J Pediatr Infect Dis 2024; 19(01): 028-038
DOI: 10.1055/s-0043-1777084
Original Article

Association between SARS-CoV-2 Seropositivity and Severity of Out-of-Hospital Acute Ischemic Stroke Following Asymptomatic/Mild COVID-19 in Children

1   Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt
Ekram A. Mahmoud
2   Department of Medical Microbiology and Immunology, Faculty of Medicine, Sohag University, Sohag, Egypt
Nesma A. Mohamed
2   Department of Medical Microbiology and Immunology, Faculty of Medicine, Sohag University, Sohag, Egypt
Ghada A. B. Abd-Elrehim
1   Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt
Eman M. Fahmy
1   Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt
› Author Affiliations
Funding None.


Objective This article investigates the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity and its association with the severity of new-onset acute ischemic stroke (AIS) among previously healthy children with asymptomatic/mild coronavirus disease 2019 (COVID-19).

Methods A case–control study that included children < 18 years with out-of-hospital AIS of undetermined etiology and a control group of healthy children. Exclusion criteria were current respiratory symptoms, previous COVID-19 diagnosis, prior COVID-19 vaccination, active SARS-CoV-2 infection, history of hospital admission in the last 6 months, and having a stroke predisposition. We screened children for SARS-CoV-2 immunoglobulin G antibodies using enzyme-linked immunosorbent assay. The severity of stroke was evaluated using the Pediatric National Institutes of Health Stroke Scale (PedNIHSS).

Results The current study included 25 children (15 males and 10 females; median age 24 months) with out-of-hospital AIS and 25 healthy controls (11 males and 14 females; median age 24 months). SARS-CoV-2 seropositivity was detected in 15 (60%) of AIS children and 11 (44%) among controls (p = 0.258). Compared with seronegative AIS children, those seropositive for SARS-CoV-2 had higher PedNIHSS scores (median 19 vs. 8.5; p = 0.001), pediatric intensive care unit admission (93.3% vs. 40%; p = 0.007), need for mechanical ventilation (53.3% vs. 10%; p = 0.040), and D-dimer levels (median 3.5 vs. 1.75 μg/mL; p < 0.001).

Conclusion SARS-CoV-2 seropositivity may be associated with more severe AIS affecting previously healthy children during the postacute phase of asymptomatic/mildly symptomatic COVID-19.

Publication History

Received: 25 June 2023

Accepted: 21 October 2023

Article published online:
11 December 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Beslow LA, Agner SC, Santoro JD. et al; International Pediatric Stroke Study Group. International prevalence and mechanisms of SARS-CoV-2 in childhood arterial ischemic stroke during the COVID-19 pandemic. Stroke 2022; 53 (08) 2497-2503
  • 2 Agrawal RK, Sharma R, Mishra A, Singh A, Narayan R, Mishra OP. Multisystem inflammatory syndrome in children associated with COVID-19 infection: clinical presentation and outcome. J Pediatr Infect Dis 2023; 18: 171-177
  • 3 Casabianca M, Caula C, Titomanlio L, Lenglart L. Neurological consequences of SARS-CoV-2 infections in the pediatric population. Front Pediatr 2023; 11: 1123348
  • 4 Temel H, Gündüz M, Arslan H. et al. Evaluation of the clinical features of 81 patients with COVID-19: an unpredictable disease in children. J Pediatr Infect Dis 2021; 16: 47-52
  • 5 LaRovere KL, Riggs BJ, Poussaint TY. et al; Overcoming COVID-19 Investigators. Neurologic involvement in children and adolescents hospitalized in the United States for COVID-19 or multisystem inflammatory syndrome. JAMA Neurol 2021; 78 (05) 536-547
  • 6 Valderas C, Méndez G, Echeverría A, Suarez N, Julio K, Sandoval F. COVID-19 and neurologic manifestations: a synthesis from the child neurologist's corner. World J Pediatr 2022; 18 (06) 373-382
  • 7 Belani P, Schefflein J, Kihira S. et al. COVID-19 is an independent risk factor for acute ischemic stroke. AJNR Am J Neuroradiol 2020; 41 (08) 1361-1364
  • 8 Kihira S, Schefflein J, Mahmoudi K. et al. Association of coronavirus disease (COVID-19) with large vessel occlusion strokes: a case-control study. AJR Am J Roentgenol 2021; 216 (01) 150-156
  • 9 Pourciau P, Smith BC. Stroke risk related to coronavirus disease-2019: what have we learned?. Crit Care Nurs Clin North Am 2023; 35 (01) 53-65
  • 10 Ciolli L, Righi V, Vandelli G. et al. In-hospital and out-of-hospital stroke in patients with COVID-19: two different diseases?. Neurol Sci 2022; 43 (04) 2203-2210
  • 11 Katz JM, Libman RB, Wang JJ. et al. COVID-19 severity and stroke: correlation of imaging and laboratory markers. AJNR Am J Neuroradiol 2021; 42 (02) 257-261
  • 12 Hautecloque G, Kempf C, Stan C. et al. Multifocal and microvascular involvement in ischemic stroke during COVID-19: a cohort study with comparison with non-COVID-19 stroke. Front Neurol 2021; 12: 732194
  • 13 Sacco RL, Kasner SE, Broderick JP. et al; American Heart Association Stroke Council, Council on Cardiovascular Surgery and Anesthesia, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular and Stroke Nursing, Council on Epidemiology and Prevention, Council on Peripheral Vascular Disease, Council on Nutrition, Physical Activity and Metabolism. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013; 44 (07) 2064-2089
  • 14 Ichord RN, Bastian R, Abraham L. et al. Interrater reliability of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) in a multicenter study. Stroke 2011; 42 (03) 613-617
  • 15 Kumar R, Sun LR, Rodriguez V. et al. Hemostatic and thrombotic considerations in the diagnosis and management of childhood arterial ischemic stroke: a narrative review. Semin Pediatr Neurol 2022; 43: 101003
  • 16 Cornet MC, Grose C, Vexler Z, Wu YW, Fullerton HJ. The role of infection and inflammation in the pathogenesis of pediatric arterial ischemic stroke. Semin Pediatr Neurol 2022; 44: 100995
  • 17 Fullerton HJ, Hills NK, Elkind MSV. et al; VIPS Investigators. Infection, vaccination, and childhood arterial ischemic stroke: results of the VIPS study. Neurology 2015; 85 (17) 1459-1466
  • 18 Vielleux MJ, Swartwood S, Nguyen D, James KE, Barbeau B, Bonkowsky JL. SARS-CoV-2 infection and increased risk for pediatric stroke. Pediatr Neurol 2023; 142: 89-94
  • 19 Merkler AE, Parikh NS, Mir S. et al. Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza. JAMA Neurol 2020; 77 (11) 1-7
  • 20 Beslow LA, Linds AB, Fox CK. et al; International Pediatric Stroke Study Group. Pediatric ischemic stroke: an infrequent complication of SARS-CoV-2. Ann Neurol 2021; 89 (04) 657-665
  • 21 AlKandari S, Prasad L, Al Shabrawy AM, Gelbaya SA. Post COVID-19 ischemic stroke in a 15-Year-old patient. Neurosciences (Riyadh) 2023; 28 (01) 62-65
  • 22 Appavu B, Deng D, Dowling MM. et al. Arteritis and large vessel occlusive strokes in children after COVID-19 infection. Pediatrics 2021; 147 (03) e2020023440
  • 23 Petat H, Hassani A, Dabaj I. et al. Ischemic stroke on SARS-CoV2 vasculitis in a healthy young girl. Health Sci Rep 2023; 6 (01) e1046
  • 24 Španělová K, Skříšovská T, Mužlayová P. et al. Cerebrovascular complications of COVID-19 disease in children: a single-center case series. Pediatr Neurol 2022; 134: 18-24
  • 25 Tiwari L, Shekhar S, Bansal A, Kumar S. COVID-19 associated arterial ischaemic stroke and multisystem inflammatory syndrome in children: a case report. Lancet Child Adolesc Health 2021; 5 (01) 88-90
  • 26 Lu Y, Zhao JJ, Ye MF. et al. The relationship between COVID-19's severity and ischemic stroke: a systematic review and meta-analysis. Neurol Sci 2021; 42 (07) 2645-2651
  • 27 Song Y, Fan H, Tang X, Luo Y, Liu P, Chen Y. The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on ischemic stroke and the possible underlying mechanisms. Int J Neurosci 2023; 133 (02) 176-185
  • 28 Diorio C, McNerney KO, Lambert M. et al. Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations. Blood Adv 2020; 4 (23) 6051-6063
  • 29 Whitworth H, Sartain SE, Kumar R. et al. Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C. Blood 2021; 138 (02) 190-198
  • 30 Stefanou Ε, Karvelas N, Bennett S, Kole C. Cerebrovascular manifestations of SARS-CoV-2: a comprehensive review. Curr Treat Options Neurol 2023; 25 (04) 71-92
  • 31 Zarifkar P, Peinkhofer C, Benros ME, Kondziella D. Frequency of neurological diseases after COVID-19, influenza A/B and bacterial pneumonia. Front Neurol 2022; 13: 904796
  • 32 Bertamino M, Signa S, Vagelli G. et al. An atypical case of post-varicella stroke in a child presenting with hemichorea followed by late-onset inflammatory focal cerebral arteriopathy. Quant Imaging Med Surg 2021; 11 (01) 463-471
  • 33 Elbadry MI, Tawfeek A, Abdellatif MG. et al. Unusual pattern of thrombotic events in young adult non-critically ill patients with COVID-19 may result from an undiagnosed inherited and acquired form of thrombophilia. Br J Haematol 2022; 196 (04) 902-922
  • 34 Nalbandian A, Sehgal K, Gupta A. et al. Post-acute COVID-19 syndrome. Nat Med 2021; 27 (04) 601-615
  • 35 Mathew T, John SK, Sarma G. et al. COVID-19-related strokes are associated with increased mortality and morbidity: a multicenter comparative study from Bengaluru, South India. Int J Stroke 2021; 16 (04) 429-436
  • 36 Yaghi S, Ishida K, Torres J. et al. SARS-CoV-2 and stroke in a New York healthcare system. Stroke 2020; 51 (07) 2002-2011
  • 37 Liu W, Han F, Wan M, Yang XZ. Integrated bioinformatics analysis identifies shared immune changes between ischemic stroke and COVID 19. Front Immunol 2023; 14: 1102281
  • 38 Morgan R, Collins RA, Nagy L. Post Covid-19 MIS-C related cerebral infarction in a pediatric patient managed with decompressive craniectomy. Pediatr Neurosurg 2023; 58: 53-57
  • 39 Fleming-Dutra KE, Wallace M, Moulia DL. et al. Interim Recommendations of the Advisory Committee on Immunization Practices for Use of Moderna and Pfizer-BioNTech COVID-19 Vaccines in Children Aged 6 Months-5 Years - United States, June 2022. MMWR Morb Mortal Wkly Rep 2022; 71 (26) 859-868
  • 40 Sun LR, Lynch JK. Advances in the diagnosis and treatment of pediatric arterial ischemic stroke. Neurotherapeutics 2023; 20 (03) 633-654