Mid- and Long-Term Atrio-Ventricular Functional Changes in Children after Recovery from COVID-19.

Background: Although most children may experience mild to moderate symptoms and do not require hospitalization, there are little data on cardiac involvement in COVID-19. However, cardiac involvement is accurately demonstrated in children with MISC. The objective of this study was to evaluate cardiac mechanics in previously healthy children who recovered from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a long-term follow-up by means of two-dimensional speckle-tracking echocardiography (STE). Methods: We analyzed a cohort of 157 paediatric patients, mean age 7.7 ± 4.5 years (age range 0.3−18 years), who had a laboratory-confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or mildly symptomatic for COVID-19. Patients underwent a standard transthoracic echocardiogram and STE at an average time of 148 ± 68 days after diagnosis and were divided in three follow-up groups (<180 days, 180−240 days, >240 days). Patients were compared with 107 (41 females­38%) age- and BSA-comparable healthy controls (CTRL). Results: Left ventricular (LV) global longitudinal strain (post-COVID-19: −20.5 ± 2.9%; CTRL: −21.8 ± 1.7%; p < 0.001) was significantly reduced in cases compared with CTRLs. No significant differences were seen among the three follow-up groups (p = NS). Moreover, regional longitudinal strain was significantly reduced in LV apical-wall segments of children with disease onset during the second wave of the COVID-19 pandemic compared to the first wave (second wave: −20.2 ± 2.6%; first wave: −21.2 ± 3.4%; p = 0.048). Finally, peak left atrial systolic strain was within the normal range in the post-COVID-19 group with no significant differences compared to CTRLs. Conclusions: Our study demonstrated for the first time the persistence of LV myocardial deformation abnormalities in previously healthy children with an asymptomatic or mildly symptomatic (WHO stages 0 or 1) COVID-19 course after an average follow-up of 148 ± 68 days. A more significant involvement was found in children affected during the second wave. These findings imply that subclinical LV dysfunction may also be a typical characteristic of COVID-19 infection in children and are concerning given the predictive value of LV longitudinal strain in the general population.

The impact of variant and vaccination on SARS-CoV-2 symptomatology; three prospective household cohorts.

OBJECTIVES: We compared age-stratified SARS-CoV-2 symptomatology of wild-type/Alpha vs Omicron BA.1/BA.2 variant infected individuals and the impact of COVID-19 booster vaccination on Omicron symptom burden. METHODS: Data from three European prospective household cohorts were used (April 2020 to April 2021 and January to March 2022). Standardized outbreak protocols included (repeated) polymerase chain reaction testing, paired serology, and daily symptom scoring for all household members. Comparative analyses were performed on 346 secondary household cases from both periods. RESULTS: Children <12 years (all unvaccinated) experienced more symptoms and higher severity scores during Omicron compared with wild-type/Alpha period (P ≤0.01). In adults, Omicron disease duration and severity were reduced (P ≤ 0.095). Omicron was associated with lower odds for loss of smell or taste (adjusted odds ratio [aOR]: 0.14; 95% CI 0.03-0.50) and higher but non-significant odds for upper respiratory symptoms, fever, and fatigue (aORs: 1.85-2.23). No differences were observed in disease severity or duration between primary vs booster series vaccinated adults (P ≥0.12). CONCLUSION: The Omicron variant causes higher symptom burden in children compared with wild-type/Alpha and lower in adults, possibly due to previous vaccination. A shift in symptoms occurred with reduction in loss of smell/taste for Omicron. No additional effect of booster vaccination on Omicron symptom burden was observed.

Early Treatments of Fragile Children with COVID-19-Results of CLEVER (Children COVID Early Treatment), a Retrospective, Observational Study.

(1) Background: SARS-CoV-2 infection is notably mild in children, though comorbidities may increase the risk of hospitalization and may represent a risk for increased disease severity. There is an urgent need for targeted therapies with an acceptable efficacy and safety profile. To date, most of the medicines for COVID-19-specific treatment are prescribed off-label for children due to a lack of clinical trials and consequent evidence in this population. (2) Methods: This was a retrospective, observational study investigating the safety of treatments for the prevention of severe COVID-19 in fragile pediatric patients who received monoclonal antibodies and antivirals for mild-to-moderate symptoms between December 2021 and July 2022. (3) Results: Thirty-two patients were included. Monoclonal antibodies were prescribed to 62%, intravenous antivirals to 22%, and oral antivirals to 16% of children. Sotrovimab was the most frequently prescribed drug among monoclonal antibodies and overall (59%). The second most prescribed drug was remdesivir (22%). No severe adverse drug reaction was reported. There was no progression to severe disease and no death cases due to COVID-19 or drug administration. At drug-type stratification, resolution of symptoms and swab positivity time showed no difference between the two groups at 7 and 28 days. Off-label prescriptions were 84% overall, and in similar proportions between the two groups. (4) Conclusions: in this small sample, antivirals seemed safe and showed no differences in efficacy as compared to MAbs for the early treatment of COVID-19 in fragile children, thus representing a valuable choice, even when administered off-label.

The Association Between Pediatric COVID-19 Vaccination and Socioeconomic Position: Nested Case-Control Study From the Pedianet Veneto Cohort.

BACKGROUND: The success of pediatric COVID-19 vaccination strongly depends on parents' willingness to vaccinate their children. To date, the role of socioeconomic position (SEP) in pediatric COVID-19 vaccination has not been thoroughly examined. OBJECTIVE: We evaluated the association between COVID-19 vaccination and SEP in a large pediatric cohort. METHODS: A case-control study design nested into a pediatric cohort of children born between 2007 and 2017, living in the Veneto Region and followed up to at least January 1, 2022, was adopted. Data on children were collected from the Pedianet database and linked with the regional COVID-19 registry. Each child vaccinated with at least one dose of any COVID-19 vaccine between July 1, 2021, and March 31, 2022, was matched by sex, year of birth, and family pediatrician to up to 5 unvaccinated children. Unvaccinated children with a positive outcome on the swab test within 180 days before the index date were excluded from the analyses. Children were geo-referenced to determine their area deprivation index (ADI)-a social and material deprivation measure calculated at the census block level and consisting of 5 socioeconomic items. The index was then categorized in quintiles based on the regional ADI level. The association between ADI quintiles and vaccination status was measured using conditioned logistic regression models to estimate odds ratios and the corresponding 95% CIs. Quantile-g-computation regression models were applied to develop a weighted combination of the individual items to estimate how much each component influenced the likelihood of vaccination. All analyses were stratified by age at vaccination (5-11 and 12-14 years). RESULTS: The study population consisted of 6475 vaccinated children, who were matched with 32,124 unvaccinated children. Increasing area deprivation was associated with a lower probability of being vaccinated, with approximately a linear dose-response relationship. Children in the highest deprivation quintile were 36% less likely to receive a COVID-19 vaccine than those with the lowest area deprivation (95% CI 0.59-0.70). The results were similar in the 2 age groups, with a slightly stronger association in 5-11-year-old children. When assessing the effects of the weighted combination of the individual items, a quintile increase was associated with a 17% decrease in the probability of being vaccinated (95% CI 0.80-0.86). The conditions that influenced the probability of vaccination the most were living on rent, being unemployed, and being born in single-parent families. CONCLUSIONS: This study has shown a significant reduction in the likelihood of receiving a COVID-19 vaccine among children living in areas characterized by a lower SEP. Findings were robust among multiple analyses and definitions of the deprivation index. These findings suggest that SEP plays an important role in vaccination coverage, emphasizing the need to promote targeted public health efforts to ensure global vaccine equity.

COVID-19 in Infants Less than 3 Months: Severe or Not Severe Disease?

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature. METHODS: Subjects under 90 days of age admitted to 35 Italian institutions for COVID-19 were included. The severity of COVID-19 was scored as mild/moderate or severe/critical following the classification reported in the literature by Venturini, Dong, Kanburoglu, and Gale. To assess the diagnostic accuracy of each classification system, we stratified all enrolled patients developing a posteriori severity score based on clinical presentation and outcomes and then compared all different scores analyzed. RESULTS: We included 216 infants below 90 days of age. The most common symptom was fever, followed by coryza, poor feeding, cough, and gastrointestinal manifestations. According to Venturini, Dong, Kanburoglu, and Gale's severity scores, 18%, 6%, 4.2%, and 29.6% of infants presented with severe/critical disease, respectively. A correlation analysis between these four scores and the a posteriori severity score assigned to all enrolled subjects was performed, and a crescent strength of correlation from Gale (R = 0.355, p < 0.001) to Venturini (R = 0.425, p < 0.001), Dong (R = 0.734, p < 0.001), and Kanburoglu (R = 0.859, p < 0.001) was observed. CONCLUSIONS: The percentage of infants with severe COVID-19 varies widely according to the score systems. A unique clinical score should be designed for neonates and infants with COVID-19.

European research networks to facilitate drug research in children.

Paediatric drug development faces several barriers. These include fragmentation of stakeholders and inconsistent processes during the conduct of research. This review summarises recent efforts to overcome these barriers in Europe. Two exemplar initiatives are described. The European Paediatric Translational Research Infrastructure facilitates preclinical research and other work that underpins clinical trials. conect4children facilitates the design and implementation of clinical trials. Both these initiatives listen to the voices of children and their advocates. Coordination of research needs specific effort that supplements work on science, resources and the policy context.

Perceived Psychological Impact on Children and Parents of Experiencing COVID-19 Infection in One or More Family Members.

SARS-CoV-2 infection may impair behavior and mental health; we explored the psychological impact on parents and children who experienced COVID-19 within their families. A cross-sectional web-based survey was conducted on families attending the COVID-19 Follow-up Clinic at the Department for Women's and Children's Health, Padua (Italy). From April 2020 to August 2021, 75 surveys were collected from 66 families (97 parents and 129 children); almost 70% of participants had COVID-19, mostly asymptomatic/mildly symptomatic, and the median time from infection to survey compilation was 164.7 days (SD 56). Most parents (>87%) reported positive relationships with family members either before, during, or after COVID-19. More than one-third of children and adolescents were unable to adapt to isolation. Among 31 pre-school children with a median age of 3 (SD 1.7), a change of one or more functions was reported for 74.2% of cases irrespective of COVID-19 status, particularly a change in circadian rhythm (25%), in relationship with parents (42.8%), and poor emotional control (36%). Among 74 children with a median age of 10.9 years (SD 2.7), 8.1% had a score indicating a disease; however, significant impairment in attention was reported for 16.7%, along with anxiety/depression and problems with conduct in 5.6% and 6.5% of cases, respectively.

Detection of Potential Arbovirus Infections and Pregnancy Complications in Pregnant Women in Jamaica Using a Smartphone App (ZIKApp): Pilot Evaluation Study.

BACKGROUND: There is growing evidence of the benefits of mobile health technology, which include symptom tracking apps for research, surveillance, and prevention. No study has yet addressed arbovirus symptom tracking in pregnancy. OBJECTIVE: This study aimed to evaluate the use of a smartphone app (ZIKApp) to self-report arbovirus symptoms and pregnancy complications and to assess compliance with daily symptom diaries during pregnancy in a cohort of women in an arbovirus-endemic, subtropical, middle-income country (Jamaica). METHODS: Pregnant women aged ≥16 years, having a smartphone, and planning on giving birth at the recruiting center were enrolled between February 2020 and July 2020. ZIKApp comprised a daily symptom diary based on algorithms to identify potential episodes of arbovirus infection and pregnancy complications. Sociodemographic, epidemiological, and obstetric information was collected at enrollment, with additional review of medical records, and users' perception was collected through an exit survey. Descriptive analyses and logistic regression analysis of possible factors associated with diary adherence were performed. RESULTS: Of the 173 women enrolled, 157 (90.8%) used ZIKApp for a median duration of 155 (IQR 127-173) days until pregnancy end, 6 (3.5%) used the app for <7 days, and 10 (5.8%) exited the study early. For each successive 30-day period from enrollment up to 150 days after enrollment, of these 157 women, 121 (77.1%) to 129 (82.2%) completed their daily symptom diary; 50 (31.8%) to 56 (35.7%) did so on the same day. Overall, 31.8% (50/157) of the women had good adherence to diary reporting (ie, they completed the task on the same day or 2 to 3 days later for ≥80% of the days enrolled). There were 3-fold higher odds of good adherence for participants aged >34 years versus those aged 25 to 29 years (adjusted odds ratio 3.14, 95% CI 1.10-8.98) and 2-fold higher odds for women with tertiary versus secondary education (adjusted odds ratio 2.26, 95% CI 1.06-4.83). Of the 161 women who ever made a diary entry, 5454 individual symptom reports were made (median 17 per woman; IQR 4-42; range 0-278); 9 (5.6%) women reported symptom combinations triggering a potential arbovirus episode (none had an adverse pregnancy outcome) and 55 (34.2%) reported painful uterine contractions or vaginal bleeding, mainly in the month before delivery. Overall, 51.8% (71/137) of the women rated the app as an excellent experience and were less likely to be poor diary adherers (P=.04) and 99.3% (138/139) reported that the app was easy to understand and use. CONCLUSIONS: This pilot found a high adherence to ZIKApp. It demonstrated the feasibility and usability of the app in an arbovirus-endemic region, supporting its future development to contribute to surveillance and diagnosis of arbovirus infections in pregnancy and to optimize maternal care.

Early Use of Sotrovimab in Children: A Case Report of an 11-Year-Old Kidney Transplant Recipient Infected with SARS-CoV-2.

BACKGROUND: The use of virus-neutralizing monoclonal antibodies has been approved in fragile populations, including kidney transplant recipients, who are at risk of developing severe COVID-19. Sotrovimab is the only currently available anti-SARS-CoV-2 neutralizing monoclonal antibody with activity against the new Omicron variant of concern. While sotrovimab has been approved in adolescents and adults, studies regarding its efficacy and safety in children aged less than 12 years old and weighing less than 40 kg are still lacking. Here, we report a first case of a child, who was treated early with sotrovimab after a kidney transplant. CASE REPORT: At the end of January 2022, a 11-year-old male child underwent a deceased-donor kidney transplant and became infected with SARS-CoV-2 during the first day after surgery. Due to the increased risk of developing severe COVID-19, based on the predominance of Omicron and the patient's renal function, the child was treated with sotrovimab. The clinical course was successful and no adverse reactions were reported. CONCLUSIONS: For the first time, we report the well-tolerated use of sotrovimab in children under 12 years old. As the pandemic affects children across the globe, urgent data on sotrovimab dosing in children with a higher risk of developing severe COVID-19 are needed.

Long-term Immune Response to SARS-CoV-2 Infection Among Children and Adults After Mild Infection.

Importance: Understanding the long-term immune response against SARS-CoV-2 infection in children is crucial to optimize vaccination strategies. Although it is known that SARS-CoV-2 antibodies may persist in adults 12 months after infection, data are limited in the pediatric population. Objective: To examine long-term anti-SARS-CoV-2 spike receptor-binding domain (S-RBD) IgG kinetics in children after SARS-CoV-2 infection. Design, Setting, and Participants: In this single-center, prospective cohort study, patients were enrolled consecutively from April 1, 2020, to August 31, 2021, at the COVID-19 Family Cluster Follow-up Clinic, Department of Women's and Children's Health, University Hospital of Padua. A cohort of 252 COVID-19 family clusters underwent serologic follow-up at 1 to 4, 5 to 10, and more than 10 months after infection with quantification of anti-S-RBD IgG by chemiluminescent immunoassay. Exposures: SARS-CoV-2 infection. Results: Among 902 study participants, 697 had confirmed SARS-CoV-2 infection, including 351 children or older siblings (mean [SD] age, 8.6 [5.1] years) and 346 parents (mean [SD] age, 42.5 [7.1] years). Among 697 cases, 674 (96.7%) were asymptomatic or mild. Children had significantly higher S-RBD IgG titers than older patients across all follow-up time points, with an overall median S-RBD IgG titer in patients younger than 3 years 5-fold higher than adults (304.8 [IQR, 139.0-516.6] kBAU/L vs 55.6 [24.2-136.0] kBAU/L, P < .001). Longitudinal analysis of 56 study participants sampled at least twice during follow-up demonstrated the persistence of antibodies up to 10 months from infection in all age classes, despite a progressive decline over time. Conclusions and Relevance: In this cohort study of Italian children and adults following SARS-CoV-2 infection different kinetics of SARS-CoV-2 antibodies were found across several age classes of individuals with asymptomatic or mild COVID-19, which could help in optimizing COVID-19 vaccination strategies and prevention policies. This work provides further evidence of sustained immune response in children up to 1 year after primary SARS-CoV-2 infection.

Preliminary Evidence on Pulmonary Function after Asymptomatic and Mild COVID-19 in Children.

BACKGROUND: While it has been described that adults can develop long-lasting deterioration in pulmonary function (PF) after coronavirus disease 19 (COVID-19), regardless of disease severity, data on the long-term pneumological impact of SARS-CoV-2 infection in children are lacking. METHODS: Performing a single-center, prospective, observational study on children aged 6-18 years with a previous diagnosis of asymptomatic/mild COVID-19, we evaluated the long-term impact of mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children. RESULTS: A total of 61 subjects underwent spirometry after a mean time of 10 ± 4 months from asymptomatic or mild infection. None of the children reported any respiratory symptoms, needed any inhaled therapy, or had abnormal lung function. CONCLUSIONS: In our study, we observed that children and adolescents did not develop chronic respiratory symptoms and did not present lung function impairment after asymptomatic or mild SARS-CoV-2 infection.

BNT162b2 Vaccine Effectiveness against Omicron in Children 5 to 11 Years of Age.

BACKGROUND: Limited evidence is available on the real-world effectiveness of the BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) and specifically against infection with the omicron variant among children 5 to 11 years of age. METHODS: Using data from the largest health care organization in Israel, we identified a cohort of children 5 to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 among newly vaccinated children during the omicron wave. Vaccine effectiveness against documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and symptomatic Covid-19 was estimated after the first and second vaccine doses. The cumulative incidence of each outcome in the two study groups through January 7, 2022, was estimated with the use of the Kaplan-Meier estimator, and vaccine effectiveness was calculated as 1 minus the risk ratio. Vaccine effectiveness was also estimated in age subgroups. RESULTS: Among 136,127 eligible children who had been vaccinated during the study period, 94,728 were matched with unvaccinated controls. The estimated vaccine effectiveness against documented infection was 17% (95% confidence interval [CI], 7 to 25) at 14 to 27 days after the first dose and 51% (95% CI, 39 to 61) at 7 to 21 days after the second dose. The absolute risk difference between the study groups at days 7 to 21 after the second dose was 1905 events per 100,000 persons (95% CI, 1294 to 2440) for documented infection and 599 events per 100,000 persons (95% CI, 296 to 897) for symptomatic Covid-19. The estimated vaccine effectiveness against symptomatic Covid-19 was 18% (95% CI, -2 to 34) at 14 to 27 days after the first dose and 48% (95% CI, 29 to 63) at 7 to 21 days after the second dose. We observed a trend toward higher vaccine effectiveness in the youngest age group (5 or 6 years of age) than in the oldest age group (10 or 11 years of age). CONCLUSIONS: Our findings suggest that as omicron was becoming the dominant variant, two doses of the BNT162b2 messenger RNA vaccine provided moderate protection against documented SARS-CoV-2 infection and symptomatic Covid-19 in children 5 to 11 years of age. (Funded by the European Union through the VERDI project and others.).

Antibiotic Prescription Patterns in the Paediatric Primary Care Setting before and after the COVID-19 Pandemic in Italy: An Analysis Using the AWaRe Metrics.

The containment measures following COVID-19 pandemic drastically reduced airway infections, but they also limited the access of patients to healthcare services. We aimed to assess the antibiotic prescription patterns in the Italian paediatric primary care setting before and after the containment measures implementation. For this retrospective analysis, we used a population database, Pedianet, collecting data of patients aged 0-14 years enrolled with family paediatricians (FP) from March 2019 to March 2021. Antibiotic prescriptions were classified according to WHO AWaRe classification. An interrupted time series evaluating the impact of the containment measures implementation on the monthly antibiotic index, on the access to watch index, and on the amoxicillin to co-amoxiclav index stratified by diagnosis was performed. Overall, 121,304 antibiotic prescriptions were retrieved from 134 FP, for a total of 162,260 children. From March 2020, the antibiotic index dropped by more than 80% for respiratory infections. The Access to Watch trend did not change after the containment measures, reflecting the propensity to prescribe more broad-spectrum antibiotics for respiratory infections even during the pandemic. Similarly, co-amoxiclav was prescribed more often than amoxicillin alone for all the diagnoses, with a significant variation in the trend slope for upper respiratory tract infections prescriptions.

Influenza Vaccination Effectiveness in Paediatric 'Healthy' Patients: A Population-Based Study in Italy.

BACKGROUND: Seasonal influenza can cause serious morbidity, mortality, and financial burden in pediatric and adult populations. The influenza vaccine (IV) is considered the most effective way to prevent influenza and influenza-like-illness (ILI) complications. OBJECTIVE: To assess the effectiveness of the IV in a cohort of healthy children in Italy. METHODS: From the Pedianet database, all healthy children aged six months-14 years between 2009-2019 were enrolled. Cox proportional-hazards models were fitted to estimate hazard ratios and the 95% confidence interval for the association between IV exposure during each season of interest (from October to April of each year) with incident influenza/ILI. Exposure was considered as a time-varying variable. Vaccine effectiveness (VE) was calculated as (1-HR) × 100. The additive and prolonged effects of IV were evaluated across the seasons. RESULTS: We found a high IV effectiveness among healthy children. No additional or prolonged effects were found. CONCLUSION: Our data indicates that IV was effective in preventing influenza/ILI in healthy children. Therefore, IV should be encouraged and provided free of charge to healthy children in all the Italian regions every year, reducing disease spread and lowering the burden on the pediatric population.

Early Use of Sotrovimab in Children: A Case Report of an 11-Year-Old Kidney Transplant Recipient Infected with SARS-CoV-2

Background: The use of virus-neutralizing monoclonal antibodies has been approved in fragile populations, including kidney transplant recipients, who are at risk of developing severe COVID-19. Sotrovimab is the only currently available anti-SARS-CoV-2 neutralizing monoclonal antibody with activity against the new Omicron variant of concern. While sotrovimab has been approved in adolescents and adults, studies regarding its efficacy and safety in children aged less than 12 years old and weighing less than 40 kg are still lacking. Here, we report a first case of a child, who was treated early with sotrovimab after a kidney transplant. Case Report: At the end of January 2022, a 11-year-old male child underwent a deceased-donor kidney transplant and became infected with SARS-CoV-2 during the first day after surgery. Due to the increased risk of developing severe COVID-19, based on the predominance of Omicron and the patient's renal function, the child was treated with sotrovimab. The clinical course was successful and no adverse reactions were reported. Conclusions: For the first time, we report the well-tolerated use of sotrovimab in children under 12 years old. As the pandemic affects children across the globe, urgent data on sotrovimab dosing in children with a higher risk of developing severe COVID-19 are needed.

Protective SARS-CoV-2 Antibody Response in Children With Inflammatory Bowel Disease.

BACKGROUND: To date, there's no evidence of an increased risk of SARS-CoV-2 infection or more severe COVID-19 in patients with inflammatory bowel disease (IBD). However, whether COVID-19 alters the clinical course of IBD or whether IBD treatment affects the immunological response to SARS-CoV-2 is still under investigation, especially in children. AIM: To assess the serological response to SARS-CoV-2 in children with IBD, and to evaluate the impact of COVID-19 on the clinical course of IBD. MATERIAL AND METHODS: This prospective study enrolled children (0-18 years) followed-up at the University Hospital of Padova for IBD, who acquired a confirmed SARS-CoV-2 infection between 02.2020 and 02.2021. The anti-SARS-CoV-2 S-RBD IgG titer was evaluated at 3 months after infection and compared to that of a control group of healthy children matched for age, sex, and COVID-19 severity. RESULTS: Twelve children with IBD (M = 5; median age 14 years) contracted COVID-19 during the study period. 11/12 patients were under immunomodulatory treatment (4/12 steroids; 6/12 azathioprine; 3/12 anti-TNFs; 2 vedolizumab; 1 ustekinumab). SARS-CoV-2 infection remained asymptomatic in 4/12 children and caused mild COVID-19 in the remaining 8. Mean anti-SARS-CoV-2 IgG S-RBD titer was similar between IBD patients and controls (27.3 ± 43.8 vs. 36.8 ± 35.3 kAU/L, p = ns). No children experienced IBD flares nor required gastroenterological support during the infection period. DISCUSSION: Children with IBD can mount a protective humoral response against SARS-CoV-2, which is comparable to that of their healthy peers regardless of ongoing immunomodulatory treatment. This study also supports the favorable course of PIBD during COVID-19 and vice-versa.

COVID-19 Lesson for Respiratory Syncytial Virus (RSV): Hygiene Works.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections (LRTIs) in infants worldwide. The global direct medical cost associated with RSV LRTIs reaches billions of dollars, with the highest burden in low-middle-income countries. Many efforts have been devoted to improving its prevention and management, including both non-pharmaceutical and pharmaceutical strategies, often with limited routine use in high-income countries due to high costs. During the ongoing COVID-19 pandemic, a dramatic decrease in RSV infections (up to 70-90%) has been reported around the globe, directly related to the implementation of containment measures (face masks, hand hygiene, and social distancing). Primary prevention has demonstrated the highest cost effectiveness ratio in reducing the burden of a respiratory infection such as RSV, never reached before. Thus, we emphasize the importance of non-pharmaceutical preventive hygiene measures that should be implemented and maintained even after the COVID-19 outbreak.

Pediatric COVID-19 Therapeutics: Seizing the Right Research and Development Opportunities to Accelerate Access for Children.

Children, although at lower risk of poor outcomes from COVID-19 relative to adults, still stand to benefit from therapeutic interventions. Understanding of COVID-19 clinical presentation and prognosis in children is essential to optimize therapeutic trials design. This perspective illustrates how to collectively accelerate pediatric COVID-19 therapeutic research and development, based on the experience of the Global Accelerator for Paediatric Formulations.

Asymptomatic and Mild SARS-CoV-2 Infections Elicit Lower Immune Activation and Higher Specific Neutralizing Antibodies in Children Than in Adults.

Background: The immune response plays a pivotal role in dictating the clinical outcome in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adults, but it is still poorly investigated in the pediatric population. Methods: Of 209 enrolled subjects, 155 patients were confirmed by PCR and/or serology as having coronavirus disease 2019 (COVID-19). Blood samples were obtained at a median of 2.8 (interquartile, 2.1-3.7) and 6.1 (5.3-7.2) months after baseline (symptom onset and/or first positive virus detection). The immune profiles of activation, senescence, exhaustion, and regulatory cells were analyzed by flow cytometry. Neutralizing antibodies (nAbs) were detected by a plaque reduction neutralization test. In available nasopharyngeal swabs at baseline, SARS-CoV-2 levels were quantified by digital droplet PCR (ddPCR). Results: Overall, COVID-19 patients had higher levels of immune activation, exhaustion, and regulatory cells compared to non-COVID-19 subjects. Within the COVID-19 group, activated and senescent cells were higher in adults than in children and inversely correlated with the nAbs levels. Conversely, Tregs and Bregs regulatory cells were higher in COVID-19 children compared to adults and positively correlated with nAbs. Higher immune activation still persisted in adults after 6 months of infection, while children maintained higher levels of regulatory cells. SARS-CoV-2 levels did not differ among age classes. Conclusions: Adults displayed higher immune activation and lower production of anti-SARS-CoV-2 nAbs than children. The different immune response was not related to different viral load. The higher expression of regulatory cells in children may contribute to reduce the immune activation, thus leading to a greater specific response against the virus.

Prioritizing the First Doses of SARS-CoV-2 Vaccine to Save the Elderly: The Case Study of Italy.

SARS-CoV-2 is currently causing hundreds of deaths every day in European countries, mostly in not yet vaccinated elderly. Vaccine shortage poses relevant challenges to health authorities, called to act promptly with a scarcity of data. We modeled the mortality reduction of the elderly according to a schedule of mRNA SARS-CoV-2 vaccine that prioritized first dose administration. For the case study of Italy, we show an increase in protected individuals up to 53.4% and a decrease in deaths up to 19.8% in the cohort of over 80's compared with the standard vaccine recalls after 3 or 4 weeks. This model supports the adoption of vaccination campaigns that prioritize the administration of the first doses in the elderly.