Coronavirus Infections in the Nervous System of Children: A Scoping Review Making the Case for Long-Term Neurodevelopmental Surveillance

Abstract

Background The objective of this study was to describe the case literature of human coronavirus infections in the nervous system of children, including from SARS-CoV-2, and to provide guidance to pediatric providers for managing the potential long-term effects on neurodevelopment of human coronavirus infections in the nervous system. Methods Using a structured strategy, the PubMed and Ovid:Embase databases were queried for articles about the clinical presentation and pathophysiology of coronavirus infections in the nervous system of children and young adults, aged 0 to 24 years. Results Of 2302 articles reviewed, 31 described SARS-CoV-2 infections in the nervous system of children and 21 described other human coronaviruses: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1. Excepting MERS-CoV, we found cases of neurological disease in children from each human coronavirus. Children with non-SARS-CoV-2 infections have suffered acute flaccid paralysis, acute disseminated encephalomyelitis, encephalitis, and seizures. In addition, cases of ischemic, hemorrhagic, and microvascular strokes have occurred in children with SARS-CoV-2. Patients with multisystem inflammatory syndrome in children have suffered encephalitis, stroke, pseudotumor cerebri syndrome, and cytotoxic lesions of deep brain structures. Despite these reports, few articles evaluated the impact of human coronavirus infections on long-term neurodevelopmental domains including cognitive, language, academic, motor, and psychosocial outcomes. Conclusions Neurological manifestations of human coronavirus infections can cause severe disease in children. The case literature suggests a critical gap in knowledge of the long-term effects on child neurodevelopment of these infections. As the current SARS-CoV-2 pandemic continues, this gap must be filled to facilitate optimal outcomes in recovering children.

Are we sure that the neurological impact of COVID 19 in childhood has not been underestimated?

“…Children with a severe chronic underlying disease, infants and toddlers and those who develop the so-called MIS-C are those with the highest incidence of neurological complications [ 7 – 9 ]. A systematic review and meta-analyses of studies involving about 3700 pediatric COVID-19 patients have shown that 17% of them had nonspecific neurologic conditions and 1% had signs and symptoms of severe brain involvement [ 7 ].…”

“…However, in some cases, very severe clinical problems associated with relevant alterations of neuroimaging, electroencephalography, nerve conduction studies and electromyography findings can develop. A not marginal number of encephalopathy, encephalitis, central or peripheral acute flaccid paralysis, acute disseminated encephalomyelitis, seizures, stroke has been diagnosed in children with laboratory confirmed SARS-CoV-2 infection [ 9 ].…”

Reply to “Coronavirus Infections in the Nervous System of Children: A Scoping Review Making the Case for Long-Term Neurodevelopmental Surveillance”

“…We thank Madaan et al for their letter in response to our scoping review on human coronavirus (HCoV) infections of the nervous system of children. 1 , 2 We agree with their consideration of the utility of the longitudinal general movements assessment (GMA) and Motor optimality score (MOS) as tools for prognostic evaluation following injuries to the nervous system including from COVID-19. 3 …”

Expanding the Spectrum of Acute Cerebellitis due to SARS-Cov-2

“…On the contrary, our case is a benign, isolated, acute cerebellitis due to SARS-CoV-2 infection which can enlarge the clinical phenotype of this new nosographic entity. The full spectrum of COVID-19-related neurological manifestations in children is not fully elucidated yet, 4 and SARS-CoV-2 can be listed as one of the pathogens causing acute cerebellitis in children, having a heterogeneous clinical severity. A close neurodevelopmental monitoring is warranted for possible longterm sequelae of this new condition.…”