Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in Households with Children, Southwest Germany, May-August 2020.

Resolving the role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in households with members from different generations is crucial for containing the current pandemic. We conducted a large-scale, multicenter, cross-sectional seroepidemiologic household transmission study in southwest Germany during May 11-August 1, 2020. We included 1,625 study participants from 405 households that each had ≥1 child and 1 reverse transcription PCR-confirmed SARS-CoV-2-infected index case-patient. The overall secondary attack rate was 31.6% and was significantly higher in exposed adults (37.5%) than in children (24.6%-29.2%; p = <0.015); the rate was also significantly higher when the index case-patient was >60 years of age (72.9%; p = 0.039). Other risk factors for infectiousness of the index case-patient were SARS-CoV-2-seropositivity (odds ratio [OR] 27.8, 95% CI 8.26-93.5), fever (OR 1.93, 95% CI 1.14-3.31), and cough (OR 2.07, 95% CI 1.21-3.53). Secondary infections in household contacts generate a substantial disease burden.

High trait anxiety during adolescence interferes with discriminatory context learning.

Persistent adult anxiety disorders often begin in adolescence. As emphasis on early treatment grows, we need a better understanding of how adolescent anxiety develops. In the current study, we used a fear conditioning paradigm to identify disruptions in cue and context threat-learning in 19 high anxious (HA) and 24 low anxious (LA) adolescents (12-17years). We presented three neutral female faces (conditioned stimulus, CS) in three contingent relations with an unconditioned stimulus (UCS, a shrieking female scream) in three virtual room contexts. The degree of contingency between the CSs and the UCSs varied across the rooms: in the predictable scream condition, the scream followed the face on 100% of trials; in the unpredictable scream condition, the scream and face appeared randomly and independently of each other; in the no-scream condition the CS was presented in the absence of any UCS. We found that the LA adolescents showed higher levels of fear-potentiated startle to the faces relative to the rooms. This difference was independent of the contingency condition. The HA adolescents showed non-differential startle between the CSs, but, in contrast to previous adult data, across both cue types displayed lowest startle to the unpredictable condition and highest startle to the no-scream condition. Our study is the first to examine context conditioning in adolescents, and our results suggest that high trait anxiety early in development may be associated with an inability to disambiguate the signalling roles of cues and contexts, and a mislabelling of safety or ambiguous signals.

Perceived social support and characteristics of social networks of families with children with special healthcare needs following the COVID-19 pandemic.

Background: Children with special healthcare needs (CSHCN) require more support than the average of their peers. Support systems for CSHCN were particularly affected by pandemic control measures. Perceived social support is a resource for health and wellbeing for CSHCN and their families. Associations of social support, mental health and socioeconomic status (SES) have been described. This study aims to (1) assess perceived social support in families with and without CSHCN; (2) describe structure and types of social networks of families with and without CSHCN; and (3) explore associations between perceived social support, disease complexity, child and caregiver mental health, and SES. Methods: This is the third of a sequential series of cross-sectional online surveys conducted among caregivers of children ≤ 18 years in Germany since the beginning of the COVID-19 pandemic, administered between 1st December 2022 and 10 March 2023. The Brief Social Support Scale (BS6) assessed perceived social support. Child and parental mental health were assessed using the Strengths and Difficulties Questionnaire (SDQ) and WHO-5 Wellbeing index. The CSHCN-Screener identified CSHCN. Descriptive statistics and linear regression modeling assessed associations between perceived social support, parent-reported child mental health problems, disease complexity, caregiver mental wellbeing and SES. Results: The final sample included 381 participants, among them 76.6% (n = 292) CSHCN. 46.2% (n = 176) of caregivers reported moderate, i.e., at least occasional social support. Social support was largely provided by informal social networks consisting of partners, relatives and neighbors/friends. Linear regression modeling revealed associations of lower perceived social support with higher disease complexity of the child, lower caregiver mental wellbeing, lower SES and increasing caregiver age. Conclusion: The results of this study describe inequalities in perceived social support according to disease complexity of the child, caregiver mental health and socioeconomic status. They highlight the importance of social support and support networks as a resource for wellbeing of caregivers and CSHCN. Moving on from the COVID-19 pandemic, recovery strategies should focus on low-threshold interventions based in the community to improve social support for families with CSHCN and actively involve caregivers in identifying needs and co-creating new approaches.

Measuring the role of conditioning and stimulus generalisation in common fears and worries.

Common and persistent fears may emerge through learning mechanisms such as fear conditioning and generalisation. Although there have been extensive studies of these learning processes in healthy but also psychiatric samples, many of the tasks used to produce conditioning and assess generalisation either use painful and aversive stimuli as the unconditioned stimuli (UCS), or suffer from poor belongingness between the conditioned stimuli and the UCS. Here, we present novel data from a paradigm designed to examine fear conditioning and generalisation in healthy individuals. Two female faces served as conditioned threat cue (CS+) and conditioned safety cue (CS-) respectively. The CS+ was paired repeatedly with a fearful, screaming face (unconditioned stimulus). Generalisation included intermediate faces which varied in their similarity to the CS+ and CS-. We measured eyeblink startle reflex and self-reported ratings. Acquired fear of the CS+ generalised to intermediate stimuli in proportion to their perceptual similarity to the CS+. Our findings demonstrate how fears of new individuals may develop based on resemblance to others with whom an individual has had negative experiences. The paradigm offers new opportunities for probing the role of generalisation in the emergence of common and persistent fears.

Anxious and non-anxious adolescents' experiences of non-clinical magnetic resonance imaging research.

Magnetic resonance imaging (MRI) has become a ubiquitous research tool for developmental neuroscientists interested in brain structure and function in children and adolescents. However, ethical concerns are sometimes raised about using MRI with children and adolescents, especially when participants have anxiety. We asked 17 clinically/sub-clinically anxious and 19 non-anxious adolescents about their experiences of taking part in MRI for research purposes. Although the anxious group reported experiencing more anxiety during the scan, these differences had attenuated by the time participants got home. We found no evidence that anxious adolescents would be less likely to choose to have another scan or would feel more nervous during another scan. There was some evidence that more trait anxious adolescents found the MRI study enjoyable. These findings should give ethics committees, clinicians, and parents confidence that so long as researchers exercise appropriate care, MRI research is acceptable to adolescents, including those with clinical anxiety.

Mental health of children with and without special healthcare needs and of their caregivers during COVID-19: a cross-sectional study.

OBJECTIVE: To describe mental health outcomes and measures of pandemic burden of children with and without special healthcare needs, and their caregivers following the second wave of the COVID-19 pandemic in Germany. DESIGN: This is the second of a sequential series of cross-sectional online surveys conducted among caregivers of children ≤18 years since the onset of the COVID-19 pandemic, administrated between 2 April 2021 and 31 July 2021. MAIN OUTCOME MEASURES: Child and parental mental health were assessed using the Strengths and Difficulties Questionnaire and WHO-5 Well-being index. Children with Special Healthcare Needs (CSHCN) were identified using the CSHCN-Screener. Descriptive statistics, linear and hierarchical logistic regression modelling assessed associations between parent-reported child mental health problems and measures of pandemic burden, disease complexity, caregiver mental well-being and socioeconomic status. RESULTS: 521 participants were included in the final sample. There was a high prevalence of parent-reported mental health problems in n=302 (66.7%) children, particularly in CSHCN. Among caregivers, n=372 (72.5%) screened positive for depression. Logistic regression modelling showed a strong association of child mental health problems and disease complexity, parental mental well-being, increase in family conflict and inadequate social support. CONCLUSIONS: Our study identifies CSHCN as a particularly vulnerable group in terms of mental health outcomes. Psychosocial factors were important predictors of parent-reported child mental health problems. Policy measures should consider the importance of social support systems for vulnerable children and their families, and aim to provide accessible mental health support for caregivers.

Impact of the COVID-19 Pandemic on Mental Health Outcomes of Healthy Children, Children With Special Health Care Needs and Their Caregivers-Results of a Cross-Sectional Study.

BACKGROUND: Several studies have described widening inequalities as a result of the COVID-19 pandemic, mostly for adult populations. Children and adolescents are particularly impacted by the indirect effects of the pandemic and lockdown measures, such as reduced access to or delays in health care and school closures. National surveys in several countries also show a rising mental health burden in children and adolescents during the COVID-19 pandemic. Children with special health care needs are a particularly vulnerable group in this context as they rely on a wide range of services, which were mostly suspended during the first wave of the pandemic. This study aims: (1) to describe the mental health outcomes of children with and without special healthcare needs and of their caregivers following the first national lockdown in Germany; (2) to investigate variations in mental health outcomes and measures of pandemic burden according to socioeconomic status; (3) to assess the impact of socioeconomic status, disease complexity and psychosocial burden on parent-reported child mental health problems. METHODS: We conducted an online survey among 1,619 caregivers of children aged 1-18 years from August 11th until October 5th 2020. Participants were recruited both from families of children with special healthcare needs and of healthy children. Inequalities were analysed by descriptive statistics, simple and hierarchical logistic regression modelling to explore the association between socioeconomic status and psychological outcome measures, disease complexity and general burden related to COVID-19. RESULTS: There was a high prevalence of 57.4% of parent-reported mental health problems in children and of a positive screening score for depression in 30.9% of parents. Parent-reported mental health problems were more likely to affect children with low socioeconomic status, with complex chronic disease and those whose parents screened positive for depression. CONCLUSIONS: This study highlights inequalities in parent-reported child mental health outcomes by socioeconomic status and disease complexity in a large sample of German families with and without children with special health care needs. Political measures should put children at the centre and aim to mitigate the unequal impact of the COVID-19 pandemic, particularly on the mental health of vulnerable children.

Patientenpartizipation in der pädiatrischen Versorgungsforschung am Universitätsklinikum Freiburg: von der Projektbeteiligung zum Patientenbeirat.

Participation of patients and relatives in research means that those affected are involved in the research process in a partnership role. Despite the growing importance of participatory approaches and the large number of available concepts, many researchers and patients are faced with the question of how participatory research can be realized and organized in concrete terms. Here we report on our experiences with two different forms of patient participation in research in the context of pediatric health care research at a university hospital: (1) In a project for the development and evaluation of a case management for patients with spinal muscular atrophy, patient representatives have an consultative role. (2) In the patient advisory board, which is to accompany the research activities of the research group at the site continuously and systematically, i.e. in all phases, the participation currently corresponds to a contributory role (involvement) which, in the future, could be moved onto the collaborative stage. In both forms of participation, the essential questions include the selection of the participating patients, the type and extent of participation, and the evaluation of the effect of participation on the research that is carried out. In our experience, both forms of participation add value to research from the perspective of all participants. At the same time, they bring different opportunities and challenges. While in project-based participation the sphere of influence is already delineated by researchers, the context of the patient advisory board provides more room and openness to develop, for example, a research agenda and thus identify new research topics. In our experience, however, sufficient resources (in terms of time and money) are required from all participants, as well as good, trusting cooperation with jointly developed processes to realize both forms of participation.

Pulmonary Function and Persistent Clinical Symptoms in Children and Their Parents 12 Months After Mild SARS-CoV-2 Infection.

Background: Pulmonary involvement is the leading cause of morbidity and mortality after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Long-term impairment has been reported in adults with severe infection. However, most infections cause only mild symptoms or are even asymptomatic, especially in children. There is insufficient evidence regarding pulmonary outcome measures in mild SARS-CoV-2. The objectives of this study were to determine spirometry parameters after SARS-CoV-2 infection and correlate those with reported persisting symptoms in children, adolescents, and adults. Methods: Data on clinical symptoms during acute infection as well as SARS-CoV-2 serology results were recorded. Twelve months after infection, spirometry was performed and information on persisting symptoms was collected using a structured questionnaire. 182 participants (108 SARS-CoV-2 positive) from 48 families were included; 53 children (< 14 years), 34 adolescents and young adults (14-25 years), and 95 adults. Results: Spirometry values did not significantly differ between the particular subgroups of the cohort (adults, adolescents, children; infected and non-infected individuals). Adults reported more symptoms during acute infection as well more persisting fatigue (29.7% of participants), reduced physical resilience (34.4%), and dyspnea (25.0%) 12 months after infection than adolescents (fatigue 26.7%, reduced physical resilience 20%, and 0% dyspnea) and children (4%, 0%, 0%, respectively). There was no correlation between persistent subjective symptoms and spirometry results. Discussion: Children and adolescents are less affected than adults by acute SARS-CoV-2 as well as by post-infection persistent symptoms. Spirometry was not able to demonstrate any differences between healthy individuals and participants who had suffered from mild SARS-CoV-2 12 months after the infection.

Role of ABO Blood Group in SARS-CoV-2 Infection in Households.

An association between certain ABO/Rh blood groups and susceptibility to SARS-CoV-2 infection has been proposed for adults, although this remains controversial. In children and adolescents, the relationship is unclear due to a lack of robust data. Here, we investigated the association of ABO/Rh blood groups and SARS-CoV-2 in a multi-center study comprising 163 households with 281 children and 355 adults and at least one SARS-CoV-2 seropositive individual as determined by three independent assays as a proxy for previous infection. In line with previous findings, we found a higher frequency of blood group A (+ 6%) and a lower frequency of blood group O (-6%) among the SARS-CoV-2 seropositive adults compared to the seronegative ones. This trend was not seen in children. In contrast, SARS-CoV-2 seropositive children had a significantly lower frequency of Rh-positive blood groups. ABO compatibility did not seem to play a role in SARS-CoV-2 transmission within the families. A correction for family clusters was performed and estimated fixed effects of the blood group on the risk of SARS-CoV-2 seropositivity and symptomatic infection were determined. Although we found a different distribution of blood groups in seropositive individuals compared to the reference population, the risk of SARS-CoV-2 seropositivity or symptomatic infection was not increased in children or in adults with blood group A or AB versus O or B. Increasing age was the only parameter positively correlating with the risk of SARS-CoV-2 infection. In conclusion, specific ABO/Rh blood groups and ABO compatibility appear not to predispose for SARS-CoV-2 susceptibility in children.

Long COVID symptoms in exposed and infected children, adolescents and their parents one year after SARS-CoV-2 infection: A prospective observational cohort study.

BACKGROUND: Long COVID in children and adolescents remains poorly understood due to a lack of well-controlled studies with long-term follow-up. In particular, the impact of the family context on persistent symptoms following SARS-CoV-2 infection remains unknown. We examined long COVID symptoms in a cohort of infected children, adolescents, and adults and their exposed but non-infected household members approximately 1 year after infection and investigated clustering of persistent symptoms within households. METHODS: 1267 members of 341 households (404 children aged <14 years, 140 adolescents aged 14-18 years and 723 adults) were categorized as having had either a SARS-CoV-2 infection or household exposure to SARS-CoV-2 without infection, based on three serological assays and history of laboratory-confirmed infection. Participants completed questionnaires assessing the presence of long COVID symptoms 11-12 months after infection in the household using online questionnaires. FINDINGS: The prevalence of moderate or severe persistent symptoms was statistically significantly higher in infected than in exposed women (36.4% [95% CI: 30.7-42.4%] vs 14.2% [95% CI: 8.7-21.5%]), infected men (22.9% [95% CI: 17.9-28.5%] vs 10.3% [95% CI: 5.8-16.9%]) and infected adolescent girls (32.1% 95% CI: 17.2-50.5%] vs 8.9% [95%CI: 3.1-19.8%]). However, moderate or severe persistent symptoms were not statistically more common in infected adolescent boys aged 14-18 (9.7% [95% CI: 2.8-23.6%] or in infected children <14 years (girls: 4.3% [95% CI: 1.2-11.0%]; boys: 3.7% [95% CI: 1.1-9.6%]) than in their exposed counterparts (adolescent boys: 0.0% [95% CI: 0.0-6.7%]; girls < 14 years: 2.3% [95% CI: 0·7-6·1%]; boys < 14 years: 0.0% [95% CI: 0.0-2.0%]). The number of persistent symptoms reported by individuals was associated with the number of persistent symptoms reported by their household members (IRR=1·11, p=·005, 95% CI [1.03-1.20]). INTERPRETATION: In this controlled, multi-centre study, infected men, women and adolescent girls were at increased risk of negative outcomes 11-12 months after SARS-CoV-2 infection. Amongst non-infected adults, prevalence of negative outcomes was also high. Prolonged symptoms tended to cluster within families, suggesting family-level interventions for long COVID could prove useful. FUNDING: Ministry of Science, Research and the Arts, Baden-Württemberg, Germany.

Robust and durable serological response following pediatric SARS-CoV-2 infection.

The quality and persistence of children's humoral immune response following SARS-CoV-2 infection remains largely unknown but will be crucial to guide pediatric SARS-CoV-2 vaccination programs. Here, we examine 548 children and 717 adults within 328 households with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. We assess serological response at 3-4 months and 11-12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Neutralization against wild type SARS-CoV-2 and the Delta VOC are analysed in a pseudotyped virus assay. Children, compared to adults, are five times more likely to be asymptomatic, and have higher specific antibody levels which persist longer (96.2% versus 82.9% still seropositive 11-12 months post infection). Of note, symptomatic and asymptomatic infections induce similar humoral responses in all age groups. SARS-CoV-2 infection occurs independent of HCoV serostatus. Neutralization responses of children and adults are similar, although neutralization is reduced for both against the Delta VOC. Overall, the long-term humoral immune response to SARS-CoV-2 infection in children is of longer duration than in adults even after asymptomatic infection.

How do social fears in adolescence develop? Fear conditioning shapes attention orienting to social threat cues.

Social fears emerging in adolescence can have negative effects on emotional well-being. Yet the mechanisms by which these risks occur are unknown. One possibility is that associative learning results in fears to previously neutral social stimuli. Such conditioned responses may alter subsequent processing of social stimuli. We used a novel conditioning task to examine how associative processes influence social fear and attention orienting in adolescents. Neutral photographs were paired with socially rewarding or aversive stimuli during conditioning; a dot-probe task then assessed biases in attention orienting. The social conditioning task modified subjective ratings of the neutral stimuli. Moreover, for the neutral stimulus that was paired with the aversive stimulus, the strength of conditioning showed a relationship with subsequent attentional vigilance. The findings elucidate mechanisms by which negative peer experiences during adolescence may affect emotional processing.

Fear responses to safety cues in anxious adolescents: Preliminary evidence for atypical age-associated trajectories of functional neural circuits.

Adolescent anxiety is common and impairing and often persists into adulthood. There is growing evidence that adult anxiety is characterized by abnormal fear responses to threat and safety cues, along with perturbations in fear-related neural circuits. Although some of this work has been extended to adolescents, with promising results, it is not yet clear whether changes in these circuits across developmental age varies between anxious and non-anxious adolescents. Here we used fMRI to examine how age modulates neural responses as adolescents are exposed to threat and safety cues. Participants were 15 anxious and 11 non-anxious adolescents (age 12-17) who completed a fear conditioning paradigm. The paradigm incorporated a threat cue comprising a neutral face which was paired with a fearful, screaming face, a safety cue comprising a different neutral face, and a control stimulus. Across the whole sample, neural activation to the threat cue (relative to the control cue) correlated positively with age in a number of regions, including the dorsal anterior cingulate and bilateral dorsolateral prefrontal cortex (PFC). However, neural activation to the safety cue (relative to the control cue) was modulated differently by age in the two groups: a more positive association between activation and age was observed in the control group compared to the anxious group in various regions including medial and dorsolateral PFC, anterior insula, and amygdala. These findings suggest that maturation of the neural substrates of fear responses to safety cues may be perturbed in anxious adolescents, potentially contributing to the emergence and maintenance of anxiety disorders in adulthood.

Executive dysfunction and autobiographical memory retrieval in recovered depressed women.

BACKGROUND AND OBJECTIVES: Depressed individuals have difficulty remembering specific autobiographical events. These deficits often persist after recovery of mood symptoms, but the mechanisms underlying impaired memory specificity in recovered depressed individuals remain unclear. Here, we sought to examine whether performance on two cognitive measures might be related to deficits in autobiographical memory retrieval in individuals with a history of depression. METHODS: Twenty-four recovered depressed women (12 with more than one previous episode) and 24 never depressed women completed two cognitive measures (Digit Span and a Number Generation Task) and tests of autobiographical memory recall. RESULTS: Overall, the recovered depressed women did not show deficits in autobiographical retrieval. However, those with more than one previous episode had impaired retrieval of categorical autobiographical memories. Moreover, depression history moderated the relationship between Digit Span and retrieval of categoric autobiographical memories such that within the whole recovered depressed group (but not the never depressed group), those with lower Digit Span also had poorer retrieval of categorical autobiographical memories. LIMITATIONS: Our sample size was small and included only women. Moreover, order effects may have been a significant factor. CONCLUSIONS: These findings support the notion that working memory is an important factor in impairing autobiographical memory in those who have recovered from depression, but suggest a complex relationship with autobiographical recall.

Adolescent and adult risk-taking in virtual social contexts.

There is a paucity of experimental data addressing how peers influence adolescent risk-taking. Here, we examined peer effects on risky decision-making in adults and adolescents using a virtual social context that enabled experimental control over the peer "interactions." 40 adolescents (age 11-18) and 28 adults (age 20-38) completed a risk-taking (Wheel of Fortune) task under four conditions: in private; while being observed by (fictitious) peers; and after receiving 'risky' or 'safe' advice from the peers. For high-risk gambles (but not medium-risk or even gambles), adolescents made more risky decisions under peer observation than adults. Adolescents, but not adults, tended to resist 'safe' advice for high-risk gambles. Although both groups tended to follow 'risky' advice for high-risk gambles, adults did so more than adolescents. These findings highlight the importance of distinguishing between the effects of peer observation and peer advice on risky decision-making.

Low-dose tryptophan depletion in recovered depressed women induces impairments in autobiographical memory specificity.

BACKGROUND: Depressed patients perform poorly on tests of autobiographical memory specificity (AMS); this may have negative consequences for other important cognitive abilities, delays recovery from mood episodes, and, in recovered patients, may mediate vulnerability to future episodes. Although the cognitive mechanisms underlying AMS deficits are beginning to be understood, the neurobiological mechanisms remain unclear. Serotonin is implicated in both depression and long-term memory; therefore, temporary lowering of brain serotonin function via acute tryptophan depletion (ATD) offers a means of studying the role of serotonin in autobiographical memory specificity. MATERIALS AND METHODS: In this study, 24 previously depressed women underwent low-dose ATD or sham depletion and completed tests of initial and delayed memory, recollection- and familiarity-based recognition, and AMS. RESULTS: ATD did not differentially affect state mood. Compared with sham depletion, ATD impaired immediate recall on the Auditory Verbal Learning Test. Although ATD did not differentially impair recollection- and familiarity-based recognition, it did slow recognition of positive words. ATD also reduced autobiographical memory specificity in response to negative cue words. DISCUSSION: The results confirm previous findings that low-dose ATD can reinstate depression-congruent biases in cognition without causing depressive mood in vulnerable populations. The ATD-induced reduction in memory specificity suggests that serotonergic dysfunction may mediate depressive deficits in autobiographical memory; the interaction of cognitive and neurobiological vulnerability mechanisms is discussed.