ABSTRACT
Background: Long COVID remains incompletely understood in children and adolescents with scant Australian data available. We aimed to assess the impacts of the 2021 Delta variant of SARS-CoV-2 outbreak on symptoms and functioning 12 weeks post-acute infection in a cohort of children and adolescents. Methods: The parents (or next of kin) of 11864 children and adolescents from a population catchment who had mandatory contact with Sydney Childrens Hospital Network facilities during acute SARS-CoV-2 infection (confirmed by PCR) were contacted by email or text message. Findings: 1731 (17.7%) responded to an online survey assessing symptoms, functional impairment. 203 of the responders (11.7%) gave answers that were consistent with continued symptoms and/or functional impairment and were flagged for clinical review. Of the 169 subsequently clinically reviewed, many had already recovered (n=63, 37.3%) or had a pre-existing condition exacerbated by COVID-19 (18, 10.7%); 64 (37.9%) were diagnosed with a Post COVID Condition (PCC). Of these, a minority we considered to have features compatible with the United Kingdom consensus cases definition for Long COVID (n=21). Interpretation: During an outbreak of the Delta variant of SARS-CoV-2 an online questionnaire with subsequent clinical review revealed self-reported non-recovery at 12 weeks in a minority of cases, with a spectrum of features. Long COVID comprised only a subset of cases with self-reported non-recover, is infrequent in children and adolescents, but still comprises a likely significant burden that warrants attention.
Subject(s)
COVID-19 , Cognition DisordersABSTRACT
A more efficient and effective adaptive humoral immune response has been proposed as the basis of the usually favourable outcome of paediatric COVID-19. The breadth of virus and vaccine immunogenicity towards the ever-mutating Spike protein amongst variants of concern (VOC) have not yet been compared between children and adults. We utilized molecular cloning and sensitive antibody detection against conformational Spike by flow cytometry to assess Spike antibodies and delineate the immunogenic region in immune naïve children and adults vaccinated by BNT162b2 and ChAdOx1, and naturally infected with Early Clade, Delta, and Omicron variants. Patient sera were analysed against SARS-CoV-2 Spike antigens including naturally occurring VOCs Alpha, Beta, Gamma, Delta, Omicron BA.1, BA.2, and BA.5 variants of interest Epsilon, Kappa, Eta, D.2, and artificial Spike mutants. There was no notable difference between breadth and longevity of antibody responses generated against VOCs in children and adults. Vaccinated individuals displayed similar immunoreactivity profiles across variants to naturally infected individuals. Delta-infected patients had an enhanced immunogenicity toward Delta and some VOCs compared to patients infected by Early Clade SARS-CoV-2. Although Omicron BA.1, BA.2, and BA.5 antibody levels were increased after Omicron infection in both children and adults, immunogenicity against Omicron subvariants was reduced. This decrease was observed across VOC infection, immunization, and age groups. Selected epistatically combined mutations led to an increase of immunogenicity in artificial Spikes, but were unable to compensate overall within Omicron. Our results reveal important molecular features central to the generation of high antibody titers and broad immunoreactivity that should be considered in future vaccine design and global serosurveillance.
Subject(s)
Migraine Disorders , Hepatitis D , COVID-19ABSTRACT
Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV-2-specific naive T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. More naive interferon-activated CD4+ T cells were recruited into the memory compartment and recovery was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.
Subject(s)
COVID-19 , Coronavirus Infections , Drug-Related Side Effects and Adverse ReactionsABSTRACT
Encephalitis is most often caused by a variety of infectious agents, the identity of which is commonly determined through diagnostic tests utilising cerebrospinal fluid (CSF). Immune-mediated disorders are also a differential in encephalitis cases. We investigated the clinical characteristics and potential aetiological agents of unexplained encephalitis through metagenomic next-generation sequencing of residual clinical samples of multiple tissue types and independent clinical review. A total of 43 specimens, from both sterile and non-sterile sites, were collected from 18 encephalitis cases with no cause identified by the Australian Childhood Encephalitis study. Samples were subjected to total RNA sequencing to determine the presence and abundance of potential pathogens, to reveal mixed infections, pathogen genotypes, and epidemiological origins, and to describe the possible aetiologies of unexplained encephalitis. From this, we identified five RNA and two DNA viruses associated with human infection from both non-sterile (nasopharyngeal aspirates, nose/throat swabs, urine, stool rectal swab) and sterile (cerebrospinal fluid, blood) sites. These comprised two human rhinoviruses, two human seasonal coronaviruses, two polyomaviruses and one picobirnavirus. With the exception of picobirnavirus all have been previously associated with respiratory disease. Human rhinovirus and seasonal coronaviruses may be responsible for five of the encephalitis cases reported here. Immune-mediated encephalitis was considered clinically likely in six cases and RNA sequencing did not identify a possible pathogen in these cases. The aetiology remained unknown in nine cases. Our study emphasises the importance of respiratory viruses in the aetiology of unexplained child encephalitis and suggests that the routine inclusion of non-CNS sampling in encephalitis clinical guidelines/protocols could improve the diagnostic yield. Author Summary Encephalitis is caused by both infectious agents and auto-immune disorders. However, the aetiological agents, including viruses, remain unknown in around half the cases of encephalitis in many cohorts. Importantly, diagnostic tests are usually based on the analysis of cerebrospinal fluid which may limit their utility. We used a combination of meta-transcriptomic sequencing and independent clinical review to identify the potential causative pathogens in cases of unexplained childhood encephalitis. Accordingly, we identified seven viruses associated with both sterile and non-sterile sampling sites. Human rhinovirus and seasonal coronaviruses were considered as most likely responsible for five of the 18 encephalitis cases studied, while immune-mediated encephalitis was considered the cause in six cases, and we were unable to determine the aetiology in nine cases. Overall, we demonstrate the role of respiratory viruses as a cause of unexplained encephalitis and that sampling sites other than cerebrospinal fluid is of diagnostic value.