The lung ultrasound in children with SARS-COV-2 infection: a national multicenter prospective study.

Coronavirus disease-19 (COVID-19) caused hospitalizations, severe disease, and deaths in any age, including in the youngest children. The aim of this multicenter national study is to characterize the clinical and the prognostic role of lung ultrasound (LU) in children with COVID-19. We enrolled children between 1 month and 18 years of age with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection who underwent a LU within 6 h from the first medical evaluation. A total of 213 children were enrolled, 51.6% were male, median age was 2 years and 5 months (interquartile range (IQR) 4 months -11 years and 4 months). One hundred and forty-eight (69.4%) children were admitted in hospital, 9 (6.1%) in pediatric intensive care unit. We found an inverse correlation between the lung ultrasound score (LUS) and the oxygen saturation at the first clinical evaluation (r = -0.16; p = 0.019). Moreover, LUS was significantly higher in patients requiring oxygen supplementation (8 (IQR 3-19) vs 2 (IQR 0-4); p = 0.001). Among LU pathological findings, irregular pleural lines, subpleural consolidations, and pleural effusions were significantly more frequent in patients needing oxygen supplementation (p = 0.007, p = 0.006, and p = 0.001, respectively).  Conclusion: This multicenter study showed that LU in children with COVID-19 can highlight pleural line irregularities, vertical artifacts, and subpleural consolidation. Notably, children with higher LUS have a higher risk of hospitalization and need for oxygen supplementation, supporting LU as a valid and safe point-of-care first level tool for the clinical evaluation of children with COVID-19. What is Known: • Few children infected with SARS-CoV-2 develop a severe disease and need oxygen therapy. • Lung ultrasound can easily detect low respiratory tract infection during SARS-CoV-2. What is New: • Children with higher lung ultrasound score have a higher risk of need for oxygen supplementation. • Irregular pleural line, sub-pleural consolidations and pleural effusions were significantly more frequent in patients needing oxygen supplementation.

National survey conducted among Italian pediatricians examining the therapeutic management of croup.

OBJECTIVES: Practice-to-recommendations gaps exist in croup management and have not been critically investigated. This study examined the therapeutic management of croup among a national sample of Italian pediatric providers. METHODS: A survey was administered online to a sample of primary care and hospital-based pediatricians. Demographic data, perception regarding disease severity, treatment and knowledge of croup, choices of croup treatment medications, and knowledge of and adherence to treatment recommendations were compared between hospital and primary care pediatricians. Oral corticosteroids alone, oral corticosteroids with or without nebulized epinephrine and nebulized epinephrine plus oral or inhaled corticosteroids were considered the correct management in mild, moderate and severe croup, respectively. The determinants for correct management were examined using multivariate logistic regression analysis. RESULTS: Six hundred forty-nine pediatricians answered at least 50% of the survey questions and were included in the analysis. Providers reported extensive use of inhaled corticosteroids for mild and moderate croup. Recommended treatment for mild, moderate and severe croup was administered in 46/647 (7.1%), 181/645 (28.0%) and 263/643 (40.9%) participants, respectively. Provider's age and knowledge of Westley Croup Score were significant predictors for correct management of mild croup. Being a hospital pediatrician and perception of croup as a clinically relevant condition were significant for moderate croup. CONCLUSIONS: Significant differences exist between recommended guidelines and clinical practice in croup management. This study suggests wide variability in both the treatment of croup and clinical decision making strategies among hospital and primary care pediatricians. Addressing this issue could lead to noteworthy clinical and economic benefits.

Exposure to outdoor air pollution and risk of hospitalization for bronchiolitis in an urban environment: A 9-year observational study.

BACKGROUND: Outdoor air pollution is supposed to influence the course of bronchiolitis, but the evidence is limited. The present study aimed at evaluating the role of outdoor air pollutants on hospitalization for bronchiolitis. METHODS: Infants aged ≤12 months referred for bronchiolitis to our Pediatric Emergency Department in Bologna, Italy, from 1 October 2011 to 16 March 2020 (nine epidemic seasons) were retrospectively included. Daily concentrations of benzene (C6 H6 ), nitrogen dioxide (NO2 ), particulate matter ≤2.5 µm (PM2.5 ), and ≤10 µm (PM10 ), and the mean values of individual patient exposure in the week and the 4 weeks before hospital access were calculated. The association between air pollutants exposure and hospitalization was evaluated through logistic regression analysis. RESULTS: A total of 2902 patients were enrolled (59.9% males; 38.7% hospitalized). Exposure to PM2.5 in the 4 weeks preceding bronchiolitis was identified as the main parameter significantly driving the risk of hospitalization (odds ratio [95% confidence interval]: 1.055 [1.010-1.102]). After stratifying by season, higher values of other outdoor air pollutants were found to significantly affect hospitalization: 4-week exposure to C6 H6 (Season 2011-2012, 4.090 [1.184-14.130]) and PM2.5 (Season 2017-2018, 1.282 [1.032-1.593]), and 1-week exposure to C6 H6 (Season 2012-2013, 6.193 [1.552-24.710]), NO2 (Season 2013-2014, 1.064 [1.009-1.122]), PM2.5 (Season 2013-2014, 1.080 [1.023-1.141]), and PM10 (Season 2018-2019, 1.102 [0.991-1.225]). CONCLUSION: High levels of PM2.5 , C6 H6 , NO2 , and PM10 may increase the risk of hospitalization in children affected by bronchiolitis. Open-air exposure of infants during rush hours and in the most polluted areas should be avoided.

Different Pediatric Acute Care Settings Influence Bronchiolitis Management: A 10-Year Retrospective Study.

Bronchiolitis is the main cause of hospitalization in infants. Diagnosis is clinical, and treatment is based on hydration and oxygen therapy. Nevertheless, unnecessary diagnostic tests and pharmacological treatments are still very common. This retrospective study aimed to evaluate whether the setting of bronchiolitis care influences diagnostic and therapeutic choices. The management of 3201 infants, referred to our Italian Tertiary Care Center for bronchiolitis between 2010 and 2020, was analyzed by comparing children discharged from the pediatric emergency department (PEDd group) undergoing short-stay observation (SSO group) and hospitalization. Antibiotic use in PEDd, SSO, and ward was 59.3% vs. 51.6% vs. 49.7%, respectively (p < 0.001); inhaled salbutamol was mainly administered in PEDd and during SSO (76.1% and 82.2% vs. 38.3% in ward; p < 0.001); the use of corticosteroids was higher during SSO and hospitalization (59.6% and 49.1% vs. 39.0% in PEDd; p < 0.001); inhaled adrenaline was administered mostly in hospitalized infants (53.5% vs. 2.5% in SSO and 0.2% in PEDd; p < 0.001); chest X-ray use in PEDd, SSO, and ward was 30.3% vs. 49.0% vs. 70.5%, respectively (p < 0.001). In a multivariate analysis, undergoing SSO was found to be an independent risk factor for the use of systemic corticosteroid and salbutamol; being discharged at home was found to be a risk factor for antibiotic prescription; undergoing SSO and hospitalization resulted as independent risk factors for the use of CXR. Our study highlights that different pediatric acute care settings could influence the management of bronchiolitis. Factors influencing practice may include a high turnover of PED medical staff, personal reassurance, and parental pressure.

Abnormal Locations of Thymic Tissue as an Uncommon Cause of Neck Masses in Children: A Practical Approach.

BACKGROUND: The thymus gland is a lymphoid organ normally located in the anterior mediastinum. Location abnormalities of the thymus, such as ectopic thymus or the superior herniation of a mediastinal thymus, could be responsible for the occurrence of cervical masses in pediatric patients, raising concerns among clinicians. The knowledge of these conditions is essential for a thorough differential diagnosis and for preventing unnecessary invasive procedures. METHODS: Descriptive retrospective series of three patients with a cervical mass, that was later diagnosed as ectopic thymic tissue. RESULTS: The thymus has a unique and distinctive ultrasound appearance that is the keystone to detecting thymic parenchyma in locations other than anterior mediastinum. In selected patients, an accurate ultrasound could be conclusive for the diagnosis, with no need for further and potentially risky procedures. CONCLUSIONS: This case series supports the use of ultrasound in both diagnosis and follow-up of thymus location abnormalities, advocating a minimal invasive and conservative approach.

Outdoor Air Pollution and Childhood Respiratory Disease: The Role of Oxidative Stress.

The leading mechanisms through which air pollutants exert their damaging effects are the promotion of oxidative stress, the induction of an inflammatory response, and the deregulation of the immune system by reducing its ability to limit infectious agents' spreading. This influence starts in the prenatal age and continues during childhood, the most susceptible period of life, due to a lower efficiency of oxidative damage detoxification, a higher metabolic and breathing rate, and enhanced oxygen consumption per unit of body mass. Air pollution is involved in acute disorders like asthma exacerbations and upper and lower respiratory infections, including bronchiolitis, tuberculosis, and pneumoniae. Pollutants can also contribute to the onset of chronic asthma, and they can lead to a deficit in lung function and growth, long-term respiratory damage, and eventually chronic respiratory illness. Air pollution abatement policies, applied in the last decades, are contributing to mitigating air quality issues, but more efforts should be encouraged to improve acute childhood respiratory disease with possible positive long-term effects on lung function. This narrative review aims to summarize the most recent studies on the links between air pollution and childhood respiratory illness.

Clinical and psychopathological profiles of children with somatic symptom disorders in a pediatric emergency unit: an observational study before and during the SARS-CoV-2 pandemic.

Somatic symptom disorders (SSDs) are a group of clinical conditions characterized by heterogeneous physical symptoms, not directly supported by a demonstrable organic process. Despite representing a growing problem in the pediatric age, the literature lacks studies assessing the psychopathological and clinical features of subjects with SSD, particularly during the SARS-CoV-2 pandemic. This is a retrospective, observational study, involving two historical cohorts of children admitted to a tertiary referral Italian hospital over the 2 years preceding and following the start of the SARS-CoV-2 pandemic. Demographic, clinical, socio-economical, and psychological variables were investigated. Standardized tests for the developmental age were administered to assess psychopathological variables. Overall rates and trends of accesses for SSD, as compared to the total accesses for any cause at the Pediatric Emergency Room during the same periods, were reported as well. Fifty-one (pre-pandemic, 29; pandemic, 22) children with SSD were enrolled (age, 11.4 ± 2.4 years, F = 66.7%). Subjects in the pandemic historical cohort reported more frequently fever (p < 0.001), headache (p = 0.032), and asthenia (p < 0.001), as well as more chronic conditions in personal and family history, and fewer previous hospital accesses, as compared to the pre-pandemic cohort. Depressed mood and anxious traits were documented in both samples. None of them had an ongoing or a previously reported SARS-CoV-2 infection. During the pandemic, a clinical psychologist was more frequently consulted before the hospital discharge to mental health services, to support the diagnosis.  Conclusion: This study showed the significant burden of SSD in children, highlighting the need to implement pediatricians' education to optimize the management of these patients. Children with SSD who accessed during the SARS-CoV-2 pandemic presented specific clinical features. Future studies, conducted on longitudinal and controlled samples, are indicated to further investigate children with these conditions. What is Known:    â€¢ Somatic symptoms disorders (SSDs) are frequent in the pediatric age, especially in early adolescence.    â€¢ Evidence remains scarce on the impact of the SARS-CoV-2 pandemic on SSDs in children. What is New:    â€¢ Children with SSD who accessed during the SARS-CoV-2 pandemic presented specific clinical features.    â€¢ The implementation of pediatricians' education and a multidisciplinary approach are needed to optimize the management of SSDs.

Visceral Leishmaniasis: Epidemiology, Diagnosis, and Treatment Regimens in Different Geographical Areas with a Focus on Pediatrics.

Visceral Leishmaniasis (VL) is a vector-borne disease caused by an intracellular protozoa of the genus Leishmania that can be lethal if not treated. VL is caused by Leishmania donovani in Asia and in Eastern Africa, where the pathogens' reservoir is represented by humans, and by Leishmania infantum in Latin America and in the Mediterranean area, where VL is a zoonotic disease and dog is the main reservoir. A part of the infected individuals become symptomatic, with irregular fever, splenomegaly, anemia or pancytopenia, and weakness, whereas others are asymptomatic. VL treatment has made progress in the last decades with the use of new drugs such as liposomal amphotericin B, and with new therapeutic regimens including monotherapy or a combination of drugs, aiming at shorter treatment duration and avoiding the development of resistance. However, the same treatment protocol may not be effective all over the world, due to differences in the infecting Leishmania species, so depending on the geographical area. This narrative review presents a comprehensive description of the clinical picture of VL, especially in children, the diagnostic approach, and some insight into the most used pharmacological therapies available worldwide.

Circulating Endothelial Cells: A New Possible Marker of Endothelial Damage in Kawasaki Disease, Multisystem Inflammatory Syndrome in Children and Acute SARS-CoV-2 Infection.

BACKGROUND: Kawasaki Disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) are pediatric diseases characterized by systemic inflammation and vascular injury, potentially leading to coronary artery lesions (CALs). Data on vascular injury occurring during acute COVID-19 (AC19) in children are still lacking. The aim of our study was to investigate endothelial injury in KD-, MIS-C- and AC19-dosing circulating endothelial cells (CECs). METHODS: We conducted a multicenter prospective study. CECs were enumerated by CellSearch technology through the immunomagnetic capture of CD146-positive cells from whole blood. RESULTS: We enrolled 9 KD, 20 MIS-C and 10 AC19. During the acute stage, the AC19 and KD patients had higher CECs levels than the MIS-C patients. From the acute to subacute phase, a significant CEC increase was observed in the KD patients, while a mild decrease was detected in the MIS-C patients. Cellular clusters/syncytia were more common in the KD patients. No correlation between CECs and CALs were found in the MIS-C patients. The incidence of CALs in the KD group was too low to investigate this correlation. CONCLUSIONS: Our study suggests a possible role of CECs as biomarkers of systemic inflammation and endothelial dysfunction in KD and MIS-C and different mechanisms of vascular injury in these diseases. Further larger studies are needed.

Prognostic Role of Lung Ultrasound in Children with Bronchiolitis: Multicentric Prospective Study.

There is increasing recognition of the role of lung ultrasound (LUS) to assess bronchiolitis severity in children. However, available studies are limited to small, single-center cohorts. We aimed to assess a qualitative and quantitative LUS protocol to evaluate the course of bronchiolitis at diagnosis and during follow-up. This is a prospective, multicenter study. Children with bronchiolitis were stratified according to clinical severity and underwent four LUS evaluations at set intervals. LUS was classified according to four models: (1) positive/negative; (2) main LUS pattern (normal/interstitial/consolidative/mixed) (3) LUS score; (4) LUS score with cutoff. Two hundred and thirty-three children were enrolled. The baseline LUS was significantly associated with bronchiolitis severity, using both the qualitative (positive/negative LUS p < 0.001; consolidated/normal LUS pattern or mixed/normal LUS p < 0.001) and quantitative models (cutoff score > 9 p < 0.001; LUS mean score p < 0.001). During follow-up, all LUS results according to all LUS models improved (p < 0.001). Better cut off value was declared at a value of >9 points. Conclusions: Our study supports the role of a comprehensive qualitative and quantitative LUS protocol for the identification of severe cases of bronchiolitis and provides data on the evolution of lung aeration during follow-up.

Social Determinants of Health and Distance Learning in Italy in the Era of the SARS-CoV-2 Pandemic.

Objectives: To investigate the experiences by distance learning (DL) method during the first wave of the SARS-CoV-2 pandemic in Italy, and to search for correlations with purported experiences and respective levels of social determinants of health (SDH). Study design and methods: Cross-sectional online survey, investigating various SDH and parents' attitude towards DL, proposed 6 months after the beginning of the pandemic to a sample population of parents with school-aged children throughout Italy. Results: A total of 3791 questionnaires were analyzed. Non-Italian parents complained more frequently of difficulties in providing support to their children in DL due to poor digital skills (p = 0.01), lack of good-quality digital equipment (p = 0.01), problems with the Italian language (p < 0.001), and a lower level of education (p < 0.001). When parents lived apart, greater difficulties in concentration in children using DL (p = 0.05) and a lower parental capacity to support DL (p = 0.002) were reported. Adequate digital structures appeared related to living in owned compared to rented property, higher levels of parental education, and better familial financial situations. Conclusions: Students from families with financial difficulties and low levels of parental education, or even those living in houses for rent or having separated parents, may be disadvantaged in an educational context since the introduction of DL.

Pulmonary and Extrapulmonary Manifestations in Hospitalized Children with Mycoplasma Pneumoniae Infection.

Mycoplasma pneumoniae (MP) is one of the main causes of both upper and lower respiratory infections in school-aged children, accounting for up to 40% of community-acquired pneumonia. Younger children are also affected, and extrapulmonary manifestations have been recently reported in the pediatric population. We carried out a retrospective analysis of MP-positive patients admitted to the Pediatric Emergency Unit of S. Orsola Malpighi University Hospital in Bologna, the largest tertiary pediatric referral center in the Emilia-Romagna region, Northern Italy, between 2012 and 2020. We identified 145 patients with MP infection (82 males and 63 females), 27% of which were younger than 2 years; the median age was 5 years (interquartile range 1-9). The clinical presentation partially differed between age groups. School-aged children were more likely to have a chest X-ray-confirmed pneumonia (p = 0.013), while younger children required oxygen therapy more often (p = 0.048). Seventy-four children (51%) showed extrapulmonary manifestations, mainly gastrointestinal (30%) and dermatological (14%). Neurological symptoms were more frequent in children older than 6 years (p = 0.006). The rate of other extrapulmonary manifestations did not differ significantly between age groups. This study shows that MP infection is a frequent cause of pediatric hospitalization, including of children younger than 2 years. Clinicians should be aware of the variable clinical expressions of MP, including extrapulmonary manifestations, to achieve a correct diagnosis and determine appropriate treatment.

Impact of Guidelines Publication on Acute Bronchiolitis Management: 10-Year Experience from a Tertiary Care Center in Italy.

Bronchiolitis is the most common lower respiratory tract infection in infants. According to evidence-based guidelines, diagnosis is clinical, there is no need for routine use of laboratory or instrumental tests and therapy is primarily supportive, based on oxygen and adequate fluid supplementation. Nevertheless, unnecessary diagnostic tests and pharmacological treatments are still very common. The aim of this retrospective cohort study was to evaluate how the management of bronchiolitis has changed in the last ten years in a Tertiary Care Center in Italy, assessing adherence to national guidelines. Considering the publication of the Italian inter-society consensus document in 2014, we compared patients admitted in the prior four epidemic seasons with patients admitted in the latter six epidemic seasons. The comparison between the two groups showed a significant reduction in the prescription of systemic corticosteroids (58.9% vs. 41.8%, p < 0.001), nebulized epinephrine (73.8% vs. 38.3%, p < 0.001) and antibiotics (59.5% vs. 42.3%, p < 0.001), together with a drastic decrease in the use of chest X-ray (92.2% vs. 54.4%, p < 0.001). On the contrary, the use of inhaled salbutamol remained substantially stable over time (39.4% vs. 37.6%, p = 0.505). Despite the encouraging results, further efforts are needed to limit the prescription of ineffective therapies like antibiotics and inhaled salbutamol.

Multisystem Inflammatory Syndrome Following SARS-CoV-2 Infection in Children: One Year after the Onset of the Pandemic in a High-Incidence Area.

SARS-CoV-2 infection in children can trigger cardiovascular manifestations potentially requiring an intensive treatment and defining a new entity named Multisystem Inflammatory Syndrome in Children (MIS-C), whose features partially overlap with Kawasaki Disease (KD). A cross-sectional study including all diagnoses of MIS-C and KD from April 2020 to May 2021 in our metropolitan area was conducted evaluating clinical, laboratory (including immunological response, cytokines, and markers of myocardial damage), and cardiac (coronary and non-coronary) features at onset of the diseases. Evolution of ventricular dysfunction, valve regurgitations, and coronary lesions was documented. The severity of the disease was also considered based on the need for inotropic support and ICU admission. Twenty-four MIS-C were diagnosed (14 boys, median age 82 months): 13/24 cases (54.17%) presented left ventricular dysfunction, 12/24 (50%) required inotropic support, and 10/24 (41.67%) developed coronary anomalies (CALs). All patients received steroids and IVIG at a median time of 5 days (IQR1:4, IQR3:6.5) from onset of fever and heart function normalized 6 days (IQR1: 5, IQR3: 7) after therapy, while CALs persisted in one. One patient (12.5%) required infliximab because of refractory disease and still presented CALs 18 days after therapy. During the same study period, 15 KD were diagnosed: none had ventricular dysfunction, while 7/15 (46.67%) developed CALs. Three out of 15 patients (20%) still presented CALs 46 days from onset. Compared to KD, MIS-C pts have significantly higher IL8 and similar lymphocytes subpopulations. Despite a more severe presentation and initial cardiac findings compared to KD, the myocardial injury in MIS-C has a rapid response to immunomodulatory treatment (median time 6 days), in terms of ventricular function, valve regurgitations, and troponin. Incidence of CALs is similar at onset, but it tends to regress in most of the cases of MIS-C differently than in KD where CALs persist in up to 40% in the subacute stage after treatment.

Potential Diagnostic and Prognostic Biomarkers for Adenovirus Respiratory Infection in Children and Young Adults.

Human Adenoviruses (HAdV) are known to be potentially associated with strong inflammatory responses and morbidity in pediatric patients. Although most of the primary infections are self-limiting, the severity of clinical presentation, the elevation of the white blood cell count and inflammatory markers often mimic a bacterial infection and lead to an inappropriate use of antibiotics. In infections caused by HAdV, rapid antigen detection kits are advisable but not employed routinely; costs and feasibility of rapid syndromic molecular diagnosis may limit its use in the in-hospital setting; lymphocyte cultures and two-sampled serology are time consuming and impractical when considering the use of antibiotics. In this review, we aim to describe the principal diagnostic tools and the immune response in HAdV infections and evaluate whether markers based on the response of the host may help early recognition of HAdV and avoid inappropriate antimicrobial prescriptions in acute airway infections.

Three-Year Trend in Escherichia coli Antimicrobial Resistance among Children's Urine Cultures in an Italian Metropolitan Area.

Urinary tract infections (UTIs) are among the most common bacterial infections in children, and Escherichia coli is the main pathogen responsible. Several guidelines, including the recently updated Italian guidelines, recommend amoxicillin-clavulanic acid (AMC) as a first-line antibiotic therapy in children with febrile UTIs. Given the current increasing rates of antibiotic resistance worldwide, this study aimed to investigate the three-year trend in the resistance rate of E. coli isolated from pediatric urine cultures (UCs) in a metropolitan area of northern Italy. We conducted a retrospective review of E. coli-positive, non-repetitive UCs collected in children aged from 1 month to 14 years, regardless of a diagnosis of UTI, catheter colonization, urine contamination, or asymptomatic bacteriuria. During the study period, the rate of resistance to AMC significantly increased from 17.6% to 40.2% (p < 0.001). Ciprofloxacin doubled its resistance rate from 9.1% to 16.3% (p = 0.007). The prevalence of multidrug-resistant E. coli rose from 3.9% to 9.2% (p = 0.015). The rate of resistance to other considered antibiotics remained stable, as did the prevalence of extended spectrum beta-lactamases and extensively resistant E. coli among isolates. These findings call into question the use of AMC as a first-line therapy for pediatric UTIs in our population, despite the indications of recent Italian guidelines.

Impact of SARS-CoV-2 Pandemic on Bronchiolitis Hospitalizations: The Experience of an Italian Tertiary Center.

SARS-CoV-2 pandemic restrictions have deeply altered the common respiratory illnesses burden. The aim of this paper was to clarify how these measures may have influenced bronchiolitis epidemiology, exploring possible explanations. We studied 342 infants hospitalized for bronchiolitis at our center from four different epidemic seasons (October-April 2017-2018, 2018-2019, 2019-2020 and 2020-2021). March-April hospitalization rate, RSV (respiratory syncytial virus) infection, pediatric intensive care unit (PICU) admission and oxygen therapy administration data were compared among different seasons to outline any changes during the SARS-CoV-2 outbreak. In March-April, 30 (23.1%), 28 (24.6%) and 5 (5.1%) infants were hospitalized for bronchiolitis, respectively, in 2017-2018, 2018-2019 and 2019-2020, with a lower rate in March-April 2020 (p < 0.001). No hospitalizations for bronchiolitis occurred during the epidemic season of 2020-2021. No significant differences in RSV infections, oxygen therapy administration and PICU admissions across seasons were outlined. In conclusion, we report a severe decrease in hospitalizations for bronchiolitis at our center throughout the entire SARS-CoV-2 outbreak rather than only during the lockdown periods. This seems to suggest a pivotal role for the systematic implementation of cost-effective non-pharmaceutical interventions (NPIs) such as compulsory face masks and hand hygiene, which were deployed for the entire pandemic, in reducing the circulation of infectious agents.

Development of a Vaccine against Human Cytomegalovirus: Advances, Barriers, and Implications for the Clinical Practice.

Human cytomegalovirus (hCMV) is one of the most common causes of congenital infection in the post-rubella era, representing a major public health concern. Although most cases are asymptomatic in the neonatal period, congenital CMV (cCMV) disease can result in permanent impairment of cognitive development and represents the leading cause of non-genetic sensorineural hearing loss. Moreover, even if hCMV mostly causes asymptomatic or pauci-symptomatic infections in immunocompetent hosts, it may lead to severe and life-threatening disease in immunocompromised patients. Since immunity reduces the severity of disease, in the last years, the development of an effective and safe hCMV vaccine has been of great interest to pharmacologic researchers. Both hCMV live vaccines-e.g., live-attenuated, chimeric, viral-based-and non-living ones-subunit, RNA-based, virus-like particles, plasmid-based DNA-have been investigated. Encouraging data are emerging from clinical trials, but a hCMV vaccine has not been licensed yet. Major difficulties in the development of a satisfactory vaccine include hCMV's capacity to evade the immune response, unclear immune correlates for protection, low number of available animal models, and insufficient general awareness. Moreover, there is a need to determine which may be the best target populations for vaccine administration. The aim of the present paper is to examine the status of hCMV vaccines undergoing clinical trials and understand barriers limiting their development.

Passive Immunoprophylaxis against Respiratory Syncytial Virus in Children: Where Are We Now?

Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, neuromuscular disorders, immunodeficiencies, and extreme preterm birth. Nevertheless, it has been shown that the majority of hospitalized RSV-infected children do not fully meet the criteria for immune prophylaxis. While waiting for an effective vaccine, passive immune prophylaxis in children is mandatory. There are a growing number of RSV passive immunization candidates under development intended for RSV prevention in all infants. In this review, we describe the state-of-the-art of palivizumab's usage and summarize the clinical and preclinical trials regarding the development of mAbs with a better cost-effectiveness ratio.