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

The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organisation (WHO) 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 more 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 from a case-number perspective these interventions succeeded in reducing the absolute number of cases of SARS-CoV-2 in the UK, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of those 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 last hypothesis provides the best explanation of the observed behaviour and dynamics of the variant, although we find that 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 to each other, and identify that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations, and its lack of rapid evolutionary rate on the 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 COVID-19 (preprint)

There are urgent calls for research into the mental health consequences of living through the COVID-19 pandemic. We describe caregiver and child mental health over 12 months using Australias only nationally representative, repeated cross-sectional survey of caregivers with children (0-17 years). N=2020 caregivers in June 2020, N=1434 in September 2020, and N=2508 in July 2021 provided data. Caregivers rated their mental health (Kessler-6), and impacts of the pandemic on their own and their childrens mental health. Data were weighted using national distribution of age, gender, number of children, state/territory and neighbourhood-level disadvantage. Mental health measures worsened over time. There was an unequal distribution of impacts based on caregiver gender, child age and family socioeconomic characteristics. Negative impacts were more common with current or cumulative lockdown. The indirect impacts of COVID-19 are real and concerning. Mental health must be central to the immediate and ongoing pandemic responses for families and children. What is known about this topic?- The global evidence shows that, for general adult populations, psychological distress peaked in the first months of the COVID-19 pandemic before appearing to rebound. - Less is known about long-term mental health consequences of living through the pandemic, especially for caregivers and children. There are urgent calls for research. - Due to low infection rates, Australias experience can provide insight into the mental health impacts of lockdown without the compounding direct harms of the virus. What this study adds- From June 2020 to July 2021, caregivers reported declining mental health and increasing negative mental health impacts of COVID-19 for themselves and their children. - There was an unequal distribution of mental health impacts based on caregiver gender, child age and family socioeconomic characteristics. - Lockdown (current or cumulative) was detrimental for caregivers and childrens mental health. Pandemic response and recovery planning must consider families mental health.

The impact of ongoing COVID-19 lockdown on family finances and mental health (preprint)

ObjectivesAustralias public health restrictions ( lockdown) in 2020 successfully contained the spread of COVID-19. These included a national initial lockdown (March-May), and ongoing lockdown (July-November) for metropolitan Victorian residents only. Australias experience offers an opportunity to assess impacts of lockdown on families with children, in the relative absence of disease morbidity and mortality. This study (1) described the experience of initial lockdown and (2) evaluated the impact of ongoing lockdown, on family finances and mental health. MethodsData were drawn from the June and September 2020 Royal Childrens Hospital National Child Health Polls. Caregivers of children from the states of Victoria and New South Wales reported on job/income loss; material deprivation (inability to pay for essential items); income-poverty; mental health (Kessler-6); impact on caregiver/child mental health; and caregiver/child coping. Data from N=1207/902 caregivers in June/September were analyzed; Aim (1) with weighted descriptives; Aim (2) with Difference-in-Difference adjusted linear regression models (New South Wales provided the comparator). ResultsFollowing initial lockdown, one-quarter of families reported job/income loss; one-third reported material deprivation. Negative impacts on mental health were reported for half the caregivers and one-third of children. Few caregivers or children had difficulties coping. During Victorias 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 negative mental health impacts by 12% for caregivers (95%CI: 6-23%) and 14% for children (95%CI: 4-20%). Female (versus male) caregivers, metropolitan (versus regional/rural) families, and families with elementary school-aged children (versus pre-/high-school) were most affected. ConclusionsOngoing lockdown had negative impacts on mental health, employment, and income, but not deprivation or poverty, likely because of the government income supplements introduced early in the pandemic. Balancing the benefits and harms of lockdown requires planned responses to outbreaks, and evidence-informed financial and mental health supports.

Clinical, Financial and Social Impacts of COVID-19 and Their Associations with Mental Health for Mothers and Children Experiencing Adversity in Australia (preprint)

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. Families who were already experiencing adversity before the COVID-19 pandemic are likely to be disproportionately affected. 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, changes to financial circumstances, financial hardship, family stress, and family resilience (termed ‘COVID-19 impacts’); and 2) associations between these 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 opportunistically conducted from May-December 2020, when children were 5.9–7.2 years old. Mothers reported COVID-19 impacts (drawn from the Coronavirus Health and Impact Survey (CRISIS), Australian Temperament Project, and Household, Income and Labour Dynamics in Australia Survey); their own mental health (Depression, Anxiety, Stress Scales short-form) and their child’s mental health (CRISIS 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. In contrast, self-quarantine (20%), financial changes (job/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 (all standardised coefficients) included self-quarantine (mother: β = 0.48, child: β = 0.47), financial hardship or change (mother: β = 0.27, child: β = 0.37) and family stress (mother: β = 0.49, child: β = 0.73). Family resilience was associated with better mental health (mother: β=-0.39, child: β=-0.47).Conclusions The financial and social impacts of Australia’s public health restrictions have substantially affected families experiencing adversity, and their mental health. Unless these impacts are addressed, the inequities arising from adversity are likely to be exacerbated. To recover from COVID-19, policy investment should include income support and universal access to family health services.

Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity (preprint)

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 data set, 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.