.Z., Y.Z.H., X.Y.Y., Q.Q.G.C.L.M. and Q.S., collected all the data. T.Z. analyzed the data. All authors participated in drafting or revising of the manuscript, and approved the final manuscript.

Corresponding author

Correspondence to Chun-Feng Liu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethical approval and consent to participate

This study was approved by the Ethics Committee of Shengjing Hospital of China Medical University (2023PS434K), and the patient consent was not required in this study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, T., Zhang, QF., Yang, HM. et al. Children with severe neurological symptoms associated with SARS-CoV-2 infection during Omicron pandemic in China. Pediatr Res 95, 1088–1094 (2024). https://doi.org/10.1038/s41390-023-02904-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-02904-8

This article is cited by

Search

Advanced search

Quick links