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.

  • Review Article
  • Published:

Neurological and neurodevelopmental effects of Covid and MIS-C on children

Pediatric Research (2025)Cite this article

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been shown to cause a unique disease phenotype in the paediatric population compared to adults, following the emergence of Multisystem Inflammatory Syndrome of Children (MIS-C) and Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). Over the course of the pandemic, neurological symptoms associated with SARS-CoV-2 have been reported in the paediatric population. The neurological and neurodevelopmental sequelae of both acute SARS-CoV-2 infection and MIS-C/PIMS-TS in the paediatric population are not well understood. Little is known about the underlying pathophysiology and the potential neurovirulence of SARS-CoV-2. Further awareness and research are needed on the neurological sequelae and long-term consequences of SARS-CoV-2 on the developing brain.

Impact

  • Detailed review of the current knowledge on neurological and neurodevelopmental effects of SARS-CoV-2 and MIS-C on the paediatric population.

  • Emphasise the importance of acknowledging the potential direct effects of SARS-CoV-2 and MIS-C on neurological and neurodevelopmental outcomes.

  • Highlight the need for further research and inclusion of paediatric patients in follow up studies of long-term effects of SARS-CoV-2 and MIS-C focusing on neurodevelopmental and neurological sequelae.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

Fig. 1: Neurological effects of Covid-19/MIS-C.

Similar content being viewed by others

References

  1. Centers for Disease Control and Prevention. Covid Data Tracker, <https://covid.cdc.gov/covid-data-tracker> (2023).

  2. Centers for Disease Control and Prevention. Information for Pediatric Healthcare Providers, <https://www.cdc.gov/coronavirus/2019-ncov/hcp/pediatric-hcp.html> (2023).

  3. Royal College of Paediatrics and Child Health. Covid-10 Research Evidence Summaries, <https://www.rcpch.ac.uk/resources/COVID-19-research-evidence-summaries> (2021).

  4. Tsankov, B. K. et al. Severe Covid-19 infection and pediatric comorbidities: a systematic review and meta-analysis. Int J. Infect. Dis. 103, 246–256 (2021).

    Article  CAS  PubMed  Google Scholar 

  5. Riphagen, S., Gomez, X., Gonzalez-Martinez, C., Wilkinson, N. & Theocharis, P. Hyperinflammatory shock in children during Covid-19 pandemic. Lancet 395, 1607–1608 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pawar, R. et al. Neonatal Multisystem Inflammatory Syndrome (Mis-N) associated with prenatal maternal Sars-Cov-2: a Case Series. Children 8 572 (2021).

  7. Nakra, N. A., Blumberg, D. A., Herrera-Guerra, A. & Lakshminrusimha, S. Multi-system inflammatory syndrome in Children (Mis-C) following Sars-Cov-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management. Children 7 69 (2020).

  8. Santos, M. O. et al. Multisystem inflammatory syndrome (Mis-C): a systematic review and meta-analysis of clinical characteristics, treatment, and outcomes. J. Pediatr. 98, 338–349 (2022).

    Article  Google Scholar 

  9. Centers for Disease Control and Prevention. Standardized Case Definition for Surveillance of Multisystem Inflammatory Syndrome in Children Associated with Sars-Cov-2 Infection, <https://www.cdc.gov/mis-c/hcp_cstecdc/index.html> (2023).

  10. World Health Organization. A Clinical Case Defintion for Post Covid-10 Condition in Children and Adolescence by Expert Consensus, <https://www.who.int/publications/i/item/WHO-2019-nCoV-Post-Covid-19-condition-CA-Clinical-case-defintion-2023-1> (2023).

  11. Feldstein, L. R. et al. Characteristics and outcomes of US children and adolescents with Multisystem Inflammatory Syndrome in Children (Mis-C) compared with severe acute Covid-19. JAMA 325, 1074–1087 (2021).

    Article  CAS  PubMed  Google Scholar 

  12. Hoste, L., Van Paemel, R. & Haerynck, F. Multisystem inflammatory syndrome in children related to Covid-19: a systematic review. Eur. J. Pediatr. 180, 2019–2034 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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 

  14. Antoon, J. W. et al. Covid-19 and acute neurologic complications in children. Pediatrics 150 69 (2022).

  15. Stafstrom, C. E. Neurological effects of Covid-19 in infants and children. Dev. Med. Child Neurol. 64, 818–829 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mulkey, S. B., Bearer, C. F. & Molloy, E. J. Indirect effects of the Covid-19 pandemic on children relate to the child’s age and experience. Pediatr. Res 94, 1586–1587 (2023).

    Article  PubMed  Google Scholar 

  17. Bauer, L. et al. The neuroinvasiveness, neurotropism, and neurovirulence of Sars-Cov-2. Trends Neurosci. 45, 358–368 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Roya College of Paediatrics and Child Health. Paediatric Multisystem Inflammatory Syndrome Temporally Associated with Covid-19 (PIMS)- Guidance for Clinicians, <https://www.rcpch.ac.uk/resources/paediatric-multisystem-inflammatory-syndrome-temporally-associated-covid-19-pims-guidance> (2020).

  19. Molloy, E. J., Nakra, N., Gale, C., Dimitriades, V. R. & Lakshminrusimha, S. Multisystem Inflammatory Syndrome in Children (Mis-C) and Neonates (Mis-N) associated with Covid-19: optimizing definition and management. Pediatr. Res 93, 1499–1508 (2023).

    Article  PubMed  Google Scholar 

  20. Zambrano, L. D. et al. Risk Factors for multisystem inflammatory syndrome in children: a case-control investigation. Pediatr. Infect. Dis. J. 42, e190–e196 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lakshminrusimha, S., Hudak, M. L., Dimitriades, V. R. & Higgins, R. D. Multisystem inflammatory syndrome in neonates following maternal Sars-Cov-2 Covid-19 infection. Am. J. Perinatol. 39, 1166–1171 (2022).

    Article  PubMed  Google Scholar 

  22. Singer, T. G., Evankovich, K. D., Fisher, K., Demmler-Harrison, G. J. & Risen, S. R. Coronavirus Infections in the nervous system of children: a scoping review making the case for long-term neurodevelopmental surveillance. Pediatr. Neurol. 117, 47–63 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Jamali, Z., Sinaei, R. & Razi, L. Multisystem Inflammatory Syndrome in a Newborn (Mis-N): clinical evidence and neurodevelopmental outcome. Curr. Pediatr. Rev. 19, 210–212 (2023).

    Article  CAS  PubMed  Google Scholar 

  24. Fink, E. L. et al. Prevalence and risk factors of neurologic manifestations in hospitalized children diagnosed with acute Sars-Cov-2 or Mis-C. Pediatr. Neurol. 128, 33–44 (2022).

    Article  PubMed  Google Scholar 

  25. Francoeur, C. et al. Severe pediatric neurological manifestations with Sars-Cov-2 or Mis-C hospitalization and new morbidity. JAMA Netw. Open 7, e2414122 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lee, I. T., Lin, P. J. & Yen, H. H. Pediatric neuroimaging findings and clinical presentations of Covid-19: a systematic review. Int. J. Infect. Dis. 138, 29–37 (2024).

    Article  CAS  PubMed  Google Scholar 

  27. Kwan, A. T. H. et al. Association of Sars-Cov-2 infection with neurological symptoms and neuroimaging manifestations in the pediatric population: a systematic review. J. Psychiatr. Res. 170, 90–110 (2024).

  28. Sakuma, H. et al. International consensus definitions for infection-triggered encephalopathy syndromes. Dev. Med. Child Neurol. 67, 195–207 (2025).

    Article  PubMed  Google Scholar 

  29. Kasai, M. et al. Clinical characteristics of Sars-Cov-2-associated encephalopathy in children: nationwide epidemiological study. J. Neurol. Sci. 457, 122867 (2024).

    Article  CAS  PubMed  Google Scholar 

  30. Ma, Y. et al. Acute necrotizing encephalopathy infected with the Sars-Cov-2 in children: case series and literature review of clinical outcomes with the use of tocilizumab. Eur. J. Paediatr. Neurol. 52, 67–75 (2024).

    Article  CAS  PubMed  Google Scholar 

  31. Helbok, R. et al. Neurocovid: it’s time to join forces globally. Lancet Neurol. 19, 805–806 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lindan, C. E. et al. Neuroimaging manifestations in children with Sars-Cov-2 infection: a multinational, multicentre collaborative study. Lancet Child Adolesc. Health 5, 167–177 (2021).

    Article  CAS  PubMed  Google Scholar 

  33. Wong, A. M. & Toh, C. H. Spectrum of neuroimaging mimics in children with Covid-19 infection. Biomed. J. 45, 50–62 (2022).

    Article  CAS  PubMed  Google Scholar 

  34. Ucan, B. et al. Multisystem inflammatory syndrome in children associated with Sars-Cov-2: extracardiac radiological findings. Br. J. Radiol. 95, 20210570 (2022).

    Article  PubMed  Google Scholar 

  35. Guerrero, J. I. et al. Central and peripheral nervous system involvement by Covid-19: a systematic review of the pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings. BMC Infect. Dis. 21, 515 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gulko, E. et al. MRI brain findings in 126 patients with Covid-19: initial observations from a descriptive literature review. Am. J. Neuroradiol. 41, 2199–2203 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Choi, Y. & Lee, M. K. Neuroimaging findings of brain MRI and CT in patients with Covid-19: a systematic review and meta-analysis. Eur. J. Radiol. 133, 109393 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  38. 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, 536–547 (2021).

    Article  PubMed  Google Scholar 

  39. LaRovere, K. L. et al. Changes in distribution of severe neurologic involvement in US pediatric inpatients with Covid-19 or multisystem inflammatory syndrome in children in 2021 Vs 2020. JAMA Neurol. 80, 91–98 (2023).

    Article  PubMed  Google Scholar 

  40. Kremer, S. et al. Brain MRI findings in severe Covid-19: a retrospective observational study. Radiology 297, E242–E251 (2020).

    Article  PubMed  Google Scholar 

  41. Molloy, E. J. & Bearer, C. F. Covid-19 in children and altered inflammatory responses. Pediatr. Res. 88, 340–341 (2020).

    Article  CAS  PubMed  Google Scholar 

  42. Rastogi, S., Gala, F., Kulkarni, S. & Gavali, V. Neurological and neuroradiological patterns with Covid-19 infection in children: a single institutional study. Indian J. Radiol. Imaging 32, 510–522 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Sa, M. et al. Systemic inflammation is associated with neurologic involvement in pediatric inflammatory multisystem syndrome associated with SARS-Cov-2. Neurol Neuroimmunol. Neuroinflammation 8 e1023 (2021).

  44. Jiang, N. M., Cowan, M., Moonah, S. N. & Petri, W. A. The impact of systemic inflammation on neurodevelopment. Trends Mol. Med. 24, 794–804 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. DeBiasi, R. L. et al. Multisystem inflammatory syndrome of children: subphenotypes, risk factors, biomarkers, cytokine profiles, and viral sequencing. J. Pediatr. 237, 125–135.e118 (2021).

    Article  CAS  PubMed  Google Scholar 

  46. Godfred-Cato, S. et al. Distinguishing multisystem inflammatory syndrome in children from Covid-19, Kawasaki Disease and Toxic Shock Syndrome. Pediatr. Infect. Dis. J. 41, 315–323 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Morrow, A. K. et al. Postacute/long covid in pediatrics: development of a multidisciplinary rehabilitation clinic and preliminary case series. Am. J. Phys. Med Rehabil. 100, 1140–1147 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Izquierdo-Pujol, J. et al. Post Covid-19 condition in children and adolescents: an emerging problem. Front. Pediatr. 10, 894204 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Landry, M. et al. Postacute sequelae of Sars-Cov-2 in university setting. Emerg. Infect. Dis. 29, 519–527 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Lopez-Leon, S. et al. Long-COVID in children and adolescents: a systematic review and meta-analyses. Sci. Rep. 12, 9950 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Morrow, A. K. et al. Long-term COVID-19 sequelae in adolescents: the overlap with orthostatic intolerance and Me/Cfs. Curr. Pediatr. Rep. 10, 31–44 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Stephenson, T. et al. Physical and mental health 3 months after Sars-CoV-2 infection (Long Covid) among adolescents in England (Clock): a national matched cohort study. Lancet Child Adolesc. Health 6, 230–239 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Avittan, H. & Kustovs, D. Cognition and mental health in pediatric patients following Covid-19. Int. J. Environ. Res. Public Health 20 5061 (2023).

  54. Morand, A. et al. Similar patterns of Eur. J. Nucl. Med. Mol. Imaging 49, 913–920 (2022).

  55. Churchill, N. W. et al. Effects of post-acute Covid-19 syndrome on the functional brain networks of non-hospitalized individuals. Front. Neurol. 14, 1136408 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Monje, M. & Iwasaki, A. The neurobiology of long Covid. Neuron 110, 3484–3496 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Davies, S. C., Walsh-Messinger, J. & Greenspan, N. Supporting Students with Post-Acute Sequelae of SARS-Cov-2 Infection: Applying Lessons Learned from Postconcussion Symptoms Vol. 50 (National Association of School Psychologists Communique, 2021).

  58. Keenan, H. T., Hooper, S. R., Wetherington, C. E., Nocera, M. & Runyan, D. K. Neurodevelopmental consequences of early traumatic brain injury in 3-year-old children. Pediatrics 119, e616–623 (2007).

    Article  PubMed  Google Scholar 

  59. Morissette, M. P., Prior, H. J., Tate, R. B., Wade, J. & Leiter, J. R. S. Associations between concussion and risk of diagnosis of psychological and neurological disorders: a retrospective population-based cohort study. Fam. Med. Community Health 8 e000390 (2020).

  60. Taquet, M. et al. Neurological and psychiatric risk trajectories after Sars-Cov-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients. Lancet Psychiatry 9, 815–827 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Morello, R. et al. Risk factors for post-Covid-19 condition (long Covid) in children: a prospective cohort study. EClinicalMedicine 59, 101961 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Knight, M. et al. Characteristics and outcomes of pregnant women admitted to hospital with confirmed Sars-Cov-2 infection in UK: national population based cohort study. BMJ 369, m2107 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Rodriguez, V. J. et al. Prevalence of neurodevelopmental delays in infants with perinatal HIV infection in comparison with HIV exposure in Rural South Africa. AIDS (2023).

  64. Almond, D. & Mazumder, B. The 1918 influenza pandemic and subsequent health outcomes: an analysis of Sipp data. Am. Econ. Rev. 95, 258–262 (2005).

    Article  PubMed  Google Scholar 

  65. Patterson, P. H. Immune involvement in schizophrenia and autism: etiology, pathology and animal models. Behav. Brain Res. 204, 313–321 (2009).

    Article  CAS  PubMed  Google Scholar 

  66. Otero, A. M. & Antonson, A. M. At the crux of maternal immune activation: viruses, microglia, microbes, and Il-17a. Immunol. Rev. 311, 205–223 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Cordeiro, C. N., Tsimis, M. & Burd, I. Infections and brain development. Obstet. Gynecol. Surv. 70, 644–655 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Al-Haddad, B. J. S. et al. Long-term risk of neuropsychiatric disease after exposure to infection in utero. JAMA Psychiatry 76, 594–602 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Shook, L. L., Sullivan, E. L., Lo, J. O., Perlis, R. H. & Edlow, A. G. Covid-19 in pregnancy: implications for fetal brain development. Trends Mol. Med. 28, 319–330 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Woods, R. M. et al. Maternal immune activation and role of placenta in the prenatal programming of neurodevelopmental disorders. Neuronal Signal 7, NS20220064 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Shuffrey, L. C. et al. Association of birth during the Covid-19 pandemic with neurodevelopmental status at 6 months in infants with and without in utero exposure to maternal Sars-Cov-2 infection. JAMA Pediatr. 176, e215563 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Cheng, Y. et al. Impact of Sars-Cov-2 Infection during pregnancy on infant neurobehavioral development: a case-control study. Front. Pediatr. 9, 762684 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Wu, T. et al. Effects of Sars-Cov-2 Infection during late pregnancy on early childhood development: a prospective cohort study. Front. Pediatr. 9, 750012 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Ayed, M. et al. Neurodevelopmental outcomes of infants born to mothers with Sars-Cov-2 infections during pregnancy: a national prospective study in Kuwait. BMC Pediatr. 22, 319 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Hessami, K. et al. Covid-19 pandemic and infant neurodevelopmental impairment: a systematic review and meta-analysis. JAMA Netw. Open 5, e2238941 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Ayesa-Arriola, R. et al. Exploring the impact of Covid-19 on newborn neurodevelopment: a pilot study. Sci. Rep. 13, 2983 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Aldrete-Cortez, V. et al. Infants prenatally exposed to Sars-Cov-2 show the absence of fidgety movements and are at higher risk for neurological disorders: a comparative study. PLoS One 17, e0267575 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Columbia University Irving Medical Center. The Combo Study (Covid-19 Mother Baby Outcomes Study) Initiative. <https://www.ps.columbia.edu/COMBO> (2023).

  79. Firestein, M. R. et al. Assessment of neurodevelopment in infants with and without exposure to asymptomatic or mild maternal Sars-Cov-2 infection during pregnancy. JAMA Netw. Open 6, e237396 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Jackson, R. et al. Association of antenatal or neonatal Sars-Cov-2 exposure with developmental and respiratory outcomes, and healthcare usage in early childhood: a national prospective cohort study. EClinicalMedicine 72, 102628 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Firestein, M. R. et al. Positive autism screening rates in toddlers born during the Covid-19 pandemic. JAMA Netw. Open 7, e2435005 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Huang, P. et al. Association between the Covid-19 pandemic and infant neurodevelopment: a comparison before and during Covid-19. Front. Pediatr. 9, 662165 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Bianco, C. et al. Pandemic beyond the virus: maternal Covid-related postnatal stress is associated with infant temperament. Pediatr. Res. 93, 253–259 (2023).

    Article  CAS  PubMed  Google Scholar 

  84. Firestein, M. R., Dumitriu, D., Marsh, R. & Monk, C. Maternal mental health and infant development during the Covid-19 pandemic. JAMA Psychiatry 79, 1040–1045 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Kyle, M. H. & Dumitriu, D. The effect of Coronavirus Disease 2019 on newborns. Curr. Opin. Pediatr. 33, 618–624 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kyle, M. H. et al. Vertical transmission and neonatal outcomes following maternal Sars-Cov-2 infection during pregnancy. Clin. Obstet. Gynecol. 65, 195–202 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Lavallee, A. & Dumitriu, D. Low risk of neurodevelopmental impairment in the Covid-19 generation should not make researchers complacent. JAMA Netw. Open 5, e2238958 (2022).

    Article  PubMed  Google Scholar 

  88. Gale, C. et al. Characteristics and outcomes of neonatal Sars-Cov-2 infection in the UK: a prospective national cohort study using active surveillance. Lancet Child Adolesc. Health 5, 113–121 (2021).

    Article  CAS  PubMed  Google Scholar 

  89. Ali, S. et al. Neonatal outcomes of maternal Sars-Cov-2 infection in the UK: a prospective cohort study using active surveillance. Pediatr. Res. 94, 1203–1208 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Sturrock, S., Ali, S., Gale, C., Battersby, C. & Le Doare, K. Neonatal outcomes and indirect consequences following maternal Sars-Cov-2 infection in pregnancy: a systematic review. BMJ Open 13, e063052 (2023).

    Article  PubMed  Google Scholar 

  91. Marlow, N. et al. No change in neurodevelopment at 11 years after extremely preterm birth. Arch. Dis. Child Fetal Neonatal Ed. 106, 418–424 (2021).

    Article  PubMed  Google Scholar 

  92. Yan, K. et al. Effects of Sars-Cov-2 infection on neuroimaging and neurobehavior in neonates. World J. Pediatr. 17, 171–179 (2021).

    Article  CAS  PubMed  Google Scholar 

  93. Goyal, M., Mascarenhas, D., Rr, P. & Nanavati, R. Long-term growth and neurodevelopmental outcomes of neonates infected with Sars-Cov-2 during the Covid-19 pandemic at 18–24 months corrected age: a prospective observational study. Neonatology 121, 450–459 (2024).

    Article  PubMed  Google Scholar 

  94. Yangin Ergon, E. et al. The long-term neurodevelopmental outcomes of toddlers with Sars-Cov-2 infection in the neonatal period: a prospective observational study. Ital. J. Pediatr. 50, 34 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Woodward, K. et al. Effect of Sars-Cov-2 infection in neonates or in pregnancy on developmental outcomes at 21–24 months (Sinepost): study protocol for a prospective cohort study. BMJ Paediatr. Open 6 e001571 (2022).

  96. Gomes, I. et al. Sars-Cov-2 infection of the central nervous system in a 14-month-old child: a case report of a complete autopsy. Lancet Reg. Health Am. 2, 100046 (2021).

    PubMed  PubMed Central  Google Scholar 

  97. Casabianca, M., Caula, C., Titomanlio, L. & Lenglart, L. Neurological consequences of Sars-Cov-2 infections in the pediatric population. Front Pediatr. 11, 1123348 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  98. Ravichandran, S. et al. Sars-Cov-2 immune repertoire in Mis-C and pediatric Covid-19. Nat. Immunol. 22, 1452–1464 (2021).

    Article  CAS  PubMed  Google Scholar 

  99. Isaza-Correa, J. et al. Innate immune dysregulation in multisystem inflammatory syndrome in children (Mis-C). Sci. Rep. 13, 16463 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Lin, J. et al. Emerging insights into the pathophysiology of multisystem inflammatory syndrome associated with Covid-19 in children. Can. J. Cardiol. 39, 793–802 (2023).

    PubMed  Google Scholar 

  101. McKenna, E. et al. Neutrophils in Covid-19: not innocent bystanders. Front. Immunol. 13, 864387 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. University of Oxford & Nuffield Department of Medicine. Recovery trial (Randomised Evaluation of Covid-19 Therapy), <https://www.recoverytrial.net>.

  103. Welzel, T. et al. Multicenter randomized trial of methylprednisolone vs. intravenous immunoglobulins to treat the pediatric inflammatory multisystem syndrome-temporally associated with Sars-Cov-2 (PIMS-TS): protocol of the swissped recovery trial. Front. Pediatr. 10, 905046 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  104. Welzel, T. et al. Methylprednisolone versus intravenous immunoglobulins in children with paediatric inflammatory multisystem syndrome temporally associated with Sars-Cov-2 (PIMS-TS): an open-label, multicentre, randomised trial. Lancet Child Adolesc. Health 7, 238–248 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Tulling, A. J. et al. Severe pediatric Covid-19 and multisystem inflammatory syndrome in children from wild-type to population immunity: a prospective multicenter cohort study with real-time reporting. Pediatr. Infect. Dis. J. 42, 1077–1085 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland

    D. Byrne & E. J. Molloy

  2. Neonatology, The Coombe Hospital, Dublin, Ireland

    D. Byrne, N. Canty & E. J. Molloy

  3. Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland

    D. Byrne, J. Meehan & E. J. Molloy

  4. Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, London, UK

    C. Gale

  5. Centre for Paediatrics and Child Health, Imperial College, London, UK

    C. Gale

  6. Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA

    D. Dumitriu

  7. Department of Pediatrics, Children’s National Hospital, Washington, DC, USA

    A. Yonts

  8. Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    S. B. Mulkey

  9. Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    S. B. Mulkey

  10. Prenatal Pediatrics Institute, Children’s National Hospital, Washington, USA

    S. B. Mulkey

  11. Trinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, Ireland

    E. J. Molloy

  12. Neonatology, Children’s Health Ireland at Crumlin, Dublin, Ireland

    E. J. Molloy

  13. Discipline of Paediatrics, Trinity Centre for Health Sciences, Children’s Hospital Ireland (CHI) at Tallaght, Tallaght University Hospital, Dublin, Ireland

    E. J. Molloy

Authors
  1. D. Byrne
    View author publications

    Search author on:PubMed Google Scholar

  2. C. Gale
    View author publications

    Search author on:PubMed Google Scholar

  3. N. Canty
    View author publications

    Search author on:PubMed Google Scholar

  4. J. Meehan
    View author publications

    Search author on:PubMed Google Scholar

  5. D. Dumitriu
    View author publications

    Search author on:PubMed Google Scholar

  6. A. Yonts
    View author publications

    Search author on:PubMed Google Scholar

  7. S. B. Mulkey
    View author publications

    Search author on:PubMed Google Scholar

  8. E. J. Molloy
    View author publications

    Search author on:PubMed Google Scholar

Contributions

All listed authors contributed equally to writing and reviewing this paper.

Corresponding author

Correspondence to E. J. Molloy.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

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

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

Byrne, D., Gale, C., Canty, N. et al. Neurological and neurodevelopmental effects of Covid and MIS-C on children. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04564-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41390-025-04564-2

Search

Advanced search

Quick links