Can neurologic manifestations predict poor outcomes in young SARS-CoV-2, MIS-C patients?

A prospective cohort study has shown that in patients aged <18 years hospitalized for acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C), neurologic manifestations during the infection are common and may predispose them more to new neurocognitive or functional morbidity at discharge.

“The results … suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurologic manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery,” said the researchers.

Eighteen percent of participants with acute SARS-CoV-2 had a severe neurologic manifestation* during hospitalization. The corresponding percentage in the MIS-C subgroup was 24.8 percent. [JAMA Netw Open 2024;7:e2414122]

Among survivors with acute SARS-CoV-2, participants with severe neurologic manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge than those without severe neurologic manifestations (27.7 percent vs 14.6 percent; p<0.001). A similar pattern was observed among survivors with MIS-C (28 percent vs 15.5 percent; p=0.002).

After adjusting for risk factors in participants with severe neurologic manifestations, the odds of having new neurocognitive and/or functional morbidity at hospital discharge were indeed higher among participants with acute SARS-CoV-2 (odds ratio [OR], 1.85; p=0.001) and MIS-C (OR, 2.18; p=0.009).

Post-discharge management guide

Children with SARS-CoV-2-related MIS-C typically warrant critical care due to multisystem organ dysfunction. Despite the high survival rates, these patients are at risk of post-critical illness sequelae. [JAMA 2021;325:1074-1087; N Engl J Med 2020;383:334-346] Evidence has also shown a correlation between neurologic manifestations of paediatric SARS-CoV-2-related conditions and morbidity and mortality. [Pediatr Neurol 2022;128:33-44; JAMA Neurol 2021;78:536-547]

The researchers conducted a secondary analysis of participants from the paediatric GCS-NeuroCOVID* cohort. They evaluated 3,568 patients (median age 8 years, 54.3 percent boys) from 46 centres in 10 countries who were hospitalized for acute SARS-CoV-2 (83.5 percent) or MIS-C (16.5 percent) between January 2, 2020 and July 31, 2021.

The most common severe neurologic manifestation in both acute SARS-CoV-2 and MIS-C patients was acute encephalopathy (61.9 percent and 76 percent, respectively).

However, the manifestations were characterized based on a review of medical records, which may have led to under- or overestimation of their true prevalence. Some diagnoses are also more challenging to evaluate in individuals of different ages and developmental stages.

“[Also, we] collected data at hospital discharge; thus, our study could not evaluate the long-term implications of these neurologic manifestations, including the potential role of long COVID. Future studies should aim to address these limitations,” the researchers added.

“[Nonetheless, the] association between severe neurologic manifestations and new neurocognitive and/or functional morbidity may suggest severe neurologic manifestations as an independent predictor of poor outcomes in hospitalized young patients with acute SARS-CoV-2 or MIS-C and therefore could be used to guide post-discharge management,” the researchers said.

“Identifying patients at the highest risk of new and persistent impairment is essential to direct them to the necessary follow-up care to best support their recovery and adaptation,” they said. “By identifying [them], future research could demonstrate the value of [follow-up] programmes and their potential effects on improving long-term outcomes.”

The researchers called for further investigation to better understand the pathophysiology behind the severe neurologic manifestations and to evaluate the role of surveillance, treatment, and follow-up of patients at high risk of neurocognitive and/or functional morbidities.