A Critical Analysis of UK Media Characterisations of Long Covid in Children and Young People (preprint)

Long Covid is the continuation or development of symptoms related to a SARSCoV2 infection. Those with Long Covid may face epistemic injustice, where they are unjustifiably viewed as unreliable evaluators of their own illness experiences. Media articles both reflect and influence perception and subsequently how people regard children and young people (CYP) with Long Covid, and may contribute to epistemic injustice.? We aimed to explore how the UK media characterises Long Covid in CYP through examining three key actor groups: parents, healthcare professionals, and CYP with Long Covid, through the lens of epistemic injustice. A systematic search strategy resulted in the inclusion of 103 UK media articles. We used an adapted corpus-assisted Critical Discourse Analysis in tandem with thematic analysis. Specifically, we utilised search terms to locate concordances of key actor groups. In the corpus, parents highlighted minimisation of Long Covid, barriers to care, and experiences of personal attacks. Mothers were presented as also having Long Covid. Fathers were not mentioned once. Healthcare professionals emphasised the rarity of Long Covid in CYP, avoided pathologizing Long Covid, and overemphasised psychological components. CYP rarely were consulted in media articles but were presented as formerly very able. Manifestations of Long Covid in CYP were validated or invalidated in relation to adults. Media characterisations contributed to epistemic injustice. The disempowering portrayal of parents promote stigma and barriers to care. Healthcare professionals' narratives often contributed to negative healthcare experiences and enacted testimonial injustice, where CYP and parents credibility was diminished due to unfair identity prejudice, in their invalidation of Long Covid. Media characterisations reveal and maintain a lack of societal framework for understanding Long Covid in CYP. The findings of this study illustrate the discursive practices employed by journalists that contribute to experiences of epistemic injustice. Based on our findings, we propose recommendations for journalists.

Differential Adaptive Immune Responses Following SARS-CoV-2 Infection in Children Compared to Adults (preprint)

BackgroundSARS-CoV-2 infection elicits distinct clinical features in children and adults. Profiling the adaptive immune response following infection in children is essential to better understand and characterize these differences. MethodsHumoral and cell-mediated immune responses from unvaccinated pediatric and adult participants were analyzed following asymptomatic or mild non-Omicron SARS-CoV-2 infection. Levels of IgG and IgA targeting spike (S), receptor-binding domain (RBD), and nucleocapsid (N) proteins of SARS-CoV-2 were measured, while neutralizing antibody (nAb) titers were assessed against three viral strains (Wuhan, Omicron BA.1 and BA.4/BA.5). Specific T-cell memory responses were investigated by quantifying interferon-gamma (IFN-{gamma}) secreting cells after stimulation with ancestral and variant strains of SARS-CoV-2, and seasonal human {beta}- coronaviruses (HCoV)-OC43 and -HKU1. ResultsThe study comprised 28 children (3 to 17 [median=10] years old) and 28 adults (19 to 62 [median=42]). At a mean time of seven months ({+/-} 2.8 months) after SARS-CoV-2 infection, children and adults mounted comparable antibody levels against S and RBD, as well as similar neutralization capacity. However, children displayed a weaker cellular memory response to SARS- CoV-2 than adults, with a median of 88 [28-184] spot forming units per million of PBMCs in children compared to 208 [141-340] in adults (***, P < .001). In children, the level of IFN-{gamma} secreting cells in response to SARS-CoV-2 corresponds to that of seasonal coronaviruses. ConclusionLong-term memory T-cell responses to SARS-CoV-2 are enhanced in adults compared to children who demonstrate equivalent responses to SARS-CoV-2 and other HCoV. HIGHLIGHTSO_LIChildren infected with SARS-CoV-2 show comparable binding and neutralizing antibody levels as adults seven months after infection. C_LIO_LIThere are notable differences in the intensity of the T-cell response following SARS-CoV- 2 infection between children and adults. C_LIO_LIChildren have more pronounced T-cell immunodominance towards the spike versus non- spike proteins compared to adults at seven months post-infection C_LIO_LIIn contrast, T-cell responses to SARS-CoV-2 are globally reduced in children compared to adults but are alike to other seasonal {beta}-coronaviruses. C_LI

Life changes and mental health among Chinese children and adolescents during the pandemic: a combination of cross-sectional, longitudinal and clustering studies (preprint)

The measures to prevent COVID-19 pandemic had caused significant life changes, which could be distressing for mental health among children and adolescents. We aimed to evaluate the short- and long-term effects of life changes on children’s mental health in a large Chinese cohort. Survey-based life changes during COVID-19 lockdown were measured among 7,829 Chinese students at Grade 1–9, including social contacts, lifestyles and family financial status. Clustering analysis was applied to identify potential patterns of these changes. Depressive and anxiety symptoms were measured using the Center for Epidemiologic Studies Depression Scale and Screen for Child Anxiety Related Emotional Disorders. Logistic regression models were used to investigate the associations between these changes, their patterns and the presence of depression/anxiety symptoms using both cross-sectional and longitudinal designs. We found that the prevalence of depression and anxiety symptoms decreased during pandemic (34.6–32.6%). However, during and shortly after lockdown, students who reported negative impacts on their study, social and outside activities and diet, and decreased electronic time and sugar-sweetened consumption, as well as family income decline and unemployment had increased risks of depressive/anxiety symptoms, and students with changed sleep time had increased depressive symptoms. These associations attenuated or disappeared one year later. Similar patterns were observed in clustering analysis, while only the group with severe impact on family financial status showed a sustained increase in depression symptoms. In summary, restrictive measures that changed children and adolescents’ daily life during COVID-19 lockdown showed negative effects on their mental health, with some commonalities and distinctions patterns in the manifestation of depression and anxiety symptoms.

Single-cell analysis of lung epithelial cells reveals age and cell population-specific responses to SARS-CoV-2 infection in ciliated cells (preprint)

The ability of SARS-CoV-2 to evade antiviral immune signaling in the airway contributes to the severity of COVID-19 disease. Additionally, COVID-19 is influenced by age and has more severe presentations in older individuals. This raises questions about innate immune signaling as a function of lung development and age. Therefore, we investigated the transcriptome of different cell populations of the airway epithelium using pediatric and adult lung tissue samples from the LungMAP Human Tissue Core Biorepository. Specifically, lung lobes were digested and cultured into a biomimetic model of the airway epithelium on an air-liquid interface. Cells were then infected with SARS-CoV-2 and subjected to single-cell RNA sequencing. Transcriptional profiling and differential expression analysis were carried out using Seurat. The clustering analysis identified several cell populations: club cells, proliferating epithelial cells, multiciliated precursor cells, ionocytes, and two biologically distinct clusters of ciliated cells (FOXJ1high and FOXJ1low). Interestingly, the two ciliated cell clusters showed different infection rates and enrichment of processes involved in ciliary biogenesis and function; we observed a cell-type-specific suppression of innate immunity in infected cells from the FOXJ1low subset. We also identified a significant number of genes that were differentially expressed in lung cells derived from children as compared to adults, suggesting the differential pathogenesis of SARS-CoV-2 infection in children versus adults. We discuss how this work can be used to identify drug targets to modulate molecular signaling cascades that mediate an innate immune response and begin to understand differences in COVID-19 outcomes for pediatric vs. adult populations.

Orphanhood and caregiver death among children in the United States due to all-cause mortality 2000-2021: A Modeling Study (preprint)

Importance: Deaths of parents and grandparent caregivers linked to social and health crises threaten child wellbeing due to losses of nurturance, financial support, physical safety, family stability, and care. Little is known about the full burden of all-causes and leading cause-specific orphanhood and caregiver death beyond estimates from select causes. Objective: To estimate 2000-2021 prevalence and incidence trends of all-cause orphanhood and caregiver death among children <18, by cause, age, race/ethnicity, and state. Data Sources: National Center for Health Statistics (NCHS) birth, death, race/ethnicity, and population data to estimate fertility rates and identify causes of death; 1983-1998 ICD-9 causes-of-death harmonized to ICD-10 classifications; 1999-2021 ICD-10 causes-of-death; CDC WONDER for state-specific estimates; and American Community Survey for grandparent population estimates. Data extraction and synthesis: We extracted U.S. population-level death, birth, population size, race, and ethnicity data from NCHS and attributed to each deceased individual the average number of children left behind according to subgroup-specific fertility rates in the previous 0-17 years. We examined prevalence and incidence of orphanhood by leading causes-of-death, including COVID-19, the leading 5 causes-of-death for 1983-2021, and additional leading causes for ages 15-44. We extended these to obtain state-level outcome estimates. Main outcome measures: National incidence and prevalence of orphanhood and caregiver death from 2000-2021, with orphanhood by year, parental cause-of-death and sex, child age, race/ethnicity, and state. Results: From 2000-2021, orphanhood and custodial/co-residing grandparent caregiver loss annual incidence and prevalence trends increased 49.2% and 8.3%, respectively. By 2021, 2.9 million children (4% of all children) had experienced prevalent orphanhood and caregiver death. Populations disproportionately affected by orphanhood included 5.0% of all adolescents; 6.5%, 4.8%, and 3.9% respectively of non-Hispanic American Indian/Alaska Native, non-Hispanic Black, and non-Hispanic White children; and children in New Mexico and Southern and Eastern States. Parental death due to drug overdose during 2020-2021 surpassed COVID-19 as the leading cause of incident and prevalent orphanhood during the COVID-19 pandemic. Conclusions and Relevance: Policies, programs, and practices aimed at orphanhood prevention, identification, and linkage to services and support of nearly 3 million bereaved children are needed, foremost prioritizing rapidly increasing overdose-linked orphanhood.

Broadly neutralizing antibodies against emerging delta-coronaviruses (preprint)

Porcine deltacoronavirus (PDCoV) spillovers were recently detected in children with acute undifferentiated febrile illness, underscoring recurrent zoonoses of divergent coronaviruses. To date, no vaccines or specific therapeutics are approved for use in humans against PDCoV. To prepare for possible future PDCoV epidemics, we isolated human spike (S)-directed monoclonal antibodies from transgenic mice and found that two of them, designated PD33 and PD41, broadly neutralized a panel of PDCoV variants. Cryo-electron microscopy structures of PD33 and PD41 in complex with the PDCoV receptor-binding domain and S ectodomain trimer provide a blueprint of the epitopes recognized by these mAbs, rationalizing their broad inhibitory activity. We show that both mAbs inhibit PDCoV by competitively interfering with host APN binding to the PDCoV receptor-binding loops, explaining the mechanism of viral neutralization. PD33 and PD41 are candidates for clinical advancement, which could be stockpiled to prepare for possible future PDCoV outbreaks.

Older Age and Vaccination Protect Against Transaminase Elevation in Pediatric SARS-CoV2 (preprint)

Objectives: SARS-CoV2 infection is reported to induce transaminase elevations. There are case reports of severe liver injury in adult SARS-CoV2 patients, and some have theorized that acute SARS-CoV2 infection may be a driver of severe liver injury in children. While pediatric hepatic injury has previously been described, clear shifts in immunogenic response secondary to prior immune exposure and vaccination since initial reports from 2020 warrant further evaluation. We sought to identify the impact of variant shifts and vaccination on this phenomenon in children. Methods: a retrospective cross sectional study of pediatric SARS-CoV2 patients seen at two hospital facilities in an urban neighborhood in New York City between March 2020 and March 2022 was conducted via chart review. Data was extracted relating to patients demographics, clinical presentation, including the level of care and the laboratory results of comprehensive metabolic panels (CMP). Results: 133 pediatric cases were identified as having SARS-CoV2 and CMP obtained in the same visit. Patients were predominantly Black (79.2%) and non-hispanic (87%) with a mean age of 9.2 years. Risk of transaminase elevation was increased in younger patients and patients with higher level of care. BMI was not a risk factor noted for transaminase elevation. Vaccination decreased degree, not incidence, of transaminase elevation but given low rates of vaccination unable to determine significance of protective efficacy. Conclusions: our study has identified a profound increased risk of transaminase elevation in younger patients, the absence of BMI as a correlating factor in our primarily black patient population, a shift towards non-specific AST elevation with variant windows, and a strong signal of vaccine protection.

Humoral immune response characteristics of the susceptible populations after the infection of SARS-CoV-2 BA.5 strain (preprint)

This study compared the humoral immune characteristics of children, elderly people, pregnant women, and adults infected with BA.5 and XBB strains in Guangzhou, China. It was found that binding and neutralizing antibodies the titers against distinct SARS-CoV-2 strains were low in the acute-phase sera of BA.5 infected patients, while the corresponding titers were significantly increased in the convalescent phase, the antibody titers against the Wuhan strain were the highest. Regardless of whether they were vaccinated, BA.5 infection did not induce high neutralizing antibodies against XBB. During the recovery phase, the titers of antiviral antibodies in the vaccinated population are more robust than those in the unvaccinated population. For BA.5 infections, the specific binding and neutralizing antibody titers in the children group were lower compared to other population groups. In the convalescence period of the disease, the titers of neutralizing antibodies against Wuhan, BA.5 and XBB strains induced by BA.5 infections are significantly correlated in pairs. XBB can induce a broader and balanced antiviral humoral immune response than BA.5 as a first-time infected strain. This finding can provide a reference for the judgment of the future epidemic law of SARS-CoV-2, and provide a scientific basis for developing novel COVID-19 vaccines, especially for discovering customized vaccines and immune strategies for different populations.

Family member and service provider experiences and perspectives of a digital surveillance and service navigation approach: A qualitative study with a culturally diverse community (preprint)

Background Children and families from priority populations experienced significant psychosocial and mental health issues to the COVID-19 pandemic. Yet they also faced significant barriers to service access, particularly families from culturally and linguistically diverse (CALD) backgrounds. With most child and family health nurse clinics ceasing in-person consultations due to the pandemic, many children missed out on health and developmental checks. The aim of this study was to investigate the perspectives and experiences of family members and service providers from an urban, CALD community regarding the implementation of a digital, developmental surveillance, Watch Me Grow-Electronic (WMG-E) program.Methods Semi-structured interviews were conducted with 17 family members, service navigators, and service providers in a multicultural community in South Western Sydney, Australia. This qualitative study formed part of a larger, two-site, randomised controlled trial of the WMG-E program. A reflexive thematic analysis approach was adopted to analyse the data.Results Participants highlighted the comprehensive and personalised support offered by existing child and family health services. The WMG-E was deemed beneficial because the weblink was easy and quick to use and it enabled access to a service navigator who support family access to relevant services. However, the WMG-E was problematic because of technology or language barriers, and it did not facilitate immediate clinician involvement when families completed the weblink.Conclusions Families and service providers found that using WMG-E empowered parents and caregivers to access developmental screening and learn more about their child’s development and engage with relevant services. This beds down a new and innovative solution to the current service delivery gap and create mechanisms that can engage families currently not accessing services, and develops and increases knowledge around navigating the health and social care services.Trial registration: The study is part of a large randomised controlled trial (Protocol No. 1.0, Version 3.1) was registered with ANZCTR (registration number: ACTRN12621000766819) on July 21st, 2021 and reporting of the trial results will be according to recommendations in the CONSORT Statement.

Increasing loneliness among children and adolescents from 2018 to 2022: A representative survey before and after the COVID-19 pandemic (preprint)

Background: Loneliness is an increasingly present topic in scientific and public discourse, and has gained relevance, especially due to the COVID-19 pandemic. Nevertheless, there is a lack of representative studies examining the prevalence of loneliness among children and adolescents before and after the pandemic. Accordingly, the present study aimed to determine the prevalence of loneliness among 11- to 15-year-old students before (2018) and after (2022) the onset of the COVID-19 pandemic and to investigate subgroup differences. Methods: In this cross-sectional Health Behaviour in School-aged Children (HBSC) study, the prevalence of loneliness was compared in representative samples in the German federal state of Brandenburg from 2018 and 2022. In 2018, data were collected from 3,057 (51.8% girls, Mage= 13.1, SD = 1.7) and, in 2022, from 3,801 (52.6% girls, Mage= 13.5, SD = 1.6) students in general education schools in grades 5, 7, and 9. Loneliness was assessed using a single item from the Center for Epidemiologic Studies Depression Scale (CES-D). The chi-square test was used to determine bivariate correlations. To validate the bivariate results, we performed a logistic regression in which we also added interaction effects to test whether loneliness developed differently depending on gender, grade, and family affluence. Results: In total, 11.8% of the students reported being lonely in 2018, and 19.3% reported being lonely in 2022. Loneliness was more prevalent among girls, nonbinary students, older adolescents, and students with lower family affluence. The increase in loneliness did not differ depending on age, gender, or family affluence. Conclusion: The findings highlight that loneliness among German children and adolescents is a widespread phenomenon that has increased significantly since 2018. The sharp increase in loneliness clarifies the need for prevention measures and further research into health-related associations of loneliness.

Parent and Service Provider Perspectives of a Digital Developmental Surveillance and Service Navigation Program, Watch Me Grow Electronic (WMG-E), in Rural and Regional Australia: A Qualitative Study (preprint)

Background Encouraging healthy childhood development and aiding the early identification of developmental difficulties are crucial to providing the best possible outcomes. Young children in rural areas are at a higher risk of missing timely developmental screening than their non-rural counterparts. This study examined the feasibility and acceptability of a digital developmental surveillance program with a service navigator, Watch Me Grow-Electronic (WMG-E), trialled in rural Australia via a randomised controlled trial (RCT).Methods Ten parents who participated in the RCT and six service providers were interviewed. All parents completed the WMG-E weblink questionnaire on their digital devices. Five parents in the intervention group received ongoing support from a service navigator after completing the questionnaire. Transcripts were analysed via reflexive thematic analysis.Results The study revealed barriers and enablers of both the existing Child and Family Health Services (CFHS) and the WMG-E program comprising of a weblink and service navigation. Enablers of the CFHS included the flexible service options and comprehensive support model, while also acknowledging the resource barriers and service capacity limitations during the COVID-19 pandemic. Enablers of WMG-E weblink included its valuable feedback on child development, digital accessibility benefits, and user-friendly interface. Barriers of the WMG-E weblink included limited clinician oversight during survey completion, and technological barriers related to the digital format. Enablers of the WMG-E service navigation included the ability to address service gaps by connecting families to local services, provide support during waitlist periods, and alleviate the strain on understaffed remote healthcare facilities.Conclusions Access to digital support was perceived as particularly valuable during the COVID-19 pandemic when services were closed. The WMG-E program offers a promising avenue to improve the accessibility and uptake of developmental screening services in rural Australia when functioning in harmony with existing care providers.Trial registration: The study is part of a large randomised controlled trial (Protocol No. 1.0, Version 3.1) was registered with ANZCTR (registration number: ACTRN12621000766819) on July 21st, 2021 and reporting of the trial results will be according to recommendations in the CONSORT Statement.

Vaccine Literacy and Hesitancy among Parents and Legal Guardians of Elementary School-Aged Children in the Midwest (preprint)

Parental refusal of childhood vaccines is a growing public health concern. Numerous reasons exist for this refusal, including religious, personal, and philosophical beliefs, and safety concerns. However, parental refusal of childhood vaccines is not simply an individualized problem for the family; this impacts herd immunity and affects the entire community. To improve vaccination rates among the pediatric population, understanding the thought process and decision-making behind parental opposition and refusal of vaccinations is essential. Using a survey developed to assess attitudes towards recommended childhood vaccines and the COVID-19 vaccine, this study examined the correlation between vaccine literacy and hesitancy among parents and legal guardians of elementary school-aged children in the Midwest. Responses were analyzed using Chi-squared tests on “R” software. Significant negative correlations were found between COVID-19 hesitancy and vaccine literacy, and resistance towards all vaccines and vaccine literacy. No significant negative correlations were found between hesitancy towards all vaccines and vaccine literacy, or hesitancy and literacy among different income and education brackets. Our results suggest that vaccine education may lessen vaccine hesitancy among parents and may be an essential factor in improving vaccination rates among the pediatric population.

Two-year Follow-up of Internet-based Parent Training with Telephone Coaching Aimed at Treating Child Disruptive Behaviors in a Clinical Setting during the COVID-19 Pandemic (preprint)

Background: There is a lack of studies examining the long-term outcomes of internet-based parent training programs implemented in clinical settings during the COVID-19 pandemic.Objective: To study two-year outcomes of families with 3–8-year-old children referred from family counseling centers to the Finnish Strongest Families Smart Website (SFSW), which provides digital parent training with telephone coaching aimed at treating child disruptive behaviors.Methods Counseling centers in Helsinki identified 50 3–8-year-old children with high levels of disruptive behavioral problems. Child psychopathology and functioning as well as parenting styles and parental mental health were reported by parents at baseline, posttreatment and at 6-, 12- and 24-month follow-ups.Results The SFSW program had positive long-term effects on child psychopathology and parenting skills. Improvements in child psychopathology, including Strengths and Difficulties Questionnaire (SDQ) total score (Cohen’s d = 0.47, p < .001), SDQ conduct scores (Cohen’s d = 0.65; p < .001) and Affective Reactivity Index (ARI) irritability scores (Cohen’s d = 0.52; p < .001) were maintained until the 24-month follow-up. Similarly, treatment effects of parenting skills measured with the Parenting Scale, including overreactivity (Cohen’s d = 0.41; p = .001) and laxness (Cohen’s d = 0.26; p = .021), were maintained until the 24-month follow-up. Parent training did not have a long-term effect on parental hostility (Cohen’s d = − 0.04; p = .70).Conclusions: The study shows that the SFSW parent training program can yield significant long-term benefits. Findings indicate that the benefits of the treatment may vary between different parenting profiles, which is important to consider when developing more personalized parenting interventions.

Long COVID in Children and Adolescents: A Retrospective Controlled Cohort Study from Iran (preprint)

Background: After recovering from the acute phase of COVID-19, some of the infected children manifest long COVID symptoms. The present study aims to identify long COVID symptoms in children and adolescents admitted to hospitals in Bushehr, Iran, during 2021 to 2023, and compare them with the non-affected group. Methods: This retrospective cohort study was conducted on 141 children and adolescents with COVID-19 and 141 non-affected peers. The data were collected using the data recorded in the patients’ records, conducting telephone interviews and completing the prevalent long COVID symptom form. Results: The mean age of the hospitalized children with COVID-19 was 79±5.24 months old, 57.4% of whom were boys. Also, 46 individuals of the infected group (32.6%) manifested long COVID symptoms. The most prevalent symptoms included fatigue (54.3%), impaired attention or concentration (41.3%) and depression or anxiety symptoms (34.7%). Significant correlation was found between disease severity and muscle and joint pain (P=0.025) as well as between length of hospital stay and cough (P=0.022), weight loss (P=0.047) and depression or anxiety symptoms (P=0.008). Older age [(6-11 y; OR=3.18, CI=1.03-9.88); (12≥ y; OR= 4.57, CI=1.40-14.96)] and having history of smoking or being exposed to secondhand smoke (OR= 12.45, CI= 3.14-49.36) were considered as risk factors for long COVID. Conclusions: Informing the public about smoking or being exposed to smoke as risk factors for long COVID, in addition to its other hazards, is of particular importance. Informing the healthcare staff and general public about the most prevalent symptoms of long COVID could be effective in timely diagnosis and treatment as well as reducing families’ stress burden.

Deep Learning Approach to Forecasting COVID-19 Cases in Residential Buildings of Hong Kong Public Housing Estates: The Role of Environment and Sociodemographics (preprint)

Introduction: The current study investigates the complex association between COVID-19 and the studied districts' socioecology (e.g. internal and external built environment, sociodemographic profiles, etc.) to quantify their contributions to the early outbreaks and epidemic resurgence of COVID-19. Methods: We aligned the analytic model's architecture with the hierarchical structure of the resident's socioecology using a multi-headed hierarchical convolutional neural network to structure the vast array of hierarchically related predictive features representing buildings' internal and external built environments and residents' sociodemographic profiles as model input. COVID-19 cases accumulated in buildings across three adjacent districts in HK, both before and during HK's epidemic resurgence, were modeled. A forward-chaining validation was performed to examine the model's performance in forecasting COVID-19 cases over the 3-, 7-, and 14-day horizons during the two months subsequent to when the model for COVID-19 resurgence was built to align with the forecasting needs in an evolving pandemic. Results: Different sets of factors were found to be linked to the earlier waves of COVID-19 outbreaks compared to the epidemic resurgence of the pandemic. Sociodemographic factors such as work hours, monthly household income, employment types, and the number of non-working adults or children in household populations were of high importance to the studied buildings' COVID-19 case counts during the early waves of COVID-19. Factors constituting one's internal built environment, such as the number of distinct households in the buildings, the number of distinct households per floor, and the number of floors, corridors, and lifts, had the greatest unique contributions to the building-level COVID-19 case counts during epidemic resurgence.

Mumps resurgence in India in the decade 2014-2023: A Trend and Geospatial Analysis (preprint)

Background Mumps, caused by the paramyxovirus, primarily affects children and adolescents and presents with parotiditis. Complications such as orchitis and meningitis can occur, especially in young adult males and vaccination reduces complications. Global mumps cases surged in the past decade, including regions like North and South America, Australia, and Iran. In India, a recent surge in mumps cases was reported in 2023. The current analysis was performed to assess the burden and trend of mumps in India over the last decade and geographical variations in its burden across India.Methods Using the weekly outbreak reports of Integrated Disease Surveillance Programme(IDSP) for the period of 2014 to 2023, number of mumps cases and outbreaks in India were plotted to see the trend of mumps in past 10 years. State wise spatial distribution of the number of mumps cases and outbreaks were also performed using QGIS for 2023 to ascertain geographical variation in mumps burden across India.Results Distinct peaks and troughs in mumps cases were observed, with notable increases in 2015, 2016, and 2019. Absence of reported cases in 2021 and a resurgence in 2023 were noted. Spatial analysis identified hot spots and clusters, indicating hyperendemic areas. State-wise wide variations were evident, with some states reported disproportionately higher number of outbreaks like Jammu and Kashmir. The impact of COVID-19 on mumps incidence was seen, with a decrease in 2020 and an increase in 2023.Conclusion Total number of mumps outbreaks and cases were reported to be highest in 2023 which is alarming and emphasizes the need for inclusion of mumps containing vaccine in form of MMR vaccine in the Universal immunization Programme (UIP) of India along with strengthening the mumps surveillance. These findings also underscore the importance of state-specific analyses and evidence-based interventions to address mumps outbreaks effectively in India.

Racial/Ethnic Differences in Long-COVID-Associated Symptoms among Pediatrics Population: Findings from Difference-in-differences Analyses in RECOVER Program (preprint)

Racial/ethnic differences are associated with the potential symptoms and conditions of post-acute sequelae SARS-CoV-2 infection (PASC) in adults. These differences may exist among children and warrant further exploration. We conducted a retrospective cohort study for children and adolescents under the age of 21 from the thirteen institutions in the RECOVER Initiative. The cohort is 225,723 patients with SARS-CoV-2 infection or COVID-19 diagnosis and 677,448 patients without SARS-CoV-2 infection or COVID-19 diagnosis between March 2020 and October 2022. The study compared minor racial/ethnic groups to Non-Hispanic White (NHW) individuals, stratified by severity during the acute phase of COVID-19. Within the severe group, Asian American/Pacific Islanders (AAPI) had a higher prevalence of fever/chills and respiratory symptoms, Hispanic patients showed greater hair loss prevalence in severe COVID-19 cases, while Non-Hispanic Black (NHB) patients had fewer skin symptoms in comparison to NHW patients. Within the non-severe group, AAPI patients had increased POTS/dysautonomia and respiratory symptoms, and NHB patients showed more cognitive symptoms than NHW patients. In conclusion, racial/ethnic differences related to COVID-19 exist among specific PASC symptoms and conditions in pediatrics, and these differences are associated with the severity of illness during acute COVID-19.

The Effectiveness of Socially Assistive Robots in Improving Children’s Pain and Negative Affectivity during Needle-based Invasive Treatment: A Systematic Review and Meta-analysis (preprint)

Background The ability of socially assistive robots (SARs) to treat dementia and Alzheimer’s disease has been verified. Currently, to increase the range of their application, there is an increasing amount of interest in using SARs to relieve pain and negative emotions among children in routine medical settings. However, there is little consensus regarding the use of these robots. Objective This study aimed to evaluate the effect of SARs on pain and negative affectivity among children undergoing invasive needle-based procedures. Design This study was a systematic review and meta-analysis of randomized controlled trials that was conducted in accordance with the Cochrane Handbook guidelines. Methods The PubMed, Embase, EBSCO, Web of Science, Cochrane Library, Embase, CNKI, and WanFang databases were searched from inception to January 2024 to identify relevant randomized controlled trials (RCTs). We used the Cochrane Risk of Bias tool 2.0 (RoB2.0) to assess the risk of bias among the included studies, and we used RevMan 6.3 software to conduct the meta-analysis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to assess the quality of the evidence. Results Ten RCTs involving 815 pediatric subjects were selected for this review and reported outcomes related to pain and emotions during IV placement, port needle insertion, flu vaccination, blood sampling, and dental treatment. Children undergoing needle-related procedures with SARs reported less anxiety (SMD= -0.36; 95% CI= -0.64, -0.09; P = 0.01) and fewer distressed avoidance behaviors (SMD= -0.67; 95% CI= -1.04, -0.30; P = 0.0004) than did those receiving typical care. There were nonsignificant differences between these groups in terms of in pain (SMD = -0.02; 95% CI = − 0.81, 0.78; P = 0.97) and fear (SMD = 0.38; 95% CI= -0.06, 0.82; P = 0.09). The results of exploratory subgroup analyses revealed no statistically significant differences based on the intervention type of robots or anesthetic use. Conclusions The use of SARs is a promising intervention method for alleviating anxiety and distress among children undergoing needle-related procedures. However, additional high-quality randomized controlled trials are needed to further validate these conclusions. Registrations The protocol of this study has been registered in the database PROSPERO (registration ID: CRD42023413279).

The relationship between maternal anxiety due to the COVID-19 pandemic and children's anxiety following school reopening in the post-pandemic era: an analytical cross-sectional study (preprint)

Background Although infection rates and mortality have decreased, COVID-19-related anxiety persists in families, especially among mothers, even in the post-pandemic period. Maternal mental health issues may jeopardize various aspects of children's development. This study aims to explore the correlation between maternal COVID-related anxiety and their children's anxiety following the reopening of primary schools in the post-pandemic era.Methods This analytical cross-sectional study involved the selection of 305 pairs of mothers and children. Data collection instruments comprised demographic questionnaires as well as assessments for COVID-related anxiety and manifest anxiety. Statistical analyses encompassed independent t-tests, one-way analysis of variance (ANOVA), and multivariate regression.Results Children's manifest anxiety was predicted by maternal anxiety related to COVID-19 (B = 0.907, P < 0.001). Moreover, significant associations were observed between the mean difference in mothers' COVID anxiety scores and their educational attainment and occupation, as well as their children's education and age, residential area, and their husbands' education and occupation (P < 0.001). Conversely, no significant differences were detected in maternal COVID anxiety scores concerning maternal age, spouse's age, and child's gender (P > 0.05).Conclusions Given the study's findings, it is recommended that nurses and psychologists provide educational interventions for mothers who need psychological support.

Analysis of Cell Immunity for Children Infected with COVID-19 and Those Vaccinated against COVID-19 Using T-SPOT®.COVID (preprint)

To elucidate the cellular immune response to coronavirus disease (COVID-19) among children, we assessed cellular immunity in 8 children post-vaccination for COVID-19 and 11 children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, using the T-SPOT®.COVID assay for both the spike (S) and nucleocapsid (N) proteins. In the vaccinated group, the T-SPOT®.COVID assay for the S protein yielded positive results in all eight children. In contrast, in the post-infection group, the assay for the N protein was positive in 5 of 11 children, with 3 of these 5 children requiring hospital admission, including 2 who needed mechanical ventilation. Therefore, the T-SPOT®.COVID assay is valuable for assessing cellular immunity against COVID-19, and most children infected with COVID-19 may not develop such immunity unless the disease severity is significant.

Evaluation of Febrile Seizure Risk Following Ancestral Monovalent COVID-19 mRNA Vaccination Among U.S. Children Aged 2-5 Years (preprint)

Importance The United States Food and Drug Administration noted a potential safety concern for seizure in children aged 2-5 years receiving the ancestral monovalent COVID-19 mRNA vaccines. Objective To evaluate febrile seizure risk following monovalent COVID-19 mRNA vaccination among children aged 2-5 years. Design, Setting, and Participants The primary analysis evaluated children who had a febrile seizure outcome in the 0-1 days following COVID-19 vaccination. A self-controlled case series analysis was performed in three commercial insurance databases to compare the risk of seizure in the risk interval (0-1 days) to a control interval (8-63 days). Exposure Receipt of dose 1 and/or dose 2 of monovalent COVID-19 mRNA vaccinations. Main Outcomes and Measures The primary outcome was febrile seizure (0-1 day risk interval). Analysis A conditional Poisson regression model was used to compare outcome rates in risk and control intervals and estimate incidence rate ratios (IRR) and 95% confidence intervals (CIs). Meta-analyses were used to pool results across databases. Results The primary meta-analysis found a statistically significant increased incidence of febrile seizure, in the 0-1 days following mRNA-1273 vaccination compared to the control interval (IRR: 2.52, 95% CI: 1.35 to 4.69, risk difference (RD)/100,000 doses = 3.22 (95%CI -0.31 to 6.75)). For the BNT162b2 vaccination, the IRR was elevated but not statistically significant (IRR: 1.41, 95%CI: 0.48 to 4.11, RD/100,000 doses = -0.25 (95%CI -2.75 to 2.24). Conclusions and Relevance Among children aged 2-5 years, the analysis showed a small elevated incidence rate ratio of febrile seizures in the 0-1 days following the mRNA-1273 vaccination. Based on the current body of scientific evidence, the safety profile of the monovalent mRNA vaccines remains favorable for use in young children.

Unlocking the Mysteries of Long COVID in Children and Young People: Insights from a Policy Review and Social Media Analysis in the UK (preprint)

There is still much unknown about the long-term consequences of COVID-19, otherwise known as post-acute sequelae of COVID (PASC). The challenge of defining the manifestation of Long COVID in children and young people (CYP) was specifically identified as a research subject by the National Institute for Health and care Research (NIHR). The lack of data relating to this age group and the impact the symptoms of PASC may have on the well-being and development of children have made research on this topic especially pressing. This healthcare policy study focuses on the applicability of Thompson et al.'s and Campbell and Carnevale’s frameworks in understanding the formulation and implementation of Long COVID healthcare policies. The analysis uses the ‘LISTEN’ method, applying a mixed method analysis of policy data and social media discourse analysis. Overall, the findings of this review of Long COVID policy guidelines for CYP and adults between 2020 and 2022, highlight increased public concern around the ethical aspects of policy-making, with high focus on Accountability and Responsiveness. The review concludes with several policy recommendations such as enhancing accountability through regular audits, promoting inclusiveness by incorporating CYP perspectives, ensuring transparency via regular updates, and maintaining equity in policy impact. Clinical policies should provide clear guidelines for healthcare providers, support mental health services for CYP and healthcare workers, and clarify school policies regarding Long COVID. Policymakers should also consider a health equity perspective in their Long COVID recovery policies.

Etiological analysis of acute respiratory infections in hospitalized children after the relaxation of COVID-19 non-pharmacological interventions in Quzhou, China (preprint)

Background: Acute respiratory infections (ARIs) can cause morbidity and mortality in children. This study was to determine the characteristics of pathogens in hospitalized children with ARIs after the relaxation of COVID-19 non-pharmacological interventions (NPIs) in Quzhou, China. Methods: Hospitalized children with ARIs were enrolled between May and October 2023, and thirteen common respiratory pathogens were tested by fluorescent quantitative polymerase chain reaction. Mono- and co-infections were assessed, and the association between pathogens and age was explored using restricted cubic spline analysis. Results: A total of 1225 children were included, 820 of them detected one pathogen and 238 of them detected two or more pathogens. Children aged 1-3 years had the highest positive detection rates. The dominant pathogen varied monthly. Mycoplasma pneumoniae (Mp) was the most common pathogen in monoinfection, followed by respiratory syncytial virus (RSV) and human rhinovirus (HRV), while influenza virus was detected at a lower rate. Mp+HRV was the most common combination of coinfections. The detection rates of Mp and HRV were higher in coinfections than in monoinfection, but there was no difference in the detection rate of RSV. In the restricted cubic spline models, a J-shaped association was consistently observed between age and Mp infection, the risk of HRV first increased and then decreased, the risk of RSV was relatively flat until 1.5 years and then decreased raplidly. Conclusion: Our study revealed the epidemiological characteristics of ARIs pathogens after the relaxation of NPIs. There is still a need to enhanced pathogen surveillance, especially for Mp.

Real-Life Practice of Kelleni’s Protocol in Treatment and Post Exposure Prophylaxis of SARS CoV-2 Omicron HV.1 and JN.1 Subvariants (preprint)

This brief report discusses the ongoing real-world practice using nitazxoanide, NSAIDs and/or azithromycin (Kelleni’s protocol) to manage the evolving manifestations of SARS CoV-2 Omicron EG.5.1, its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt. These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as persistent severe cough, high fever, change of voice and marked bone aches in high risk groups of adults. It’s suggested that the ongoing SARS CoV-2 evolution is continuing to mostly affect the high risk groups of patients, to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts. We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients, at least until the currently encountered surge of infections subsides.

Postpartum suicidal ideation in Austria and Germany during the COVID-19 pandemic (preprint)

Introduction: Postpartum suicidal ideation is a significant concern, as it poses a risk for future suicide attempts, particularly in high income countries, where suicide ranks among the leading causes of death for postpartum mothers. The literature indicates a global average prevalence of postpartum suicidal ideation of approximately 7%, but for Austria and Germany there are few studies on this subject. Methods: In a web-based survey for Austrian and German mothers of children born during the COVID-19 pandemic, several measures of mental health (depression, stress), social support and other parenting and pandemic-related questions were assessed in 1964 mothers. Based on the answers for the last item of the Edinburgh Postpartum Depression Scale, the suicidality risk and the presence or absence of suicidal ideation were computed. Furthermore, possible risk or protective factors for suicidality were investigated. Results: The prevalence of suicidal ideation was 7.3%, which is in the range of the global prevalence reported in the literature, but two times higher than previous reports on German mothers. The three strongest risk factors for suicidal ideation were (i) high levels of stress (increased risk by 350%), (ii) a lack of perceived social support (increased risk by 265%), and (iii) a perceived negative effect of the pandemic on the relationship with the partner (increased risk by 223%). Not receiving help from family and friends, having a lower income, and feeling negatively impacted by the pandemic also significantly increased the risk of suicidal ideation. Discussion and conclusion: The results indicate a higher prevalence of suicidality than previously reported in German mothers, and confirm the risk factors previously associated with depression and suicidality. These risk and protective factors could be targets of social and public health policies, while the first step should be a general screening program for suicidality in this population group.

Study on Microbial Diversity of Clothing in Maternal and Infant Population (preprint)

With the improvement of Chinese people's living standards, the maintenance of infants and young children is becoming more and more sophisticated. Coupled with the impact of the COVID-19 epidemic in the past few years, mother-to-child families have paid unprecedented attention and expectations to household appliances with sterilization and disinfection functions. In addition to washing machines as household clothing care equipment, clothing care machines with further sterilization, drying, and disinfection functions for infant and young children's clothing are gradually entering households, especially in southern China during the rainy season. In order to thoroughly solve the problem of sterilization of clothing from the source, the distribution of microbial contamination of clothing should be fully investigated. At present, there are few systematic studies on microbial community structure in clothing in China. Therefore, the purpose of this study is to analyze the microbial community structure in Chinese maternal and infant household clothing and explore the key factors affecting the microbial community structure of clothing. A plate culture method and a high-throughput sequencing technology are utilized to comprehensively analyze the community structure of the microorganism in the clothes of the mother and infant. The Chao and Shannon index were used as indicators to explore the key factors affecting the microbial community structure of clothing by one-way analysis of variance. In this study, 149 strains of microorganisms were isolated from 24 clothing samples of mothers and infants, including 102 strains of bacteria, covering 16 genera. The bacteria with higher isolation frequency and wider distribution were Staphylococcus and Micrococcus, Moraxella; 47 strains of fungi covering 24 genera were isolated and the fungi with higher isolation frequency and wider distribution were Cladosporium, Alteraria, Rhodotorula. At present, the sterilization technology of clothing care machine has not been fully investigated in combination with the distribution of clothing microorganisms. Based on the specific distribution of microorganisms in clothing and the types of microorganisms contained, clothing care machines can provide more targeted sterilization treatment for clothing. This study will help to thoroughly address the sterilization and disinfection of microorganisms in clothing from the source.

Impact of the severe acute respiratory syndrome coronavirus 2 pandemic on the incidence of type 1 diabetes mellitus in children in Yamanashi, Japan (preprint)

It is hypothesized that the biopsychosocial stress associated with the severe acute respiratory syndrome coronavirus 2 pandemic (SARS-CoV-2), in combination with the immunologic effects of SARS-CoV-2 and pancreatic β-cell dysfunction, may have contributed to the onset of type 1 diabetes (T1D) in children. We documented the incidence rates of T1D in Yamanashi Prefecture, Japan, from 1986 to 2018 and expanded our analysis to include cases from 2019 to 2022 to assess the influence of coronavirus disease 2019 (COVID-19) on the incidence of T1D. The annual increase in standardized incidences of T1D among 0- to 14-year-olds was 2.089% per year from 1986 to 2019 (p = .0772) and 2.183% per year from 1986 to 2022 (p = .0331). For the 5-9 year age group, the annual increase in crude incidence from 1986 to 2019 was 6.607% per year (p < .01), and from 1986 to 2022, it was 6.270% per year (p < .001). In Yamanashi Prefecture, Japan, the incidence of pediatric T1D increased during the COVID-19 pandemic from 2020 to 2022. However, this trend was an extension of the increase prior to 2019, suggesting that no direct or indirect effect of COVID-19 on this trend was identified.

Pilot Randomised Controlled Trial - Nurture Early for Optimal Nutrition (NEON) Study: Community facilitator-led participatory learning and action (PLA) women's groups to improve infant feeding, care and dental hygiene practices in South Asian infants aged < 2 years in East London (preprint)

Background: The first 1000-days of life are a critical window and can result in adverse-health consequences due to inadequate nutrition. South-Asian (SA) communities face significant health-disparities, particularly in maternal and child-health. Community-based-interventions, often employing Participatory-Learning-and-Action (PLA) approaches, have effectively addressed health-inequalities in lower-income-nations. The aim of this study was to assess the feasibility of implementing a PLA-intervention to improve infant-feeding and care-practices in SA communities in London. Methods: Comprehensive-analyses were conducted to assess the feasibility/fidelity of this pilot-randomised-controlled-trial. Summary-statistics were computed to compare key-metrics (participant consent-rates, attendance, retention, intervention-support, perceived-effectiveness) against predefined-progression-rules guiding towards a definitive-trial. Secondary-outcomes were analysed, drawing insights from sources, such as The-Children's-Eating-Behaviour-Questionnaire (CEBQ), Parental-Feeding-Style-Questionnaires (PFSQ), 4-Day-Food-diary, and the Equality-Impact-Assessment (EIA) tool. Video-analysis of children's mealtime behaviour trends was conducted. Feedback-interviews were collected from participants. Results: Process-outcome measures met predefined-progression-rules for a definitive-trial which deemed the intervention as feasible. The secondary-outcomes analysis revealed no significant changes in children's BMI z-scores. This could be attributed to the abbreviated follow-up period of 6-months, reduced from 12-months, due to COVID-19-related delays. CEBQ analysis showed increased food-responsiveness, along with decreased emotional-over/undereating. A similar trend was observed in PFSQ. The EIA-tool found no potential discrimination areas, and video-analysis revealed a decrease in force-feeding-practices. Participant-feedbacks revealed improved awareness and knowledge-sharing. Conclusion: The study validates the feasibility of a community-oriented, co-adapted Participatory-Learning-and-Action approach for optimising infant-care among South-Asians in high-income countries. It underscores the potential of such interventions in promoting health-equity and improving health-outcomes. Further research is required to evaluate their wider impact.

Rates of Trauma Exposure, Posttraumatic Stress Disorder (PTSD), Depressive, and Anxiety Symptoms in Primary School Children: Findings Six Months before Covid-19 Pandemic (preprint)

Studies on mental health rates among primary school children are still limited particularly related to psychological trauma and its relationship to other mental health challenges. This is the first cross-sectional study examining the rates of trauma exposure, posttraumatic stress disorder (PTSD), depressive, and anxiety symptoms in primary school children before covid-19 pandemic in Malaysia. Two hundred and twenty-one students participated in this study. They were recruited from four primary schools that volunteered to participate in the study. PTSD) Checklist for DSM-5 (PCL-5), Child PTSD Symptoms Scale-5 (CPSS-5), The Center for Epidemiologic Studies Depression Scale version (CESD) and the Spence Children's Anxiety Scale (SCAS) were used to survey psychological symptoms. Most of the students, or 54.3% of them, have experienced at least one traumatic event. Of 221 students, 39.4% reported having PTSD symptoms, 38% reported having depressive symptoms and 19% reported having anxiety symptoms. Female students were more likely to report PTSD symptoms compared to male students. The first regression analysis model showed that only depressive symptoms were significant predictors for PTSD. In the second model, religion, family income, anxiety and PTSD symptoms were significant predictors of depressive symptoms. In the third model, only depressive symptoms were significant predictors of anxiety. Findings, limitations, research future directions and recommendations were discussed.

Sex differences in symptoms following the administration of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years of age in Germany (CoVacU5): a retrospective cohort study (preprint)

Background Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany. Methods This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10g BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. Results The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3g BNT162b2, no sex differences were noted, but after a first dose of 5 or 10g BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p<0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p<0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p<0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms. Conclusions Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies. (German Clinical Trials Register ID: DRKS00028759).

Using the role model approach to optimise caregiver administration of sulfadoxine- pyrimethamine amodiaquine to children aged 3–59 months in Burkina Faso, Chad and Togo: findings from an evaluation (preprint)

Background Seasonal malaria chemoprevention (SMC) is a World Health Organization-recommended intervention for the prevention of malaria among children at high risk in areas with seasonal transmission. During the coronavirus disease 2019 (COVID-19) pandemic, SMC drug distribution was rapidly adapted to reduce contact and mitigate the risk of transmission between communities and community distributors, with caregivers administering doses. To address the challenges and find local solutions to improve administration and adherence, the role model approach was designed, implemented and evaluated in selected communities of Burkina Faso, Chad and Togo. This paper describes the results of this evaluation.Methods Focus group discussions were held with primary caregivers in all three countries to understand their perceptions of the approach’s acceptability and feasibility. In Burkina Faso and Togo, household surveys assessed the characteristics of caregivers reached by role model activities. Key indicators on SMC coverage and adherence allowed for an assessment of caregiver engagement outcomes related to participation in activities. We tested statistical associations between participation in role model activities and caregiver beliefs related to SMC.Results The majority of caregivers believed the approach to have a positive effect on drug administration, with most adopting the promoted strategies. Greater involvement of fathers in drug administration and acknowledgement of their joint responsibility was a notable positive outcome. However, several barriers to participation were noted and there was criticism of the group approach. In Burkina Faso and Togo, end-of-round survey results revealed that 98.4% of respondents agreed the approach improved their knowledge and skills in malaria prevention, while 100% expressed a desire to continue practicing the behaviours learned. However, there was a relatively low level of awareness of the approach among communities. Participation was strongly associated with participants’ self-reported belief in ease of remembering to administer, and ease of administering, SMC medicines.Conclusion Caregivers perceived the role model approach to be beneficial in aiding drug administration, with other positive impacts also reported. Replication and scale-up should utilise the most popular communication channels and existing community structures to ensure activities are promoted effectively. A mixture of group and one-on-one approaches should be used where appropriate and feasible.

Computing psycholinguistic analysis by examining topic modelling and sentiment analysis during COVID-19: changes in wording and emotions for public health (preprint)

Between 2020 and 2022, lockdown and restraining measures as a result of the COVID-19 pandemic led to changes in daily routines and also in language usage. At certain points during the pandemic, populations in some countries were unwilling or unlikely to respond to government messages, either because of the tone and analytic discourse used by leaders, or because they did not understand the messages. Linguistic markers and meanings were therefore linked to low levels of engagement, negative emotions and high levels of analytical thinking, especially in relation to the discourses of influential global speakers. We subjected sixteen speeches by eight country leaders to topic modelling and sentiment analysis in order to understand how the psychological functions of language were affected during two different periods of the COVID-19 pandemic. In this topic analysis we organize 39,073 words collected from sixteen authentic speeches delivered in two different periods of the acute phase of the pandemic. These were encoded in the Linguistic Inquiry Word Count program (LIWC), with the main aim being to identify differences between the periods. We examined the following aspects: (1) the emotional tone, analytical thinking and clout (empathy dimension); (2) the changes in these three dimensions or factors between periods 1 and 2 (February and May 2020). We observed a negative relationship between emotional tone and analytical thinking and a positive relationship between clout and emotional tone. When we considered the changes in pandemic circumstances, the psycholinguistic profiles of eight country leaders demonstrated fluctuations in language and emotions. Further reviews and research should focus on the current language and deficit wording of this population (leaders). We also note that psychologists and schoolteachers can play an important role in supporting language programmes with positive wording and by emphasising the collateral effects of face-to-face classes when teaching children to read and write.

Parents’ Participation in Care during Neonatal Intensive Care Unit Stay in COVID-19 Era: A Quantitative Observational Study (preprint)

Background: During the stay in the neonatal intensive care unit, parents play a crucial role in the care of their infants. Recent studies reported a decrease in parental participation due to Coronavirus Disease (COVID-19) pandemic that determined restricted access policies in hospitals. The aim of this study is to describe the barriers to a good parents’ participation during the stay in the neonatal intensive care unit in the COVID-19 era. Methods: A quantitative observational study was carried out. Results: 270 parents participated in this study. Mothers’ participation in care seems to be higher as compared to fathers (p = 0.017). Parents who lived the birth of their first child reported a better level of participation in care when compared to those who lived the birth of their second born (p = 0.005). Parents of extremely preterm neonates reported a lower interaction with their infant if compared to parents of term newborns (p < 0.001). Conclusions: Some more disadvantaged categories have reported lower scores: cultural and linguistic minorities, parents of multiple children and fathers. COVID-19 pandemic made several Family Centred Care activities not possible with a higher impact on those who benefited the most of these facilities. This study was prospectively registered by the IRB-CRRM of the University “G. d’Annunzio” Chieti-Pescara on the 23/01/2024 with registration number CRRM;2023_12_07_01.

Cancer is not a risk factor for severe COVID-19 in children, except in patients with recent allogeneic hematopoietic stem cell transplantion recipients or comorbidities. (preprint)

The EPICO-SEHOP platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 15%), except in children with recent alloHSCT (less than 300 days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.

Long-term Effects of the COVID-19 Lockdown on Weight Status, Eating Habits, and Lifestyle Changes Related to School-aged Children in Bandar Abbas, Iran (preprint)

Background During the COVID-19 pandemic, school closures caused destructive changes in student weight status, eating habits, screen exposure, sleep patterns, psychological responses, and activity behaviors. Despite the end of the lockdown and reopening of schools, the long-term effects of quarantine on the lifestyle and weight status of children and adolescents remain unknown. On the other hand, there is a chance that these negative changes become more prominent during extended school holidays such as summer breaks. This study aimed to determine the long-term effects of the lockdown on the weight status and lifestyle of children and adolescents after the eighth wave of the disease in Iran.Method This descriptive cross-sectional study was conducted from April to May 2022. The target population comprises one hundred students aged between 10 and 16 years. Our study obtained students' weight and height data from records maintained by school principals or sports teachers before and after the quarantine period. The BMI z score (zBMI) was calculated for each time point. The researchers also provided a questionnaire to collect the students’ demographic and lifestyle status changes during school closures.Results We found that the zBMI increased significantly from − 0.02 ± 1.64 to 0.36 ± 1.12, and the statistics of the overweight and obese population increased by 3% during quarantine (P ≤ 0.05). These changes were more pronounced in males and students aged 14–16 years. We also found that eating habits, sleep time, sleep patterns, screen time, and physical activity had significant negative changes during quarantine, and a significant increase in zBMI was observed among students who experienced negative eating behaviors, altered sleep patterns, and decreased physical activity during school closures. Conclusion: As prolonged school closures due to the COVID-19 lockdown aggravated students’ health and lifestyle status, our findings can aid in proper planning to establish an appropriate framework for the diet, physical activity, and sleep quality of students during extended school closures.

Contact behaviour before, during and after the COVID-19 pandemic in the Netherlands: evidence from contact surveys in 2016-2017 and 2020-2023 (preprint)

Background: The first wave of the COVID-19 pandemic in 2020 was largely mitigated by reducing contacts in the general population. In 2022 most contact-reducing measures were lifted. Aim We assess whether the population has reverted to pre-pandemic contact behaviour and how this would affect the transmission potential of a newly emerging pathogen. Methods The PIENTER Corona study was held every 2-6 months in the Netherlands from April 2020, as a follow-up on the 2016-2017 PIENTER3 study. In both studies, participants (ages 1-85) reported the number and age group of all face-to-face persons contacted on the previous day. The contact behaviour during and after the COVID-19 pandemic was compared to the pre-pandemic baseline. Results We found an average of 15.2 (13.3-16.9, 95% CI) community contacts per person per day in the post-pandemic period, which is 14% lower than the baseline value of 17.6 (16.3-18.9). Children have the highest number of contacts as before the pandemic. Mainly adults aged 20-59 have not reverted to their pre-pandemic behaviour, possibly because this age group works more often from home. Although the number of contacts is structurally lower compared to the pre-pandemic period, the effect on the potential spread of a newly emerging respiratory pathogen is limited if all age groups were equally susceptible. If younger age groups were less susceptible, as observed during the first COVID-19 wave, the transmission potential as well as the required control effort would be lower. Conclusion Continuous monitoring of contacts is needed to be prepared for a future pandemic.

Stress vulnerability and resilience in children facing COVID-19-related discrimination: a quasi-experimental study using polygenic, brain, and sociodemographic data (preprint)

During the pandemic, perceived COVID-19-related discrimination aggravated children's stress levels. The remaining question is to evaluate the individual variability in these effects and to identify vulnerable or resilient populations and why. Using the Adolescent Brain and Cognitive Development dataset ( N = 1,116) and causal machine learning approach - Generalized Random Forest, we examined the average and individual treatment effects of perceived discrimination on stress levels immediately and six months later. Their variability and key factors were also assessed. We observed significant variability in the acute effects of perceived discrimination across children and pinpointed the frontotemporal cortical volume and white matter connectivity (streamline counts) as key factors of stress resilience and vulnerability. The variability of these neurostructural factors partially originated from the environmental and genetic attributes. The finding was replicated in held-out samples ( N = 2,503). Our study has the potential for personalized prescriptive modeling to prevent children's future psychopathology after the pandemic.

Infection episodes and islet autoantibodies in children at increased risk for type 1 diabetes before and during the COVID-19 pandemic (preprint)

Purpose. To determine the impact of the COVID-19 pandemic on the incidence rates of infection and islet autoimmunity in children at risk for type 1 diabetes. Methods. 1050 children aged 4 to 7 months with an elevated genetic risk for type 1 diabetes were recruited from Germany, Poland, Sweden, Belgium and the UK. Reported infection episodes and islet autoantibody development were monitored until age 40 months from February 2018 to February 2023. Results. The overall infection rate was 311 (95% Confidence Interval [CI], 304–318) per 100 person years. Infection rates differed by age, country, family history of type 1 diabetes, and period relative to the pandemic. Total infection rates were 321 per 100 person-years (95% CI, 304–338) in the pre-pandemic period (until February 2020), 160 (95% CI, 148–173) per 100 person-years in the first pandemic year (March 2020 - February 2021; P < 0.001) and 337 (95% CI, 315–363) per 100 person-years in subsequent years. Similar trends were observed for respiratory and gastrointestinal infections. Islet autoantibody incidence rates were 1.6 (95% CI, 1.0-2.4) per 100 person-years in the pre-pandemic period, 1.2 (95% CI, 0.8–1.9) per 100 person-years in the first pandemic year (P = 0.46), and 3.4 (95% CI, 2.3–4.8) per 100 person-years in subsequent years (P = 0.005 vs. pre-pandemic year; P < 0.001 vs. first pandemic year). Conclusions. The COVID-19 pandemic significantly altered infection patterns. Islet autoantibody incidence rates increased two-fold when infection rates returned to pre-pandemic levels.

Heterogeneous hybrid immunity against Omicron variant JN.1 at 11 months following breakthrough infection (preprint)

A highly transmissible SARS-CoV-2 variant JN.1 is rapidly spreading throughout the nation, becoming the predominant strain in China and worldwide. However, the current immunity against the circulating JN.1 at population level has yet to be fully evaluated. We recruited representative cohorts with stratified age groups and diverse combinations of vaccination and/or infection in recent months, and promptly assessed humoral immunity for these subjects predominantly exhibiting hybrid immunity. We report that at 11 months following BA.5-wave breakthrough infection (BTI), these vaccinated individuals generally showed above-the-threshold yet low level of neutralizing activity against JN.1, with slightly greater potency observed in children and adolescents compared to adults and seniors. Meanwhile, XBB/EG.5-wave reinfection post-BTI significantly boosted the neutralizing antibodies against Omicron variants, including JN.1 in both adults (13.4- fold increase) and seniors (24.9-fold increase). To better understand respiratory mucosal protection against JN.1 over an extended period of months post-BTI, we profiled the humoral immunity in bronchoalveolar lavage samples obtained from vaccinated subjects with or without BTI, and revealed increased potency of neutralizing activity against the BA.5 and JN.1 variants in the respiratory mucosa through natural infection. Notably, at 11 months post-BTI, memory B cell responses against prototype and JN.1 were detectable in both blood and respiratory mucosa, displaying distinct memory features in the circulation and airway compartments. XBB/EG.5-wave reinfection drove the expansion of JN.1-specific B cells, along with the back-boosting of B cells responding to the ancestral viral strain, suggesting the involvement of immune imprinting. Together, this study indicates heterogeneous hybrid immunity over 11 months post-BTI, and underscores the vulnerability of individuals, particularly high-risk seniors, to JN.1 breakthrough infection. An additional booster with XBB-containing vaccine may greatly alleviate the onward transmission of immune-evasive SARS-CoV-2 variants.

The seroprevalence of SARS-CoV-2-specific antibodies in Australian children: a cross sectional study (preprint)

Background: Following reduction of public health and social measures concurrent with SARS-CoV-2 Omicron emergence in late 2021 in Australia, COVID-19 case notification rates rose rapidly. As rates of direct viral testing and reporting dropped, true infection rates were most likely to be underestimated. Objective: To better understand infection rates and immunity in this population, we aimed to estimate SARS-CoV-2 seroprevalence in Australians aged 0-19 years. Methods: We conducted a national cross sectional serosurvey from June 1, 2022, to August 31, 2022, in children aged 0-19 years undergoing an anesthetic procedure at eight tertiary pediatric hospitals. Participant questionnaires were administered, and blood samples tested using the Roche Elecsys Anti-SARS-CoV-2 total spike and nucleocapsid antibody assays. S and N seroprevalence adjusted for geographic and socioeconomic imbalances in the participant sample compared to the Australian population was estimated using multilevel regression and poststratification within a Bayesian framework. Results: Blood was collected from 2,046 participants (median age: 6.6 years). Adjusted seroprevalence of spike-antibody was 92.1 % (95% credible interval (CrI) 91.0-93.3%) and nucleocapsid-antibody was 67.0% (95% CrI 64.6-69.3). In unvaccinated children spike and nucleocapsid antibody seroprevalences were 84.2% (95% CrI 81.9-86.5) and 67.1% (95%CrI 64.0-69.8), respectively. Seroprevalence increased with age but was similar across geographic distribution and socioeconomic quintiles. Conclusion: Most Australian children and adolescents aged 0-19 years, across all jurisdictions were infected with SARS-CoV-2 by August 2022, suggesting rapid and uniform spread across the population in a very short time period. High seropositivity in unvaccinated children informed COVID-19 vaccine recommendations in Australia. Funding: Australian Government Department of Health and Aged Care.

Age-Specific All-Cause Mortality Disparities by Race and Ethnicity During the COVID-19 Pandemic (preprint)

BACKGROUND. The end of the public health emergency provides an opportunity to fully describe disparities during the Covid-19 pandemic. METHODS. In this retrospective cohort analysis of US deaths during the Covid-19 public health emergency (March 2020-April 2023), all-cause excess mortality and years of potential life lost (YPLL) were calculated by race or ethnicity overall and by age groups (ages <25 years, 25-64 years, [≥]65 years). Temporal correlations with Covid-19-specific mortality were measured. RESULTS. >1.38 million all-cause excess deaths and ~23 million corresponding YPLL occurred during the pandemic. Had the rate of excess mortality observed among the White population been observed among the total population, >252,300 (18%) fewer excess deaths, and >5,192,000 fewer (22%) YPLL would have occurred. The highest excess mortality rates were among the American Indian/Alaska Native (AI/AN, 822 per 100,000; ~405,700 YPLL) and the Black (549 per 100,000; ~4,289,200 YPLL) populations. The highest relative increase in mortality was observed in the AI/AN population (1.34; 95% CI 1.31-1.37), followed by Hispanic (1.31; 95% CI 1.27-1.34), Native Hawaiian or Other Pacific Islander (1.24; 95% CI 1.21-1.27), Asian (1.20; 95% CI 1.18-1.20), Black (1.20; 95% CI 1.18-1.22) and White (1.12; 95% CI 1.09-1.15) populations. Greater disparities occurred among children and adults <65 years. CONCLUSIONS. Excess mortality occurred in all groups during the Covid-19 pandemic, with disparities by race and ethnicity, especially in younger and middle-aged populations. >252,000 and 5.2 million fewer YPLL would have been observed had increases in mortality among the total population been similar to the White population.

Messenger Rna Covid-19 Vaccination in Brazil: Uncertain Benefits and Risks Should Lead to Informed Choice by Health System Users, and Not to Imposition (preprint)

Purpose. In 2024, COVID-19 vaccination became mandatory in Brazil for children aged 6 months to 4 years. In Brazil, the product available for this purpose is the Pfizer BNT162b2 Messenger RNA COVID-19 Vaccine, whose potential risks related to long-term human genomic changes are still uncertain compared to immunizations based on other platforms.  Methods. the epidemiology of Severe Acute Respiratory Syndrome was evaluated in Brazil, in the years 2022 and 2023, in children aged 6 months to 4 years, based on available public data.  Results. The number needed to treat (NNT) with BNT162b2 to prevent one death from COVID-19 in this age group can range from 208,856 to 548,246. The number needed to harm (NNH) to cause a vaccine-associated death can range from 42,373 to 909,090.  Conclusions. The results of this study indicate a borderline short-term risk/benefit ratio of BNT162b2 vaccine for the Brazilian population aged 6 months to 4 years. Given that there is no clear benefit from its mandatory use in this age group and the uncertainty regarding potential risks to human health in the long term due to possible retroposition (reverse transcription) with incorporation into the genome of parts of the genetic sequence introduced into humans as RNA exogenous by BNT162b, it is recommended that its use should not be mandatory and that vaccines based on other platforms should remain available, ensuring the right to informed choice by the health system users.

Understanding of the standard language version versus the plain language version of recommendations from guidelines by parents, youth, and adults in the Czech Republic

Prognostic factors for mortality, ICU, MIS-C and hospital admission due to SARS-CoV-2 in paediatric patients: A systematic review and meta-analysis (preprint)

ABSTRACT Background: There is a paucity of data on the factors associated with severe COVID-19 disease, especially in children. This systematic review and meta-analysis aim to identify the risk factors for acute adverse outcomes of COVID-19 within paediatric populations, using the recruitment setting as a proxy of initial disease severity. Methods: A systematic review and meta-analysis were performed representing published evidence from the start of the pandemic up to 14 February 2022. Our primary outcome was the identification of risk factors for adverse outcomes, stratified by recruitment setting (community, hospital). No geographical restrictions were imposed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the certainty in the body of evidence for each meta-analysis. In anticipation of significant clinical and methodological heterogeneity in the meta-analyses, we fitted logistic regression models with random effects. Findings: Our review identified 47 studies involving 94,210 paediatric cases of COVID-19. Infants up to 3 months were more likely to be hospitalised than older children. Gender and ethnicity were not associated with an increased likelihood of adverse outcomes among children within the community setting. Concerning comorbidities, having at least one pre-existing disease increased the odds of hospitalisation. Concerning BMI, underweight children and severely obese were noted to have an increased likelihood of hospital admission. The presence of metabolic disorders and children with underlying cardiovascular diseases, respiratory disorders, neuromuscular disorders and neurologic conditions were also more likely to be hospitalised. Concerning underlying comorbidities, paediatric hospitalised patients with congenital/genetic disease, those obese, with malignancy, cardiovascular diseases and respiratory disease were associated with higher odds of being admitted to ICU or ventilated. Interpretation: Our findings suggest that age, male, gender, and paediatric comorbidities increased the likelihood of hospital and ICU admission. Obesity, malignancy, and respiratory and cardiovascular disorders were among the most important risk factors for hospital and ICU admission among children with COVID-19. The extent to which these factors were linked to actual severity or where the application of cautious preventive care is an area in which further research is needed.

Thelung ultrasound in children with SARS-COV 2 infection: a national multicenter prospective study (preprint)

Covid-19 causedhospitalizations, 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 (LUS) in children with Covid-19. We enrolled children between 1 month and 18 years of age diagnosed with SARS-CoV2 infection and whounderwenta lung ultrasound within 6 hours from firstmedical evaluation. A total of 213 children were enrolled, 51.6%were male, median age was2 years and 5 months (IQR 4mm- 11 yearsand4 months).One hundred and fortyeight (69.4%) children were admitted in hospital, 9 (6.1%) in pediatric intensive care unit.We found an inverse correlation between the LUS score and the oxygen saturationatthe clinical evaluation (r = − 0.16; p = 0.019). Moreover, LUS scores were significantly higher in patients requiring oxygen supplementation (8 (IQR 3–19) vs 2 (IQR 0–4); p = 0.001). Among LUS pathological findings, irregular pleural line, sub-pleural consolidations and pleural effusions were significantly more frequentin patients whoneeded oxygen supplementation (p = 0.007; p = 0.006 andp = 0.001, respectively). Conclusion: This multicentric study confirmed that LUS is able to detect Covid-19 low respiratory tract involvement, which is characterized by pleural line irregularities, vertical artifacts and subpleural consolidations. Notably, children with higher LUS score have an higher risk of hospitalization or need for oxygen supplementation, supporting LUS as a valid and safe point-of-care first level tool for the clinical evaluation of children with Covid-19.

Impacts of the COVID-19 pandemic on pediatric and adult patients with haemophilia (preprint)

Background:The COVID-19-associated mortality rate of haemophilia patients is similar to that of the general population, but the risk of hospitalization and bleeding is higher. However, the specific impact of this infection on haemophilia patients has not been reported yet. In this study, we aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on the infection susceptibility, symptoms, drug use, and social intercourse of patients with haemophilia. Methods: A survey was distributed to a total of 265 patients with haemophilia [adult (n = 185) and pediatric patients (n = 80)] in the Fujian haemophilia therapeutic center (Fuzhou City, China) during the COVID-19 pandemic, and data were collected between January 2022 and January 2023. The impacts of SARS-CoV-2 infection on haemophilia symptoms, drug use, and social intercourse of these patients were investigated, and the association between the recovery time and disease conditions was explored in infected patients. Results: During the COVID-19 pandemic, compared with adult patients, pediatric patients had reduced social intercourse and outdoor activities because of the fear of contracting COVID-19 (85.0% vs. 66.5%; P = 0.002). Bleeding events were also significantly fewer in children than in adults (61.2% vs. 81.1%; P = 0.001). The SARS-CoV-2 infection rate was significantly higher in patients living in urban areas than in those living in rural areas (74.3% vs. 53.6%; P < 0.001). The duration of achieving symptomatic recovery from COVID-19 was not significantly associated with hemorrhage, type and classification of haemophilia, presence of inhibitors, complications, and vaccination status. Conclusion: Having COVID-19 infection did not significantly influence the symptoms and treatments in patients with haemophilia. Compared with adults, pediatric patients had significantly fewer bleeding events.

Rates of Positive M-CHAT-R Screenings by Pandemic Birth and Prenatal SARS-CoV-2 Exposure (preprint)

Maternal stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Children born during the COVID-19 pandemic, including those exposed prenatally to maternal SARS-CoV-2 infections, are reaching the developmental age for the assessment of risk for neurodevelopmental conditions. We examined associations between birth during the COVID-19 pandemic, prenatal exposure to maternal SARS-CoV-2 infection, and rates of positive screenings on the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R). Data were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. Participants completed the M-CHAT-R as part of routine clinical care (COMBO-EHR cohort) or for research purposes (COMBO-RSCH cohort). Maternal SARS-CoV-2 status during pregnancy was determined through electronic health records. The COMBO-EHR cohort includes n=1664 children (n=442 historical cohort, n=1222 pandemic cohort; n=997 SARS-CoV-2 unexposed prenatally, n=130 SARS-CoV-2 exposed prenatally) who were born at affiliated hospitals between 2018-2023 and who had a valid M-CHAT-R score in their health record. The COMBO-RSCH cohort consists of n=359 children (n=268 SARS-CoV-2 unexposed prenatally, n=91 SARS-CoV-2 exposed prenatally) born at the same hospitals who enrolled into a prospective cohort study that included administration of the M-CHAT-R at 18-months. Birth during the pandemic was not associated with greater likelihood of a positive M-CHAT-R screen in the COMBO-EHR cohort. Maternal SARS-CoV-2 was associated with lower likelihood of a positive M-CHAT-R screening in adjusted models in the COMBO-EHR cohort (OR=0.40, 95% CI=0.22 - 0.68, p=0.001), while analyses in the COMBO-RSCH cohort yielded similar but non-significant results (OR=0.67, 95% CI=0.31-1.37, p=0.29).These results suggest that children born during the first 18 months of the COVID-19 pandemic and those exposed prenatally to a maternal SARS-CoV-2 infection are not at greater risk for screening positive on the M-CHAT-R.

Real-world Effectiveness and Causal Mediation Study of BNT162b2 on Long COVID Risks in Children and Adolescents (preprint)

BackgroundThe impact of pre-infection vaccination on the risk of long COVID remains unclear in the pediatric population. Further, it is unknown if such pre-infection vaccination can mitigate the risk of long COVID beyond its established protective benefits against SARS-CoV-2 infection. ObjectiveTo assess the effectiveness of BNT162b2 on long COVID risks with various strains of the SARS-CoV-2 virus in children and adolescents, using comparative effectiveness methods. To disentangle the overall effectiveness of the vaccine on long COVID outcomes into its independent impact and indirect impact via prevention of SARS-CoV-2 infections, using causal mediation analysis. DesignReal-world vaccine effectiveness study and mediation analysis in three independent cohorts: adolescents (12 to 20 years) during the Delta phase, children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. SettingTwenty health systems in the RECOVER PCORnet electronic health record (EHR) Program. Participants112,590 adolescents (88,811 vaccinated) in the Delta period, 188,894 children (101,277 vaccinated), and 84,735 adolescents (37,724 vaccinated) in the Omicron period. ExposuresFirst dose of the BNT162b2 vaccine vs. no receipt of COVID-19 vaccine. MeasurementsOutcomes of interest include conclusive or probable diagnosis of long COVID following a documented SARS-CoV-2 infection, and body-system-specific condition clusters of post-acute sequelae of SARS-CoV-2 infection (PASC), such as cardiac, gastrointestinal, musculoskeletal, respiratory, and syndromic categories. The effectiveness was reported as (1-relative risk)*100 and mediating effects were reported as relative risks. ResultsDuring the Delta period, the estimated effectiveness of the BNT162b2 vaccine against long COVID among adolescents was 95.4% (95% CI: 90.9% to 97.7%). During the Omicron phase, the estimated effectiveness against long COVID among children was 60.2% (95% CI: 40.3% to 73.5%) and 75.1% (95% CI: 50.4% to 87.5%) among adolescents. The direct effect of vaccination, defined as the effect beyond their impact on SARS-CoV-2 infections, was found to be statistically non-significant in all three study cohorts, with estimates of 1.08 (95% CI: 0.75 to 1.55) in the Delta study among adolescents, 1.24 (95% CI: 0.92 to 1.66) among children and 0.91 (95% CI: 0.69 to 1.19) among adolescents in the Omicron studies. Meanwhile, the estimated indirect effects, which are effects through protecting SARS-CoV-2 infections, were estimated as 0.04 (95% CI: 0.03 to 0.05) among adolescents during Delta phase, 0.31 (95% CI: 0.23 to 0.42) among children and 0.21 (95% CI: 0.16 to 0.27) among adolescents during the Omicron period. LimitationsObservational study design and potentially undocumented infection. ConclusionsOur study suggests that BNT162b2 was effective in reducing risk of long COVID outcomes in children and adolescents during the Delta and Omicron periods. The mediation analysis indicates the vaccines effectiveness is primarily derived from its role in reducing the risk of SARS-CoV-2 infection. Primary Funding SourceNational Institutes of Health.

A systematic review and analysis of health risks associated with zootherapeutic practices in Africa (preprint)

Background: Over five billion people globally rely on a plant- and animal-based pharmacopoeia for their healthcare needs. The inhalation, topical application, subcutaneous injection, or ingestion of animal products - such as faeces, fur, milk, blood, brain tissue, or meat - likely facilitates the spill over of zoonotic pathogens. Certain practices use species known to be involved in the transmission of pathogens of public health relevance, such as reservoir species for filoviruses, poxviruses, and coronaviruses. These practices and the public health risk they entail have not been previously reviewed and analysed for the African continent. Methods We first conducted a systematic review of literature using web-scraping algorithms targeted at peer-reviewed (PubMed) and peer-reviewed or grey literature (Google Scholar) databases, followed by manual search of reference lists published before July 30th, 2023. We used terms encompassing zoo*, animal*, health*, practice*, tradition* followed by a list of all 54 African countries in combination with Boolean operators. We then created a categorical score reflecting the risk of zoonotic pathogen spill over for each recorded zootherapeutic practice, and compared this risk between geographic regions and between demographic groups. Findings A total of 53 studies were included, reporting the use of over 2,000 zootherapeutic practices. Half of the included studies were published after 2020. Nigerian, Ethiopian, Tanzanian and South African practices were comparatively well documented. The mean total risk score was significantly lower in western (p < 0.0001), central (p < 0.003), and southern (p < 0.0001) Africa, compared to eastern Africa, while there was no significant difference between eastern and northern Africa. Further, we found that physically sick children are overall at increased risk for pathogen spill over (p = 0.001) compared to physically sick adults, and that pregnant or lactating women are exposed to animal tissues of significantly greater infectious potential (p = 0.032). Interpretation The WHO recently hosted its first global summit on Traditional, Complementary and Integrative Medicine (TCIM), highlighting its importance to fulfil SDG 3: Health and Wellbeing. Where other forms of healthcare are unavailable or inefficient, zootherapeutic practices can provide valuable solutions to acute, chronic, physical, and psychological issues. However, significant risks of zoonotic disease transmission exist. This article aims to guide research on sustainable alternatives to mainstream medical treatments that balance cultural significance and public health.

Impact of COVID-19 pandemic on physical health among children: difference-in-differences analyses of nationwide school health checkup database (preprint)

Purpose: The COVID-19 pandemic posed tremendous challenges for children, requiring them to adapt to changes in social environments. However, the long-term effects of the pandemic on various aspects of physical health at a national level remain unclear. Methods: In this retrospective cohort study, we analyzed data from nationwide health checkup records among children aged 7–15 years. The dataset comprised 3,544,146 records from 393,794 individuals who graduated from junior high school during fiscal years 2007 to 2022. Difference-indifferences (DID) analyses with multiple time periods were used to examine the impact of COVID-19 on physical health outcomes. Results: Compared with the pre-pandemic period, the COVID-19 pandemic was associated with excess increases in obesity for boys and girls, persisting over the 3 years (DID estimate, +0.42%; 95%CI, 0.23 to 0.61). Also, it was associated with excess increases in underweight (DID estimate, +0.28%; 95%CI, 0.25 to 0.32) and poor visual acuity among boys in the 3 rd year (DID estimate, +1.80%; 95%CI, 1.30 to 2.30]). There were excess reductions in dental caries (DID estimate,-1.48%; 95%CI,-2.01 to-0.95]), glucosuria (DID estimate,-0.55; 95%CI,-0.88 to-0.23), and hematuria (DID estimate,-0.43%; 95%CI,-0.73 to-0.13]) during the 3 rd year of the pandemic. Conclusions: These findings underscore the multifaceted impact of the pandemic on various health indicators for school-aged children. This information could be valuable for public health policy and pediatric healthcare planning in the post-pandemic era. 

Comparative Clinical Assessment and Risk Stratification of COVID-19 and Influenza Infections in Adults and Children: A Comprehensive Systematic Review and Meta-Analysis (preprint)

Background and objective Coronavirus disease 2019 (COVID-19) is a viral disease that rapidly spread over the world, prompting to it to be declared a global pandemic. Since the illness exhibits similar symptoms as influenza, it can be challenging to tell the two diseases apart, especially during the influenza season. Therefore, it was necessary to carry out a comparative study to assess the clinical risks and outcomes of COVID-19 and influenza.Methods The search for relevant articles was carried out through the database search method and a manual search which involved going through the reference lists of articles related to the topic for additional studies. The Quality appraisal was carried out using the Newcastle Ottawa tool, while data analysis was done using the Review Manager Software (RevMan 5.4.1).Results The meta-analysis results show that COVID-19 patients had similar lengths of hospital stay (SMD: -0.25; 95% CI: -0.60 to 0.11; p = 0.17). However, COVID-19 patients had significantly higher mortality rates (RR: 0.28; 95% CI: 0.21 to 0.37; p < 0.0001), in-hospital complications (RR: 0.57; 95% CI: 0.50 to 0.65; p < 0.00001), intensive care unit (ICU) admissions (OR: 0.48; 95% CI: 0.37 to 0.61; p < 0.00001), length of ICU stay (SMD: -0.45; 95% CI: -0.83 to 0.06; p = 0.02), and mechanical ventilation use (OR: 0.36; 95% CI: 0.28 to 0.46; p < 0.00001).Conclusion The findings suggest that COVID-19 is more severe than influenza. Therefore, “flu-like” symptoms should not be dismissed without a clear diagnosis, especially during the winter seasons when influenza is more common.

Immune escape of Omicron lineages BA.1, BA.2, BA.5.1, BQ.1, XBB.1.5, EG.5.1 and JN.1.1 after vaccination, infection and hybrid immunity (preprint)

Since their emergence in late 2021, SARS-CoV-2 Omicron replaced earlier variants of concern and marked a new phase in the SARS-CoV-2 pandemic. Until the end of 2023, Omicron lineages continue to circulate and continue to evolve, with new lineages causing infection waves throughout 2022 and 2023. In the population, this leads to a complex immunological exposure background, characterized by immunity derived through vaccination, in the 5th year of the pandemic in the majority of individuals followed by at least one or even multiple infections or only natural infection in individuals that did not receive a vaccine. In this study, we use eight authentic SARS-CoV-2 isolates (ancestral lineage B.1 and the seven Omicron lineages BA.1, BA.2, BA.5.1, BQ.1, XBB.1.5, EG.5.1 and JN.1.1) in a live virus neutralization assay to study immune escape in 97 human sera or plasma of different immunological backgrounds (vaccination, hybrid immunity due to one or two natural infections and natural infection without vaccination in children and adults). We showed a gradually increasing immune escape after vaccination and hybrid immunity in from B.1 to BA.1/BA.2 to BA.5.1 to BQ.1 to XBB.1.5 to EG.5.1, but remarkably, no more enhanced immune escape of JN.1.1 compared to EG.5.1, with the latter two showing almost identical neutralization titers in individuals with hybrid immunity due to one or more infections. In vaccinated but never infected individuals, neutralization was markedly reduced or completely lost for XBB.1.5., EG.5.1 and JN.1.1, while in those with hybrid immunity, titers were reduced but almost all sera still showed some degree of neutralization. After a single infection without vaccination, reduced or complete loss of neutralization occurred for BQ.1, XBB.1.5, EG.5.1 and JN.1.1 compared to BA.1/BA.2. Furthermore, we observed that, although absolute titers differed between groups, the pattern of immune escape between the variants remains comparable across groups, with strongest loss of neutralization for BQ.1, XBB.1.5, EG.5.1 and JN.1.1 was observed across the different immunological backgrounds. Our results show gradually increasing antibody escape of evolving Omicron lineages over the last two years of Omicron circulation until variant EG.5.1, but not anymore for the currently dominant lineages JN.1.1, suggesting other mechanisms than immune escape to be behind the rapid global emergence of JN.1.

Questionnaire-Based Investigation of COVID-19 Vaccine Hesitancy among Omani Parents in the Outpatient Pediatric Departments of Sultan Qaboos University Hospital: A Cross-Sectional Study (preprint)

Background: Vaccinating children against COVID-19 is an essential public health approach for preventing infection in children and adults. This study aimed to explore parents' attitudes toward and the rate of COVID-19 vaccine hesitancy among children in Oman. Methods: This cross-sectional study used an online, self-administered questionnaire. The 9-item questionnaire was validated earlier and administered between June 2021 and May 2022. Multiple logistic regression was used to determine the factors associated with vaccine hesitancy. The parents received a pre-validated Google questionnaire. Responses from the parents of children younger than 11 years of age were accepted. Results: 384 participants completed the questionnaire, including 207 males (54%). The response rate was 86% (384/447). Of the 384 participants, 69% of the parents hesitated to vaccinate their children aged 1-11-year-old children). In parents of children aged 1–4 years, parental vaccination status was significantly associated with vaccine hesitancy (odds ratio [OR]: 0.116, 95% confidence interval [CI]: 0.044–0.306; p < 0.001). Additionally, vaccine hesitancy was significantly more common in mothers than in fathers (OR: 0.451, 95% CI: 0.240–0.848; p = 0.013). . Mothers of children were 77% more likely to be hesitant than fathers (.78, 95% confidence intervals (CI) = 0.50–0.1.23; p = 0.283). Conclusion: Many parents hesitated to vaccinate their children against COVID-19. Consequently, future awareness campaigns and strategies should target new vaccines. The results of our study show that the Arabic version of the 5-point Likert Scale for Vaccination Hesitancy is a valid and reliable tool.

Difference in TMPRSS2 usage by Delta and Omicron variants of SARS-CoV-2: Implication for a sudden increase among children (preprint)

It has been postulated from a combination of evidence that a sudden increase in COVID-19 cases among pediatric patients after onset of the Omicron wave was attributed to a reduced requirement for TMPRSS2-mediated entry in pediatric airways with lower expression levels of TMPRSS2. Epidemic strains were isolated from the indigenous population in an area, and the levels of TMPRSS2 required for Delta and Omicron variants were assessed. As a result, Delta variants proliferated fully in cultures of TMPRSS2-positive Vero cells but not in TMPRSS2-negative Vero cell culture (350-fold, Delta vs 9.6-fold, Omicron). There was no obvious age-dependent selection of Omicron strains affected by the TMPRSS2 (9.6-fold, Adults vs. 12-fold, Children). A phylogenetic tree was generated and Blast searches (up to 100 references) for the spread of strains in the study area showed that each strain had almost identical homology (>99.5%) with foreign isolates, although indigenous strains had obvious differences from each other. This suggested that the differences had been present abroad for a long period. Therefore, the lower requirement for TMPRSS2 by Omicron strains might be applicable to epidemic strains globally. In conclusion, the property of TMPRSS2-independent cleavage makes Omicron proliferate with ease and allows epidemics among children with fewer TMPRSS2 on epithelial surfaces of the respiratory organs.

Provider and community perspectives of integrated COVID-19 and routine childhood immunisation programmes in Nigeria: a qualitative exploratory study (preprint)

Background In Nigeria, COVID-19 vaccines were delivered through outreach activities and integrated with routine immunisation. However, evaluations of integrated approaches for novel vaccines are scarce. We aimed to understand the perceived benefits and challenges of integrating the COVID-19 vaccine within routine- immunisation in Nigeria and identify ways to strengthen this approach.Methods We conducted 30 semi-structured interviews with community members and healthcare workers in primary healthcare (PHC) facilities in Jigawa (n = 16) and Oyo (n = 14) states, Nigeria in August 2022. Participants were selected purposively from PHC facilities. Healthcare worker and community interviews were analysed separately using thematic analysis.Results We identified four themes that describe the community response, perceived impact, and health system adaptions to the challenges associated with the integrated vaccine delivery approach. Community members expressed concern that children might be given COVID-19 vaccines instead of routine immunisations, while others appreciated the integrated approach due to their trust in the efficacy of COVID-19 vaccines, government, and healthcare providers. Healthcare providers perceived the integrated approach as improving vaccination coverage and awareness but noted additional problems of increased workload, vaccine scarcity, and prolonged clinic visits. Insufficient resources were subsisting barriers to effective integration in both states, but the provider’s gender was also a challenge in Jigawa state. Additionally, the use of incentives to generate demand had ambiguous effects in Jigawa state.Conclusion Taking an integrated approach to deliver COVID-19 vaccines was acceptable by health workers but resisted from the community. Addressing persistent challenges in existing vaccination programmes is pertinent to enhance effectiveness and acceptability of the integrated approach.

How can advocates leverage power to advance comprehensive regulation on ultra- processed foods? Learning from advocate experience in Argentina (preprint)

Background. The use of corporate power to undermine public health policy processes is increasingly well understood; however, relatively little scholarship examines how advocates can leverage power to promote successful health policy decisions. The objective of this paper is to explore how advocates leveraged three forms of power – structural, instrumental and discursive – to promote the successful passage of the Promotion of Healthy Eating Law (Ley 27,642) in Argentina, one of the most comprehensive policies to introduce mandatory front-of-package (FOP) warning labels and regulate the marketing and sales of ultra-processed foods (UPFs) adopted to date.Methods. We conducted seventeen semi-structured interviews with advocates from different sectors, including civil society, international agencies, and government. Both data collection and analysis were guided by Milsom’s conceptual framework for analyzing power in public health policymaking, and the data was analyzed using hybrid deductive and inductive thematic analysis.Results. Advocates harnessed structural power through informal networks and formal coalitions, enabling them to convene discussion spaces with decision-makers, make strategic use of limited resources, and cultivate the diverse expertise (e.g., research, nutrition science, advocacy, law, political science, activism and communications) needed to support the law through different phases of the policy process. Advocates wielded instrumental power through amassing an armada of localized evidence to promote robust policy design, conducting targeted advocacy, and exposing conflicts of interest to harness public pressure. Adopting a rights-based discourse, including of children and adolescents and of consumers to transparent information, enabled advocates to foster a favorable perception of the law amongst both decision-makers and the public. Key contextual enablers of success include a political window of opportunity, the COVID-19 pandemic, securing of international funding for advocacy purposes, and the ability to learn from the regional precedent of similar policies.Conclusions. Public health policymaking, particularly when encroaching upon corporate interests, is characterized by stark imbalances of power that hinder successful policy decisions. The strategies identified in the case of Argentina provide important insights as to how advocates might harness and exercise structural, instrumental, and discursive power to counter corporate influence and promote the successful adoption of comprehensive UPF regulation.

School-aged children’s movement behaviours and subjective health complaints in Japan: A cross-sectional study during COVID-19 pandemic-related school closure and after school reopening (preprint)

Background: Social restrictions associated with the COVID-19 pandemic have altered children’s movement behaviours and impacted their mental health. However, the influence of social restrictions on subjective health complaints remains inadequately understood. This study compared adherence to 24-hour movement behaviour guidelines and the prevalence of subjective health complaints during school closure and one year after reopening. We also examined how combinations of adherence to movement behaviour recommendations relate to subjective health complaints. Methods: A repeated cross-sectional survey was conducted at two points. The first survey in May 2020 included 1535 (766 boys and 769 girls) participants during school closures, while the second survey from May to July 2021 involved 1125 (583 boys and 542 girls) participants one year after school reopening. The questionnaire covered socio-demographics, physical activity, screen time, sleep, and subjective health complaints. Differences between periods were analysed using chi-square tests. Logistic regression models assessed the association between adherence to guidelines and subjective health complaints. Results: During school closure, children were more likely to meet ‘only sleep’ recommendations and experience irritability and lethargy symptoms as compared to one year after school reopening. Irrespective of sex, those adhering to two or all three recommendations (excluding physical activity and screen time) had a lower risk of symptoms related to physical and mental pain, fatigue, irritability, and lethargy as compared to those who met no recommendation. Conclusions: Children should meet at least one physical activity or screen time recommendation in addition to sleep recommendations for subjective health. Strategies considering the priority of each movement behaviour are crucial, even during abnormal situations, such as pandemic-related social restrictions. This study offers insightful findings concerning children’s mental health issues during unprecedented and massive disasters or crises.

Longitudinal 5-year-tracking of isometric Plank test strength in children and adolescents: A pre and post-COVID-19 social distancing study (preprint)

Purpose: to compare the effects of plank strength levels over a 5-year period (2018 vs. 2023) considering the impact of the COVID-19 pandemic in children and adolescents.  Methods: This is a retrospective longitudinal case study that employed a quantitative approach, developed with schoolchildren from a school located in the South Brazil. The initial sample consisted of 221 students (58.8% boys) aged 6 to 11 years evaluated in 2018 (baseline). The same group of students was reevaluated in 2023 (follow-up) when they were aged 11 to 16 years. The assessment of isometric strength in the plank test was conducted by adapting the "core" strength test. The test was performed twice within the same session, and the best measurement was recorded. Additionally, a retest was conducted 7 days later. The abdominal resistance strength was evaluated through the sit-up test, according to the protocol of Projeto Esporte Brasil.  Results: Regarding the results of the pre-pandemic (baseline) compared to the post-pandemic (follow-up) in girls, a significant negative effect over the 5-year period was observed in the comparison of raw values for isometric strength in the Plank Test's first three measurements at baseline, compared to the follow-up. Similar 5-year negative effects were observed in boys as those seen in girls, both in the raw values, and in the age-adjusted values, where no significant differences were found.  Conclusion: isometric strength levels on the Plank test remained stable over the 5-year period, despite the impact of the COVID-19 pandemic, demonstrating consistent core strength in schoolchildren.

Impact of Shifting University Policies During the COVID-19 Pandemic on Self-Reported Employee Social Networks (preprint)

Objectives: To ascertain if faculty and staff were the link between the two COVID-19 outbreaks in a rural university county, and if the local university's COVID-19 policies affected contact rates of their employees across all its campuses. Methods: We conducted two anonymous, voluntary online surveys for faculty and staff of a PAC-12 university on their contact patterns both within and outside the university during the COVID-19 pandemic. One was asked when classes were virtual, and another when classes were in-person but masking. Participants were asked about the individuals they encountered, the type and location of the interactions, what COVID-19 precautions were taken - if any, as well as general questions about their location and COVID-19. Results: We received 271 responses from the first survey and 124 responses from the second. The first survey had a median of 3 contacts/respondent, with the second having 7 contacts/respondent (p<0.001). During the first survey, most contacts were family contacts (Spouse, Children), with the second survey period having Strangers and Students having the most contact (p<0.001). Over 50% of the first survey contacts happened at their home, while the second survey had 40% at work and 35% at home. Both respondents and contacts masked 42% and 46% of the time for the two surveys respectively (p<0.01). Conclusion: For future pandemics, it would be wise to take employees into account when trying to plan for the safety of university students, employees, and surrounding communities. The main places to be aware of and potentially push infectious disease precautions would be on campus, especially confined spaces like offices or small classrooms, and the home, as these tend to be the largest areas of non-masked close contact.

SARS-COV-2 Reinfection and Multisystem Inflammatory Syndrome in Children (MIS-C) Risk: Matched Case-control Study

A Study to Learn About Variant-Adapted COVID-19 RNA Vaccine Candidate(s) in Healthy Children

Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic susceptibility to childhood-onset asthma (preprint)

Asthma is a complex disease caused by genetic and environmental factors. Epidemiological studies have shown that in children, wheezing during rhinovirus infection (a cause of the common cold) is associated with asthma development during childhood. This has led scientists to hypothesize there could be a causal relationship between rhinovirus infection and asthma or that RV-induced wheezing identifies individuals at increased risk for asthma development. However, not all children who wheeze when they have a cold develop asthma. Genome-wide association studies (GWAS) have identified hundreds of genetic variants contributing to asthma susceptibility, with the vast majority of likely causal variants being non-coding. Integrative analyses with transcriptomic and epigenomic datasets have indicated that T cells drive asthma risk, which has been supported by mouse studies. However, the datasets ascertained in these integrative analyses lack airway epithelial cells. Furthermore, large-scale transcriptomic T cell studies have not identified the regulatory effects of most non-coding risk variants in asthma GWAS, indicating there could be additional cell types harboring these 'missing regulatory effects'. Given that airway epithelial cells are the first line of defense against rhinovirus, we hypothesized they could be mediators of genetic susceptibility to asthma. Here we integrate GWAS data with transcriptomic datasets of airway epithelial cells subject to stimuli that could induce activation states relevant to asthma. We demonstrate that epithelial cultures infected with rhinovirus significantly upregulate childhood-onset asthma-associated genes. We show that this upregulation occurs specifically in non-ciliated epithelial cells. This enrichment for genes in asthma risk loci, or 'asthma heritability enrichment' is also significant for epithelial genes upregulated with influenza infection, but not with SARS-CoV-2 infection or cytokine activation. Additionally, cells from patients with asthma showed a stronger heritability enrichment compared to cells from healthy individuals. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.

Parental Experiences of Distance Learning in Families With and Without an Adolescent With ADHD/ASD: A Large Qualitative Survey Study (preprint)

One of the greatest COVID-19 related challenges for children and their families was managing distance learning due to school closures. We also know from previous research that families with a child with a neurodevelopmental disorder such as ADHD or ASD were struggling more than others, but also experiences some positive effects. However, few qualitative studies have been conducted. The present study therefore aimed to investigate parental experiences of negative and positive effects of distance learning during the COVID-19 pandemic in a large sample of families with an adolescent with ADHD and/or ASD and a matched comparison group (n = 682). Data was collected through open-ended questions as part of a larger survey study. Five main themes, with different sub-themes were identified for both negative and positive effects: 1) Teaching, 2) Social, 3) Support, 4) Child factors, and 5) Home environment. In addiction, the main themes “Technical problems” were identified for negative effects. Families with a child with ADHD/ASD reported negative effects related to “Child factors” and “Support” more frequently than the controls, as well as negative effects related to some aspects of “Teaching” and “Technical problems”. Regarding positive effects, significant group differences were primarily found for the theme “Child factors”. These findings are discussed botn in terms of how to best prepare for possible future pandemics, but also how to best provide educational support for children with ADHD and/or ASD when schools are open.

SARS-CoV-2 Seroepidemiology and Antibody Levels in Children during BA.5 Predominance Period (preprint)

This is a SARS-CoV-2 seroepidemiological study in pediatric population(0-16 years) during BA.5 Omicron predominance period in Athens metropolitan area. Serum samples were tested for SARS-CoV-2 nucleocapsid antibodies(Abs-N), representing natural infection during three sub-periods of BA.5 predominance: 01/05/2022-31/08/2022(period A), 01/09/2022-31/12/2022(period B) and July 2023(period C) and epidemiological data were collected. Additionally in period C Abs-N seronegative samples were tested for SARS-CoV-2 spike antibodies(Abs-S). A total of 878 children were tested (males:51.3%) with median age(IQR): 108(36-156) months and seropositivity during the 3 subperiods was: A:292/417(70%), B:288/356(80.9%), C:89/105(84.8%), P-value<0.001. SARS-CoV-2 seropositivity increased for from period A to C for 0-1-year (P-value: 0.044), 1-4 years (P-value: 0.028) and 6-12 years children (P-value: 0.003). Children 6-12y had the highest seroposi-tivity rates in all subperiods (A: 77.3%, B: 91.4% and C: 95.8%). A significant correlation of monthly SARS-CoV-2 median antibody titers with monthly seropositivity rates was detected (rs:0.812, P-value:0.008). During period C, an additional 12/105 (11.4%) Abs-S seropositive and Abs-N ser-onegative samples were detected and total seropositivity was estimated at 96.2% (101/105). The increased SARS-CoV-2 seropositivity detected in current seroepidemiology study illustrates a high exposure rate during BA.5 predominance period. These data could guide public health decisions regarding immunization strategies and protection measures.

Psychosomatic health complaints among children and adolescents during the COVID-19 pandemic – Results of the longitudinal German COPSY study (preprint)

Background The period throughout the coronavirus disease 2019 (COVID-19) pandemic presented major challenges for children’s and adolescents’ wellbeing and psychosocial adjustment and had a great impact on their mental health. Psychosomatic health complaints are highly common in childhood and adolescence and present an important indicator of mental health and wellbeing.Methods The nationwide, longitudinal COPSY-study (COvid-19 and PSYchological Health) has monitored changes in mental health among children and adolescents in Germany since the beginning of the COVID-19 pandemic in five survey waves (2020–2022). In total, n = 1673 children and adolescents aged 11 years and older and their parents participated in at least one survey wave. Self-reported psychosomatic health complaints were assessed in each survey wave, using a modified version of an internationally validated eight-item symptom checklist (HBSC-SCL). A mixed model panel regression analysis was conducted to examine longitudinal changes in psychosomatic health complaints and to identify psychosocial and pandemic-related risk factors as well as resources. Risk estimations were used to explore the effect of a reported previous infection with COVID-19 on psychosomatic health complaints.Results Psychosomatic health complaints among children and adolescents increased over the course of the COVID-19 pandemic. Girls and children of mentally ill or highly burdened parents were at particular risk. A higher subjective perceived burden of the pandemic as well as COVID-19 related worries were significantly associated with a higher level of psychosomatic health complaints. Overall, Long-COVID was diagnosed by a clinical expert in 2.9% of children with previously reported COVID-19. An infection with COVID-19 was no significant risk factor for psychosomatic health complaints in general but increased the risk of sleeping difficulties and loss of concentration in autumn 2022. Personal resources, a positive family climate, and more perceived social support were significantly associated with less psychosomatic health complaints.Conclusions Three years after the start of the COVID-19 pandemic, children and adolescents are suffering from multiple psychosomatic health complaints. Medium and long-term consequences of the pandemic and associated measures are therefore suspected. Targeted health promotion and intervention strategies are needed to protect and maintain children’s and adolescents’ health.

Immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) using two-dose primary protocol in children and adolescents (Immunita-002, Brazil): A phase IV six-month follow up (preprint)

Introduction: Vaccines are essential for the prevention and control of several diseases, indeed, monitoring the immune response generated by vaccines is crucial. The immune response generated by vaccination against SARS-CoV-2 in children and adolescents is not well defined regarding to the intensity and medium to long-term duration of a protective immune response, which may point out the need of booster doses and might support the decisions in public health.Objective The study aims to evaluate the immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) in a two-dose primary protocol in children and adolescent aging from 3 to 17 years old in Brazil.Methods Participants were invited to participate in the research at two public healthcare centers located in Serrana (São Paulo) and Belo Horizonte (Minas Gerais), Brazil. Participants underwent medical interviews to gather their medical history, including COVID-19 history and medical records. Physical exams were conducted, including weight, blood pressure, temperature, and pulse rate measurements. Blood samples were obtained from the participants before vaccination, 1 month after the first dose, and 1, 3, and 6 months after the second dose and were followed by a virtual platform for monitoring post-vaccination reactions and symptoms of COVID-19. SARS-CoV-2 genome from Swab samples of COVID-19 positive individuals were sequenced by NGS. Total antibodies were measured by ELISA and neutralizing antibodies to B.1 lineage and Omicron variant (BA.1) quantified by PRNT and VNT. The cellular immune response was evaluated by flow cytometry by the quantification of systemic soluble immune mediators.Results The follow-up of 640 participants showed that the CoronaVac vaccine (Sinovac/Butantan Institute) was able to significantly induce the production of total IgG antibodies to SARS-CoV-2 and the production of neutralizing antibodies to B.1 lineage and Omicron variant. In addition, a robust cellular immune response was observed with wide release of pro-inflammatory and regulatory mediators in the early post-immunization moments. Adverse events recorded so far have been mild and transient except for seven serious adverse events reported on VigiMed.Conclusions The results indicate a robust and sustained immune response induced by the CoronaVac vaccine in children and adolescents up to six months, providing evidences to support the safety and immunogenicity of this effective immunizer.

A genetically modulated Toll-like-receptor-tolerant phenotype in peripheral blood cells of children with multisystem inflammatory syndrome. (preprint)

Dysregulated innate immune responses contribute to multisystem inflammatory syndrome in children (MIS-C), characterized by gastrointestinal, mucocutaneous, and/or cardiovascular injury occurring weeks after SARS-CoV-2 exposure. To investigate innate immune functions in MIS-C, we stimulated ex vivo peripheral blood cells from MIS-C patients with agonists of Toll-like receptors (TLR), key innate immune response initiators. We found severely dampened cytokine responses and elevated gene expression of negative regulators of TLR signaling. Increased plasma levels of zonulin, a gut leakage marker, were also detected. These effects were also observed in children enrolled months after MIS-C recovery. Moreover, cells from MIS-C children carrying rare genetic variants of lysosomal trafficking regulator (LYST) were less refractory to TLR stimulation and exhibited lysosomal and mitochondrial abnormalities with altered energy metabolism. Our results strongly suggest that MIS-C hyperinflammation and/or excessive or prolonged stimulation with gut-originated TLR ligands drive immune cells to a lasting refractory state. TLR hyporesponsiveness is likely beneficial, as suggested by excess lymphopenia among rare LYST variant carriers. Our findings point to cellular mechanisms underlying TLR hyporesponsiveness; identify genetic determinants that may explain the MIS-C clinical spectrum; suggest potential associations between innate refractory states and long COVID; and highlight the need to monitor long-term consequences of MIS-C.

Evaluation of Diagnoses and Clinical Outcomes in Children Undergoing MRI Scans

The Impact of the COVID-19 pandemic on diagnosis rates and abandonment of treatment in West Java, Indonesia (preprint)

The impact of the Covid-19 pandemic on the care of children with cancer in LMIC is of great concern, particularly on diagnosis and abandonment of treatment rates. Data supporting this concern however is limited to survey and anecdotal information. A retrospective with two cohorts design was used to compare new diagnosis and monthly abandonment rate in Java, Indonesia. We found that new diagnoses rates had dropped significantly during Indonesia’s first wave as compared to a pre-pandemic cohort [rate ratio 0.57, 95th (CI) 0.41-0.79)] and that as the first wave progressed, abandonment rates also rose in a statistically significant manner.

Unusual presentation of Thrombotic Thrombocytopenic Purpra in a newly diagnosed pediatric patient with Systemic Lupus Erythematosus in the setting of MIS-C (preprint)

The understanding of Coronavirus disease 2019 (COVID-19) immune dysregulation is evolving. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with alternations in both innate and adaptive immunity, probably caused by a complex interplay of genetics and environmental exposure with various triggers. A rare hematological complication of SLE as well as recently reported in adult with COVID-19 is thrombotic thrombocytopenic purpura (TTP). We report a pediatric case with features suggestive of multisystem inflammatory syndrome in children (MIS-C) with coronary artery ectasia, TTP, autoimmune hemolytic anemia (AIHA) and thrombocytopenia with new onset SLE as well.

Covid-19 lockdown: management of children with recurrent wheezing and asthma in Spain. (preprint)

Introduction: The effect of lockdown measures due to COVID-19 pandemic in children with respiratory underlying conditions are still unclear. We analyzed the impact of lockdown measures in the management and evolution of children with asthma and preschool wheeze during the first wave of COVID-19. Matherial and Methods: observational study carried out in children with recurrent wheezing or asthma before and after the implementation of the lockdown by using: a questionnaire aimed to examine pre-existing respiratory disorders, step treatment (according to Spanish Guide for Asthma Management) and level of asthma control before/after lockdown (CAN questionnaire), COVID history and laboratory testing including IgG SARS-CoV-2. Results: we enrolled 475 asthmatic and preschool wheezers (60.6% males), mean age 5.6 years. There were not differences in asthma treatment comparing both periods, since 81.7% maintained the same treatment (p=0.103). According to CAN questionnaire 87.7% remained well controlled during confinement. Nearly a third of children (34.9%) needed reliever treatment, mainly in older children. Determination of IgG SARS-CoV-2 was performed in 233 children (49.1%) of whom 17 (7.3%) tested positive. Seven patients positive to IgG SARS-CoV-2 were assisted in the emergency department and two required hospital admission. Conclusions: During the COVID-19 lockdown most of the children with asthma and recurrent wheezing maintained their preventive treatments unchanged and remained well controlled from their underlying disease. Our results suggest that children that tested positive to IgG SARS-CoV-2 showed significant increase in paediatric hospital admissions and attendances to urgent care settings.

COMPARISON OF ANXIETY LEVELS AMONG HEALTHCARE WORKERS WITH BECK ANXIETY INVENTORY DURING COVID-19 PANDEMIC (preprint)

Aim: The aim of this study is to investigate the anxiety levels of healthcare workers (HCWs) in hospitals in Istanbul, which is one of the cities most affected by the COVID-19 pandemic. Methods: The study was conducted online with 177 HCWs (127 doctors, 31 nurses, 15 paramedics, 4 health technicians) due to the pandemic. Beck Anxiety Invantory (BAI) was used for anxiety levels. Results: The anxiety levels of HCWs were found as 48% “minimal”, 23.7% “mild”, 17.5% “moderate”, 10.7% “severe”. The mean BAI score of other HCWs is from doctors (15.94 ± 12.776 vs 9.53 ± 8.868), the mean BAI score of women is from men (14.07 ± 10.899 vs 7.61 ± 8.681), for those who have no children, the mean BAI score is from those with a child (13.77 ± 11.713 vs 9.66 ± 9.260), and the mean BAI score of those who were over 65 years old or had a relative with chronic disease at home was higher than the others (14.11 ± 9.752 vs 10.44 ± 9.752) (p <0.05). The mean BAI score of those who did not examine COVID-19 patients were higher than the examiners (11.47 ± 10.693 vs 1.23 ± 10.394), and the mean BAI score of night shift workers (12.42 ± 11.063 vs 9.515 ± 9.255) than the others (p> 0.05). Conclusion: Healthcare workers actively working during the COVID-19 pandemic have high levels of anxiety. Working conditions of health workers should be improved and psychosocial support activities for them should be implemented continuously.

Children with allergic asthma sensitized to house dust mites getting better health during COVID-19 pandemic (preprint)

Background: Since December 2019, 2019 novel corona virus (2019-nCov) disease (COVID-19) has extended to most parts of China with more than 80 thousand cases. From Feb 1 to Mar 31 of 2020, all children were asked to stay indoors in China. Then how it affected allergic asthma (AA) sensitized to house dust mites (HDM) in children was interestingly to clarify. Objective: To investigate the changes of clinical characteristics of children with AA sensitized to HDM during COVID-19 pandemic. Method: The data including asthma symptom scores(SS), visual analog scores (VAS), asthma quality of life questionnaire (AQLQ) and medicine scores (MS) as well as respiratory infections, cares, staying up late and diets, collected from children with AA sensitized to HDM from Feb 1 to Mar 31 of 2019 and 2020 retrospectively, were analyzed. Results: There were 85 children with AA sensitized to HDM included in this research. Compared with SS, VAS, AQLQ and MS of the patients from Feb 1 to Mar 31 of 2019, SS, VAS, AQLQ and MS of the patients improved significantly (p<0.05) during COVID-19 pandemic. No respiratory infections occurred among them and they got better cares, had better diets and stayed up late less during COVID-19 pandemic. Conclusion: During COVID-19 pandemic, children with AA sensitized to HDM got better health for staying indoors, which might be associated with no respiratory infections, better cares, better diets and less staying up late.

Clinical Characteristics and Outcomes of Children and Adolescents with cancer infected with SARS-CoV2 at a Tertiary Care Medical Center in Jordan. (preprint)

Background: Our knowledge about SARS-CoV2 infection is still evolving, its effects and complications on children and adolescents with cancer need to be studied more. The aim of this study is to present our experience with SARS-CoV2 infection in this population and to highlight specific complications and outcomes. Methods: This is a retrospective and prospective observational study, involved 21 cancer patients below the age of 18 years in north Jordan. Data regarding age, sex, cancer type, phase of treatment, duration between infection and chemotherapy and others were collected and reviewed. Results: A total of 21 patients with malignancy were included. Mean age of 8.5 years. Two patients (9.5%) had died; 4.7% is COVID related mortality and 4.7% related to cancer progression. Four patients had disease progression following SARS-CoV2 infection. Six cases developed hematological malignancy weeks to months after SARS-CoV2 infection and one patient was diagnosed with malignancy concomitantly with COVID-19 infection. Out of 15 patients with pre-existing malignancy, 1 patient (7%) developed pulmonary embolism, 4 (27%) patients were diagnosed with pneumonia and one patient was diagnosed with pericarditis (7%), 2 (13%) patients were admitted to pediatric intensive care unit. Regarding oxygen requirements; a total of 3 (20%) patients required some form of Oxygen supplementation. Conclusion: Diagnosis of COVID19 should not distract physicians from investigating new malignancy or relapse as they may come together or may be the result of COVID-19 infection. More studies and investigations are needed to identify the contribution of corona virus in pathogenesis of cancer.

Sleep patterns and screen time in US school children during the first 6 months of the COVID-19 pandemic (preprint)

Objective: This study compared sleep duration, screen exposure and sleep quality in school-aged children before COVID-19 to that during school closures and again when schools re-opened in fall 2020. Study design: Cross-sectional anonymous, online survey of parents of children 5-13 years old. Methods: Questions elicited information about sleep timing and quality, screen time, and schooling at three distinct periods: before the pandemic, when schools first closed in March 2020 and then re-opened in the fall. Results: Respondents described 101 children who were an average of 8.5 years old and 51% male. In lockdown, children slept an average of 25 minutes more (95%CI 00:13-00:38) due to delays in bedtime by 29 minutes (95%CI 0:00-0:58) and wake time by 75 minutes (95% CI 0:57-1:34). When schools re-opened, sleep duration returned to pre-pandemic levels, but sleep onset and offset times remained later. Despite more sleep, sleep quality and habits (e.g. bedtime refusal) worsened during lockdown and did not normalize in fall 2020. During lockdown, screen time increased in 65% of all children, and 96% of those in private schools. When school reopened in the fall, 78% of children in hybrid/virtual learning had screen time over 4 hours daily. Less daily screen time was associated with 2-fold higher odds of better sleep (OR 2.66, 95%CI 1.15-6.14). Conclusions: Although, school-aged children had an increase in sleep time when schools were closed, sleep quality and habits worsened. Upon return to school, sleep times and sleep quality did not normalize and were related to increased screen time.

WHAT THE COVID-19 PANDEMIC TAUGHT US IN CHILDREN (preprint)

Objective: The COVID-19 pandemic is an important cause of morbidity and mortality, which has had a negative impact worldwide. We aimed to contribute to the medical literature by sharing the knowledge and experience of pediatric patients who were diagnosed as having COVID-19 in a one-year period. Method: Patients aged 1 month to 18 years who were diagnosed as having COVID-19 in our clinic, between March 2020 and April 2020, from when COVID-19 was declared as a pandemic, were included in the study. Results: Four hundred sixty-seven children were included in the study. There were 34 (7.3%) patients under one year of age, 111 (23.8%) between 1-5 years, 98 (30.4%) between 5-10 years, 142 (30.4%) between 11-15 years, and 82 (17.6%) age over 15 years. Fever (88.2%), vomiting (32.4%), and diarrhea (29.4%) in patients aged under 1 year, sore throat (36.6%) in patients aged 11-15 years, and dysgeusia (11%), anosmia (14.6%), headache (18.3%), malaise (40.8%), myalgia (28%), and dyspnea (17.1%) in those aged over 15 years of age were found significantly more common compared with the other age groups. Thirty-five (7.5%) patients were asymptomatic, 365 (78.1%) had mild disease, 35 (7.5%) were moderate, 27 (5.8%) were severe, and five (1.07%) were critical. Leukocyte count, erythrocyte sedimentation rate, ferritin, and C-reactive protein values were significantly higher in hospitalized patients. Four patients died during the study period (0.8%, 4/494). Conclusion: Although COVID-19 has an asymptomatic and mild course in children, it should be kept in mind that it may have a severe course.

Assessment of SARS-CoV-2 immunity in convalescent children and adolescents (preprint)

Background: Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Method: Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. Results: : SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of recovery time. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged <12 years correlated with higher SARS-CoV-2 RBD IgG levels, whereas higher level of CD8+ T cells in children aged ≥12 years, suggesting the importance of a T cell-dependent humoral response in younger children under 12 years. Conclusion: Both cellular and humoral immunity against SARS-CoV-2 infections can be induced in pediatric patients. Our important findings provide fundamental knowledge on the immune memory responses to SARS-CoV-2 in recovered pediatric patients.

Respiratory illness virus infections with special emphasis on Covid-19 (preprint)

Viruses that emerge pose challenges for treatment options as their uniqueness would not know completely. In spite of large diversity, viruses share common characteristics for infection. There are at least 12 different respiratory borne viruses that belong to different virus taxonomic families. Many of these viruses multiply and cause damage to the upper and lower respiratory tracts. The description about these viruses in comparison to each other with reference to their epidemiology, molecular characteristics, disease manifestations, diagnosis and treatment is lacking. Such information helps to diagnose, differentiate and for formulating the control measures at faster pace. The leading cause of acute illness worldwide are the acute respiratory infections (ARIs) and are being responsible for nearly 4 million deaths every year which are mostly in young children and infants. Among the above ARIs, influenza, respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV-3), Streptococcus pneumoniae, Haemophilus influenzae and corona viruses are the main infectious agents. WHO recognized respiratory syncytial virus, parainfluenza viruses, coronavirus, rhinovirus, and human metapneumovirus [non-influenza RNA respiratory viruses (NIRVs)], as considerable global health burden. Lower respiratory tract infections are the fourth most common cause of death globally, after the non-infectious chronic conditions. This review aimed at presenting the characteristics of different viruses causing the respiratory infections highlighting the uniqueness of Covid-19. We expect that this review would help in understanding the similarities and differences among the closely related viruses causing respiratory infections and hence to formulate the specific preventive or control measures.

Successful ECMO therapy in a child with COVID-19-associated ARDS and Ewing's Sarcoma. (preprint)

Most children and adolescents with SARS-CoV-2 infection shows asymptomatically or with mild symptoms. There are few reported cases of extracorporeal membrane oxygenation (ECMO) in pediatric patients with coronavirus disease 2019 (COVID-19). We present a previously healthy 13-year-old male, diagnosed with metastatic Ewing’s sarcoma at the same time as catastrophic acute respiratory distress syndrome due to COVID-19, which was successfully supported by veno-venous ECMO, while he received the corresponding chemotherapy protocol. ECMO can be used as salvage therapy in oncology pediatric patients with respiratory failure secondary to COVID-19. In addition, successful chemotherapy can be administered while patients are supported on ECMO.

Frequency of SARS-CoV2 infection in day care centers during reopening of the school activities (preprint)

Background: SARS-Cov2 already has over than 215 million people and more than 4.5 million fatalities. The beginning of the pandemic condition has led the health authorities in several countries to adopt no-pharmacological preventive measures, such as schools closures. The return took place at a time when the country had the highest rates of infection and mortality. In particular because of the circulation of the gamma variant (P.1) and the vaccination program were beginning in the country. Therefore, we aimed to investigate the prevalence of SARS-CoV2 in daycares after the return of educational activities. Methods The study involved seven childcare facilities. Swab samples from the nasopharynx and region were collected from each participant. This study was carried out between March 16 and September 3, 2021. Viral RNA was extracted using Invitrogen’s RNA purification kit. Viral diagnosis was obtained using RT-PCR, through the TaqMan system. Viral detection was performed with Seegene panel, Allplex TM 2019-nCoV Assay kit. Results and Conclusion: The study population included 201 participants among daycare workers and children. Only one sample (0,5%) was tested positive for the presence of SARS-CoV-2, which was an asymptomatic childcare worker, and no secondary cases were detected. Considering that the return to day care activities occurred in a period with high number of cases of deaths and lack of vaccines throughout the country, it is believed that the several preventive measures used by the day care center could be an indication of effectiveness in preventing transmission of SARS-CoV2.

Clinical characteristics and outcomes of SARS-CoV-2 infection in pediatric oncology patients in the province of Quebec (preprint)

Children with SARS-CoV-2 infection have been consistently described with milder clinical outcomes compared to adults. However, data pertaining to the clinical evolution of SARS-CoV-2 infection in children with cancer remain scarce. In this descriptive cohort study, we report the clinical characteristics and outcomes of 31 pediatric oncology patients with SARS-CoV-2 infection in the province of Quebec, Canada. Most patients were asymptomatic or had mild symptoms, with only 2 COVID-19-related hospitalizations and no COVID-19-related deaths. The favorable outcomes in our cohort may be explained by Quebec’s universal access to health care and regionalization of pediatric oncology care in tertiary centers exclusively.

Lung ultrasound an alternative to computed tomography and chest X-ray in the diagnosis of children infected with SARS-CoV-2: a systematic review of literature (preprint)

Abstract Background: Lung ultrasound (LUS) has become an important tool in diagnosing and following an adult patient with COVID-19; however, the literature for the pediatric age group is limited. Herein, we reviewed the up-to-date literatures on ultrasound use for COVID-19 pediatric patients for better management of COVID-19 in children. Methods and Objectives: The search terms “COVID-19,” “SARS-CoV2,” “coronavirus,” “2019-nCoV,” “lung ultrasound,” “sonography,” “adolescents” “children,” “childhood” and “newborn” were searched on the online databases PubMed, Embase and Medline. Articles meeting the inclusion criteria were included in the analysis and review. Results: We identified only fifteen studies to date using LUS to diagnose SARS-CoV-2 infection in children. These studies involved a total of 334 newborns, children and adolescents. Regarding the use of chest X-ray (CXR) and LUS in pediatric patients with COVID-19, we identified six studies with a total of 162 participants, with the following results: 33patients(14.11%) with lung abnormalities on lung US had a normal CXR; however, no patients with normal lung US had abnormalities on the CXR. In addition, regarding the use of computed tomography (CT) and LUS in pediatric patients with COVID-19 infection, we identified five studies with a total of 50 participants and 3 patients(6%) with lung abnormalities on chest LUS had a normal CT. Conclusion: Our findings suggest that LUS is a useful tool in the diagnosis of children and reduction in chest CT assessments may be possible when LUS is used in early diagnosis and follow-up monitoring of COVID-19 pneumonia in the children.

Analysis of a direct access testing system for the detection of SARS-CoV-2 in the paediatric population attending school (preprint)

Abstract Rationale, aims and objectives During the COVID-19 pandemic, in order to keep schools open and reduce SARS-CoV spreading, it is necessary to identify and isolate early SARS-CoV-2 positive paediatric patients (PP). The aim of this study was to describe the appropriateness of school hot spot (HS) setting for SARS-CoV 2 testing based on open access of PP. Method A cross-sectional study was performed between September 2020 and March 2021 among a sample of 13,283 PP in four different hospital settings. We collected: date of swab execution, type of swab, execution setting of the swab, result of the swab, information about community spread of the virus in the 14 days prior to the swab execution, sex and age. Results In Our sample, females were 45.8%. The swabs executed in all the hospital settings had a lower likelihood of resulting positive compared with the school HS setting. New-borns below 3 months and patients aged between 11 and 13 years old reported a higher probability of a swab tested positive compared to adolescents. Instead, children aged between 3 months and 2 years and aged between 3 years and 5 years were less likely to result positive. Conclusion We found a high prevalence of PP positive to the test for the detection of SARS-CoV-2 at the school hot spot compared with other settings. The open access modality to the nasopharyngeal swab was effective in identifying PP with COVID-19. Public health authorities should implement these testing modality in order to reduce SARS-CoV-2 infections in school settings.

Comparison of respiratory pathogens in children with lower respiratory tract infections before and during the COVID-19 pandemic in Shanghai, China (preprint)

Objectives: This study aimed to assess the impact of COVID-19 on the prevalence of respiratory pathogens among hospitalized children with lower respiratory tract infections (LTRIs) in Shanghai. Methods: Respiratory specimens were collected from children with LTRIs in Children’s Hospital of Fudan University from February 2019 to January 2021 and common respiratory pathogens were detected using multiplex PCR. The data of 13 respiratory pathogens were analyzed and compared between the year of 2020 (from February 2020 to January 2021) and 2019 (from February 2019 to January 2020). Results: A total of 1049 patients were enrolled, including 417 patients in 2019 and 632 patients in 2020. In 2020, 27.53% of patients were tested positive for at least one pathogens, which was significantly lower than that in 2019 (78.66%). The top three pathogens were Mp, ADV and RV in 2019, whereas RV, RSV and PIV were the predominant ones in 2020. The positive rates of Mp, ADV, RV, PIV, InfB, H3N2 and H1N1 were significantly decreased in 2020. RV was the most detectable respiratory pathogen in 2020, and become the most frequent pathogen in all five age groups. PIV had a high prevalence from October to December 2020 which was even higher than that in 2019. InfA was not detected in 2020. Co-infection was significantly less frequent in 2020. Conclusions: The public health interventions aiming to eliminate COVID-19 have great impact on the prevalence of common respiratory pathogens. The prevalence of RV and PIV reminds us a possible resurgence of some pathogens.

New Pediatric Leukemia and Lymphoma Diagnoses During the Coronavirus-2019 Pandemic, a New York Perspective (preprint)

Viral infections and seasonality are linked with trends in new pediatric leukemia and lymphoma cases. The COVID-19 pandemic disrupted this norm, and subsequently the international medical community observed a decrease in new diagnoses of hematologic cancers in children. However, this was not the trend observed at Cohen Children’s Medical Center where, despite examining fifteen months during the COVID-19 pandemic, we did not see a statistically significant decrease in monthly cases. Rather, cases remained constant as compared to pre-COVID-19 periods. This warrants further study at a multi-institutional level to investigate the association between COVID-19 and rates of pediatric leukemia and lymphoma.

Molecular Detection of Common Respiratory Viruses among Acute Respiratory Illness Cases in Ethiopia: Finding from Influenza Sentinel Surveillance System (preprint)

Background: Acute respiratory illnesses (ARI) are among the major public health problems both in developed and developing countries. Studies describing about the types and magnitude of viral etiologies responsible for acute respiratory infections in Ethiopia are limited. Method: A cross sectional study was conducted on samples collected from the influenza surveillance sites in Ethiopia using Multiplex PCR. Throat/throat and nasopharyngeal swab samples were collected from the sentinel sites between January 2015 to December 2016. For the current study, samples were selected by systematic random sampling technique for detection of Parainfluenza viruses1-4 (PIV1-4), Human coronaviruses (HCoV), Human metapneumoviruses A/B (HMPV A/B); Rhinovirus (RV); Respiratory syncytial viruses A/B (RSV A/B); Human adenovirus (HAdV), Enterovirus (EV), Human parechovirus (HPeV),Human bocavirus (HBoV) and Influenza virus C (INF C). Descriptive statistics was done using SPSS version 20. Result: A total of 422 samples constituting 202 (47.9%) from male patients were tested. Among all samples 55.5% (n= 234/422) were positive for at least one respiratory virus. Respiratory viruses were co-detected in 18.2% (n=77) of the samples and 79.2% (n=61/77) were from SARI cases (p=0.007). The most frequently detected respiratory viruses were RV (18.7%), RSV A/B, (12.8%), HAdV (11.4%) and PIV1-4 (7.3%). Conclusion: The study identified range of respiratory viruses circulation among samples from ILI and SARI cases mainly among under-five children. Large scale study is recommended to better understand the seasonal variation, spectrum of illness and severity of ARI due to the different respiratory viruses.

Unveiling Pandemic Patterns: A Detailed Analysis of Transmissibility and Severity Parameters Across Four COVID-19 Waves in Bogotá, Colombia (preprint)

This retrospective study on COVID-19's four waves in Bogotá, Colombia, scrutinises 1.77 million cases from March 2020 to April 2022, revealing significant shifts in both transmissibility and severity. The study highlights dynamic changes in the instantaneous reproduction number (Rt), with the highest values (> 2.5) corresponding to the ancestral and Omicron variants. There was a notable 88% decrease in the Case Fatality Ratio (CFR) from the first to the fourth wave, emphasising changing severity levels. The third wave, marked by the Mu variant, saw the highest case and death counts, yet paradoxically showed a decrease in CFR and an increase in the hospitalisation fatality ratio. Conversely, the fourth wave, dominated by Omicron, had the lowest severity despite higher hospitalisation rates in children. Additionally, the study records a consistent reduction in average hospital and ICU stay durations, from 10.84 days to 7.85 days and from 16.2 days to 12.4 days respectively, across the waves. These findings underscore the importance of ongoing epidemiological surveillance and adaptable public health strategies in lower-middle-income regions like Bogotá, deepening our understanding of COVID-19's impact in Latin America.

MIS-C, inherited metabolic diseases and methylmalonic acidemia: a case report and review of the literature (preprint)

Bacground Methylmalonic acidemia (MMA) secondary to mutase deficiency, mut0, is an inborn error of metabolism causing complete enzyme deficiency. Multisystem Inflammatory Syndrome in Children (MIS-C) is a hyperinflammatory syndrome characterized by fever, inflammation, multiorgan impairment that manifests 14–60 days after the SARS-CoV-2 infection in patients aged < 21 years. Case presentation We describe the clinical case of a 2-year-old child with MMA secondary to mutase deficiency, with the documented homozygous mutation c.2179 C > T of MMUT gene, associated to mut0 phenotype. One month after SARS-CoV-2 infection, he presented fever, rash, significant increase of C-reactive protein (CRP), ferritin, triglycerides, (interleukin) IL-6, PRO-BNP, compatible with the diagnosis of MIS-C. He was treated with intravenous immunoglobulins (2gr/Kg), methylprednisolone (2 mg/Kg/day), with rapid clinical improvement. Ten days later, he showed the worsening of clinical conditions, with the recurrence of fever, vasculitic rash with palmoplantar extension, further increase of ferritin (1033 ug/l), IL-6 (146 pg/ml), PRO-BNP (5117 pg/ml), triglycerides, anemia, thrombocytopenia, metabolic acidosis with hyperlactatemia (180 mg/dl), increased urinary methylmalonic acid (200 mmol/mCreat), multiorgan failure. He was treated with sodium bicarbonate, thiamine, coenzyme Q, vitamin C, methylprednisolone and anakinra (2 mg/Kg/day). Three days after the start of anakinra, he showed a significant improvement of clinical and biochemical parameters and defervescence. 20 days later, a sepsis from Staphylococcus Aureus and Candida Albicans required the interruption of anakinra, with the worsening of the clinical and haematological parameters and the exitus. Conclusions Only a few cases of patients with inherited metabolic diseases (IMD) and MIS-C are described. However, to our knowledge, this is the first case of MIS-C in MMA described. The description of these clinical cases is a precious lesson for pediatricians to manage IMD therapeutic emergencies. Anakinra must be considered as a safe treatment of choice in IMD patients with MIS-C. The use of anakinra in patients with a severe form of MMA is safe and can be employed to treat MIS-C, gaining a substantial clinical and biochemical improvement.

Did Inequalities in Mothers’ and Children’s Health and Well-Being in Japan Increase Through the Pandemic? Evidence From Nationwide Surveys and Routinely Collected Data (preprint)

Marginalised families faced significant challenges during the COVID-19 pandemic. This study explores inequalities in Japanese mothers’ and children’s health and wellbeing and family economic stability before and during the pandemic. Data sources were: nationwide surveys in 2019 and 2021 of families with children using medical institutions across Japan; infant mortality and adolescent suicide rates between 2018 and 2021 from publicly available sources. Outcomes by poor and non-poor families were compared for 2019 and 2021 using simple descriptive statistics. Poor mothers' part-time working increased from 41% to 61% and regular employment was reduced by two-thirds. Well-being of poor mothers worsened from 39% to 55%. Employment opportunities and wellbeing did not change for non-poor mothers. School subsidies among poor families increased from 23% to 55%. The infant mortality rate (IMR) among unemployed families increased significantly from 12.9/1,000 to 18.2/1,000 between 2018 and 2021 compared with a decreasing overall IMR from 1.9/1000 to 1.7/1000. Suicide rates in 10-19 year olds increased over the same period although no socio-economic indicators were available. Inequalities in mothers’ and children’s health and well-being indicators and family economics increased between 2019 to 2021 in Japan. This study cannot attribute cause but suggests a possible role of the pandemic.

Intimate Partner Violence among Indian Ever Married Women: Exploring the Insights from Tree-Based Machine Learning Approaches (preprint)

Background: Intimate partner violence (IPV) is a global concern with severe consequences, encompassing physical, sexual, and psychological harm within relationships. Worldwide, 736 million women have experienced IPV, necessitating urgent attention. In India, despite a slight improvement, IPV remains prevalent, exacerbated by the COVID-19 pandemic.Addressing IPV requires understanding its determinants, rooted in societal norms and gender imbalances. This paper aims to bridge research gaps by applying machine learning alongside traditional methods to predict and understand IPV prevalence, considering different socio-economic and socio-demographic factors. Methods: The study has used data from the fifth round of National Family Health Survey. Descriptive statistics was used to analyse the sample characteristics.Multivariate logistic regression analysis was subsequently applied to determine the associations between IPV and associated risk factors. The instances of the prevalence of IPV was analysed using a combination of four distinct machine learning algorithms: decision trees (DTs), random forest (RF), gradient boosting (GB), and logistic regression (LR). Results:Prevalence of IPV among ever married women is found to be 68.71%.Older age, belonging to Scheduled Tribes, Other Backward Classes, being Hindu or Christian, employment status, higher number of children, marrying after 18, lower wealth quintile, husbands' alcohol consumption, regional disparities, rural residence, marital control, decision-making autonomy, justification of beating, and marital dynamics were all significant factors influencing IPV risk.Based on recall and F1 gradient boosting has better predictive performance than other machine learning models considered. The top ten predictors for IPV, included marital control, alcohol consumption, justified beating, region, decision-making autonomy, education years for both spouses, number of children, wealth index, and current working status. Conclusion: The study aimed to identify women vulnerable to IPV using three tree-based machine learning models on data from a national survey in India. The preference for gradient boosting was highlighted for its higher sensitivity, crucial for accurately identifying women genuinely at risk of IPV.Further the study encompassed the use of logistic regression as a base model for interpretation, revealing hidden patterns and relationships through machine learning analysis. Overall, the research contributes valuable insights into IPV among Indian women within the context of machine learning.

Analysis of Medication Utilization in Isolated Areas of Fever Clinics During the COVID-19 Epidemic Outbreak: A Multicenter Study in General Hospitals in China (preprint)

Objective: To analyze the demographic characteristics and patterns of medication use among patients in fever clinics (FCs) during the COVID-19 outbreak in China and provide information for COVID-19 treatment. Method: Various-grade general hospitals in China were selected, and patient information was extracted during the initial wave of the COVID-19 epidemic. Demographic characteristics were analyzed, including visit time, age, sampling morbidity rate, and disease distribution. Prescription information from the FC database was extracted to analyze drug use and the rationality of the medication. Result: Between September 1 and December 31, 2022, 41,445 patients received treatment at FCs in 11 included hospitals. After the relaxation of COVID-19 control measures, there was a rapid increase in the number of daily patient visits (peaking >1,000 people/day, with a growth rate of 158.8%). The highest sampling morbidity rate was observed among individuals over 85 years old (>100 person-times/million population), followed by children (60-94 person-times/million population). Respiratory system diseases (39,295 cases) were the most diagnosed, with respiratory system infections (21,201 cases) and fever (15,132 cases) the most common. The proportion and frequency of use of essential national drugs were 34.3% and 73.1%, respectively, while those for the drugs recommended in the national COVID-19 treatment guidelines were 6.1% and 43.2%, respectively. Ibuprofen, acetaminophen, and Lianhua Qingwen had the highest frequency of drug use. The most prescribed drugs by cost were immunoglobulin, azivudine, and cefoperazone sulbactam. The water-electrolyte balance regulator drugs, respiratory system drugs, anti-infective drugs, and traditional Chinese patent drugs were the most frequently used. In contrast, immunomodulators, anti-infectives, and Chinese patent drugs had the largest monetary amounts. There was a significant difference in medication rationality between different hospital grades (P<0.001), with tertiary teaching hospitals having the highest rate. Conclusion: Strict epidemic control measures and the role of FCs played a crucial role in controlling the spread of the COVID-19 epidemic. Patients treated in FCs predominantly suffered from respiratory diseases, with older patients and children identified as high-risk populations. Physicians often choose national guidelines, essential drugs, and traditional Chinese for COVID-19 treatment. Tertiary teaching hospitals played a crucial role during the epidemic outbreak.

Development and validation of a federated learning framework for detection of subphenotypes of multisystem inflammatory syndrome in children (preprint)

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-acute sequela of SARS-CoV-2 infection. The highly diverse clinical features of MIS-C necessities characterizing its features by subphenotypes for improved recognition and treatment. However, jointly identifying subphenotypes in multi-site settings can be challenging. We propose a distributed multi-site latent class analysis (dMLCA) approach to jointly learn MIS-C subphenotypes using data across multiple institutions. Methods We used data from the electronic health records (EHR) systems across nine U.S. childrens hospitals. Among the 3,549,894 patients, we extracted 864 patients < 21 years of age who had received a diagnosis of MIS-C during an inpatient stay or up to one day before admission. Using MIS-C conditions, laboratory results, and procedure information as input features for the patients, we applied our dMLCA algorithm and identified three MIS-C subphenotypes. As validation, we characterized and compared more granular features across subphenotypes. To evaluate the specificity of the identified subphenotypes, we further compared them with the general subphenotypes identified in the COVID-19 infected patients. Findings Subphenotype 1 (46.1%) represents patients with a mild manifestation of MIS-C not requiring intensive care, with minimal cardiac involvement. Subphenotype 2 (25.3%) is associated with a high risk of shock, cardiac and renal involvement, and an intermediate risk of respiratory symptoms. Subphenotype 3 (28.6%) represents patients requiring intensive care, with a high risk of shock and cardiac involvement, accompanied by a high risk of >4 organ system being impacted. Importantly, for hospital-specific clinical decision-making, our algorithm also revealed a substantial heterogeneity in relative proportions of these three subtypes across hospitals. Properly accounting for such heterogeneity can lead to accurate characterization of the subphenotypes at the patient-level. Interpretation Our identified three MIS-C subphenotypes have profound implications for personalized treatment strategies, potentially influencing clinical outcomes. Further, the proposed algorithm facilitates federated subphenotyping while accounting for the heterogeneity across hospitals.

Safety Monitoring of Bivalent COVID-19 mRNA Vaccines Among Recipients 6 months and Older in the United States (preprint)

Importance Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes post-licensure. Objective To evaluate health outcomes following bivalent COVID-19 Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273.222) vaccination among individuals 6 months and older in the United States. Design Monthly monitoring of health outcomes from August 2022 to July 2023 in four administrative claims databases. Descriptive analyses monitored vaccine uptake, outcome counts and coadministration of bivalent COVID-19 and influenza vaccines. Sequential analyses tested for elevated risk of each outcome in a prespecified post-vaccination risk interval, or a period of hypothesized elevation based on clinical guidance, compared to a historical baseline. Participants and Exposures Persons 6 months and older who received a bivalent COVID-19 BNT162b2 or mRNA-1273.222 vaccine during the study period, with continuous enrollment in a medical insurance plan from the start of an outcome-specific clean interval to the COVID-19 vaccination date. Vaccines were identified using product-specific codes from medical coding systems. Health Outcomes Twenty outcomes were monitored in BNT162b2 vaccine recipients 6 months-4 years, and mRNA-1273.222 vaccine recipients 6 months-5 years. Twenty-one outcomes were monitored in BNT162b2 vaccine recipients 5-17 years and mRNA-1273.222 vaccine recipients 6-17 years. Eighteen outcomes were monitored in persons 18 years and older for both mRNA vaccines. Results Overall, 13.9 million individuals 6 months and older received a single bivalent COVID-19 mRNA vaccine. The statistical threshold for a signal was met for two outcomes in one database: anaphylaxis following bivalent BNT162b2 and mRNA-1273.222 vaccines in persons 18-64 years and myocarditis/pericarditis following bivalent BNT162b2 vaccines in individuals 18-35 years. There were no signals identified in young children. Conclusions Results were consistent with prior observations from published studies on COVID-19 vaccine safety. This study supports the safety profile of bivalent COVID-19 mRNA vaccines and the conclusion that the benefits of vaccination outweigh the risks.

How did CariesCare International performed under pandemic conditions in children: 1-year multicenter single-group interventional study (preprint)

Background:In 2020, CariesCare International (CCI) -derived from ICCMS- was plannedto be tested for caries-control effectiveness in children by means of a multicenter randomized clinical trial (RCT). Nevertheless, due to the pandemic, RCTs proved unfeasible and aerosol-generating procedures (AGP) were associated with a spread of COVID-19. Consequently, the study design required to be modified to a single-interventional study and CCI had to be adapted excluding AGP and reducing on-site consultation (CCI-adapted). Objective: This 12-month multicenter single-group interventional study aimed at assessing the effect of a pandemic CCI-adapted protocol on caries control in children. Methods: Twenty-one Latin American and European centers with n³20 3-8-year-old children per center were invited to participate; 17 obtained IRB and signed written informed consents. Trained examiners assessed at baseline (T0) and 1-year follow-up (T1y) (blind to the intervention): CCI-caries risk, oral-health-related practices; dmf/DMFS with ICDAS-merged-Epi visual caries severity and activity criteria; dental sepsis and toothache. Individual- and tooth-surface-level personalized care plan was then performed by dental practitioners previously trained in CCI-adapted. After 5 months, parents’ and dentists’ dental-care-process acceptance (Treatment Evaluation Inventory) was assessed. The one-year caries-control effect of CCI-adapted was assessed in terms of tooth-surface and individual-level caries-progression control; oral-health behavior improvement, and caries-care system acceptability. Results: Sixteen centers finished the study (94.1%; Latin America: n=13; Europe: n=3), with 337 children (78.6%;mean age of 5.5±1.6 years). There was a T0 to T1y significant decrease (p<0.05) in the mean number of tooth surfaces with caries lesions (7.7±9.1 to 2.8±4.6), with active caries lesions (6.8±8.8 to 0.8±2.2), and a tooth-surface caries-progression control of 99.3%. In the majority of children there was a significant (p<0.05) control of: caries progression (79.5%), high-caries risk (86.6%), and non-adequate oral-health behavior (72.7%). There was a very high (parents) and a high-very high (dentists) acceptability of CCI. Conclusion: Given the challenge of the pandemic, this single-group interventional CCI-adapted study showed one-year control of caries progression, caries risk, and high parents’ and dentists’ CCI acceptance. Trial registration:Retrospectively‐registered‐ClinicalTrials.gov NCT04666597 07/12/2020 (Protocol version 2): https://register.clinicaltrials. gov/prs/app/action/SelectProtocol?sid=S000AGM4&selectaction=Edit&uid=U00019IE&ts=2&cx=uwje3h