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.

Post COVID-19 conditions in Children and Adolescents at 3 months following a Delta outbreak in Australia: a cohort study (preprint)

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.

Infection and vaccine induced Spike antibody responses against SARS-CoV-2 Variants of concern in immune naïve children and adults (preprint)

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.

COVID-19 in children in NSW, Australia, during the 2021 Delta outbreak: Severity and Disease spectrum (preprint)

Objective(s): To describe the severity and clinical spectrum of SARS-CoV-2 infection in Australian children during the 2021 Delta outbreak. Design, Setting & Participants: A prospective cohort study of children <16 years with a positive SARS-CoV-2 nucleic acid test cared for by the Sydney Children's Hospital Network (SCHN) virtual and inpatient medical teams between 1 June-31 October 2021. Main outcome measures: Demographic and clinical data from all admitted patients and a random sample of outpatients managed under the SCHN virtual care team were analysed to identify risk factors for admission to hospital. Results: There were 17,474 SARS-CoV-2 infections in children <16 years in NSW during the study period, of whom 11,985 (68.6%) received care coordinated by SCHN. Twenty one percent of children infected with SARS-CoV-2 were asymptomatic. For every 100 SARS-CoV-2 infections in children <16 years, 1.26 (95% CI 1.06 to 1.46) required hospital admission for medical care; while 2.46 (95% CI 2.18 to 2.73) required admission for social reasons only. Risk factors for hospitalisation for medical care included age <6 months, a history of prematurity, age 12 to <16 years, and a history of medical comorbidities (aOR 7.23 [95% CI 2.92 to 19.4]). Of 17,474 infections, 15 children (median age 12.8years) required ICU admission; and 294 children required hospital admission due to social or welfare reasons. Conclusion: The majority of children with SARS-CoV-2 infection (Delta variant) had asymptomatic or mild disease. Hospitalisation was uncommon and occurred most frequently in young infants and adolescents with comorbidities. More children were hospitalised for social reasons than for medical care.

Off-season RSV epidemics in Australia after easing of COVID-19 restrictions (preprint)

Human respiratory syncytial virus (RSV) is an important cause of acute respiratory infection (ARI) with the most severe disease in the young and elderly. Non-pharmaceutical interventions (NPIs) and travel restrictions for controlling COVID-19 have impacted the circulation of most respiratory viruses including RSV globally, particularly in Australia, where during 2020 the normal winter epidemics were notably absent. However, in late 2020, unprecedented widespread RSV outbreaks occurred, beginning in spring, and extending into summer across two widely separated states of Australia, Western Australia (WA) and New South Wales (NSW) including the Australian Capital Territory (ACT). Genome sequencing revealed a significant reduction in RSV genetic diversity following COVID-19 emergence except for two genetically distinct RSV-A clades. These clades circulated cryptically, likely localized for several months prior to an epidemic surge in cases upon relaxation of COVID-19 control measures. The NSW/ACT clade subsequently spread to the neighbouring state of Victoria (VIC) and caused extensive outbreaks and hospitalisations in early 2021. These findings highlight the need for continued surveillance and sequencing of RSV and other respiratory viruses during and after the COVID-19 pandemic as mitigation measures introduced may result in unusual seasonality, along with larger or more severe outbreaks in the future.