ABSTRACT
INTRODUCTION: Our objective was to characterize testing and treatments provided for hospitalized children with and without severe neurologic manifestations with acute SARSCoV- 2 infection or Multisystem Inflammatory Syndrome in Children (MIS-C). METHOD(S): Multinational cross-sectional study of children age < 18 y hospitalized with SARS-CoV-2-related condition between January 2020-July 2021. Admission laboratory, neurologic testing, and treatments related to SARS-CoV-2 conditions were analyzed by severe neurologic manifestation status, a composite of those with univariate logistic regression p< 0.05 for unfavorable outcome (Pediatric Cerebral Performance Category Score 3-6 at hospital discharge). Multivariable logistic regression to identify laboratory values associated with severe neurologic manifestation was performed. RESULT(S): Of 3,556 children, 818 (23%) had severe neurologic manifestation. Children with severe neurologic manifestation were younger (median 5 interquartile range [1-12] vs. 9 [1.1-14] y) and had more MIS-C vs. acute SARSCoV- 2 (35% vs. 22%), pre-existing disease (68% vs. 48%), and death (5% vs. 0.5%), all p< 0.001. Blood fibrinogen was lower in children with (341 [230, 500]) vs. without (410 [274, 537] mg/dl) severe neurologic manifestation, p< 0.001. More children with severe neurologic manifestations had electroencephalography (23% vs. 2.7%), head CT (24% vs. 6%), and brain MRI (16% vs. 4%) performed, p< 0.001, but results were not more frequently abnormal between groups. Cerebrospinal fluid was sampled in 19% vs. 9%, p< 0.001, and intracranial pressure monitors were placed in 5 (1%) vs. 14 (0.5%), p=0.179. Children with severe neurologic manifestation received more steroids (25% vs. 16%) and remdesivir (15% vs. 7%), p< 0.001. After adjustment, higher lymphocytes (odds ratio 1.0003 [95% confidence interval 1.00009, 1.0005]) and lower fibrinogen (0.998 [0.996, 0.999]), p< 0.05, were associated with severe neurologic manifestation status. CONCLUSION(S): Modest laboratory signatures of severe neurologic manifestations in children hospitalized with SARSCoV- 2 related conditions were found. Despite association with worse outcomes, relatively few children received contemporary neurological testing and SARS-CoV-2 related treatments.
ABSTRACT
INTRODUCTION: We aimed to describe neurologic outcomes in hospitalized children diagnosed with acute SARS-CoV-2 infection or Multisystem Inflammatory Syndrome in Children (MIS-C). METHOD(S): Multinational (n=50 centers), cross-sectional study of neurologic manifestations in children < 18 y old hospitalized with a positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020-July 2021. Multivariable logistic regression to identify risk factors for unfavorable outcome at hospital discharge (Pediatric Cerebral Performance Category Score 3-6) was performed. Severe neurologic manifestation included those with univariate logistic regression significant to p< 0.05 for unfavorable outcome: dysautonomia, stroke, encephalopathy, cardiac arrest, meningitis/encephalitis, coma, seizures, weakness, and delirium. RESULT(S): Of 3,556 children (46% female), 3333 (94%) had acute SARS-CoV-2 and 223 (6%) had MIS-C. Unfavorable outcome occurred in 368 (11%) children and 39 (1.1%) died. Children with unfavorable outcome were older (median 9 interquartile range [4-14] vs. 8 [1-14] y, p< 0.001), and more likely to have neurologic comorbidity (72% vs. 10%, p< 0.001), worse Glasgow coma scale score (GCS) group (19% with combined GCS 9-15 vs. 1.7% with GCS< 9, p< 0.001), any neurologic manifestation (52% vs. 37%, p< 0.001), and severe neurologic manifestation (48% vs. 20%, p< 0.001) compared to children with favorable outcome. In multivariate logistic regression, older age (odds ratio 1.1 95% confidence interval [1.0, 1.1], total pre-existing conditions (2.1 [1.8, 2.5]), severe neurologic manifestation (3.4 [2.0, 6.0], and worse GCS group (4.0 [2.6, 5.9]) were associated with unfavorable outcome. CONCLUSION(S): Children with severe neurologic manifestation, pre-existing conditions, and children of older age hospitalized with acute SARS-CoV-2 infection or MIS-C have worse hospital discharge outcomes. Follow-up of these children is necessary to identify and manage neurologic and functional impairment.
ABSTRACT
INTRODUCTION: Children with comorbidities are at increased risk of severe disease due to SARS-CoV-2 (COVID-19) infection and Multisystem Inflammatory Syndrome-Children (MIS-C). We hypothesized that children with comorbidities hospitalized with COVID-19 or MIS-C will experience more neurologic manifestations and worse outcomes compared to children without comorbidities. METHODS: Secondary study of the Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID) study, a multinational study enrolling children < 18 years of age hospitalized with confirmed/presumed COVID-19 or MIS-C. Neurological manifestations, lengths of hospital and intensive care unit (ICU) stay, hospital disposition and mortality were analyzed by comorbidity status. A multivariable logistic regression was performed to analyze the association of comorbidity with neurologic manifestation. RESULTS: Overall, 824 (55%) children had any comorbidity and 646 (43%) had any neurologic manifestation. Children with comorbidity were older (median [interquartile range] 9.5 [4-15] vs. 6.4 [0.5-12], had more COVID-19 (58%) vs. MIS-C (32%) and ICU admissions (39% vs. 29%), and longer hospital length of stay (9 [2-9] vs. 5 [2-6] days), all p< .001;mortality was similar (1.5% vs. 0.5%, p=.067). The most common comorbidities were neurologic and respiratory (20% each). Children with comorbidity more frequently had any neurologic manifestation (61% vs. 39%), and seizures/status epilepticus (11% vs. 4%), p< .001). There were no differences between comorbidity vs no comorbidity groups for the most common neurologic manifestations including headache (21% vs. 20%) and acute encephalopathy (17% vs. 15%). Older age (odds ratio 1.1 [95% confidence interval 1.1-1.1]), ICU stay (2.6 [1.9-3.4]), MIS-C (2.2 [1.5-3.2]), and neurologic (2.8 [1.9-4.1]) comorbidity were associated with neurologic manifestation while cardiovascular morbidity was protective for neurologic manifestation (.5 [.3-.8]), all p< .05. CONCLUSIONS: Children with comorbidity, especially neurologic, who are hospitalized with COVID-19 related conditions are at increased risk of neurologic manifestations. Assessment of post-hospital neurodevelopmental outcomes to determine the impact of neurologic manifestations in children with comorbidity and COVID-19 related conditions is critically needed.