Peripheral nervous system involvement in SARS-CoV-2 infection: a review of the current pediatric literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the pathogen responsible for the pandemic health emergency declared by the World Health Organization in March 2020. During the first part of the pandemic, adults showed mild to severe respiratory symptoms. Children seemed initially exempt, both from acute and subsequent complications. Hyposmia or anosmia were promptly identified as the main symptoms of acute infection, so neurotropism of SARS-CoV-2 was immediately suspected. (1, 2). As the emergency progressed, post infectious neurological complications were described also in pediatric population (3). Cases of cranial neuropathy in connection with acute SARS-CoV-2 infection have been reported in pediatric patients, as an isolate post infectious complication or in the context of the multisystem inflammatory syndrome in children (MIS-C) (4-6). Neuroinflammation is thought to be caused by several mechanisms, among which immune/autoimmune reactions (7), but so far, no specific autoantibody has been identified. SARS-CoV-2 can enter the central nervous system (CNS) directly and/or infect it retrogradely, through the peripheral nervous system (PNS), after replicating peripherally; several factors regulate invasion and subsequent neuroinflammation. Indeed, direct/secondary entry and replication can activate CNS-resident immune cells that, together with peripheral leukocytes, induce an immune response and promote neuroinflammation. In addition, as we will discuss in the following review, many cases of peripheral neuropathy (cranial and non-cranial) have been reported during or after SARS-CoV-2 infection. However, some authors have pointed out that the increase of cranial roots and ganglia in neurological imaging is not always observed in children with cranial neuropathy. (8). Even if a variety of case reports were published, opinions about an increased incidence of such neurologic diseases, linked to SARS-CoV-2 infection, are still controversial (9-11). Facial nerve palsy, ocular movements abnormalities and vestibular alterations are among the most reported issues in pediatric population (3-5). Moreover, an increased screen exposure imposed by social distancing led to acute oculomotion's disturbance in children, not primarily caused by neuritis (12, 13). The aim of this review is to suggest food for thought on the role of SARS-CoV-2 in neurological conditions, affecting the peripheral nervous system to optimize the management and care of pediatric patients.

The BNT162b2 vaccine induces humoral and cellular immune memory to SARS-CoV-2 Wuhan strain and the Omicron variant in children 5 to 11 years of age.

SARS-CoV-2 mRNA vaccines prevent severe COVID-19 by generating immune memory, comprising specific antibodies and memory B and T cells. Although children are at low risk of severe COVID-19, the spreading of highly transmissible variants has led to increasing in COVID-19 cases and hospitalizations also in the youngest, but vaccine coverage remains low. Immunogenicity to mRNA vaccines has not been extensively studied in children 5 to 11 years old. In particular, cellular immunity to the wild-type strain (Wuhan) and the cross-reactive response to the Omicron variant of concern has not been investigated. We assessed the humoral and cellular immune response to the SARS-CoV-2 BNT162b2 vaccine in 27 healthy children. We demonstrated that vaccination induced a potent humoral and cellular immune response in all vaccinees. By using spike-specific memory B cells as a measurable imprint of a previous infection, we found that 50% of the children had signs of a past, undiagnosed infection before vaccination. Children with pre-existent immune memory generated significantly increased levels of specific antibodies, and memory T and B cells, directed against not only the wild type virus but also the omicron variant.

Neurological and psychological effects of long COVID in a young population: A cross-sectional study.

Aim: We evaluated the long-term clinical status of pediatric patients after testing positive for COVID-19. We hypothesized that there are similar symptoms to those that have been described in adults and children and that pediatric patients with neurophysiologic symptoms still present 3-5 months after infection have psychological consequences that interfere with their adaptive functioning. Method: We recruited 322 COVID-19-positive pediatric patients, between 1.5 and 17 years old, from the outpatient clinic for COVID-19 follow-up. Neurological symptoms were analyzed at onset, after 1 month, and after 3-5 months. A psychological assessment with standardized questionnaires was also conducted to determine the impact of the disease. Results: At the onset of COVID-19, 60% of the total sample exhibited symptoms; this decreased after 1 month (20%) but stabilized 3-5 months after disease onset (22%). Prevailing long-COVID neurological symptoms were headache, fatigue, and anosmia. In the 1.5-5-year-old subgroup, internalizing problems emerged in 12% of patients. In the 6-18-year-old subgroup, anxiety and post-traumatic stress showed significant associations with neurological symptoms of long COVID. Conclusions: These data demonstrate that long COVID presents various broad-spectrum symptoms, including psychological and long-lasting cognitive issues. If not treated, these symptoms could significantly compromise the quality of life of children and adolescents.

COVID-19, Anosmia, and Allergies: Is There a Relationship? A Pediatric Perspective.

BACKGROUND: Between June and July 2020, we evaluated children and adolescents concerning post-infection surveillance after a COVID-19 positivity during the lockdown. We aimed to assess whether the anamnestic presence of allergies could correlate with the presence of SARS-CoV-2 symptoms, and in particular with anosmia. MATERIAL AND METHODS: For each patient, we collected anamnestic data, the presence of allergies documented by performing skin prick tests, and COVID-19 symptoms. Then, if over six years of age, each patient underwent an active anterior rhinomanometry. RESULTS: A total of 296 patients were enrolled, of whom 105 (35.4%) reported allergies. Considering COVID-19 symptoms, 74 subjects (25%) presented an asymptomatic form, 222 (75%) reported symptoms, and anosmia recurred in 60 subjects (27.03%). A statistically significant relationship was found between allergies and symptomatic COVID-19 (p = 0.042), allergies, and anosmia (p = 0.05), and allergies and anosmia in males (p = 0.007). Moreover, anosmic patients presented a higher body mass index, older age, and a longer COVID-19 duration with statistical significance (p = 0.001, 0.001, 0.006, respectively). CONCLUSIONS: Allergic subjects seem to develop symptomatic COVID-19 more frequently and allergies appear to be a protective factor from anosmia's onset in males.

COVID-19 and abducens nerve palsy in a 9-year-old girl-case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although many reports have detailed a range of neurological symptoms in SARS-CoV-2-infected patients, studies of neuro-ophthalmological manifestations are still scarce. CASE PRESENTATION: We report a 9-year-old girl with abducens nerve palsy after COVID-19 with no evidence of other neurological disease on neuroimaging. At 2-month follow-up clinical conditions were improved. CONCLUSIONS: The palsy may have occurred due to a possible post-infectious immune-mediated mechanism underlying the neuropathy, as opposed to direct viral infiltration. Despite being rare, this complication must be taken into account.

Short-Term Side Effects and SARS-CoV-2 Infection after COVID-19 Pfizer-BioNTech Vaccine in Children Aged 5-11 Years: An Italian Real-World Study.

Vaccination against COVID-19 is the most effective tool to protect both the individual and the community from this potentially life-threatening infectious disease. Data from phase-3 trials showed that two doses of the BNT162b2 vaccine were safe, immunogenic, and effective against COVID-19 in children aged 5-11 years. However, no surveys in real-life settings have been carried out in this age range. Here, we conducted a cross-sectional study to evaluate the short-term adverse reactions (ARs) and the rate of protection against infection of the BNT162b2 vaccine in children aged 5-11 years by the compilation of two surveillance questionnaires conceived using Google Forms. Five-hundred and ninety one children were included in the analysis. ARs were reported by 68.9% of the children, being mainly local. The incidence of systemic ARs, especially fever, was higher after the second dose. The incidence of infection after completing the immunization accounted for 13.6% of the children. COVID-19 symptoms reported were mild, with the exception of one case of pneumonia. Only 40% of infected participants needed to take medication to relieve symptoms, mostly paracetamol and NSAIDs, and none reported persistent symptoms. The Pfizer-BioNTech vaccine in children aged 5-11 years is safe and well tolerated. The mild clinical course of COVID-19 in immunized children confirmed the favorable risk-benefit ratio, encouraging parents to immunize their children.