Corrigendum: Translatability of findings from cynomolgus monkey to human suggests a mechanistic role for IL-21 in promoting immunogenicity to an anti-PD-1/IL-21 mutein fusion protein.

[This corrects the article DOI: 10.3389/fimmu.2024.1345473.].

Translatability of findings from cynomolgus monkey to human suggests a mechanistic role for IL-21 in promoting immunogenicity to an anti-PD-1/IL-21 mutein fusion protein.

AMG 256 is a bi-specific, heteroimmunoglobulin molecule with an anti-PD-1 antibody domain and a single IL-21 mutein domain on the C-terminus. Nonclinical studies in cynomolgus monkeys revealed that AMG 256 administration led to the development of immunogenicity-mediated responses and indicated that the IL-21 mutein domain of AMG 256 could enhance the anti-drug antibody response directed toward the monoclonal antibody domain. Anti-AMG 256 IgE were also observed in cynomolgus monkeys. A first-in-human (FIH) study in patients with advanced solid tumors was designed with these risks in mind. AMG 256 elicited ADA in 28 of 33 subjects (84.8%). However, ADA responses were only robust and exposure-impacting at the 2 lowest doses. At mid to high doses, ADA responses remained low magnitude and all subjects maintained exposure, despite most subjects developing ADA. Limited drug-specific IgE were also observed during the FIH study. ADA responses were not associated with any type of adverse event. The AMG 256 program represents a unique case where nonclinical studies informed on the risk of immunogenicity in humans, due to the IL-21-driven nature of the response.

Somatic symptoms following sexual assault in adolescents: a prospective longitudinal study.

Adults and young people with somatoform disorders and somatic symptoms retrospectively report high rates of sexual abuse. We aimed to assess somatic symptoms in young people in the aftermath of a sexual assault and to document links with assault characteristics, with psychopathology and with related functional impairment. This was a prospective cohort study of adolescents seen in specialized clinics in London in the first 6 weeks following a sexual assault and at 4-5 months follow-up. We enquired about somatic symptoms (headaches, abdominal pain and sickness) pre and post assault, and we assessed psychiatric disorders and functional impairment at follow-up using validated scales. Information was obtained on 94 females (mean age 15.6, SD 1.3). There was a statistically significant increase in the number of adolescents reporting somatic symptoms at 4-5-month follow-up (65/94, 69%) (p = 0.035), compared with estimated pre-assault rates (52/94, 55%) and a significant increase in somatic symptoms at follow-up among the victims of violent sexual abuse (p < .001). Subjects with somatic symptoms at follow-up had significant higher rates of psychiatric disorders - especially generalised anxiety disorder, panic disorder and major depressive disorders - as well as lower psychosocial functioning (p < 0.01), than those without somatic symptoms.

Risk factors for long covid in previously hospitalised children using the ISARIC Global follow-up protocol: A prospective cohort study

BackgroundThe long-term sequelae of coronavirus disease 2019 (Covid-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with Covid-19 and associated risk factors. MethodsThis is a prospective cohort study of children ([≤]18 years old) admitted with confirmed Covid-19 to Z.A. Bashlyaeva Childrens Municipal Clinical Hospital in Moscow, Russia. Children admitted to the hospital during the first wave of the pandemic, between April 2, 2020 and August 26, 2020, were included. Telephone interview using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Covid-19 Health and Wellbeing paediatric follow up survey. Persistent symptoms (>5 months) were further categorised by system(s) involved. FindingsOverall, 518 of 853 (61%) of eligible children were available for the follow-up assessment and included in the study. Median age was 10.4 years (IQR, 3-15.2) and 270 (52.1%) were girls; median follow-up since hospital discharge was 256 (223-271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%,) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: age "6-11 years" (odds ratio 2.74 (95% confidence interval 1.37 to 5.75) and "12-18 years" (2.68, 1.41 to 5.4), and a history of allergic diseases (1.67, 1.04 to 2.67). InterpretationA quarter of children experienced persistent symptoms months after hospitalization with acute covid-19 infection, with almost one in ten experiencing multi-system involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up. Our findings highlight the need for replication and further investigation of potential mechanisms as well as clinical support to improve long term outcomes in children. FundingNone. O_TEXTBOXResearch in contextO_ST_ABSEvidence before this studyC_ST_ABSEvidence suggests that Covid-19 may result in short- and long-term consequences to health. Studies in children and adolescents are limited and available evidence is scarce. We searched Embase for publications from inception to April, 25, 2021, using the following phrases or combinations of phrases "post-covid condition" or "post-covid syndrome" or "covid sequalae" or "post-acute covid" or "long covid" or "long hauler" with "pediatric*" or "paediatric*" or "child*" or "infant*" or "newborn*" or "toddler*" or "neonate*" or "neonatal" or "adolescent*" or "teen*". We found small case series and small cohort studies looking at Covid-19 consequences in children. No large cohort studies of previously hospitalised children, assessing symptom duration, categorisation or attempting multivariable analyses to identify independent risk factors for long Covid development were identified. Added value of this studyTo our knowledge, this is the largest cohort study with the longest follow-up since hospital discharge of previously hospitalised children. We found that even months after discharge from the hospital, approximately a quarter of children experience persistent symptoms with one in ten having multi-system involvement. Older age and allergic diseases are associated with Covid-19 consequences. Parents of some children report emotional and behavioural changes in their children after Covid-19. Implications of all the available evidenceOur findings highlight the need for continued global research of Covid-19 consequences in the paediatric population. Older children admitted to the hospital should be carefully monitored upon discharge. Large, controlled studies aiming to identify risk groups and potential intervention strategies are required to fill knowledge gaps. C_TEXTBOX

Factors influencing primary care attendance in adolescents with high levels of depressive symptoms.

BACKGROUND: Although depression is common amongst adolescents attending general practice, little is known about factors which influence consultation. This study aims to identify factors that contribute to GP attendance in adolescents with high levels of mood symptoms. METHODS: Case-control study of 13 to 17-year-olds attending (cases, N = 156) and not attending (controls, N = 120) an urban general practice during a 6-month period; questionnaires on depressive symptoms (Mood and Feelings Questionnaire), physical symptoms (Child Somatisation Inventory), socio-demographic data and attitudes were completed. RESULTS: Attenders had significantly more depressive and physical symptoms. In the comparison between 63 attenders and 34 non-attenders with a high level of depressive symptoms, attendance was significantly linked to lower socio-economic status, non-White ethnicity, non-intact families, and not believing that doctors are only interested in physical symptoms. On logistic regression analysis, attendance in males with depressive symptoms was predicted by more physical and less marked depressive symptoms; in females by non-White ethnicity and not believing doctors are only interested in physical symptoms. CONCLUSION: Both socio-demographic factors and adolescent attitudes influence general practitioner attendance in adolescents with high levels of depressive symptoms. These findings may help inform interventions to facilitate help seeking in primary care for young people with high levels of depressive symptoms.

Functional Symptoms and Somatoform Disorders in Children and Adolescents: The Role of Standardised Measures in Assessment.

Functional or unexplained medical symptoms (physical symptoms that are not adequately explained by organic factors and where a major role for psychological factors is assumed) are common amongst children in the general population but can also be an expression of somatisation and somatoform disorders. Co-morbid psychopathology is common. We describe measures mostly used in research into problems related to somatisation in children and adolescents that may be helpful to clinical researchers. Some address the nature and severity of physical symptoms, others document illness attitudes, beliefs and functional impairment, and a third group assesses emotional symptoms. Questionnaires can be helpful for clinicians in quantifying (i) the nature and severity of somatic symptoms and associated functional impairment, (ii) contributory health attitudes and illness beliefs and (iii) co-morbid or primary anxiety and depressive disorders. Together with pain and activity diaries and careful documentation of school attendance, these measures may also be helpful in monitoring treatment response.

Paediatric Liaison Work by Child and Adolescent Mental Health Services.

BACKGROUND: Although psychiatric morbidity is common amongst paediatric patients, little is known about the availability of CAMH paediatric liaison services. METHOD: We surveyed all Trusts with specialist CAMH services and paediatric units in Greater London, enquiring about the nature of liaison that CAMHS provide. RESULTS: We found that although liaison paediatric work was common, dedicated paediatric liaison services were provided by only a minority of specialist multidisciplinary CAMHS. Their work involved most aspects of child psychopathology, and included emergencies and children with joint physical and psychiatric problems. About 2/3 of paediatricians were satisfied with CAMHS liaison services, but virtually all desired to see them developed further. There were few indications of co-ordination between specialist multidisciplinary CAMHS and other paediatric psychosocial support services.

Practitioner review: chronic fatigue syndrome in childhood.

BACKGROUND: Chronic fatigue syndrome (CFS) is being increasingly recognized in children and adolescents. Yet comparatively little attention has been given in the literature to management. METHODS: Description of the main features of the disorder, precipitating and maintaining factors and diagnostic assessment. Outline of different views on the nature and treatment of CFS in childhood. Description of a rehabilitation program based on cognitive behavior therapy and graded activity. RESULTS: Using adult research criteria, CFS can be diagnosed in children and adolescents. In its severe form it is often triggered by infectious illness episodes. It is commonly associated with mood disorders in the child and with mental distress and high levels of emotional involvement in parents. A number of patient support groups hold the view that CFS is a medical disorder, contest a psychiatric contribution and advocate 'pacing' as an approach to rehabilitation which includes avoiding activities. To date there is no empirical evidence for the efficacy of this approach. Research in adults, open and clinical reports in children support the use of graded activity and family cognitive behavior therapy. The main aim is to enable children, with the help of their family, to carry out their own rehabilitation with some support and guidance from a health professional. Engaging the child and family in treatment and forming a therapeutic alliance is a continual process and a crucial aspect of management, as many families view the condition as a medical disorder and are initially ambivalent towards this approach. CONCLUSIONS: There is controversy about the nature and management of CFS in childhood but a rehabilitation program based on family cognitive behavior therapy can be implemented and seems to hold most promise in the management of children with CFS. Family engagement is a crucial aspect of management.

The Interface Between Physical and Mental Health Problems and Medical Help Seeking in Children and Adolescents: A Research Perspective.

This paper addresses child and adolescent psychopathology as it presents to general practitioners and paediatricians, and explores psychosocial aspects of unexplained medical symptoms in children and adolescents. High rates of psychopathology have been identified amongst children and adolescents attending general practice and paediatric services, most of it ''hidden'' at presentation and emotional in nature. It is often linked to poor physical well being and to maternal stress focused on the child. It may be of special relevance to medical help seeking in socio-economically advantaged areas. Co-morbid psychopathology, mainly emotional disorders, is common amongst children with unexplained medical symptoms. However, there are specific psychosocial aspects that differentiate these children from those with emotional disorders. They involve disease beliefs, illness behaviour and predicament. The latter may be characterised by special reactivity to stress in children with personality vulnerability, in a context of parents with high levels of mental distress, unexplained medical symptoms and emotional over-involvement with the child. There is comparatively little interface work between CAMHS and primary health care. An important research priority would seem to lie in the development of interventions that can be adapted for use by primary care staff. Similarly, there are few dedicated CAMHS paediatric liaison teams. Their more extensive development should help attend in a more informed and focused way than at present to children and adolescents suffering from unexplained physical symptoms and disorders. Further research is needed into vulnerability mechanisms and maintaining factors, health beliefs, treatment engagement and interventions.