Associations between ongoing COVID-19 lockdown and the financial and mental health experiences of Australian families.

In 2020, Australia's successful COVID-19 public health restrictions comprised a national "initial lockdown" (March-May) and "ongoing lockdown" (July-November) for metropolitan Victorian residents only. We evaluated associations between ongoing lockdown and family finances and mental health. In the June and September 2020 Royal Children's Hospital National Child Health Polls, caregivers of children in Victoria and New South Wales (NSW) reported the following: job/income loss; material deprivation (inability to pay for essential items); income poverty; mental health (Kessler-6); perceived impact on caregiver/child mental health; and caregiver/child coping. Data from caregivers (N = 1207/902) in June/September were analysed using difference-in-difference modelling (NSW provided the comparator). During Victoria's ongoing lockdown, job/income loss increased by 11% (95%CI: 3%-18%); Kessler-6 poor mental health by 6% (95%CI: -0.3%-12%) and perceived negative mental health impacts by 14% for caregivers (95%CI: 6%-23%) and 12% for children (95%CI: 4%-20%). Female (vs. male) caregivers, metropolitan (vs. regional/rural) families, and families with elementary school-aged children (vs. pre-/high-school) were the most affected. The ongoing lockdown was associated with negative experiences of mental health, employment and income, but not deprivation or poverty, likely because of government income supplements introduced early in the pandemic. Future lockdowns require planned responses to outbreaks and evidence-informed financial and mental health supports.

The Adverse Outcome Pathway Framework Applied to Neurological Symptoms of COVID-19.

Several reports have shown that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to also be neurotropic. However, the mechanisms by which SARS-CoV-2 induces neurologic injury, including neurological and/or psychological symptoms, remain unclear. In this review, the available knowledge on the neurobiological mechanisms underlying COVID-19 was organized using the AOP framework. Four AOPs leading to neurological adverse outcomes (AO), anosmia, encephalitis, stroke, and seizure, were developed. Biological key events (KEs) identified to induce these AOs included binding to ACE2, blood-brain barrier (BBB) disruption, hypoxia, neuroinflammation, and oxidative stress. The modularity of AOPs allows the construction of AOP networks to visualize core pathways and recognize neuroinflammation and BBB disruption as shared mechanisms. Furthermore, the impact on the neurological AOPs of COVID-19 by modulating and multiscale factors such as age, psychological stress, nutrition, poverty, and food insecurity was discussed. Organizing the existing knowledge along an AOP framework can represent a valuable tool to understand disease mechanisms and identify data gaps and potentially contribute to treatment, and prevention. This AOP-aligned approach also facilitates synergy between experts from different backgrounds, while the fast-evolving and disruptive nature of COVID-19 emphasizes the need for interdisciplinarity and cross-community research.

The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK.

The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organization as Alpha. Originating in early autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK and the imposition of new restrictions, in particular, the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages that preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically infected individual. We conclude that the latter provides the best explanation of the observed behaviour and dynamics of the variant, although the individual need not be immunocompromised, as persistently infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs and find that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations and a lack of the rapid evolutionary rate on its ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms), it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence.

Child and caregiver mental health during 12 months of the COVID-19 pandemic in Australia: findings from national repeated cross-sectional surveys.

BACKGROUND: There are calls for research into the mental health consequences of living through the COVID-19 pandemic. Australia's initial, effective suppression of COVID-19 offers insights into these indirect impacts in the relative absence of the disease. We aimed to describe the mental health experiences of Australian caregivers and children over 12 months, reporting differences related to demographic, socioeconomic and lockdown characteristics. METHODS: Data were from Australia's only nationally representative, repeated cross-sectional survey of caregivers with children (0-17 years). N=2020 caregivers participated in June 2020, N=1434 in September 2020 and N=2508 in July 2021. Caregivers reported their mental health (poor vs not, Kessler-6), and perceived impacts of the pandemic on theirs and their children's mental health (negative vs none/positive). Data were weighted to approximate population distributions of caregiver age, gender, sole caregiving, number and ages of children, state/territory and neighbourhood-level disadvantage. RESULTS: Perceived impacts on mental health were more frequently negative for female (vs male) caregivers and older (vs younger) children. Poor caregiver mental health (Kessler-6) was more common for families experiencing socioeconomic adversity (especially financial), while perceived impacts were more frequently negative for more socially advantaged groups. Caregivers who experienced the least total lockdown reported similar mental health over time. Otherwise, poor mental health and perceived negative impacts increased over time with increasing total length of lockdown. CONCLUSION: Despite Australia's low infection rates, the negative mental health experiences of the COVID-19 pandemic are real and concerning. Addressing poor mental health must be central to ongoing pandemic recovery efforts for families and children.

COVID-19 through Adverse Outcome Pathways: Building networks to better understand the disease - 3rd CIAO AOP Design Workshop.

On April 28-29, 2021, 50 scientists from different fields of expertise met for the 3rd online CIAO workshop. The CIAO project "Modelling the Pathogenesis of COVID-19 using the Adverse Outcome Pathway (AOP) framework" aims at building a holistic assembly of the available scientific knowledge on COVID-19 using the AOP framework. An individual AOP depicts the disease progression from the initial contact with the SARS-CoV-2 virus through biological key events (KE) toward an adverse outcome such as respiratory distress, anosmia or multiorgan failure. Assembling the individual AOPs into a network highlights shared KEs as central biological nodes involved in multiple outcomes observed in COVID-19 patients. During the workshop, the KEs and AOPs established so far by the CIAO members were presented and posi­tioned on a timeline of the disease course. Modulating factors influencing the progression and severity of the disease were also addressed as well as factors beyond purely biological phenomena. CIAO relies on an interdisciplinary crowd­sourcing effort, therefore, approaches to expand the CIAO network by widening the crowd and reaching stakeholders were also discussed. To conclude the workshop, it was decided that the AOPs/KEs will be further consolidated, inte­grating virus variants and long COVID when relevant, while an outreach campaign will be launched to broaden the CIAO scientific crowd.

Connecting healthcare with income maximisation services, and their financial, health and well-being impacts for families with young children: a systematic review protocol.

INTRODUCTION: Poverty has far-reaching and detrimental effects on children's physical and mental health, across all geographies. Financial advice and income-maximisation services can provide a promising opportunity for shifting the physical and mental health burdens that commonly occur with financial hardship, yet awareness of these services is limited, and referrals are not systematically integrated into existing healthcare service platforms. We aim to map and synthesise evidence on the impact of healthcare-income maximisation models of care for families of children aged 0-5 years in high-income countries on family finances, parent/caregiver(s) or children's health and well-being. METHODS AND ANALYSIS: To be included in the review, studies must be families (expectant mothers or parents/caregivers) of children who are aged between 0 and 5 years, accessing a healthcare service, include a referral from healthcare to an income-maximisation service (ie, financial counselling), and examine impacts on child and family health and well-being. A comprehensive electronic search strategy will be used to identify studies written in English, published from inception to January 2021, and indexed in MEDLINE, EMBase, PsycINFO, CINAHL, Proquest, Family & Society Studies Worldwide, Cochrane Library, and Informit Online. Search strategies will include terms for: families, financial hardship and healthcare, in various combinations. Bibliographies of primary studies and review articles meeting the inclusion criteria will be searched manually to identify further eligible studies, and grey literature will also be searched. Data on objective and self-reported outcomes and study quality will be independently extracted by two review authors; any disagreements will be resolved through a third reviewer. The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. ETHICS AND DISSEMINATION: Ethical approval is not required. The results will be disseminated widely via peer-reviewed publication and presentations at conferences related to this field. PROSPERO REGISTRATION NUMBER: CRD42020195985.

Clinical, financial and social impacts of COVID-19 and their associations with mental health for mothers and children experiencing adversity in Australia.

BACKGROUND: Australia has maintained low rates of SARS-COV-2 (COVID-19) infection, due to geographic location and strict public health restrictions. However, the financial and social impacts of these restrictions can negatively affect parents' and children's mental health. In an existing cohort of mothers recruited for their experience of adversity, this study examined: 1) families' experiences of the COVID-19 pandemic and public health restrictions in terms of clinical exposure, financial hardship family stress, and family resilience (termed 'COVID-19 impacts'); and 2) associations between COVID-19 impacts and maternal and child mental health. METHODS: Participants were mothers recruited during pregnancy (2013-14) across two Australian states (Victoria and Tasmania) for the 'right@home' trial. A COVID-19 survey was conducted from May-December 2020, when children were 5.9-7.2 years old. Mothers reported COVID-19 impacts, their own mental health (Depression, Anxiety, Stress Scales short-form) and their child's mental health (CoRonavIruS Health and Impact Survey subscale). Associations between COVID-19 impacts and mental health were examined using regression models controlling for pre-COVID-19 characteristics. RESULTS: 319/406 (79%) mothers completed the COVID-19 survey. Only one reported having had COVID-19. Rates of self-quarantine (20%), job or income loss (27%) and family stress (e.g., difficulty managing children's at-home learning (40%)) were high. Many mothers also reported family resilience (e.g., family found good ways of coping (49%)). COVID-19 impacts associated with poorer mental health (standardised coefficients) included self-quarantine (mother: ß = 0.46, child: ß = 0.46), financial hardship (mother: ß = 0.27, child: ß = 0.37) and family stress (mother: ß = 0.49, child: ß = 0.74). Family resilience was associated with better mental health (mother: ß = -0.40, child: ß = -0.46). CONCLUSIONS: The financial and social impacts of Australia's public health restrictions have substantially affected families experiencing adversity, and their mental health. These impacts are likely to exacerbate inequities arising from adversity. To recover from COVID-19, policy investment should include income support and universal access to family health services.

Study protocol for the Healthier Wealthier Families (HWF) pilot randomised controlled trial: testing the feasibility of delivering financial counselling to families with young children who are identified as experiencing financial hardship by community-based nurses.

INTRODUCTION: Poverty and deprivation can harm children's future health, learning, economic productivity and societal participation. The Australian Healthier Wealthier Families project seeks to reduce the childhood inequities caused by poverty and deprivation by creating a systematic referral pathway between two free, community-based services: universal, well-child nursing services, which provide health and development support to families with children from birth to school entry, and financial counselling. By adapting the successful Scottish 'Healthier Wealthier Children' model, the objectives of this Australian pilot are to test the (1) feasibility of systematising the referral pathway, and (2) short-term impacts on household finances, caregiver health, parenting efficacy and financial service use. METHODS AND ANALYSIS: This pilot randomised controlled trial will run in three sites across two Australian states (Victoria and New South Wales), recruiting a total of 180 participants. Nurses identify eligible caregivers with a 6-item, study-designed screening survey for financial hardship. Caregivers who report one or more risk factors and consent are randomised. The intervention is financial counselling. The comparator is usual care plus information from a government money advice website. Feasibility will be evaluated using the number/proportion of caregivers who complete screening, consent and research measures, and access financial counselling. Though powered to assess feasibility, impacts will be measured 6 months post-enrolment with qualitative interviews and questionnaires about caregiver-reported income, loans and costs (adapted from national surveys, for example, the Household, Income and Labour Dynamics in Australia Survey); health (General Health Questionnaire 1, EuroQol five-dimensional questionnaire, Depression, Anxiety, Stress Scale short-form); efficacy (from the Longitudinal Study of Australian Children); and financial service use (study-designed) compared between arms. ETHICS AND DISSEMINATION: Ethics committees of the Royal Children's Hospital (HREC/57372/RCHM-2019) and South West Sydney Local Health District (2019/ETH13455) have approved the study. Participants and stakeholders will receive results through regular communication channels comprising meetings, presentations and publications. TRIAL REGISTRATION NUMBER: ACTRN12620000154909; prospectively registered. Pre-results.

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.

Prospective multicentre cohort study of transthoracic echocardiography provision in the South West of the UK during the first wave of SARS-CoV-2 pandemic.

AIMS: It was predicted internationally that transthoracic echocardiography (TTE) would be vital during the SARS-CoV-2 outbreak. We therefore, designed a study to report the demand for TTE in two large District General Hospitals during the rise in the first wave of the SARS-CoV-2 pandemic in the UK. A primary clinical outcome of 30-day mortality was also assessed. METHODS: The TTE service across two hospitals was reconfigured to maximise access to inpatient scanning. All TTEs of suspected or confirmed SARS-CoV-2 patients over a 3-week period were included in the study. All patients were followed up until at least day 30 after their scan at which point the primary clinical outcome of mortality was recorded. Comparative analysis based on mortality was conducted for all TTE results, biochemical markers and demographics. RESULTS: 27 patients with confirmed SARS-CoV-2 had a TTE within the inclusion window. Mortality comparative analysis showed the deceased group were significantly older (mean 68.4, SD 11.9 vs 60.5, SD 13.0, p=0.03) and more commonly reported fatigue in their presenting symptoms (29.6% vs 71.4%, p=0.01). No other differences were identified in the demographic or biochemical data. Left ventricular systolic dysfunction was noted in 7.4% of patients and right ventricular impairment or dilation was seen in 18.5% patients. TTE results were not significantly different in mortality comparative analysis. CONCLUSION: This study demonstrates an achievable approach to TTE services when under increased pressure. Data analysis supports the limited available data suggesting right ventricular abnormalities are the most commonly identified echocardiographic change in SARS-CoV-2 patients. No association can be demonstrated between mortality and TTE results.