Indeed, in pathological conditions, several cytokines and maternal leukocytes cross the placenta and can be harmful to fetal development. SARS-CoV-2 Infections in ChildrenДЄlthough children are less susceptible to severe COVID-19, a remaining question that is under debate is related to the long-term impact of mild or subclinical SARS-CoV-2 infection in the developing brain, where complex neural networks are undergoing an intense remodeling process modulated by neural activity and immunological components of the CNS, such as microglia, cytokines, chemokines, the complement system, and peripheral immune cells (reviewed in ), that results in synaptic pruning and formation of functional neural circuitry. It is not yet known for sure which pathway SARS-CoV-2 uses to reach the nervous system, but two pathways already known as routes of entry for other viruses are considered: the hematogenic pathway, in which the virus could infect leukocytes and blood-brain barrier (BBB) cells, or alternatively, the virus could infect peripheral neurons reaching the brain through axonal transport. In the central nervous system (CNS), glial cells and neurons express this receptor. Like SARS-CoV, SARS-CoV-2 uses the ACE2 receptor, human angiotensin converter 2, for cellular invasion, binding to it through its spike (S) protein. Furthermore, it has been shown that SARS-CoV-2 is able to infect human neural progenitor cells. A study with biomarkers also provided evidence of neuronal injury and glial activation in patients with COVID-19, strongly suggesting that SARS-CoV-2 has a neurotropic activity. In addition to the most common symptoms, neurological manifestations in response to SARS-CoV-2 infection include headache, anosmia, disturbances of consciousness, infectious encephalopathies, and neuroinflammatory syndromes, such as the acute demyelinating encephalomyelitis.

The present review discusses those conditions in the perspective of the understanding of risk factors that should be considered and the possible emergence of neurodevelopmental disorders in COVID-19-infected children.Д¬OVID-19 is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that belongs to the same betacoronavirus strain of SARS-CoV and MERS-CoV viruses, and their similarities may be helpful for a better understanding of this new disease and the implications on brain inflammation. Together, those factors may pose additional risk factors for SARS-CoV-2 infection impacting mechanisms of neural development such as synaptic pruning and neural circuitry formation. Additionally, transient thyrotoxicosis induced by SARS-CoV-2 with secondary autoimmune hypothyroidism has been reported, which could go undetected during pregnancy. Along with the viral induction of neuroinflammation, other noninfectious conditions may interact to produce additional inflammation, such as the nutritional imbalance of fatty acids and polyunsaturated fatty acids and alcohol consumption during pregnancy.

As with other viral infections, such as rubella, influenza, and cytomegalovirus, SARS-CoV-2 induces a surge of proinflammatory cytokines that affect microglial function, which can be harmful to brain development. However, several cases of neurological symptoms with neuroinflammatory syndromes, such as the multisystem inflammatory syndrome (MIS-C), following mild cases, have been reported. COVID-19, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) betacoronavirus, affects children in a different way than it does in adults, with milder symptoms.

Inflammation of the brain