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.

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.

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.

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.

Hospitalizations and emergency department visits trends among elderly individuals in proximity to death: a retrospective population-based study.

Acute healthcare services are extremely important, particularly during the COVID-19 pandemic, as healthcare demand has rapidly intensified, and resources have become insufficient. Studies on specific prepandemic hospitalization and emergency department visit (EDV) trends in proximity to death are limited. We examined time-trend specificities based on sex, age, and cause of death in the last 2 years of life. Datasets containing all hospitalizations and EDVs of elderly residents in Friuli-Venezia Giulia, Italy (N = 411,812), who died between 2002 and 2014 at ≥ 65 years, have been collected. We performed subgroup change-point analysis of monthly trends in the 2 years preceding death according to sex, age at death (65-74, 75-84, 85-94, and ≥ 95 years), and main cause of death (cancer, cardiovascular, or respiratory disease). The proportion of decedents (N = 142,834) accessing acute healthcare services increased exponentially in proximity to death (hospitalizations = 4.7, EDVs = 3.9 months before death). This was inversely related to age, with changes among the youngest and eldest decedents at 6.6 and 3.5 months for hospitalizations and at 4.6 and 3.3 months for EDVs, respectively. Healthcare use among cancer patients intensified earlier in life (hospitalizations = 6.8, EDVs = 5.8 months before death). Decedents from respiratory diseases were most likely to access hospital-based services during the last month of life. No sex-based differences were found. The greater use of acute healthcare services among younger decedents and cancer patients suggests that policies potentiating primary care support targeting these at-risk groups may reduce pressure on hospital-based services.

Change in healthcare during Covid-19 pandemic was assessed through observational designs.

OBJECTIVE: Methodological challenges for investigating the changes in healthcare utilization during COVID-19 pandemic must be considered for obtaining unbiased estimates. STUDY DESIGN AND SETTING: A population-based study in the Lombardy region (Italy) measured the association between the level of epidemic restrictions (increasing exposure during pre-epidemic, post-lockdown, and lockdown periods) and the recommended healthcare (outcome) for patients with schizophrenia, heart failure, chronic obstructive pulmonary disease, breast cancer, and pregnancy women. Two designs are applied: the self-controlled case series (SCCS) and the usual cohort design. Adjustments for between-patients unmeasured confounders and seasonality of medical services delivering were performed. RESULTS: Compared with pre-epidemic, reductions in delivering recommended healthcare during lockdown up to 73% (95% confidence interval: 63%-80%) for timeliness of breast cancer surgery, and up to 20% (16%-23%) for appropriated gynecologic visit during pregnancy were obtained from SCCS and cohort design, respectively. Healthcare provision came back to pre-epidemic levels during the post-lockdown, with the exception of schizophrenic patients for whom the SCCS showed a reduction in continuity of care of 11% (11%-12%). CONCLUSION: Strategies for investigating the changes in healthcare utilization during pandemic must be implemented. Recommendations for taking into account sources of systematic uncertainty are discussed and illustrated by using motivating examples.

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.

Mild SARS-CoV-2 Infections and Neutralizing Antibody Titers.

BACKGROUND: Recent evidence suggests that neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 may persist over time; however, knowledge regarding pediatric subjects is limited. METHODS: A single-center, prospective observational study was conducted on 57 family clusters of coronavirus disease 2019, including children of neonatal and pediatric age attending the University Hospital of Padua (Italy). For each patient, blood samples were collected for both the quantification of nAbs through a plaque reduction neutralizing test and the detection of antinucleocapsid-spike protein immunoglobulin G and/or immunoglobulin M. RESULTS: We analyzed 283 blood samples collected from 152 confirmed coronavirus disease 2019 cases (82 parents and 70 children or older siblings of median age of 8 years, interquartile range: 4-13), presenting asymptomatic or with mildly symptomatic disease. Despite the decrease of immunoglobulin G over time, nAbs were found to persist up to 7 to 8 months in children, whereas adults recorded a modest declining trend. Interestingly, children aged <6 years, and, in particular, those aged <3 years, developed higher long-lasting levels of nAbs compared with older siblings and/or adults. CONCLUSIONS: Mild and asymptomatic severe acute respiratory syndrome coronavirus 2 infections in family clusters elicited higher nAbs among children.