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1.
Preprint en Inglés | bioRxiv | ID: ppbiorxiv-481609

RESUMEN

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 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 which 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.

2.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21262708

RESUMEN

BackgroundThere are calls for research into the mental health consequences of living through the COVID-19 pandemic. Australias 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. MethodsData were from Australias 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 versus not, Kessler-6), and perceived impacts of the pandemic on theirs and their childrens mental health (negative versus 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. ResultsPerceived impacts on mental health were more frequently negative for female (versus male) caregivers and older (versus younger) children. Poor caregiver mental health (K6) 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 K6 over time. Otherwise, poor mental health and perceived negative impacts increased over time with increasing total length of lockdown. ConclusionDespite Australias 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. 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 improve. - Less is known about mental health over time 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 with minimal compounding harms of the virus. What this study adds- From June 2020 to July 2021, Australias lockdowns were detrimental for caregiver and child mental health. - Negative mental health experiences differed by caregiver gender, child age and family socioeconomic characteristics. - Pandemic response and recovery planning must consider both family mental health and socioeconomic security.

3.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21262087

RESUMEN

ObjectivesIn 2020, Australias 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 the relationships between ongoing lockdown and family finances and mental health. MethodsIn the June and September 2020 Royal Childrens Hospital National Child Health Polls, caregivers of children in Victoria and New South Wales reported: 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 N=1207/902 caregivers in June/September were analysed using Difference-in-Difference modelling (New South Wales provided the comparator). ResultsDuring 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 perceived negative mental health impacts by 14% for caregivers (95%CI: 6-23%) and 12% 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 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.

4.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20166082

RESUMEN

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.

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