Impact of SARS-CoV-2 Pandemic on the Severity and Outcome of Guillain–Barré Syndrome in Children

INTRODUCTION

Guillain–Barré syndrome (GBS) is an immune-mediated demyelinating disease of the nerve roots triggered by various viruses, bacteria, and vaccines. Some of the triggering agents include Epstein–Barr virus, Cytomegalovirus, Zika virus, Adenovirus, Influenza viruses, Campylobacter jejuni, and Influenza vaccines.^[1] The SARS-COV-2 pandemic started in December 2019 in Wuhan, China, and the outbreak spread to other parts of the world. The World Health Organization declared the SARS-COV-2 outbreak a pandemic in February 2020.

SARS-COV-2 virus, like other viruses, has been known to be the triggering factor for GBS in a multicentric study from Italy.^[2] This study by Fiosto et al. included GBS cases that had occurred in SARS-CoV-2-infected adults and observed that the incidence of GBS was higher in SARS-CoV-2-infected patients than in the general population and suggested that this virus could trigger GBS as a late immune-mediated complication.^[2] The outcome and severity of GBS in SARS-CoV-2-infected patients was worse than in the general population. Similar studies in the pediatric population are lacking. Hence, this study was conducted to evaluate the severity, outcome, and clinico-epidemiological characteristics of GBS cases before and after the SARS-COV-2 pandemic in the pediatric population.

The primary aim of this descriptive study was to document the clinico-epidemiological, neurological, and electrophysiological characteristics of GBS cases admitted during the COVID-19 pandemic. We also aimed to assess the severity and outcome of GBS by the Medical Research Council (MRC) score at admission and discharge, Hughes disability scale, incidence of cranial nerve palsy, duration of hospital stay, intensive care unit admission, ventilatory dependence, and death. The severity and outcome were compared between the different electrophysiological variants and the study groups enrolled before and during the pandemic.

MATERIAL AND METHODS

Consecutive sampling was done for recruiting cases from before and during the pandemic. Case records of children diagnosed with GBS before the SARS-COV-2 pandemic (Group A) who were admitted from July 2018 to February 2020 (20 months) were evaluated. Children diagnosed with GBS during the pandemic (Group B), admitted from March 2020 to July 2021(total of 17 months), were enrolled prospectively. The inclusion criteria included children from 6 months to 12 years who presented with features of acute flaccid paralysis meeting the case definition of Brighton’s Collaboration GBS working group criteria. ^[3] Acute flaccid paralysis with bladder and/or bowel disturbance at onset, weakness with definitive sensory level, electrolyte abnormalities, high-grade fever with altered sensorium, spasticity, evidence of space-occupying lesions, or any abnormalities of the spinal cord were excluded. The clinical profile, such as age, gender, predominant presenting complaints, reflexes, and cranial nerve involvement, and electrophysiological variants of GBS based on nerve conduction studies (NCS), were assessed. Scales used: The Hughes disability scale was used to grade the severity of GBS at admission.^[4] The MRC score for 6 antigravity muscle groups involving shoulder abductors, elbow flexor, wrist extensor, hip flexor, knee extensor, and plantar dorsiflexors was calculated at admission and at discharge to decide the outcome of the disease.^[5] The maximum score given for a single muscle group was 5; the best sum score obtained was 60. The lower the MRC sum score, the more severe the weakness. Prognostic outcome was assessed based on the modified Erasmus GBS outcome score (mEGOS) at admission. The mEGOS is a prognostic model that accurately predicts the chance of being able to walk unaided by 6 months.^[6]

The data of GBS cases before the pandemic were collected retrospectively, and the variables such as age, gender, clinical features, cranial nerve involvement, cerebrospinal fluid (CSF) analysis, nerve conduction study (NCS) reports, cranial nerve palsies, duration of hospital stay, need for ventilator, need for tracheostomy, and death were documented. Case records in which not all the variables were recorded were excluded from the study. COVID-19 antibody status was assessed for all the cases of GBS who were recruited in Group B. Based on the scales mentioned above, severity and outcome were compared between the two groups.

RESULTS

Of the 34 case records of GBS admitted prior to the pandemic, 31 were included in Group A; 3 were excluded due to incomplete documentation. 27 cases were enrolled during the pandemic in Group B. The comparison of the clinical profile is given in Table 1.

Approximately 72% of the children had no history suggestive of preceding diarrhea or any illness before the onset of weakness. None of the children in either group were noted to have altered sensorium or sensory involvement. All GBS-affected children had acellular CSF cell cytology. The mean CSF protein was 86.72 mg/dL and 98.55 mg/dL in Group A and Group B, respectively (P = 0.34). Complete blood count, renal function test, liver function tests, and serum electrolytes were found to be normal in all GBS-affected children. None of the children required treatment with plasmapheresis. Neurological manifestations and electrophysiological variants are mentioned in Table 2.

The variables comparing the treatment and outcome of children with GBS are compared with respect to the pandemic, and the summary of the results is shown in Table 3. Intravenous immunoglobulin was used in all cases in the dose of 2 gram per Kg. None of the cases received repeat doses in both the groups.

Comparison of the severity of GBS before and after the pandemic:

Hughes score at admission, MRC score at admission and discharge, duration of hospital stay, need for ventilation or tracheostomy, death, cranial nerve palsies, and autonomic symptoms were used to assess the severity of the GBS cases in our study and were comparable in both groups [Table 4].

A total of two deaths–one in each group–were observed, and arrhythmia (ventricular tachycardia) was identified as the cause of death in both cases. To assess differences in severity, the Hughes score was categorized into two groups (scores below 4 and scores 4 or above). No significant difference in severity based on the Hughes score was observed between the two groups (P = 1.00). A statistically significant difference was observed in the median Erasmus scores on admission between the two groups. Although the duration of hospital stay tended toward significance–patients in Group B were discharged approximately 4 days earlier than those in Group A–the limited sample size precluded definitive conclusions.

The mEGOS was calculated to predict outcomes within the first 6 months. The mean mEGOS in the 1^st week of admission was 5 in Group A and 6 in Group B (P = 0.04), indicating a statistically significant difference. The mEGOS was also categorized into two groups (scores ≤4 and >4), and outcomes were analyzed accordingly. A score >4 was observed in 48% of children in Group A and 81% in Group B (P = 0.009) [Figure 1].

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Figure 1:

(a) Comparison of the mean Modified Erasmus GBS Outcome Score (mEGOS) and (b) The proportion of cases with mEGOS >4 in Group A and Group B. GBS: Guillain Barré syndrome, mEGOS: Modified Erasmus GBS outcome score.

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Table 5 summarizes severity indicators of Guillain-Barré Syndrome, showing comparable Hughes disability scores and MRC grading across AIDP, AMAN, and AMSAN.

A comparison of severity across the electrophysiological variants of GBS during the pandemic, based on the assessed variables, did not yield statistically significant findings [Figures 2 and 3].

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Figure 2:

Severity of the Hughes score in the three electrophysiological variants. AMAN: Acute motor axonal neuropathy, AMSAN: Acute motor-sensory axonal neuropathy and demyelinating types.

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Figure 3:

Comparison of the Medical Research Council score at discharge in relation to the electrophysiological variant. AMSAN: Acute motor-sensory axonal neuropathy, AMAN: Acute motor axonal neuropathy, AIDP: Acute inflammatory demyelinating polyneuropathy, MRC: Medical Research Council.

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COVID-19 antibody status was tested in children recruited during the pandemic. Four children were not tested (as consent could not be obtained), 13 (52%) were negative, and 10 children (40%) were positive.

DISCUSSION

The emergence of SARS-COV-2 has raised concerns about its potential to increase GBS incidence and severity in children, as observed in adults during the pandemic.^[2] However, our study observed no statistically significant increase in GBS cases or severity in the pediatric population during the pandemic period of 17 months compared to the pre-pandemic study period of 20 months, aligning with findings from large-scale epidemiological studies in adults that reported no association between COVID-19 and increased GBS incidence.^[1]

While the incidence and clinical presentation, including cranial nerve palsies and autonomic involvement, were comparable across pre-pandemic and pandemic periods, the mEGOS was significantly higher in the pandemic group (mean 5.5 vs. 4, P = 0.04). The mEGOS, a validated predictor of 6-month functional outcomes,^[6-9] indicated a theoretically increased risk of delayed recovery in patients diagnosed during the pandemic period. However, this did not translate into differences in ventilator requirements, tracheostomy, or mortality between groups, indicating that despite higher mEGOS, short-term outcomes remained comparable. This paradox observed may be due to the small sample size or due to variations in the timing of hospital presentation and supportive care received.

The absence of a significant difference in severity based on the Hughes disability scale at admission and discharge supports the view that SARS-COV-2 infection does not necessarily worsen pediatric GBS severity.^[1,10] Our findings are consistent with studies that noted no significant differences in progression between demyelinating and axonal variants in terms of clinical severity and outcomes.^[11,12]

Interestingly, the frequency of electrophysiological variants during the pandemic showed a non-significant increase in the demyelinating variant Acute Inflammatory Demyelinating Polyneuropathy (AIDP) compared to acute motor axonal neuropathy, shifting from 26% pre-pandemic to 44% during the pandemic. Previous studies have reported that AIDP is associated with a higher incidence of cranial nerve involvement, a trend reflected in our data.^[13,14] We observed that children with AIDP had higher rates of cranial nerve palsies and lower MRC scores at discharge, indicating relatively slower recovery, though these findings did not reach statistical significance probably due to the small cohort size.

Cranial nerve palsies, particularly lower cranial nerve involvement, were present in nearly half of the children in both groups. Bulbar palsy serves as a marker for potential respiratory failure, necessitating close monitoring for elective intubation and ventilation.^[13] Ventilator requirement was comparable across groups.

Regarding limitations, the small sample size failed to detect subtle differences in severity and outcomes, potentially leading to type II errors. A multicenter design with a larger cohort would improve statistical power and external validity, particularly in assessing rare but critical outcomes like the need for prolonged ventilation or mortality.^[10] In addition, the lack of long-term follow-up data impeded the assessment of functional recovery and late complications, crucial in understanding the true impact of SARS-COV-2 on pediatric GBS. During pandemic, COVID-19 antibody status was available in 23 GBS children of whom 10 (40%) were positive. The small numbers limited the correlation analysis between confirmed SARS-COV-2 exposure and GBS presentation, a factor worth addressing in future prospective studies.

The pathophysiology of GBS involves immune cross-reactivity due to molecular mimicry, a mechanism that could theoretically apply to SARS-COV-2 as well, given its spike protein’s potential for ganglioside binding.^[7] However, the low rate of confirmed COVID-19 infection in our cohort, along with similar clinical profiles across groups, suggests that SARS-COV-2 may not be a significant trigger for pediatric GBS in our setting, or its role may be overshadowed by other concurrent viral triggers and host-specific immune responses.^[2,9,15]

In conclusion, our study suggests that the SARS-COV-2 pandemic did not significantly alter the incidence, clinical presentation, or short-term outcomes of pediatric GBS. Although mEGOS scores on admission were higher during the pandemic, this did not translate into worse short-term outcomes. Our study emphasizes the need for larger, multicenter, prospective studies with extended follow-up to elucidate the true impact of SARS-COV-2 on pediatric GBS and its electrophysiological variants. Close monitoring for cranial nerve involvement and proactive supportive care remain critical in managing pediatric GBS, irrespective of the pandemic context.^[13]

CONCLUSION

The SARS-COV-2 pandemic seems to have no impact on GBS presentation, severity, and outcomes, and long-term follow-up studies are needed.