Presence and Significance of Multiple Respiratory Viral Infections in Children Admitted to a Tertiary Pediatric Hospital in Italy.

Viral co-infections are frequently observed among children, but whether specific viral interactions enhance or diminish the severity of respiratory disease is still controversial. This study aimed to investigate the type of viral mono- and co-infections by also evaluating viral correlations in 3525 respiratory samples from 3525 pediatric in/outpatients screened by the Allplex Respiratory Panel Assays and with a Severe Acute Respiratory Syndrome-COronaVirus 2 (SARS-CoV-2) test available. Overall, viral co-infections were detected in 37.8% of patients and were more frequently observed in specimens from children with lower respiratory tract infections compared to those with upper respiratory tract infections (47.1% vs. 36.0%, p = 0.003). SARS-CoV-2 and influenza A were more commonly detected in mono-infections, whereas human bocavirus showed the highest co-infection rate (87.8% in co-infection). After analyzing viral pairings using Spearman's correlation test, it was noted that SARS-CoV-2 was negatively associated with all other respiratory viruses, whereas a markedly significant positive correlation (p < 0.001) was observed for five viral pairings (involving adenovirus/human bocavirus/human enterovirus/metapneumoviruses/rhinovirus). The correlation between co-infection and clinical outcome may be linked to the type of virus(es) involved in the co-infection rather than simple co-presence. Further studies dedicated to this important point are needed, since it has obvious implications from a diagnostic and clinical point of view.

Molecular characterization of SARS-CoV-2 Omicron clade and clinical presentation in children.

Since its emergence, SARS-CoV-2 Omicron clade has shown a marked degree of variability and different clinical presentation compared with previous clades. Here we demonstrate that at least four Omicron lineages circulated in children since December 2021, and studied until November 2022: BA.1 (33.6%), BA.2 (40.6%), BA.5 (23.7%) and BQ.1 (2.1%). At least 70% of infections concerned children under 1 year, most of them being infected with BA.2 lineages (n = 201, 75.6%). Looking at SARS-CoV-2 genetic variability, 69 SNPs were found to be significantly associated in pairs, (phi < - 0.3 or > 0.3 and p-value < 0.001). 16 SNPs were involved in 4 distinct clusters (bootstrap > 0.75). One of these clusters (A23040G, A27259C, T23617G, T23620G) was also positively associated with moderate/severe COVID-19 presentation (AOR [95% CI] 2.49 [1.26-4.89] p-value: 0.008) together with comorbidities (AOR [95% CI] 2.67 [1.36-5.24] p-value: 0.004). Overall, these results highlight the extensive SARS-CoV-2 Omicron circulation in children, mostly aged < 1 year, and provide insights on viral diversification even considering low-abundant SNPs, finally suggesting the potential contribution of viral diversification in affecting disease severity.

Increased bronchiolitis burden and severity after the pandemic: a national multicentric study.

BACKGROUND: The coronavirus 2019 (COVID-19) related containment measures led to the disruption of all virus distribution. Bronchiolitis-related hospitalizations shrank during 2020-2021, rebounding to pre-pandemic numbers the following year. This study aims to describe the trend in bronchiolitis-related hospitalization this year, focusing on severity and viral epidemiology. METHODS: We conducted a retrospective investigation collecting clinical records data from all infants hospitalized for bronchiolitis during winter (1st September-31th March) from September 2018 to March 2023 in six Italian hospitals. No trial registration was necessary according to authorization no.9/2014 of the Italian law. RESULTS: Nine hundred fifty-three infants were hospitalized for bronchiolitis this last winter, 563 in 2021-2022, 34 in 2020-2021, 395 in 2019-2020 and 483 in 2018-2019. The mean length of stay was significantly longer this year compared to all previous years (mean 7.2 ± 6 days in 2022-2023), compared to 5.7 ± 4 in 2021-2022, 5.3 ± 4 in 2020-2021, 6.4 ± 5 in 2019-2020 and 5.5 ± 4 in 2018-2019 (p < 0.001), respectively. More patients required mechanical ventilation this winter 38 (4%), compared to 6 (1%) in 2021-2022, 0 in 2020-2021, 11 (2%) in 2019-2020 and 6 (1%) in 2018-2019 (p < 0.05), respectively. High-flow nasal cannula and non-invasive respiratory supports were statistically more common last winter (p = 0.001 or less). RSV prevalence and distribution did not differ this winter, but coinfections were more prevalent 307 (42%), 138 (31%) in 2021-2022, 1 (33%) in 2020-2021, 68 (23%) in 2019-2020, 61 (28%) in 2018-2019 (p = 0.001). CONCLUSIONS: This study shows a growth of nearly 70% in hospitalisations for bronchiolitis, and an increase in invasive respiratory support and coinfections, suggesting a more severe disease course this winter compared to the last five years.

Bronchiolitis guidelines: what about the Italian situation in a primary care setting?

Acute viral bronchiolitis is the most common cause of hospitalization in children under 12 months of age. The variable clinical presentation and the potential for sudden deterioration of the clinical conditions require a close monitoring by healthcare professionals.In Italy, first access care for children is provided by primary care physicians (PCPs) who often must face to a heterogeneous disease presentation that, in some cases, make the management of patient with bronchiolitis challenging. Consequently, Italian studies report poor adherence to national and international guidelines processed to guide the clinicians in decision making in acute viral bronchiolitis.This paper aims to identify the potential factors contributing to the lack of adherence to the suggested guidelines derived by clear and evidence-based recommendations among primary care physicians operating in an outpatient setting, with a specific focus on the context of Italy. Particularly, we focus on the prescription of medications such as ß2-agonists, systemic steroids, and antibiotics which are commonly prescribed by PCPs to address conditions that can mimic bronchiolitis.

Respiratory syncytial virus: can we still believe that after pandemic bronchiolitis is not a critical issue for public health?

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide. Since the beginning of the COVID-19 pandemic, non-pharmacological interventions were applied, interfering with the circulation of most respiratory viruses, including RSV. The aim of this study is to analyze the RSV infection trend among hospitalized infants during the actual epidemic season (2022-2023) in comparison with the last pre-pandemic season (2018-2019), in order to outline whether significant differences emerge due to COVID-19 pandemia. We retrospectively reviewed medical data on infants hospitalized at the Bambino Gesù Children's Hospital with diagnosis of bronchiolitis in the current epidemic season and in the last pre-pandemic season, 2018-2019. RSV remains the main etiological agent of bronchiolitis in terms of frequency and severity of infections in the ongoing epidemic season. The first RSV case of the 2022-2023 season was detected at week 42 vs week 47 in the 2018-2019 season. The length of epidemic season was of 17 weeks in 2022-2023 vs 18 weeks in 2018-2019. Comparing the two seasons, age at admission was significantly higher in the current season (median age 2022-2023 65 days vs median age 2018-2019 58 days), but the disease severity was similar.       Conclusions: The 2022-2023 bronchiolitis season in Italy started earlier than the usual pre-pandemic seasons but seasonality pattern may be going back to the pre-pandemic one. This season was not more severe than the previous ones. The impact of RSV disease on health care systems and costs remains a critical issue. What is Known: • RSV is one of the major leading causes of hospitalization among children aged less than 3 months. SarsCOV2 pandemic interfered with the seasonal circulation of most respiratory viruses, Including RSV. What is New: • The 2022-2023 bronchiolitis season in Italy started and peaked earlier than the usual pre-pandemic seasons but seasonality pattern may be realigning to the pre-pandemic one. The impact of RSV disease on health care systems and costs is concerning.

"Multidisciplinary management of post- infective osteoarthritis and secondary condylar resorption of temporomandibular joint: a case report in a 9 years-old female patient and a review of literature".

BACKGROUND: Osteoarthritis and condylar resorption of temporomandibular joint (TMJ) has rarely been reported in children as consequence of otologic disease. We describe the management of a case in a 9-year-old female as long-term complication of an otomastoiditis and review the literature currently available on this topic. CASE PRESENTATION: A nine-years-old female patient referred to Emergency Room of Bambino Gesù Children's Research Hospital, IRCCS (Rome,Italy) for an acute pain in the left preauricular area and reduced mandibular movements. In the medical history an otomastoiditis and periorbital cellulitis was reported at the age of six with complete remission of symptoms after antibiotic treatment. No recent history of facial trauma and no previous orthodontic treatment were reported. She was referred to a pediatric dentist that conducted a clinical examination according to the Diagnostic Criteria of Temporomandibular Disorders (DC/TMD) and was diagnosed with bilateral myalgia of the masticatory muscles and arthralgia at the level of the left TMJ. Then, a complete diagnostic path was performed that included multidisciplinary examinations by a rheumatologist, infectious disease specialist, ear nose and throat (ENT) doctor, a maxillofacial surgeon and a medical imaging specialist. Differential diagnosis included juvenile idiopathic arthritis, idiopathic condylar resorption, trauma, degenerative joint disease, neurological disease. Finally, unilateral post-infective osteoarthritis of the left TMJ with resorption of mandibular condyle was diagnosed. The patient went through a pharmacological therapy with paracetamol associated to counselling, jaw exercises and occlusal bite plate. After 1 month, the patient showed significant reduction of orofacial pain and functional recovery that was confirmed also one-year post-treatment. The novelty of this clinical case lies in the accurate description of the multidisciplinary approach with clinical examination, the differential diagnosis process and the management of TMD with conservative treatment in a growing patient. CONCLUSIONS: Septic arthritis of temporomandibular joint and condylar resorption were described as complications of acute otitis media and/or otomastoiditis in children. We evidenced the importance of long-term follow-up in children with acute media otitis or otomastoiditis due to the onset of TMJ diseases. Furthermore, in the multidisciplinary management of orofacial pain the role of pediatric dentist is crucial for the diagnostic and therapeutic pathway to avoid serious impairment of mandibular function.

The Disappearance of Respiratory Viruses in Children during the COVID-19 Pandemic.

BACKGROUND: Social distancing measures are used to reduce the spreading of COVID-19. The aim of this study was to assess the impact of local restrictions on the transmission of respiratory virus infections. METHODS: we retrospectively analyzed the nasopharyngeal samples of all patients (0-18 years old) admitted with respiratory symptoms in a large Italian tertiary hospital during the last three seasons from 2018 to 2021. RESULTS: A strong reduction in all viral respiratory infections was observed in the last season (2020-2021) compared to the two previous seasons (-79.69% and -80.66%, respectively). In particular, we found that during the epidemic period 2018-2019 and 2019-2020, the total number of Respiratory Syncytial Virus (RSV) cases was, respectively 726 and 689, while in the last season a total of five cases was detected. In the first months of 2018-2019 and 2019-2020, the total flu infections were 240 and 354, respectively, while in the last season we did not detect any influenza virus. As other viruses, the presence of Rhinovirus declined, but to a lesser extent: a total of 488 cases were assessed compared to the 1030 and 1165 cases of the two previous respective epidemic seasons. CONCLUSIONS: Public health interventions and distancing (including continuous use of face masks) settled to counter the pandemic spread of COVID-19 had a macroscopic impact on all respiratory virus transmission and related diseases, with a partial exception of Rhinovirus. The absence of viruses' circulation could result in a lack of immunity and increased susceptibility to serious infections in the next seasons.

Pertussis in early life: underdiagnosed, severe, and risky disease. A seven-year experience in a pediatric tertiary-care hospital.

AIM: Pertussis continues to be a common worldwide infection in pediatric and adult populations.We aimed to study epidemiological and clinical characteristics of infants and children admitted for pertussis to a tertiary-care hospital and to investigate the risk factors for pediatric intensive care unit (PICU) admission. MATERIALS AND METHODS: With a retrospective study, we analyzed all medical reports of patients admitted to Bambino Gesù Children's Hospital in Rome from January 2011 to December 2018 with a diagnosis of pertussis. RESULTS: We examined 195 patients. The majority of hospitalized children (66.15%) were <3 months of age. No mother had received pertussis containing vaccine during pregnancy. Ten cases required admission in PICU. The age at admission was lower in PICU patients with respect to ward patients (42.8 vs 240 days; p < .0007), length of hospital stay was longer in PICU group (24.7 vs 7.52 days; p < .003). Patients who needed PICU admission had greater white blood cell count at hospital admission compared with those hospitalized in the pediatric ward. One infant died and one had encephalitis. CONCLUSIONS: Pertussis is a remerging disease. In infants, it is associated with significant morbidity and mortality. In recent years, many countries have implemented different vaccination strategies and public health measures to prevent the increase in pertussis cases. Maternal vaccination has been shown to be highly protective for infants <3 months of age before they can develop their own immunity via vaccination.

Sex differences in blood pro-oxidant status and platelet activation in children admitted with respiratory syncytial virus bronchiolitis: a pilot study.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in the pediatric population worldwide and an important cause of death in developing countries. It has been demonstrated that the balance between oxidant and antioxidant systems is disrupted in children with bronchiolitis and that oxidative stress contributes to the pathogenesis of this disease. Platelets play an important role in antimicrobial host defenses and contribute to pulmonary vascular repair being either targets or source of reactive oxidizing species. The main purpose of this study was to assessing sex differences in clinical characteristics and platelets activation during RSV bronchiolitis in infancy. METHODS: In this retrospective study a total of 203 patients (112 boys and 91 girls) with bronchiolitis, aged 12 months or less, admitted to the Bambino Gesù Pediatric Hospital of Rome (Italy) in the period from January to December 2017, were enrolled. Moreover, in a select group of patients (15 boys and 12 girls) with diagnosis of moderate bronchiolitis from RSV, a pilot study on oxidative stress and platelet characteristics was carried out by electron paramagnetic resonance and flow cytometry respectively. Age-matched healthy control subjects (10 boys and 10 girls) were chosen as controls. Data were analyzed using Student' T test, Chi Squared test and one-way ANOVA test. RESULTS: This study highlights the influence of sex in the clinical course of bronchiolitis. In particular we found: i) a higher incidence of bronchiolitis in boys than in girls (55% vs 45%); ii) higher C reactive protein values in girls than boys (1.11 mg/dL vs 0.92 mg/dL respectively; p < 0.05); iii) a different degree of thrombocytosis during hospitalization (mild in the girls and severe in the boys). Moreover, in selected patients we found that compared to girls with bronchiolitis, boys showed: i) higher percentage of activated platelets (8% vs 2% respectively; p < 0.05) and iii) higher number of platelets forming homotypic aggregates (2.36% vs 0.84% respectively, p < 0.05). CONCLUSION: The present study affirm that the bronchiolitis is an infection in which sex seems to act as a modulating factor only in the clinical course, influencing also the choice of the therapy should be made.

[Vaccination in childhood: how to protect the "unprotectable"?] / Le vaccinazioni dell'infanzia: proteggere gli "improteggibili".

The failure of immunization coverage is the primary reason for the transmission and the spread of the diseases in young infants not eligible for vaccination because of age and in immunocompromised individuals. In both these categories measles, pertussis and varicella could be devastating. Pertussis, measles and varicella in the first year of life are responsible to the ED admission, the hospitalization and, exceptionally, the death. The only way to protect very young infants and immunocompromised individuals is to obtain the adequate coverage in all the population.

Fatal varicella pneumonia in an unvaccinated child with Down Syndrome: a case report.

BACKGROUND: Varicella is an acute infectious disease common during childhood. It has mostly an uncomplicated course in early childhood. Neverthless, it may result in severe complications, especially in particular age groups and clinical conditions. Down Syndrome represents a risk factor for developing complications, because of the frequent comorbidities and their immunodeficiency. CASE PRESENTATION: A 2-year-old white Caucasian female affected by Down Syndrome was referred to our hospital for cardiac arrest in course of varicella disease. After cardiopulmonary resuscitation and stabilization, her clinical conditions didn't improve and she developed a massive pulmonary hemorrage, which led her to exitus. CONCLUSIONS: Mortality due to varicella infection is rare, but it is more common in subjects with immune deficit or chronic pathologies, and in particular age-groups. The importance of the vaccine for preventable infectious diseases is stressed in this paper, in which we present a case of death in an unvaccinated cardiopathic child with Down Syndrome affected by varicella.

Pertussis in infants: an underestimated disease.

BACKGROUND: The clinical diagnosis of pertussis is not easy in early infancy since clinical manifestations can overlap with several different diseases. Many cases are often misclassified and underdiagnosed. We conducted a retrospective study on infants to assess how often physicians suspected pertussis and the actual frequency of Bordetella pertussis infections. METHODS: We analyzed all infants with age ≤90 days hospitalized from March 2011 until September 2013 for acute respiratory symptoms tested with a Real Time Polymerase Chain Reaction able to detect Bordetella pertussis and with a Real Time Polymerase Chain Reaction for a multipanel respiratory virus. Therefore, we compared patients with pertussis positive aspirate, patients with respiratory virus positive aspirate and patients with negative aspirate to identify symptoms or clinical findings predictive of pertussis. RESULTS: Out of 215 patients analyzed, 53 were positive for pertussis (24.7 %), 119 were positive for respiratory virus (55.3 %) and 43 had a negative aspirate (20 %). Pertussis was suspected in 22 patients at admission and 16 of them were confirmed by laboratory tests, while 37 infants with different admission diagnosis resulted positive for pertussis. The sensitivity of clinical diagnosis was 30.2 % and the specificity 96.3 %. Infants with pertussis had more often paroxysmal cough, absence of fever and a higher absolute lymphocyte count than infants without pertussis. CONCLUSIONS: Pertussis is a serious disease in infants and it is often unrecognized; some features should help pediatricians to suspect pertussis, but clinical suspicion has a low sensitivity. We suggest a systematic use of Real Time Polymerase Chain Reaction to support the clinical suspicion of pertussis in patients with less than 3 months of age hospitalized with acute respiratory symptoms.

Hypertransaminasemia and hypophosphoremia in an adolescent with anorexia nervosa: an event to watch for.

BACKGROUND: Anorexia Nervosa is a Psychiatric eating disorder of adolescence age with a high morbidity and mortality. CASE PRESENTATION: We describe a common case of anorexia nervosa (AN) in a female adolescent complicated by less known conditions related to refeeding syndrome. At admission, the girl showed a mild hypercholesterolemia with progressive normalization of the values. The initial low hypertransaminasemia worsened after refeeding until very high levels and hypophosphoremia was also described. Only a controlled caloric intake and a specific electrolyte supplementation led to the improvement of hematologic values and the clinical condition of the patient. CONCLUSIONS: Refeeding complications must be always suspected because of life-threatening risk. More attention should be paid not only to the acute state of the disease but also to the prevention and the management of refeeding-related manifestations.

Linezolid therapy in a perinatal late-onset Staphylococcus aureus sepsis complicated by spondylodiscitis and endophthalmitis.

We report the case of a two-month-old immunocompetent girl affected by Staphylococcus aureus sepsis complicated with pneumonia and pleural effusion, spondylodiscitis and endophthalmitis treated with linezolid. She developed a S. aureus sepsis in the neonatal period antibiotically treated with clinical resolution. Ten days after therapy discontinuation, the infant experienced a new S. aureus sepsis complicated by pneumonia with pleural effusion. Due to the presence of dorsal swelling, a pulmonary computer tomography was performed that showed a dorsal D5-D6 spondylodiscitis. Since the sepsis was scarcely responsive to several appropriate antibiotics, we finally decided to treat the patient with linezolid. A few weeks after changing antibiotics, the child underwent an ophthalmologic visit. Due to the finding of ocular lesions, imaging examinations were performed. The diagnosis was compatible with retinoblastoma, such that the eye was enucleated. Nevertheless, histological and microbiological investigations did not confirm the tumour hypothesis, but revealed a S. aureus abscess with retinal detachment. The child completed antibiotic therapy with linezolid and was visited periodically at the Infectious Disease Unit for a follow-up. She underwent progressive resolution of discitis and did not present any further flare of sepsis. Nevertheless, she still has a replacement device in her right eye and a D5-D6 severe kyphosis with spinal fusion.

Serum soluble ST2 as diagnostic marker of systemic inflammatory reactive syndrome of bacterial etiology in children.

BACKGROUND: Accurate and timely diagnosis of community-acquired bacterial versus viral infections in children with systemic inflammatory response syndrome (SIRS) remains challenging both for clinician and laboratory. In the quest of new biochemical markers to distinguish bacterial from viral infection, we have explored the possible role of the soluble secreted form of ST2 (sST2). METHODS: This explorative prospective cohort study included children with SIRS who were suspected of having community-acquired infections. Plasma samples for sST2 measurement were obtained from 64 hospitalized children, 41 of whom had SIRS of bacterial etiology and 23 SIRS of viral etiology, and from 20 healthy, age- and sex-matched control children. sST2 measurement was carried out by enzyme-linked immunosorbent assay in parallel with standard measurements of procalcitonin (PCT) and C reactive protein (CRP). RESULTS: Our findings demonstrate that children with SIRS associated with bacterial infection present significantly increased levels of sST2, when compared with patients with SIRS of viral etiology and healthy children. More important, receiver operating characteristic curve analysis indicated that sST2 has a significant diagnostic performance with respect to early identification of SIRS of bacterial etiology, which was similar to that of PCT and greater than that of CRP. Finally, the combination of sST2 plus PCT and/or CRP, and PCT plus CRP increased their sensitivity and negative predictive value compared with sST2, PCT and CRP alone. CONCLUSIONS: In conclusion, sST2 level may prove useful in predicting bacterial etiology in children with SIRS.

Cardiopulmonary response to exercise and cardiac assessment in patients with turner syndrome.

Turner syndrome (TS) is a chromosomal disorder; however, little is known about the exercise tolerance of patients with this syndrome. The aim of the present study was to measure the maximal aerobic capacity and cardiac function using cardiopulmonary exercise testing and lung function tests and to evaluate the cardiac parameters using echocardiography in patients with TS and control subjects. A total of 50 women with TS (mean age 21.3 ± 8.5 years) and 56 age-matched controls (mean age 21.1 ± 3.7 years) were enrolled from the Pediatric Department of "Sapienza" University of Rome and underwent cardiopulmonary exercise testing, lung function testing, and echocardiography. The maximal oxygen uptake was lower in the patients with TS than in the controls (28.4 ± 4.0 vs 35.6 ± 6.2 ml/min/kg; p <0.0001). Also, the forced expiratory volume in 1 second, expressed as a percentage of the predicted value, was greater in the patients with TS than in the controls (116.2 ± 15.2% vs 102.8 ± 4.8%, p <0.0001). The patients with TS had a smaller left ventricle than did the controls. Tissue Doppler imaging revealed subclinical systolic and diastolic dysfunction in the left ventricle in those with TS but not in the controls. The left ventricular mass index was greater in the patients with TS than in the controls (38.6 ± 9.3 vs 27.2 ± 4.5 g/m(2.7), p <0.0001). In conclusion, the patients with TS had a lower maximal aerobic capacity and exercise tolerance than did the controls. The anatomic and functional cardiac aspects were peculiar to those with TS and might represent a specific cardiac phenotype.