Reactogenicity, immunogenicity and breakthrough infections following heterologous or fractional second dose COVID-19 vaccination in adolescents (Com-COV3): A randomised controlled trial.

BACKGROUND: This was the first study to investigate the reactogenicity and immunogenicity of heterologous or fractional second dose COVID-19 vaccine regimens in adolescents. METHODS: A phase II, single-blind, multi-centre, randomised-controlled trial recruited across seven UK sites from September to November 2021, with follow-up visits to August 2022. Healthy 12-to-16 years olds were randomised (1:1:1) to either 30 µg BNT162b2 (BNT-30), 10 µg BNT162b2 (BNT-10), or NVX-CoV2373 (NVX), 8 weeks after a first 30 µg dose of BNT162b2. The primary outcome was solicited systemic reactions in the week following vaccination. Secondary outcomes included immunogenicity and safety. 'Breakthrough infection' analyses were exploratory. FINDINGS: 148 participants were recruited (median age 14 years old, 62% female, 26% anti-nucleocapsid IgG seropositive pre-second dose); 132 participants received a second dose. Reactions were mostly mild-to-moderate, with lower rates in BNT-10 recipients. No vaccine-related serious adverse events occurred. Compared to BNT-30, at 28 days post-second dose anti-spike antibody responses were similar for NVX (adjusted geometric mean ratio [aGMR]) 1.09 95% confidence interval (CI): 0.84, 1.42] and lower for BNT-10 (aGMR 0.78 [95% CI: 0.61, 0.99]). For Omicron BA.1 and BA.2, the neutralising antibody titres for BNT-30 at day 28 were similar for BNT-10 (aGMR 1.0 [95% CI: 0.65, 1.54] and 1.02 [95% CI: 0.71, 1.48], respectively), but higher for NVX (aGMR 1.7 [95% CI: 1.07, 2.69] and 1.43 [95% CI: 0.96, 2.12], respectively). Compared to BNT-30, cellular immune responses were greatest for NVX (aGMR 1.73 [95% CI: 0.94, 3.18]), and lowest for BNT-10 (aGMR 0.65 [95% CI: 0.37, 1.15]) at 14 days post-second dose. Cellular responses were similar across the study arms by day 236 post-second dose. Amongst SARS-CoV-2 infection naïve participants, NVX participants had an 89% reduction in risk of self-reported 'breakthrough infection' compared to BNT-30 (adjusted hazard ratio [aHR] 0.11 [95% CI: 0.01, 0.86]) up until day 132 after second dose. BNT-10 recipients were more likely to have a 'breakthrough infection' compared to BNT-30 (aHR 2.14 [95% CI: 1.02, 4.51]) up to day 132 and day 236 post-second dose. Antibody responses at 132 and 236 days after second dose were similar for all vaccine schedules. INTERPRETATION: Heterologous and fractional dose COVID-19 vaccine schedules in adolescents are safe, well-tolerated and immunogenic. The enhanced performance of the heterologous schedule using NVX-CoV2373 against the Omicron SARS-CoV-2 variant suggests this mRNA prime and protein-subunit boost schedule may provide a greater breadth of protection than the licensed homologous schedule. FUNDING: National Institute for Health Research and Vaccine Task Force. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number registry: 12348322.

Food insecurity as experienced by New Zealand women and their children.

Food insecurity, defined as uncertainty in reliably accessing adequate quantities of nutritious food, is an issue for many families and children, including in New Zealand. Drawing on the experiences of mothers, this study explored the nature, causes and impact of food insecurity for their families. Semi-structured face-to-face interviews conducted with six female sole-parents were complemented with food insecurity data from the NZ Health Survey and Youth2000 surveys. Interviews were audio-recorded, transcribed and emergent themes analysed. The major driver of food insecurity was low income relative to essential household outgoings. Coping strategies employed invariably involved reducing the quantity and quality of food consumed. Negative impacts of food insecurity included significant stress, neglect of personal needs and missing meals in favour of children. Concerns expressed for children included reduced provision of nutritious food and constrained social and recreational opportunities. Participants described the daily struggle of feeding their household despite personal sacrifices, a range of coping strategies and community support. Quantitative data showed persistent high prevalence of household food insecurity with inequity by ethnicity and disability status. Findings highlight food insecurity as an ongoing public health issue for which urgent action is required to reduce its damaging impacts on families and children.

Sleep and Night-time Caregiving in Parents of Children and Adolescents with Type 1 Diabetes Mellitus - A Qualitative Study.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a common chronic illness of childhood, with parents assuming considerable responsibility for night-time diabetes caregiving. This qualitative study explored diabetes-related factors affecting, and solutions proposed to improve, parental sleep. PARTICIPANTS: 10 mothers and 10 fathers of children ≤18 years of age with T1DM in Otago, New Zealand. METHODS: Semi-structured individual interviews were audio-recorded, transcribed, and systematically coded for themes. Parents completed the Pittsburgh Sleep Quality Index (PSQI) and habitual sleep of parents and children were assessed via 7-day actigraphy. RESULTS: Parents (n = 20) and their children with T1DM (n = 16) were aged between 32 and 54 years, and 1 and 17 years, respectively. PSQI revealed poor quality sleep in 13/20 parents. A range of diabetes-related factors, including glucose monitoring and fear of hypoglycemia, contributed to parental sleep disturbance, including awakenings and the perception of "sleeping lightly". Two distinct time periods resulted in greater sleep disturbance, notably, following T1DM diagnosis and when transitioning to using a new diabetes technology. Factors influencing maternal and paternal sleep were similar, but, generally, mothers described greater night-time care burden and sleep disturbance. While the use of diabetes technologies was generally advocated to improve parental sleep and the provision of nocturnal T1DM care, they were also perceived to potentially contribute to parental sleep disturbance. CONCLUSIONS: Pediatric diabetes care teams should be aware of diabetes-related factors potentially affecting parental sleep, the mixed impacts of diabetes technologies, and consider tailored parental support and education to reduce the burden of nocturnal care.

Impact of type 1 diabetes mellitus, glucose levels, and glycemic control on sleep in children and adolescents: a case-control study.

STUDY OBJECTIVES: To assess differences in habitual sleep patterns and sleep states between children and adolescents with type 1 diabetes mellitus (T1DM) and control subjects, and to explore the relationships between sleep, glucose levels, and glycemic control. METHODS: Participants included 82 children (5-18 years); 41 with T1DM (cases), and 41 healthy control subjects group matched for age and sex. Sleep was measured by 7-day actigraphy and single-night home-based polysomnography (PSG) recordings. Hemoglobin A1c (HbA1c) and 7 days of continuous glucose monitoring (CGM) data were collected in cases. Regression analyses were used to model all within- and between-group comparisons adjusted for age, sex, and BMI z-scores. RESULTS: There were no significant differences in sleep duration, efficiency, or awakenings as measured by actigraphy and PSG between cases and controls, nor sleep states measured by PSG. However, cases had significantly later sleep onset and offset than controls (both p < 0.05), partially moderated by age. Cases with suboptimal glycemic control (HbA1c ≥ 58 mmol/mol [≥7.5%]) had significantly shorter actigraphy-derived total sleep time (TST) (mean difference = -40 minutes; 95% confidence interval = -77, -3), with similar differences in TST measured by PSG. Cases with mean CGM glucose levels ≥10 mmol/L (≥180 mg/dL) on PSG night had significantly more stage N3 (%) sleep and less stage REM (%) sleep (both p < 0.05). CONCLUSIONS: Short- and long-term suboptimal glycemic control in T1DM children appears to be associated with sleep alterations. Pediatric diabetes care teams should be aware of potential interrelationships between sleep and T1DM, including management and glycemic control.