Skip to main content
NCBI home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2023 Feb 15;52(8):1169–1176. doi: 10.1007/s11055-023-01344-5

Neurological Aspects of the Sequelae of COVID-19 in Children

S A Nemkova 1,✉
PMCID: PMC9930062  PMID: 36817565

Abstract

It has now been established that neurological and neuropsychiatric disorders persist for prolonged periods in a significant proportion of adult patients who have had COVID-19, though there is much less information about the manifestations of post-COVID syndrome (PCS) in children and adolescents. This review presents data on the features of the course of PCS in young patients, and considers the options for treating these patients. The results of studies on the use of Cortexin for correcting cognitive and emotional disorders are analyzed.

Keywords: COVID-19, postcovid syndrome, treatment, Cortexin

Footnotes

Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 122, No. 4, Iss. 1, pp. 23–30, April, 2022.

References

  • 1.Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020;395(10223):470–473. doi: 10.1016/S0140-6736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.P. Zimmermann, L. F. Pittet, and N. Curtis, “How common is long COVID in children and adolescents?” Pediatr. Infect. Dis. J., 40, No. 12, 482 (2021). [DOI] [PMC free article] [PubMed]
  • 3.Features of the Clinical Manifestations and Treatment of the Disease Caused by the New Coronavirus Infection (COVID-19) in Children. Methodological Guidelines, Russian Federation Ministry of Health (2020), Version 2.
  • 4.J. Blankenburg, M. K. Wekenborg, J. Reichert, et al., “Mental health of adolescents in the pandemic: long-COVID19 or long-pandemic syndrome?” medRxiv, 2021.2021.05.11.21257037, 10.1101/2021.05.11.21257037.
  • 5.Gugliandolo A, Chiricosta L, Calcaterra V, et al. SARS-CoV-2 infected pediatric cerebral cortical neurons: transcriptomic analysis and potential role of toll-like receptors in pathogenesis. Int. J. Mol. Sci. 2021;22:8059. doi: 10.3390/ijms22158059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Labò N, Ohnuki H, Tosato G. Vasculopathy and coagulopathy associated with SARS-CoV-2 infection. Cells. 2020;9:1583. doi: 10.3390/cells9071583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Kempuraj D, Selvakumar GP, Ahmed ME, et al. COVID-19, mast cells, cytokine storm, psychological stress, and neuroinflammation. Neuroscientist. 2020;26:402–414. doi: 10.1177/1073858420941476. [DOI] [PubMed] [Google Scholar]
  • 8.Coperchini F, Chiovato L, Ricci G, et al. The cytokine storm in COVID-19: further advances in our understanding the role of specific chemokines involved. Cytokine Growth Factor Rev. 2021;58:82–91. doi: 10.1016/j.cytogfr.2020.12.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Cooper KW, Brann DH, Farruggia MC, et al. COVID-19 and the chemical senses: supporting players take center stage. Neuron. 2020;107:219–233. doi: 10.1016/j.neuron.2020.06.032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Meinhardt J, Radke J, Heppner FL. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat. Neurosci. 2021;24:168–175. doi: 10.1038/s41593-020-00758-5. [DOI] [PubMed] [Google Scholar]
  • 11.COVID-19 Rapid Guideline: Managing the Long-Term Effects of COVID-19, NICE Guideline, December 2020, https://www.nice.org.uk/guidance/ng188. [PubMed]
  • 12.Marshall M. How COVID-19 can damage the brain. Nature. 2020;585:342–343. doi: 10.1038/d41586-020-02599-5. [DOI] [PubMed] [Google Scholar]
  • 13.Bryce C, Grimes Z, Pujadas E, Ahuja S, et al. Pathophysiology of SARS-CoV-2: targeting of endothelial cells renders a complex disease with thrombotic microangiopathy and aberrant immune response. The Mount Sinai COVID-19 autopsy experience. Mod. Pathol. 2021;34(8):1456–1467. doi: 10.1038/s41379-021-00793-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Camargo-Martínez W, Lozada-Martínez I, Escobar-Collazos A, et al. Post-COVID 19 neurological syndrome: implications for sequelae’s treatment. J. Clin. Neurosci. 2021;88:219–225. doi: 10.1016/j.jocn.2021.04.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Features of the Course of Long COVID Infection. Therapeutic and Rehabilitation Measures. Methodological Guidelines, Moscow (2021), https://www.rnmot.ru›public/uploads/2022/rnmot.
  • 16.Carfi A, Bernabei R, Landi F, et al. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324(6):603–605. doi: 10.1001/jama.2020.12603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Taquet M, Geddes JR, Husain M, et al. 6-month neurological and psychiatric outcomes in 236,379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry. 2021;8(5):416–427. doi: 10.1016/S2215-0366(21)00084-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Putilina MV, Mutovina ZYu, Kurushina OV, et al. Assessment of the efficacy of Cortexin in the treatment of neurological impairments in patients with post-COVID syndrome. Results of the CORTEX multicenter observational program. Zh. Nevrol. Psikhiatr. 2022;122(1):84–90. doi: 10.17116/jnevro202212201184. [DOI] [PubMed] [Google Scholar]
  • 19.F. M. Iqbala, K. Lama, V. Sounderajaha, J. M. Clarkeb, et al., “Characteristics and predictors of acute and chronic post-COVID syndrome: A systematic review and meta-analysis,” EClinicalMedicine, 36, 100899 (2021), 10.1016/j.eclinm.2021.100899. [DOI] [PMC free article] [PubMed]
  • 20.J. O. Ahmed, S. A. Ahmed, M. N. Hassan, and H. Fahmi, “Post COVID-19 neurological complications; a meta-analysis,” Ann. Med. Surg (Lond.), 3, 103440 (2022), 10.1016/j.amsu.2022.103440. [DOI] [PMC free article] [PubMed]
  • 21.Ludvigsson JF. Case report and systematic review suggest that children may experience similar long-term effects to adults after clinical COVID-19. Acta Paediatr. 2021;110(3):914–921. doi: 10.1111/apa.15673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Buonsenso D, Munblit D, De Rose C, et al. Preliminary evidence on long COVID in children. Acta Paediatr. 2021;110(7):2208–2211. doi: 10.1101/2021.01.23.21250375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.LaRovere KL, Riggs BJ, Poussaint TY, et al. Neurologic Involvement in children and adolescents hospitalized in the United States for COVID-19 or multisystem inflammatory syndrome. JAMA Neurol. 2021;78(5):536–547. doi: 10.1001/jamaneurol.2021.0504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Miller F, Nguyen V, Navaratnam AMD, et al. Prevalence of persistent symptoms in children during the COVID-19 pandemic: evidence from a household cohort study in England and Wales. BMJ. 2021 doi: 10.1101/2021.05.28.21257602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Radtke T, Ulyte A, Puhan MA, Kriemler S. Long-term symptoms after SARS-CoV-2 infection in children and adolescents. JAMA. 2021;34(8):23–29. doi: 10.1001/jama.2021.11880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.T. Stephenson, R. Shafran, B. De Stavola, et al., “Long COVID – the physical and mental health of children and non-hospitalised young people 3 months after SARS-CoV-2 infection; a national matched cohort study (The CLoCk) Study,” Research Square, BMJ Open, 11, No. 8, e052838 (2021), 10.21203/rs.3.rs-798316/v1. [DOI] [PMC free article] [PubMed]
  • 27.Brackel LH, Lap CR, Buddingh EP, et al. Pediatric long-COVID: An overlooked phenomenon? Pediatr. Pulmonol. 2021;56(8):2495–2502. doi: 10.1002/ppul.25521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Molteni E, Sudre CH, Canas LS, et al. Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2. Lancet Child Adolesc. Health. 2021;3:45–49. doi: 10.1016/S2352-4642(21)00198-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.D. Buonsenso, F. Espuny Pujol, D. Munblit, et al., “Clinical characteristics, activity levels and mental health problems in children with long COVID: a survey of 510 children,” Preprints, 2021030271 (2021), 10.20944/preprints202103.0271.v1. [DOI] [PMC free article] [PubMed]
  • 30.Consiglio CR, Cotugno N, Sardh F. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020;183(4):968–981. doi: 10.1016/j.cell.2020.09.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Blomberg B, Mohn KG, Brokstad KA, et al. Long COVID in a prospective cohort of home-isolated patients. Nat. Med. 2021;27:1607–1613. doi: 10.1038/s41591-021-01433-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Smane L, Stars I, Pucuka Z, et al. Persistent clinical features in paediatric patients after SARS-CoV-2 virological recovery: a retrospective population-based cohort study from a single centre in Latvia. BMJ Paediatr. Open. 2020;4:e000905. doi: 10.1136/bmjpo-2020-000905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.J. Nogueira López, C. Grasa, C. Calvo, et al., “Long-term symptoms of COVID-19 in children,” Acta Paediatr., 110, 2282–2283 (2021). [DOI] [PMC free article] [PubMed]
  • 34.Lin JE, Taylor AA, Sewell B, et al. Neurological issues in children with COVID-19. Neurosci. Lett. 2021;743:56–61. doi: 10.1016/j.neulet.2020.135567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.A. A. Kholin, N. N. Zavadenko, Yu. E. Nesterovskii, et al., “Features of neurological manifestations of COVID-19 in children and adults,” Zh. Nevrol. Psikhiat., 120, No. 9, 114–120 (2020), 10.17116/jnevro2020120091114. [DOI] [PubMed]
  • 36.Stafstrom EC. Neurological effects of COVID-19 in infants and children. DMCN. 2022;53:818–829. doi: 10.1111/dmcn.15185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Nikolopoulou GB, Maltezou HC. COVID-19 in children: where do we stand? Arch. Med. Res. 2022;53:1–8. doi: 10.1016/j.arcmed.2021.07.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Sa M, Mirza L, Carter M, et al. Systemic inflammation is associated with neurologic involvement in pediatric inflammatory multisystem syndrome associated with SARS-CoV-2. Neurol. Neuroimmunol. Neuroinflamm. 2021;8:e999. doi: 10.1212/NXI.0000000000000999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.J. G. Wang, Z. J. Zhong, M. Li, et al., “Coronavirus disease 2019-related multisystem inflammatory syndrome in children: a systematic review and meta-analysis,” Biochem. Res. Int., 5596727 (2021). [DOI] [PMC free article] [PubMed]
  • 40.Abrams JY, Godfred-Cato SE, Oster ME, et al. Multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2: a systematic review. J. Pediatr. 2020;226:45–54. doi: 10.1016/j.jpeds.2020.08.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.P. K. Panda, I. K. Sharawat, P. Panda, et al., “Neurological complications of SARS-CoV-2 infection in children: a systematic review and meta-analysis,” J. Trop. Pediatr., 67, fmaa070 (2021). [DOI] [PMC free article] [PubMed]
  • 42.O’Loughlin L, Toledo NA, Budrie L, et al. A systematic review of severe neurological manifestations in pediatric patients with coexisting SARS-CoV-2 infection. Neurol. Int. 2021;13:410–427. doi: 10.3390/neurolint13030041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Malyavin AG. Sequelae of COVID-19 coronavirus infection: prevalence and approaches to the treatment of long-COVID symptoms. Terapiya. 2021;10:23–28. [Google Scholar]
  • 44.Nemkova SA, Maslova OI, Karkashadze GA, et al. Use of a polypeptide stimulator in the complex treatment of cognitive disorders in children with diseases of the central nervous system. Pediatrich. Farmakol. 2012;9(5):80–86. doi: 10.15690/pf.v9i5.460. [DOI] [Google Scholar]
  • 45.Nemkova SA, Zavadenko NN, Suvorinova NYu. use of Cortexin in complex neurorehabilitation in children. Ross. Vestn. Perinatol. Pediatr. 2015;2:37–44. [Google Scholar]
  • 46.Platonova TN. Use of Cortexin in the complex treatment of diseases of the nervous system in children. Terra Medica, No. 2000;4:50–53. [Google Scholar]
  • 47.Yu M, Stepaniche and N. V. Gulyaeva, Effects of the drug Cortexin on free radical oxidation and inflammatory processes in rats with normal and accelerated aging. Neirokhimiya. 2018;2(35):11–18. [Google Scholar]
  • 48.S. A. Rumyantseva, V. V. Afanas’ev, E. V. Silina, et al., “Methods of rational pharmacocorrection and prevention of secondary ischemia and vasospasm in patients with cerebral circulatory disorders of various types,” Trudnyi Patsient, 6, No. 7, 19–25 (2010).
  • 49.Yakovlev AA, Gulyaeva NV. Molecular partners of Cortexin in the brain. Neirokhimiya. 2017;1:91–96. [Google Scholar]
  • 50.L. S. Chutko, Yu. D. Kropotov, S. Yu. Surushkina, et al., “Use of Cortexin in neurasthenia in adolescents,” Zh. Nevrol. Psikhiatr., No. 2, 50–51 (2006). [PubMed]
  • 51.V. P. Zykov, E. B. Serebrennikova, T. N. Panchenko, and Ya. B. Sycheva, “Results of a multicenter study of the efficacy of Cortexin in cognitive dysfunction in children,” Zh. Nevrol. Psikhiatr., 118, No. 3, 27–31 (2018), 10.17116/jnevro20181183127-31. [DOI] [PubMed]
  • 52.Shabalov NP, Skoromets AA, Platonova TN. Long-term use of Cortexin in pediatric neurological practice. Terra Medica, No. 2004;1:2–4. [Google Scholar]
  • 53.Yang C, Hawkins KE, Doré S, Candelario-Jalil E. Neuroinflammatory mechanisms of blood–brain barrier damage in ischemic stroke. Am. J. Physiol. Cell Physiol. 2019;316(2):135–153. doi: 10.1152/ajpcell.00136.2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Chiesa-Estomba CM, Lechien JR, Radulesco T, Michel J. Patterns of gustatory recovery in patients affected by the COVID-19 outbreak. Virol. Sin. 2020;35(6):45–49. doi: 10.1007/s12250-020-00272-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Philpott CM, Erskine SE, Clark A, Leeper A. A randomised controlled trial of sodium citrate spray for non-conductive olfactory disorders. Clin. Otolaryngol. 2017;42(6):1295–1302. doi: 10.1111/coa.12878. [DOI] [PubMed] [Google Scholar]
  • 56.L. M. J. dos Santos, “Can vitamin B12 be an adjuvant to COVID-19 treatment?” GSC Biol. Pharmaceut. Sci., 11, No. 03, 001–005 (2020), 10.30574/gscbps.2020.11.3.0155.
  • 57.Bousquet PJ, Akdis CA, Jutel M, Bachert C. Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement. Allergy. 2020;75(10):2440–2444. doi: 10.1111/all.14302. [DOI] [PubMed] [Google Scholar]

Articles from Neuroscience and Behavioral Physiology are provided here courtesy of Nature Publishing Group

RESOURCES