International Care programs for Pediatric Post-COVID Condition (Long COVID) and the way forward.

BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care. METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care. RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support. CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration. IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.

Stakeholder perspectives of immunisation delivery for adolescents with disability in specialist schools in Victoria, Australia: 'we need a vaccination pathway'.

BACKGROUND: Adolescents with disability have lower vaccination rates than the general population, including HPV vaccination. Understanding the multi-level influences on vaccination in specialist schools is crucial to achieve optimal vaccination coverage and vaccination experiences for adolescents living with disability. OBJECTIVE: To identify and improve understanding of the facilitators and barriers of HPV vaccination among adolescents with intellectual disabilities or autism in Victorian specialist schools to inform strategies to increase vaccination acceptance and uptake. METHODS: Qualitative interviews with key stakeholders (adolescents with disabilities, parents, school and council immunisation staff) from six specialist schools in Victoria, Australia. Data were analysed thematically. Inductively derived themes were then deductively mapped across the UNICEF 'Journey to Immunization' model. RESULTS: 32 interviews were conducted with stakeholders (2 adolescents, 7 parents, 13 school staff, 10 council staff). Trust in vaccines was high, but knowledge of the HPV vaccine was limited. Barriers included lack of accessible information for parents, the consent process, behavioural challenges and vaccine-related anxiety among students. The immunisation program in special schools was perceived as convenient, however preparing students for vaccination day and catering to individual student needs were key. Participants expressed a need for more parent information about options and additional support for vaccination outside of the school program. CONCLUSIONS: Our study identified a range of facilitators and barriers to the school immunisation program for students with disabilities in specialist schools. The next phase of this work will use co-design workshops to build on the suggestions for improvement and opportunities that could be leveraged to improve vaccination uptake.

A novel anterior nasal swab to detect respiratory viruses: a prospective study of diagnostic accuracy.

Detection of respiratory viruses requires testing of the upper respiratory tract to obtain specimens for analysis. However, nasal and throat swabs can cause discomfort and procedural anxiety in children. Respiratory sampling methods which are accurate and less invasive are needed. We aim to determine the positive and negative percentage agreement of a novel anterior nasal swab (ANS) compared with the combined throat and anterior nasal swab (CTN), the reference standard, for detection of respiratory viruses. Children 5 - 18 years of age presenting to a tertiary paediatric hospital with respiratory symptoms were tested with both swabs in randomised order. Respiratory samples were tested on a multiplex RT-PCR panel. Viral detections, RT-PCR cycle-threshold values and child/parent/clinician experience of the swab were recorded. There were 157 viral detections from 249 participant CTN swabs. In comparison with the CTN, the overall positive and negative percentage agreement of ANS for detection of respiratory viruses was 96.2% (95% CI, 91.8-98.3%) and 99.8% (95% CI, 99.6-99.9%), respectively. The ANS was "extremely comfortable", or only a "little uncomfortable" for 90% of children compared with 48% for CTN. 202 children (84%) rated the ANS as the preferred swab, and 208 (87%) indicated they would prefer ANS for future testing. The ANS required additional laboratory handling processes compared to the CTN. The ANS has high positive percentage agreement and is comparable to the current standard of care. The high acceptability from the less invasive ANS provides a more comfortable method for respiratory virus testing in children.Trial registrationClinicalTrials.gov ID NCT05043623.

Virology and immune dynamics reveal high household transmission of ancestral SARS-CoV-2 strain.

BACKGROUND: Household studies are crucial for understanding the transmission of SARS-CoV-2 infection, which may be underestimated from PCR testing of respiratory samples alone. We aim to combine the assessment of household mitigation measures; nasopharyngeal, saliva, and stool PCR testing; along with mucosal and systemic SARS-CoV-2-specific antibodies, to comprehensively characterize SARS-CoV-2 infection and transmission in households. METHODS: Between March and September 2020, we obtained samples from 92 participants in 26 households in Melbourne, Australia, in a 4-week period following the onset of infection with ancestral SARS-CoV-2 variants. RESULTS: The secondary attack rate was 36% (24/66) when using nasopharyngeal swab (NPS) PCR positivity alone. However, when respiratory and nonrespiratory samples were combined with antibody responses in blood and saliva, the secondary attack rate was 76% (50/66). SARS-CoV-2 viral load of the index case and household isolation measures were key factors that determine secondary transmission. In 27% (7/26) of households, all family members tested positive by NPS for SARS-CoV-2 and were characterized by lower respiratory Ct values than low transmission families (Median 22.62 vs. 32.91; IQR 17.06-28.67 vs. 30.37-34.24). High transmission families were associated with enhanced plasma antibody responses to multiple SARS-CoV-2 antigens and the presence of neutralizing antibodies. Three distinguishing saliva SARS-CoV-2 antibody features were identified according to age (IgA1 to Spike 1, IgA1 to nucleocapsid protein (NP)), suggesting that adults and children generate distinct mucosal antibody responses during the acute phase of infection. CONCLUSION: Utilizing respiratory and nonrespiratory PCR testing, along with the measurement of SARS-CoV-2-specific local and systemic antibodies, provides a more accurate assessment of infection within households and highlights some of the immunological differences in response between children and adults.

Elevated Cardiac Troponin to Detect Acute Cellular Rejection After Cardiac Transplantation: A Systematic Review and Meta-Analysis.

Cardiac troponin is well known as a highly specific marker of cardiomyocyte damage, and has significant diagnostic accuracy in many cardiac conditions. However, the value of elevated recipient troponin in diagnosing adverse outcomes in heart transplant recipients is uncertain. We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library from inception until December 2020. We generated summary sensitivity, specificity, and Bayesian areas under the curve (BAUC) using bivariate Bayesian modelling, and standardised mean differences (SMDs) to quantify the diagnostic relationship of recipient troponin and adverse outcomes following cardiac transplant. We included 27 studies with 1,684 cardiac transplant recipients. Patients with acute rejection had a statistically significant late elevation in standardised troponin measurements taken at least 1 month postoperatively (SMD 0.98, 95% CI 0.33-1.64). However, pooled diagnostic accuracy was poor (sensitivity 0.414, 95% CrI 0.174-0.696; specificity 0.785, 95% CrI 0.567-0.912; BAUC 0.607, 95% CrI 0.469-0.723). In summary, late troponin elevation in heart transplant recipients is associated with acute cellular rejection in adults, but its stand-alone diagnostic accuracy is poor. Further research is needed to assess its performance in predictive modelling of adverse outcomes following cardiac transplant. Systematic Review Registration: identifier CRD42021227861.

Characteristics and outcomes of SARS-CoV-2 infection in Victorian children at a tertiary paediatric hospital.

AIM: Victoria experienced two 'waves' of COVID-19 between March and September 2020 and more cases than any other jurisdiction in Australia. Although world-wide reports of COVID-19 reflect that children are less likely to experience severe disease compared with adults, hospitalisations and deaths have been reported. We report testing and outcomes of children with SARS-CoV-2 infection presenting to a tertiary paediatric hospital in Melbourne. METHODS: We conducted a prospective cohort study at The Royal Children's Hospital (RCH), including all children and adolescents (aged 0-18 years) who presented and were tested for SARS-CoV-2 over a 6-month period, between 21 March 2020, up to the 21 September 2020. Detailed epidemiological and clinical data were recorded. RESULTS: A total of 19 708 tests for SARS-CoV-2 were performed in 14 419 patients. One hundred and eighty patients tested positive for SARS-CoV-2 (1.2%). 110 (61%) were symptomatic, 60 (33%) were asymptomatic and 10 (6%) were pre-symptomatic. Close contacts of a positive case were associated with a higher risk of a testing positive for SARS-CoV-2 (120/2027 (6%) vs. 60/14589 (0.4%), RD 5.5 (95% CI 4.5 to 6.5), P < 0.001). Eighteen (10%) SARS-CoV-2-positive patients were admitted to hospital with one patient requiring intensive care. All patients recovered fully with no deaths. CONCLUSION: In Victorian children presenting to a tertiary hospital, SARS-CoV-2 infection caused predominantly mild or asymptomatic infection, with most children not requiring hospitalisation.

Acceptability of an asymptomatic COVID-19 screening program for schools in Victoria, Australia: a qualitative study with caregivers from priority populations.

BACKGROUND: An asymptomatic COVID-19 rapid antigen testing (RAT) screening program was implemented in Victorian schools in January 2022, to support keeping schools open throughout the pandemic. This study explored compliance with the program among caregivers from priority populations in Victorian mainstream and specialist schools. METHODS: We conducted semi-structured interviews between 7-31 March 2022 with caregivers of school-aged children participating in the RAT program in Victoria. Participants were asked about awareness, acceptability, compliance, frequency, and barriers to testing. Recordings were transcribed and deductively analysed using a framework approach. RESULTS: Fifty caregivers participated. They expressed confusion about the 'recommended' program, assuming it was mandatory. Caregivers wanted notification from schools of positive cases to increase motivation for compliance. Culturally and linguistically diverse (CALD) families were compliant; however, in-language resources were limited. Aboriginal or Torres Strait Islander (Koori) families tested less regularly and received information from their community rather than school. Caregivers of children living with disabilities reported behavioural challenges to testing, resulting in distress or non-compliance, and received non-specific information for their children. CONCLUSIONS: To increase engagement with future surveillance programs, caregivers need clarity about optionality, conducting tests, reporting results, and timely notification of cases. Requirements unique to each priority population include: accurate in-language information for CALD caregivers, community-led communication for Koori caregivers, tailored information, less testing, and flexibility for caregivers of children living with a disability. Keeping schools open and having tailored strategies to ensure equitable access for priority populations are essential for future pandemic management.

Training health workers and community influencers to be Vaccine Champions: a mixed-methods RE-AIM evaluation.

INTRODUCTION: Increasing trust and confidence in vaccines is a global priority, as countries have grappled with delivering COVID-19 vaccines, maintaining routine childhood vaccination rates and introducing new vaccines. Community-based vaccine promotion interventions are commonly implemented, but effectiveness evidence is limited. In 2022, supported by the Australian Government and in partnership with Fiji's Ministry of Health and UNICEF, we codesigned, delivered and comprehensively evaluated a vaccine education and communication training programme for health workers and community influencers to promote COVID-19 and routine immunisation. METHODS: The Vaccine Champions programme included three phases: (1) codesign with Fiji stakeholders; (2) vaccine education and communication training for Vaccine Champions and (3) support for Champions to deliver community vaccine discussion sessions over 6 months.The RE-AIM framework evaluation measured programme reach, effectiveness, adoption, implementation and maintenance. Mixed-methods data were collected through interviews, surveys and field notes, integrating qualitative and quantitative data to triangulate findings. Primary outcomes included Champions' knowledge, communication self-efficacy, trust in COVID-19 vaccines, programme satisfaction and community members' intention to vaccinate. RESULTS: We trained 35 Champions (27/35 female), including health workers, faith and community influencers. Half had a health background (17/35). Champions conducted 54 discussion sessions, reaching 1717 community members. Most Champions (22/35) conducted at least 1 session, with 16 running 3 or more. Champions who did not run sessions reported barriers like lack of confidence and competing duties. Training increased Champions' communication self-efficacy and trust in COVID-19 vaccines. Community member intention to vaccinate increased from 41% (394/960) to 83% (822/991) before and after a session. The programme was well received with interest in continued engagement. CONCLUSION: Training health workers and community Vaccine Champions can promote vaccine confidence. Programmes require government support and engagement for sustainability. Robust evaluation frameworks are needed to build the evidence base.

Barriers to COVID-19 vaccination of migrant populations: A qualitative interview study of immunisation providers in Victoria, Australia.

INTRODUCTION: This study aimed to understand barriers and enablers, future strategies, communication approaches and resources needed for COVID-19 vaccination among migrant communities in Melbourne, Australia. MATERIAL AND METHODS: We interviewed 24 immunisation providers who deliver immunisation services to migrant populations in Melbourne. We used the WHO Behavioural and Social Drivers framework (underlined) to organise barriers and enablers to COVID-19 vaccination. RESULTS: Participants believed migrants had concerns about vaccine safety and efficacy and saw vaccines as minimally beneficial in the 'low COVID-19' environment of Australia (what people think and feel). Healthcare providers with established relationships within migrant communities played key roles in vaccine advocacy (social processes). Migrants' vaccine motivation was mediated by health literacy, institutional trust and previous experiences with health services. Practical issues included perceived lack of information on vaccine booking process and accessibility challenges. CONCLUSIONS: Strategies to increase migrant vaccine coverage should utilise immunisation providers with community links and trusted local vaccine ambassadors to engage and address community vaccine concerns.

Complications of Influenza A or B Virus Infection in Individuals With SCN1A-Positive Dravet Syndrome.

BACKGROUND AND OBJECTIVES: To determine the frequency and spectrum of complications of influenza infection in individuals with SCN1A-positive Dravet syndrome (SCN1A-DS). METHODS: Individuals with SCN1A-DS were identified in neurologists' care at 2 hospitals in Melbourne, Australia, with additional searches of EEG databases, the Victorian PAEDS FluCan influenza database, and the University of Melbourne Epilepsy Genetics Research Program database. Medical records were searched and families questioned to identify individuals who had an influenza infection; reported infections were confirmed by pathology report. For these individuals, we obtained baseline clinical characteristics and clinical details of the influenza infection. RESULTS: Twenty-one of 82 individuals (26%) had 24 documented influenza infections (17 influenza A and 7 influenza B) at age 0.5-25 years (median 4 years). All presented to hospital, 18/24 (75%) for status epilepticus or seizure exacerbations. Recovery was prompt in 18/24 (75%) infections, delayed but complete in 1/24 (4%) and incomplete in 5/24 (21%). One child died from influenza pneumonia, and long-term neurologic sequelae were seen with 4 infections. These individuals were poorly responsive after termination of status epilepticus. Brain imaging in 2 showed cerebral edema and 1 also having imaging features of laminar necrosis. All have ongoing neurologic deficits compared with their baseline, 1 having profound global impairment. DISCUSSION: Our data show that patients with SCN1A-DS are highly susceptible to neurologic complications during and severe sequelae after influenza infection, including moderate to severe persistent neurologic impairments and death. Safe administration of the seasonal influenza vaccine should be prioritized for this population.

Behavioural and social drivers of COVID-19 vaccination in Vietnam: a scoping review.

BACKGROUND: Understanding of the behavioural and social drivers (BeSD) of vaccination is key to addressing vaccine hesitancy and accessibility issues. Vietnam's national COVID-19 vaccination programme resulted in high uptake of primary doses among adults, but lower booster doses for adults and primary doses for 5-11 years. This scoping review assessed BeSD influencing COVID-19 vaccine uptake in Vietnam to design interventions on reaching the national vaccination targets. METHOD: We conducted a scoping review by searching PubMed, MedRxiv, LitCOVID, COVID-19 LOVE platform, WHO's COVID-19 research database and seven dominant Vietnamese language medical journals published in English or Vietnamese between 28 December 2019 and 28 November 2022. Data were narratively synthesised and summarised according to the four components of the WHO BeSD framework. The drivers were then mapped along the timeline of COVID-19 vaccine deployment and the evolution of the pandemic in Vietnam. RESULTS: We identified 680 records, of which 39 met the inclusion criteria comprising 224 204 participants. Adults' intention to receive COVID-19 vaccines for themselves (23 studies) ranged from 58.0% to 98.1%. Parental intention to vaccinate their under 11-year-old children (six studies) ranged from 32.8% to 79.6%. Key drivers of vaccination uptake were perceived susceptibility and severity of disease, perceived vaccine benefits and safety, healthcare worker recommendation, and positive societal perception. Commonly reported COVID-19 vaccines' information sources (six studies) were social and mainstream media (82%-67%), television (72.7%-51.6%) and healthcare workers (47.5%-17.5%). Key drivers of COVID-19 uptake remained consistent for both adults and children despite changes in community transmission and vaccine deployment. CONCLUSION: Key enablers of vaccine uptake for adults and children included perceived disease severity, perceived vaccine benefits and safety and healthcare worker recommendations. Future studies should assess vaccine communication targeted to these drivers, national policies and political determinants to optimise vaccine uptake.

Catch-up immunisation for migrant children in Melbourne: A qualitative study with providers to determine key challenges.

BACKGROUND: Current models of immunisation service delivery in Australia are not meeting the needs of migrant children, who experience a higher burden of vaccine preventable disease and lower immunisation rates compared to non-migrant children. Understanding the experiences of immunisation providers is critical for designing effective and tailored interventions to improve this service. This study aimed to identify the facilitators and barriers to providers delivering a comprehensive catch-up immunisation service to migrant children in Melbourne, Australia. METHODS: Semi-structured interviews with council and general practice immunisation providers were conducted. Recorded interviews were transcribed and coded inductively using thematic analysis. Identified themes were then deductively categorised according to the Capability, Opportunity and Motivation of Behaviour (COM-B) model. RESULTS: Twenty-four providers (five practice nurses, six general practitioners, six council nurses and seven council administration officers) were interviewed between March and June 2021. Fourteen themes were identified that contributed to the delivery of an effective catch-up immunisation service. Capability themes included training, experience and skills to perform the service and communicate with families. Opportunity themes incorporated time, workplace norms, traits of migrant families, costs, systems and resources. Themes related to motivation were provider responsibility, beliefs about migrant health, and immunisation prioritisation. CONCLUSIONS: Key barriers for providers to deliver a comprehensive catch-up immunisation service were related to opportunity. Developing an online tool to support catch-up schedule development and reporting, and funding provider time to calculate the schedule are primary actions that could overcome opportunity barriers. Capability and motivation barriers for general practitioners included limited time, skills, and motivation compared to nurses. These barriers may be overcome with improvements to training that focus on upskilling nurses to deliver the catch-up service. Service delivery challenges are multifactorial, requiring a range of strategies to optimise this service and increase immunisation coverage in migrant children.

Vaccine Champions Training Program: Empowering Community Leaders to Advocate for COVID-19 Vaccines.

Strong community engagement has been critical to support COVID-19 vaccine uptake in Australia and elsewhere. Community engagement builds trust, enables tailored information dissemination and shapes social norms. Engagement is particularly important in communities with greater vaccine hesitancy, lower health literacy and mistrust in authorities. Early in 2021, as a team of vaccine social scientists and clinicians, we developed a program to train and empower community, faith, industry and healthcare leaders to advocate for COVID-19 vaccines as "vaccine champions". We partnered with the Victorian Department of Health to deliver 91 online Vaccine Champions sessions from March 2021 to June 2022. Over 80 people who received this training were supported by the Department of Health to become formal vaccine champions, independently delivering over 100 locally tailored information sessions. Our survey evaluation of 20 sessions delivered in 2022 found most participants (94%, 118/125) felt more confident to discuss safety and effectiveness of COVID-19 vaccines and find relevant information after attending a session. We also recorded >90% participant satisfaction with training content, format and presentation. Qualitative feedback from two group interviews highlighted the value of vaccine communication role plays and opportunities for discussion. In this brief report, we present an overview of the Vaccine Champions program, evaluation and next steps.

Prognostic Significance of Elevated Troponin in Adult Heart Transplant Recipients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Cardiac troponin is a highly specific biomarker of myocardial injury that is of prognostic significance in a range of cardiovascular diseases. However, the prognostic value of elevated troponin in cardiac transplant recipients is uncertain. We aimed to evaluate the prognostic value of elevated cardiac troponin in predicting adverse recipient outcomes following heart transplant. MATERIALS AND METHODS: We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library from inception until December 2020 and included studies reporting associations between elevated recipient troponin and outcomes after cardiac transplant. We generated summary odds ratios for associations with short- and long-term adverse events and used descriptive analyses where meta-analyses were inappropriate. RESULTS: We included 15 studies involving 1830 patients undergoing cardiac transplant. The risk of primary graft failure was greater in recipients with elevated troponin than in those without (odds ratio = 3.09; 95% CI, 1.08-8.87). Considerable interstudy heterogeneity (I2 statistic 98%) was partially explained by variations in study design, troponin subtype, and overall risk of bias. Descriptive analyses suggested associations between elevated recipient troponin and long-term adverse cardiac events, coronary artery disease, and mortality. CONCLUSIONS: Elevated cardiac troponin in cardiac transplant recipients may be prognostic for primary graft failure, adverse cardiac events, coronary artery disease, and mortality. Further high-quality, prospective, and multicenter research is needed to demonstrate the clinical applicability of these findings.

Donor Cardiac Troponin for Prognosis of Adverse Outcomes in Cardiac Transplantation Recipients: a Systematic Review and Meta-analysis.

BACKGROUND: Cardiac troponin is a highly specific and widely available marker of myocardial injury, and elevations in cardiac transplant donors may influence donor selection. We aimed to investigate whether elevated donor troponin has a role as a prognostic biomarker in cardiac transplantation. METHODS: In a systematic review and meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library, without language restriction, from inception to December 2020. We included studies reporting the association of elevated donor troponin with recipient outcome after cardiac transplant. We generated summary odds ratios and hazard ratios for the association of elevated donor troponin with short- and long-term adverse outcomes. Methodological quality was monitored using the Quality In Prognosis Studies tool, and interstudy heterogeneity was assessed using a series of sensitivity and subgroup analyses. RESULTS: We included 17 studies involving 15 443 patients undergoing cardiac transplantation. Elevated donor troponin was associated with increased odds of graft rejection at 1 y (odds ratio, 2.54; 95% confidence interval, 1.22-5.28). No significant prognostic relationship was found between donor troponin and primary graft failure, short- to long-term mortality, cardiac allograft vasculopathy, and pediatric graft loss. CONCLUSIONS: Elevated donor troponin is not associated with an increased short- or long-term mortality postcardiac transplant despite increasing the risk of graft rejection at 1 y. Accordingly, an elevated donor troponin in isolation should not exclude donation.

Functional correlates of clinical phenotype and severity in recurrent SCN2A variants.

In SCN2A-related disorders, there is an urgent demand to establish efficient methods for determining the gain- (GoF) or loss-of-function (LoF) character of variants, to identify suitable candidates for precision therapies. Here we classify clinical phenotypes of 179 individuals with 38 recurrent SCN2A variants as early-infantile or later-onset epilepsy, or intellectual disability/autism spectrum disorder (ID/ASD) and assess the functional impact of 13 variants using dynamic action potential clamp (DAPC) and voltage clamp. Results show that 36/38 variants are associated with only one phenotypic group (30 early-infantile, 5 later-onset, 1 ID/ASD). Unexpectedly, we revealed major differences in outcome severity between individuals with the same variant for 40% of early-infantile variants studied. DAPC was superior to voltage clamp in predicting the impact of mutations on neuronal excitability and confirmed GoF produces early-infantile phenotypes and LoF later-onset phenotypes. For one early-infantile variant, the co-expression of the α1 and ß2 subunits of the Nav1.2 channel was needed to unveil functional impact, confirming the prediction of 3D molecular modeling. Neither DAPC nor voltage clamp reliably predicted phenotypic severity of early-infantile variants. Genotype, phenotypic group and DAPC are accurate predictors of the biophysical impact of SCN2A variants, but other approaches are needed to predict severity.

Comparison of Seroconversion in Children and Adults With Mild COVID-19.

Importance: The immune response in children with SARS-CoV-2 infection is not well understood. Objective: To compare seroconversion in nonhospitalized children and adults with mild SARS-CoV-2 infection and identify factors that are associated with seroconversion. Design, Setting, and Participants: This household cohort study of SARS-CoV-2 infection collected weekly nasopharyngeal and throat swabs and blood samples during the acute (median, 7 days for children and 12 days for adults [IQR, 4-13] days) and convalescent (median, 41 [IQR, 31-49] days) periods after polymerase chain reaction (PCR) diagnosis for analysis. Participants were recruited at The Royal Children's Hospital, Melbourne, Australia, from May 10 to October 28, 2020. Participants included patients who had a SARS-CoV-2-positive nasopharyngeal or oropharyngeal swab specimen using PCR analysis. Main Outcomes and Measures: SARS-CoV-2 immunoglobulin G (IgG) and cellular (T cell and B cell) responses in children and adults. Seroconversion was defined by seropositivity in all 3 (an in-house enzyme-linked immunosorbent assay [ELISA] and 2 commercial assays: a SARS-CoV-2 S1/S2 IgG assay and a SARS-CoV-2 antibody ELISA) serological assays. Results: Among 108 participants with SARS-CoV-2-positive PCR findings, 57 were children (35 boys [61.4%]; median age, 4 [IQR, 2-10] years) and 51 were adults (28 women [54.9%]; median age, 37 [IQR, 34-45] years). Using the 3 established serological assays, a lower proportion of children had seroconversion to IgG compared with adults (20 of 54 [37.0%] vs 32 of 42 [76.2%]; P < .001). This result was not associated with viral load, which was similar in children and adults (mean [SD] cycle threshold [Ct] value, 28.58 [6.83] vs 24.14 [8.47]; P = .09). In addition, age and sex were not associated with seroconversion within children (median age, 4 [IQR, 2-14] years for both seropositive and seronegative groups; seroconversion by sex, 10 of 21 girls [47.6%] vs 10 of 33 boys [30.3%]) or adults (median ages, 37 years for seropositive and 40 years for seronegative adults [IQR, 34-39 years]; seroconversion by sex, 18 of 24 women [75.0%] vs 14 of 18 men [77.8%]) (P > .05 for all comparisons between seronegative and seropositive groups). Symptomatic adults had 3-fold higher SARS-CoV-2 IgG levels than asymptomatic adults (median, 227.5 [IQR, 133.7-521.6] vs 75.3 [IQR, 36.9-113.6] IU/mL), whereas no differences were observed in children regardless of symptoms. Moreover, differences in cellular immune responses were observed in adults compared with children with seroconversion. Conclusions and Relevance: The findings of this cohort study suggest that among patients with mild COVID-19, children may be less likely to have seroconversion than adults despite similar viral loads. This finding has implications for future protection after SARS-CoV-2 infection in children and for interpretation of serosurveys that involve children. Further research to understand why seroconversion and development of symptoms are potentially less likely in children after SARS-CoV-2 infection and to compare vaccine responses may be of clinical and scientific importance.