REVIEW published: 18 February 2021 doi: 10.3389/fneur.2020.613832 Neurologic Care of COVID-19 in Children Susana Boronat* Pediatric Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Most children with SARS-CoV-2 infection have relatively mild clinical symptoms without fever or pneumonia, although severe cases with multiple-organ failure have been reported. Neurological symptoms, which have been mainly reported in adults, are very rare in children. This article will review 2 different aspects of neurological involvement related to this infection in children. In the first part, we will review the neurological abnormalities reported in children caused by this viral infection. Adults frequently report muscle pain, headache, anosmia, dysgeusia, and occasionally more severe central or peripheral nervous system damage. Neurological involvement seems infrequent in children, although some cases have been reported. In the second part, we will discuss the COVID-19 pandemic impact on the healthcare system of some countries, causing collateral damage to general pediatric care and in particular to those children affected with chronic diseases, mainly neurological conditions, including autism, intellectual disability, attention deficit and hyperactivity disorder (ADHD), neuromuscular disorders, cerebral Edited by: Fernando Testai, palsy, and epilepsy, and patients needing neurosurgical procedures. University of Illinois at Chicago, Keywords: SARS-CoV-2, seizures, epilepsy, neurocognitive, behavior, stress, child abuse United States Reviewed by: Karin Diserens, Centre Hospitalier Universitaire INTRODUCTION Vaudois (CHUV), Switzerland Alessandra Splendiani, The SARS-CoV-2 incubation period is usually 3–7 days, ranging from 1 to 14 days, and patients University of L’Aquila, Italy usually recover within 2 weeks. Typical clinical manifestations are dry cough and fever. Children are more frequently asymptomatic or they present with mild symptoms. Very rarely, severe *Correspondence: Susana Boronat pediatric cases may progress to acute respiratory failure and multiple-organ failure. The pediatric sboronat@santpau.cat inflammatory multisystem syndrome, also referred to as Kawasaki-like SARS-CoV-2 syndrome, is a severe clinical picture that has been reported in children and shows persistent fever with Specialty section: multisystem organ involvement along with elevated inflammatory markers. It seems to appear in This article was submitted to a late phase, as positive immunoglobulin G tests for SARS-CoV-2 have been reported in many Neurocritical and Neurohospitalist cases (1–3). Care, In Table 1, we summarize the main topics of this article, including the main clinical neurological a section of the journal manifestations in children, current knowledge about treatment, and consequences of the COVID19 Frontiers in Neurology pandemic to children with neurological diseases. Received: 22 October 2020 Accepted: 31 December 2020 Published: 18 February 2021 NEUROLOGICAL MANIFESTATIONS RELATED TO SARS-CoV-2 Citation: INFECTION Boronat S (2021) Neurologic Care of COVID-19 in Children. Adults frequently report muscle pain, headache, anosmia, and dysgeusia and occasionally more Front. Neurol. 11:613832. severe central or peripheral nervous system damage. Within 214 patients from Wuhan reported by doi: 10.3389/fneur.2020.613832 Mao and colleagues, 78 (36%) had neurological involvement, including neuralgic pain, myopathy, Frontiers in Neurology | www.frontiersin.org 1 February 2021 | Volume 11 | Article 613832 Boronat Neurologic Care of COVID-19 Children TABLE 1 | Summary. or hypoxia may also play a causative role in some of these encephalopathic patients (6). Neurological involvement in children • Encephalopathy related to infection with SARS-CoV-2 • Inflammatory central nervous In one study, within 27 children with pediatric multisystem system lesions inflammatory syndrome related to SARS-CoV-2 infection, 4 • Seizures (15%) had encephalopathy. Cerebellar and brainstem signs and • Stroke muscle weakness were also detected. All patients improved • Hyposmia and hypogeusia and 2 showed total recovery. Interestingly, on the brain MRI, • Muscular involvement • Guillain-Barré syndrome the splenium of the corpus callosum showed signal changes • Other rare manifestations in all 4 patients. Other studies, including cerebrospinal fluid Current treatment recommendations cells and PCR for SARS-CoV-2, oligoclonal band test or CNS for children with SARS-CoV-2 autoantibodies were negative in all patients. Slow background infection activity was detected in the 3 patients who had EEG studies, Consequences of the COVID19 • Cerebral palsy and mild myopathic and neuropathic changes were seen in pandemic to children with • Neuromuscular disorders all 3 patients who were assessed by neurophysiologic studies neurological diseases • Migraines • Neurosurgical conditions (7). A previously healthy 16-year-old positive for SARS- • Epilepsy CoV-2 developed seizures, encephalopathy, and syndrome of • Behavioral problems inappropriate anti-diuretic hormone (SIADH). Her CSF testing • Autism and intellectual disability was negative for SARS-CoV-2. Although a thorough workup • Attention deficit and hyperactivity revealed no other infectious or autoimmune pathologies, MR disorder • Psychiatric disorders imaging was not obtained (8). A lethargic 4-year-old girl with multisystem inflammatory syndrome associated with COVID19 showed aseptic meningitis and cytokine storm an low levels of BDNF (9). altered states of consciousness, and stroke. These symptoms were more frequent in severe cases (46 vs. 30% in non-severe) (4). Inflammatory Central Nervous System A recent meta-analysis including 41 articles showed a wide spectrum of neurological manifestations due to SARS-CoV-2 Lesions infection. The most frequent neurological symptoms included The SARS-CoV-2-related pediatric multisystem inflammatory anosmia (36–86%) and dysgeusia (33–89%). More severe cases syndrome is characterized by a Kawasaki-like illness with showed inflammation of the central nervous system, stroke, or persistent fever and multisystem organ involvement, including Guillain–Barré syndrome (5). cardiac dysfunction, with elevated inflammatory markers. Consistent with other cases with encephalopathy showing slow EEG background activity and lesions in the corpus callosum NEUROLOGICAL INVOLVEMENT IN (7, 10), a 2-year-old presenting with altered mental status was found also to have a moderate background slowing in the CHILDREN RELATED TO INFECTION WITH EEG, but in this case, the MRI lesions involved the bilateral SARS-CoV-2 lateral thalamic nuclei, showing restricted diffusion without T2 or FLAIR anomalies (11). These lesions may resemble an Twenty-one studies (14 about non-specific and 7 about specific acute necrotizing encephalopathy (ANE), although without a neurological involvement) have been included in a systematic hemorrhagic component in this case. ANE is a rare manifestation review of neurological manifestations in children published of some viral infections, such as influenza, leading to bilateral in September 2020. Out of 3,707 children, 581 (16%) had thalamic damage and has been related to intracranial cytokine non-specific neurological manifestations, such as headache and storms, which result in blood–brain barrier breakdown. At the fatigue, and 42 (1%) had specific neurological involvement onset of his encephalopathy, CSF SARS-CoV-2 PCR was negative, including encephalopathy (25), meningeal signs (17), and/or but interleukin-6 was elevated and went down gradually as he seizures (12), which were more common in children with severe improved. Although more frequent in children, ANE can also illness. Very rarely, Guillain–Barré syndrome, cranial nerve affect adults, and it has been reported in an adult patient with palsies, or intracranial hemorrhage were reported (6). SARS-CoV-2 infection (12). Next, I will review the current literature about One case of acute disseminated encephalomyelitis has been specific neurological abnormalities in children infected reported in a 12-year-old girl with SARS-CoV-2 infection. Five with SARS-CoV-2. days after the initial presentation with headache, rash, and fever, she had respiratory failure related to generalized motor Encephalopathy weakness. MRI showed an extensive cervical myelopathy and Encephalopathy of variable severity is the predominant definite restricted diffusion involving cerebral white matter, including neurological complication in children, usually in the setting the splenium of the corpus callosum (13). Another two children of COVID-19 pediatric multisystem inflammatory syndrome. have been reported with lesions of the corpus callosum, affecting In these cases, aside from the infection process, septic shock mainly splenium, in the context of SARS-CoV-2-related pediatric Frontiers in Neurology | www.frontiersin.org 2 February 2021 | Volume 11 | Article 613832 Boronat Neurologic Care of COVID-19 Children inflammatory multisystem syndrome (14). These cases suggest mechanism might also be possible in children. However, stroke that the splenium of corpus callosum may be a specially in children due to SARS-CoV-2 infection is exceptional, so the vulnerable area for inflammatory lesions in the context of SARS- presence in adults of other risk factors for stroke seems to be very CoV-2 infection with CNS involvement. important for pathogenicity (25). Recently, an international study with children with Coinfection by SARS-CoV-2 and tuberculous meningitis in encephalopathy related to SARS-CoV-2 infection and abnormal a child was complicated by cerebral sinus venous thrombosis neuroimaging findings was performed. Data were reviewed by and arterial ischemic stroke, with elevated D-dimer, fibrinogen, a child neurologist, a pediatric infectious diseases expert, and and ferritin levels, suggesting that both microorganisms induced a central neuroradiology panel. Neurological disease related an important inflammatory prothrombotic situation leading to to SARS-CoV-2 infection was reviewed in 38 children from these complications (26). France (n = 13), the UK (n = 8), the USA (n = 5), Brazil One case with multisystem inflammatory syndrome (n = 4), Argentina (n = 4), India (n = 2), Peru (n = 1), and that presented with status epilepticus showed an occipital Saudi Arabia (n = 1). The most common imaging abnormalities intracerebral hemorrhage (18). were post-infectious immune-mediated acute disseminated A previously healthy 14-year-old boy suffered an infarct encephalomyelitis changes of the brain (16 patients), myelitis involving middle and anterior right cerebral arteries. He (8 patients), and neural enhancement (13 patients). Corpus developed arrhythmia with refractory shock, requiring callosum splenial lesions (7 patients) and myositis (4 patients) extracorporeal life support, and died from the cerebral infarct. were predominantly observed in children with multisystem Postmortem microbiology was positive for SARS-CoV-2 (27). inflammatory syndrome (15). A previously healthy 13-year-old girl who presented with loss of consciousness and was SARS-CoV-2 positive and had a Seizures ruptured pseudoaneurysm of the left middle cerebral artery (28). Pediatric seizures associated with SARS-CoV-2 infection are Other stroke events have been associated with multisystem usually acute symptomatic seizures and mainly occur during inflammatory syndrome in pediatric patients. A previously febrile episodes (6). healthy 5-year-old who developed cardiogenic shock and Two cases of febrile status epilepticus (16, 17) and two cases required extracorporeal membrane oxygen had a right of status epilepticus in the setting of multisystem inflammatory middle cerebral artery infarction, cerebral edema, and diffuse syndrome due to SARS-CoV-2 have been reported (18, 19). One contralateral subarachnoid hemorrhage and died. A 2-month- of these cases showed an occipital intracerebral hemorrhage (18). old requiring extracorporeal membrane oxygen with refractory Seizures have been reported as early as the first months of seizures developed multiple hemorrhagic infarctions. Although life, with or without fever. A 6-week-old with positive SARS- he tested negative for SARS-CoV-2 antibodies, his clinical CoV-2 PCR presented with fever, cough, and brief episodes presentation was suspicious for SARS-CoV-2 infection with of impaired responsiveness with upward gaze and stiffening elevated IL-6 levels (29). of both legs. EEG showed intermittent delta rhythm. All the Two children of 8 and 16 years of age suffered arterial other exams, including brain MRI, were normal (20). One male ischemic strokes due to acute intracranial large vessel occlusion infant aged 26 days with SARS-CoV-2 infection and fever had 2 within 3–4 weeks of SARS-CoV-2 infection. One case presented episodes of generalized hypertonia. The EEG was normal (21). with bilateral middle cerebral artery strokes and the other A 3-month-old girl was reported to present with non-febrile with multiple-organ system dysfunction. Neither patient fulfilled focal seizures with impaired consciousness during SARS-CoV- criteria for multisystem inflammatory syndrome in children 2 infection at days 6 and 9 from onset, with normal EEG and (MIS-C) given absence of fever. These data suggest that systemic MRI. D-Dimer and ferritin levels were increased. In this case, post-infectious arteritis with cerebrovascular involvement may whole-exome sequencing was performed, revealing a pathogenic complicate SARS-CoV-2 infection (30). frameshift mutation in the PRRT2 gene in both the mother and the infant. The mother had two late infantile febrile convulsions with normal neurological development. The authors suggested Hyposmia and Hypogeusia Anosmia/hyposmia and dysgeusia have been reported in 30–80% that SARS-CoV-2 may trigger non-febrile seizures in infants with cases of SARS-CoV-2 in the adult population. As the olfactory a genetic predisposition (22). neuroepithelium expresses ACE-2, a direct invasion by the virus A child presenting as isolated afebrile seizure in the setting causing inflammatory changes locally would lead to hyposmia, of SARS-CoV-2 infection without other symptoms has also been usually showing in the early stages of the disease (6). In children, reported (23). An adolescent with respiratory symptoms and hyposmia with or without hypogeusia was detected in 17 out of lethargy showed epileptic apneic episodes (24). 27 (62%) cases (31). One child presented with isolated anosmia (32) and three adolescents showed these isolated symptoms in the Stroke absence of other symptomatology (33). Although SARS-CoV-2 predisposes to stroke in adults (4, 5), it is not the case for children, as other risk factors for stroke in children are usually absent. Angiotensin-converting enzyme 2 Muscular Involvement (ACE-2), located in the brain vascular endothelium, acts as a In a comparison between 7 children and 25 adults, while 13 receptor for the virus, so clotting and infarction related to this adults (52%) complained of muscle pain, none of the children Frontiers in Neurology | www.frontiersin.org 3 February 2021 | Volume 11 | Article 613832 Boronat Neurologic Care of COVID-19 Children did. However, children showed elevation of creatine kinase levels CONSEQUENCES OF THE COVID19 more frequently than adults (57 vs. 4%) (34). PANDEMIC REGARDING CHILDREN HEALTH CARE Guillain–Barré Syndrome Two cases of Guillain–Barré syndrome have been reported in The COVID-19 pandemic has become an enormous challenge for children. An 11-year-old boy showed an acute inflammatory many healthcare systems, mainly in the management of chronic demyelinating polyneuropathy variant (35) and a 15-year-old boy patients. Children with neurological conditions are especially presented with an acute motor axonal neuropathy (36). Both vulnerable to this situation. showed a favorable response to intravenous immunoglobulin. Delayed Access to Medical Care Cranial Polyneuropathy Measures introduced by governments to try to delay the spread At day 21 of a hematopoietic stem cell transplantation, a 6-year- of infection have impaired the access to emergency departments old patient with cerebral vasculopathy due to sickle cell anemia or primary care facilities for illnesses not related to SARS- presented with dysfunction of cranial nerves V, VII, and IX. CoV-2 infection. Evidence from previous epidemics found Inflammatory anomalies were detected in these nerves in the that hospital avoidance during outbreaks of MERS and SARS brain MRI (37). was common, but emergency departments returned early to normality following these pandemics, as they lasted 2–3 months. Orbital Cellulitis With Intracranial This is not the case scenario for the COVID-19 pandemic, with Extension still many months of pandemic ahead of us (42). This expected Two adolescents with sinusitis and orbital cellulitis were prolonged reduced access to health care will be damaging to reported. One had a hemorrhagic abscess, and the other an children, mainly neurologically affected children with special intracranial epidural abscess, with meningeal enhancement or needs, including cerebral palsy or epilepsy. extension in both cases (38). Lazzerini et al. reported some consequences from delayed access to medical care during COVID-19 pandemic in Italy during a week in March 2020. Twelve cases of delayed access Current Treatment Recommendations for to hospital care leading to severe complications or death Children With SARS-CoV-2 Infection were detected. These complications included mainly diabetic General management of children with SARS-CoV-2 infection is ketoacidosis, sepsis, seizures, and bowel obstruction. Half of the based on supportive therapy. children were admitted to an ICU and four died. In all cases, Based on findings from the RECOVERY trial, corticosteroids parents reported avoiding accessing hospital because of fear of are recommended in adult patients who are mechanically infection with SARS-CoV-2 (43). ventilated or who require supplemental oxygen. Because only a Children with previous neurological conditions, including few pediatric patients were included in this trial, it is difficult cerebral palsy or severe intellectual disability or autism, may to extend these recommendations for children. Dexamethasone be especially vulnerable, mainly because of their inability to may be used in pediatric patients requiring mechanical communicate and because their parents are used to deal at home ventilation, but it is generally not recommended for those who with their chronic conditions. Two children with cerebral palsy require only minimal oxygen support (39) (Coronavirus disease died in the ambulance on the way to the hospital, one after 10 19 NIH Treatment Guidelines). days of fever and the other after 3 days of bloody stools. A child In a trial of adults hospitalized with SARS-CoV-2, remdesivir, with intellectual disability due to Mowat–Wilson syndrome, in a viral RNA–dependent RNA polymerase inhibitor, was shown dialysis for chronic renal insufficiency, arrived at the hospital to decrease time to recovery, but the effects are not known in after 3 days of hypoactivity and died 4 days later in the ICU (43). the pediatric population (40) A phase 2/3 trial of remdesivir This data demonstrates that children with neurological disorders was initiated in June 2020 for children (ClinicalTrials.gov ID: are specially fragile in this situation, as 3 of the 4 deaths affected NCT04431453). Convalescent plasma, which has recently been patients with neurological conditions. approved by the FDA for emergency use, has shown some efficacy in reducing mortality in critically ill patients (41) A phase 1 clinical trial of convalescent plasma in children is ongoing Changes in Modalities of Care (ClinicalTrials.gov ID: NCT04377672). The COVID-19 pandemic has prompted to introduce rapidly There are insufficient data in children to recommend telemedicine as one of the main modalities for patient clinic either for or against the use of other treatments that are follow-ups. Visits by e-mail, telephone, or teleconference were currently under investigation (Coronavirus disease 19 NIH quickly established at many hospital and primary care facilities in Treatment Guidelines). order to limit the spread of the virus. In some countries, including Given the current scarce evidence of these treatments in Spain, COVID-19 pandemic has accelerated the implantation of pediatric patients, the standard management of neurologic telemedicine in clinical care and it is planned to add this new complications, including ischemic stroke, seizures, and modality to classical practice, during and once the pandemic inflammatory lesions, is recommended at this point (39). is over. Frontiers in Neurology | www.frontiersin.org 4 February 2021 | Volume 11 | Article 613832 Boronat Neurologic Care of COVID-19 Children Impact on Mental Health the pandemic, around 90% of caregivers were satisfied with the Children are at risk of suffering the consequences of parental efficacy of telephonic consultations (51). affected mental health driven by stress related to the COVID-19 pandemic. Also, children themselves may have problems coping Neurosurgical Conditions with the situation, leading to hyperactivity, challenging behavior, In general, urgent neurosurgery, for example, in cases of shunt depression, and anxiety. Children with normal development may malfunction, has not been delayed. It has been successfully overcome the situation only with supportive intervention, but it performed during the pandemic with adequate measures of may be more challenging in children with previous behavioral or security in the operating room (52). psychiatric problems. An Italian study found increased anxiety in a study of 148 Epilepsy healthy adolescents. The items concerning breathing difficulties The COVID-19 pandemic has an important impact in care of and sleep disorder were the most affected (44). people with epilepsy. A group of international epilepsy experts published a CONSEQUENCES TO PATIENTS WITH consensus statement on June 2020 in order to provide clinical guidelines for epileptic patients (53). PREVIOUS NEUROLOGICAL DISEASES This situation poses a risk to good epilepsy control, as patients Cerebral Palsy may be unable to get the proper information to adjust drugs Patients with cerebral palsy, who usually are prone to lung or dosages, leading to self-prescription or stop of medications problems, may be at risk for more severe respiratory symptoms without physician advice. due to SARS-CoV-2 infection, requiring more frequently The Pediatric Epilepsy Research Consortium and the Child ICU admissions. Also, they are specially at risk of suffering Neurology Society collaborated to issue recommendations for consequences for delayed access to the emergency department diagnosis, treatment, and follow-up of infantile spasms in this in case of an acute illness. Also, limited access to chronic special time (54) advocating for oral therapies as initial treatment care programs, including physical therapy, botulinum toxin or and use of telemedicine. Also, a guideline for Chinese epileptic chronic surveillance, has been problematic for these children. children has been published. The authors emphasize the use For example, orthopedic follow-ups in children with cerebral of telemedicine for care and provide a useful guideline of palsy try to identify early hip displacement in order to medications for SARS-CoV-2 that might have interactions with establish treatment at the right time, before the hip becomes antiepileptic drugs (55). painful. The COVID-19 pandemic has led to the cancellation A Spanish survey in April 2020 assessed the impact of the of clinical appointments and elective surgeries at many COVID-19 pandemic in patients with genetic developmental hospitals, worsening the standard of care that these patients epileptic encephalopathies. Within 277 responders, 39 (14%) need (45). reported seizure frequency increase and 87 (30%) cases showed behavioral deterioration during the lockdown. In addition, nine Neuromuscular Disorders patients experienced some degree of neurological regression Patients with neuromuscular disorders, including spinal and there was one case of status epilepticus. The main factors muscular atrophy or muscular dystrophies, are especially at contributing to seizure or behavioral changes were inability to get risk for respiratory complications in the setting of SARS- the proper access to medical care, including difficulties reaching CoV-2. Specific consensus recommendations have been their neurologist, avoidance of seeking medical advice in the published to guide clinicians through these times of continuous emergency department due to fear of infection, loss of regular adaptation of clinical care to the special needs of these stimulation and physical therapies, cancelation of essential patients (46, 47). medical appointments, and difficulties finding their antiepileptic drugs at a pharmacy. The oversaturation of the healthcare system Migraines was especially important in Madrid and Barcelona, the Spanish Patients with migraine are specifically vulnerable to this situation. regions with the highest incidence of COVID-19. Also, new-onset Disruption of sleep and dietary habits, high psychosocial stress depression or anxiety in caregivers, living in small homes without and social isolation, may lead to worsening of headaches. a terrace or yard, and economic problems were factors leading to A survey of 1,018 adult patients showed an increase in worsening of these patients (56). migraine frequency and severity, and more transformation to chronic migraine. The authors identified some risk factors Behavioral Issues for migraines worsening, including difficult access to their Children with behavioral problems treated with regular neurologist, chronic treatment abandonment, disruption of sleep psychological therapy are at high risk of worsening during and dietary schedules, comorbidity with anxiety and depression, the COVID-19 pandemic, due to isolation from peers, family and working during the pandemic (48). Two Italian studies stress, and imposed changes in routine. Some countries have showed a general improvement in children and adolescents implemented online therapy programs that allow to maintain with primary headaches and migraines during the lockdown. physical distance and provide emotional support at the same Reduction in school-related stress seems to be the main factor time. Mental health of parents must be assessed, as they have (49, 50). In a study of children with migraine in India during direct impact on their child’s behavior (57). Frontiers in Neurology | www.frontiersin.org 5 February 2021 | Volume 11 | Article 613832 Boronat Neurologic Care of COVID-19 Children Autism and Intellectual Disability 16% of children show non-specific neurological symptoms Lifestyle changes imposed by the COVID-19 pandemic are as headache, while more severe and specific neurological hard especially for those with intellectual disability and/or complications occur only around 1% of cases. autism, as they have problems with understanding the situation, Children with SARS-CoV-2 multisystem inflammatory communicating, and expressing their feelings, which may lead syndrome are especially at risk for neurological complications. to behavioral problems, including self-aggressions. Because of Encephalopathy is the more frequent abnormality, sometimes their need of predictable routines, and preference for certain with symptomatic seizures, and it is usually transitory, without activities, they may feel frustrated with schedule changes. Their long-term neurological sequelae. In some patients, EEG and progress is at risk, and they may even show regression of some brain MRI show transient abnormalities, which usually resolve skills. Scheduling specific times for wake and sleep, exercise, with time (6, 7). schoolwork, and meals is important for all children and even The COVID-19 pandemic has supposed a struggle for more in individuals with neurodevelopmental problems (58). healthcare systems around the world. Children with neurological conditions and their families are especially vulnerable. Attention Deficit and Hyperactivity Current data support the beneficial role of telemedicine Disorder (ADHD) in the care of these patients. Parents of children with Children with ADHD are also at risk in this situation. The neurological conditions need support, and they have to be loss of daily routine will worsen ADHD symptoms. The encouraged to seek medical attention when needed and go psychological stress lived by parents during the COVID-19 to the emergency departments to avoid delay in diagnosis pandemic may exacerbate the children’s symptoms As expected, a and treatment of potentially life-threatening conditions, such study among Chinese school-aged children with ADHD showed as infections, appendicitis, and shunt malfunctions. Delays in that symptoms were significantly worse during the COVID- getting the adequate medical attention and other problems with 19 outbreak compared to normal state (59). The European neurologically affected children during the pandemic leading to ADHD Guidelines Group (EAGG) has addressed these issues and severe problems and even death have been clearly documented. developed a guideline for the management of ADHD through the Risk of abuse and neglect of children during the COVID- pandemic (60). 19 outbreak may peak due to parents’ stress related to a mix of factors, including fear of illness, working from home while caring Psychiatric Disorders for children, financial insecurity, and lack of free time outdoors. Individuals with mental health conditions are especially With schools closed and families isolated in their homes, children vulnerable to worsening of their symptoms during this are separated from teachers and healthcare workers, which are pandemic. Some individuals manifest these mental issues as an important source of protection as they may detect and report somatic complains, such as pain or breathing difficulties. Somatic suspected abuse (62, 63). A rise in pediatric blunt trauma, symptom disorders may peak in this setting, as demonstrated including skull and long bones fractures, face contusions, and by a case report of a 16-year-old adolescent, who despite testing intracranial hemorrhages, was reported in a hospital during the negative for SARS-CoV-2, had an obsessive preoccupation about COVID-19 pandemic (64). This difficult time for some families, being infected and required an admission to the Psychiatric Unit, struggling with psychological stress and financial problems, must showing a rapid response to antidepressant and antipsychotic raise high suspicion for child abuse in some cases, mainly in medications (61). behavior-challenging individuals such as those with ADHD, autism, and neurodevelopmental disorders (59, 63). DISCUSSION The healthcare system of every country has the obligation to assure adequate care for these children until the end of We have reviewed the neurological clinical findings in children the pandemic. infected with SARS-CoV-2 published at this time, but it is expected to gather more knowledge in the future, as the COVID- AUTHOR CONTRIBUTIONS 19 pandemic evolves. Neurological complications of SARS-CoV-2 infection in The author confirms being the sole contributor of this work and children are much less frequent than in adult population. Around has approved it for publication. REFERENCES 4. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. 1. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in JAMA Neurol. (2020) 77:683–90. doi: 10.1001/jamaneurol.2020.1127 children. N Engl J Med. (2020) 382:1663–5. doi: 10.1056/NEJMc2005073 5. 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The use, distribution or for the management of chinese children with epilepsy during the COVID-19 reproduction in other forums is permitted, provided the original author(s) and the outbreak. Front Pediatr. (2020) 8:495. doi: 10.3389/fped.2020.00495 copyright owner(s) are credited and that the original publication in this journal 56. Aledo-Serrano Á, Mingorance A, Jiménez-Huete A, Toledano R, is cited, in accordance with accepted academic practice. No use, distribution or García-Morales I, Anciones C, et al. Genetic epilepsies and COVID-19 reproduction is permitted which does not comply with these terms. Frontiers in Neurology | www.frontiersin.org 8 February 2021 | Volume 11 | Article 613832