Evolutionary remodelling of N-terminal domain loops fine-tunes SARS-CoV-2 spike.

The emergence of SARS-CoV-2 variants has exacerbated the COVID-19 global health crisis. Thus far, all variants carry mutations in the spike glycoprotein, which is a critical determinant of viral transmission being responsible for attachment, receptor engagement and membrane fusion, and an important target of immunity. Variants frequently bear truncations of flexible loops in the N-terminal domain (NTD) of spike; the functional importance of these modifications has remained poorly characterised. We demonstrate that NTD deletions are important for efficient entry by the Alpha and Omicron variants and that this correlates with spike stability. Phylogenetic analysis reveals extensive NTD loop length polymorphisms across the sarbecoviruses, setting an evolutionary precedent for loop remodelling. Guided by these analyses, we demonstrate that variations in NTD loop length, alone, are sufficient to modulate virus entry. We propose that variations in NTD loop length act to fine-tune spike; this may provide a mechanism for SARS-CoV-2 to navigate a complex selection landscape encompassing optimisation of essential functionality, immune-driven antigenic variation and ongoing adaptation to a new host.

Nutrients or processing? An analysis of food and drink items from the UK National Diet and Nutrition Survey based on nutrient content, the NOVA classification and front of package traffic light labelling.

UK front of package labelling (FOPL) informs consumers on the nutrient content of food. However, FOPL does not consider food processing, and with the UK government being urged to act on ultra-processed food (UPF), whether UPF should be added to FOPL is unclear. This study compared food and drink in the UK National Diet and Nutrition Survey (NDNS) Intake24 database based on FOPL, nutrient content and NOVA classification, to understand whether UPF are covered by dietary recommendations for foods high in fat, salt and sugar. NDNS items were coded into minimally processed food (MPF), processed culinary ingredients, processed food and UPF according to the NOVA classification and FOPL traffic lights. UPF contained greater energy, fat, saturated fat (SF), total sugar (TS) and salt than MPF. UPF had a greater odds of containing red FOPL and an unhealthier overall FOPL score (OR:4·59 (95 % CI: 3·79, 5·57); OR:7·0 (95 % CI: 6·1, 8·2), respectively) and lower odds of containing green FOPL (OR:0·05 (95 % CI: 0·03, 0·10)), compared with MPFs. For items with no red FOPL, UPF still contained greater energy, fat, SF, TS and salt than MPF. However, several UPF have healthier FOPL scores. UPF had an unhealthier nutritional profile and FOPL score than MPF. For items with no red FOPL, UPF still had an unhealthier profile than MPF, with a higher energy density. Importantly, not all UPF were unhealthy according to FOPL. These results indicate partial overlap between FOPL, nutrient content and NOVA classification of UK food and drink products, with implications for UK food and drink labelling.

Who consumes ultra-processed food? A systematic review of sociodemographic determinants of ultra-processed food consumption from nationally representative samples.

Ultra-processed food (UPF) intake is associated with increased non-communicable disease risks. However, systematic reports on sociodemographic predictors of UPF intake are lacking. This review aimed to understand UPF consumption based on sociodemographic factors, using nationally representative cohorts. The systematic review was pre-registered (PROSPERO:CRD42022360199), following PRISMA guidelines. PubMed/MEDLINE searches ('ultra-processed/ultraprocessed' and 'ultra-processing/ultraprocessing') until 7 September 2022 retrieved 1131 results. Inclusion criteria included: observational, nationally representative adult samples, in English, in peer-reviewed journals, assessing the association between sociodemographics and individual-level UPF intake defined by the NOVA classification. Exclusion criteria included: not nationally representative, no assessment of sociodemographics and individual-level UPF intake defined by NOVA. Risk of bias was assessed using the Newcastle­Ottawa Scale (NOS). Fifty-five papers were included, spanning thirty-two countries. All thirteen sociodemographic variables identified were significantly associated with UPF intake in one or more studies. Significant differences in UPF intake were seen across age, race/ethnicity, rural/urbanisation, food insecurity, income and region, with up to 10­20% differences in UPF intake (% total energy). Higher UPF intakes were associated with younger age, urbanisation and being unmarried, single, separated or divorced. Education, income and socioeconomic status showed varying associations, depending on country. Multivariate analyses indicated that associations were independent of other sociodemographics. Household status and gender were generally not associated with UPF intake. NOS averaged 5·7/10. Several characteristics are independently associated with high UPF intake, indicating large sociodemographic variation in non-communicable disease risk. These findings highlight significant public health inequalities associated with UPF intake, and the urgent need for policy action to minimise social injustice-related health inequalities.

The impact of living through COVID-19 pandemic on mental health, food insecurity, loneliness and health behaviours in people with obesity.

BACKGROUND: The COVID-19 pandemic has negatively impacted people living with obesity. The aim was to examine the continued impact of the COVID-19 pandemic on the mental health of people living with obesity and associations with food insecurity, loneliness and health-related behaviours. METHODS: The study recruited 1187 UK adults living with obesity who completed an online survey, which examined mental health and associations with food insecurity, loneliness and health-related behaviours from July 2020 (end of the first lockdown in the United Kingdom) to the point they completed the survey in 2021. Regression analyses were used to examine relationships between outcome variables and demographic factors, and hierarchical linear regression models were used to assess levels of loneliness, depression and well-being. RESULTS: Participants reported worse loneliness, depression, well-being and food insecurity compared to pre-COVID. However, participants reported attempting to lose weight, healthier food shopping, diet and increased physical activity. Quality and quantity of sleep deteriorated compared to prior to COVID-19. CONCLUSIONS: Adults living with obesity in the United Kingdom report a continued negative impact of the COVID-19 pandemic upon their mental health together with increased loneliness and food insecurity. However, our findings suggest that UK adults living with obesity have increased their engagement in positive health behaviours and were attempting to lose weight.

Ultra-processed Food and Obesity: What Is the Evidence?

PURPOSE OF REVIEW: Obesity is a growing global healthcare concern. A proposed driver is the recent increase in ultra-processed food (UPF) intake. However, disagreement surrounds the concept of UPF, the strength of evidence, and suggested mechanisms. Therefore, this review aimed to critically appraise the evidence on UPF and obesity. RECENT FINDINGS: Observational studies demonstrate positive associations between UPF intake, weight gain, and overweight/obesity, more clearly in adults than children/adolescents. This is supported by high-quality clinical data. Several mechanisms are proposed, but current understanding is inconclusive. Greater UPF consumption has been a key driver of obesity. There is a need to change the obesogenic environment to support individuals to reduce their UPF intake. The UPF concept is a novel approach that is not explained with existing nutrient- and food-based frameworks. Critical analysis of methodologies provides confidence, but future observational and experimental research outputs with greater methodological rigor will strengthen findings, which are outlined.

UPDATE trial: investigating the effects of ultra-processed versus minimally processed diets following UK dietary guidance on health outcomes: a protocol for an 8-week community-based cross-over randomised controlled trial in people with overweight or obesity, followed by a 6-month behavioural intervention.

INTRODUCTION: Obesity increases the risk of morbidity and mortality. A major driver has been the increased availability of ultra-processed food (UPF), now the main UK dietary energy source. The UK Eatwell Guide (EWG) provides public guidance for a healthy balanced diet but offers no UPF guidance. Whether a healthy diet can largely consist of UPFs is unclear. No study has assessed whether the health impact of adhering to dietary guidelines depends on food processing. Furthermore, our study will assess the impact of a 6-month behavioural support programme aimed at reducing UPF intake in people with overweight/obesity and high UPF intakes. METHODS AND ANALYSIS: UPDATE is a 2×2 cross-over randomised controlled trial with a 6-month behavioural intervention. Fifty-five adults aged ≥18, with overweight/obesity (≥25 to <40 kg/m2), and ≥50% of habitual energy intake from UPFs will receive an 8-week UPF diet and an 8-week minimally processed food (MPF) diet delivered to their home, both following EWG recommendations, in a random order, with a 4-week washout period. All food/drink will be provided. Participants will then receive 6 months of behavioural support to reduce UPF intake. The primary outcome is the difference in weight change between UPF and MPF diets from baseline to week 8. Secondary outcomes include changes in diet, waist circumference, body composition, heart rate, blood pressure, cardiometabolic risk factors, appetite regulation, sleep quality, physical activity levels, physical function/strength, well-being and aspects of behaviour change/eating behaviour at 8 weeks between UPF/MPF diets, and at 6-month follow-up. Quantitative assessment of changes in brain MRI functional resting-state connectivity between UPF/MPF diets, and qualitative analysis of the behavioural intervention for feasibility and acceptability will be undertaken. ETHICS AND DISSEMINATION: Sheffield Research Ethics Committee approved the trial (22/YH/0281). Peer-reviewed journals, conferences, PhD thesis and lay media will report results. TRIAL REGISTRATION NUMBER: NCT05627570.

Longitudinal changes and correlates of meeting WHO recommended levels of physical activity in the UK during the COVID-19 pandemic: Findings from the HEBECO study.

BACKGROUND: The COVID-19 pandemic has seen repeated government enforced restrictions on movement. This study aimed to evaluate longitudinal trends in physical activity (PA) in a self-selected UK-based sample and identify the key correlates of these trends. METHODS: From 23 April 2020 to 30 January 2021, measures of PA engagement were collected in a sample of 1,947 UK-based adults. Generalised estimating equations (GEE) explored trends in PA engagement over time, and how sociodemographic, health and contextual factors impacted participant's attainment of World Health Organization (WHO) recommended levels of PA (constituting muscle strengthening activity (MSA), and moderate or vigorous PA (MVPA)). RESULTS: While one in five achieved the recommended levels of PA in the first UK lockdown in April-June 2020 (19.5%, 95%CI: 17.8-21.3%) and a similar proportion in June-July 2020 (17.7%, 95%CI: 16.1-19.5%), this reduced during the period of eased restrictions in August-September 2020 (15.2%, 95%CI: 13.7-16.9%) and the second UK lockdown in November 2020-January 2021 (14.1%, 95%CI: 12.6-15.9%). Similar trends were observed for MSA and MVPA individually. Better quality of life, higher socioeconomic position and pre-COVID-19 PA levels were associated with meeting the WHO recommended levels of PA, while those living with overweight or obesity, a limiting health condition, or isolating showed the inverse associations. Time-specific associations with MSA or MVPA were observed for gender and age. CONCLUSION: Reductions in PA levels throughout the first strict lockdown continued without reversal during the ensuing period. The association of negative change with socioeconomic and health-related indices points towards deepening health inequities during the pandemic.

Barriers to and Facilitators of the Use of Digital Tools in Primary Care to Deliver Physical Activity Advice: Semistructured Interviews and Thematic Analysis.

BACKGROUND: Physical inactivity is a leading risk factor for many health conditions, including cardiovascular disease, diabetes, and cancer; therefore, increasing physical activity (PA) is a public health priority. Health care professionals (HCPs) in primary care are pivotal in addressing physical inactivity; however, few HCPs provide PA advice to patients. There can be obstacles to delivering PA advice, including lack of time, confidence, or knowledge. Digital technology has the potential to overcome obstacles and facilitate delivering PA advice. However, it is unknown if and how digital tools are used to deliver PA advice in primary care consultations and what factors influence their use. OBJECTIVE: We aimed to understand the use of digital tools to support primary care consultations and to identify the barriers to and facilitators of using these systems. METHODS: Overall, 25 semistructured interviews were conducted with primary care HCPs. Professionals were sampled based on profession (general practitioners, practice nurses, and health care assistants), prevalence of long-term conditions within their practice area, and rural-urban classification. The data were analyzed thematically to identify the influences on the use of digital tools. Themes were categorized using the COM-B (capability, opportunity, and motivation-behavior) model and the Theoretical Domains Framework to identify the barriers to and facilitators of using digital tools to support the delivery of PA advice in primary care consultations. RESULTS: The identified themes fell within 8 domains of the Theoretical Domains Framework. The most prominent influence (barrier or facilitator) within psychological capability was having the skills to use digital tools. Training in the use of digital tools was also mentioned several times. The most notable influences within physical opportunity were limited digital tools to prompt/support the provision of PA advice, time constraints, efficiency of digital tools, simplicity and ease of use of digital tools, and integration with existing systems. Other physical opportunity influences included lack of access to digital tools and technical support in the use of digital tools. Within social opportunity, a notable barrier was that digital tools reduce interpersonal communication with patients. Patient preference was also identified. Several important influences were within reflective motivation, including confidence to use digital tools, beliefs about the usefulness of digital tools, the belief that digital tools "are the way forward," beliefs related to data privacy and security concerns, and perceptions about patient capabilities. About automatic motivation, influences included familiarity and availability regarding digital tools and the fact that digital tools prompt behavior. CONCLUSIONS: A variety of influences were identified on the use of digital tools to support primary care consultations. These findings provide a foundation for designing a digital tool addressing barriers and leverages the facilitators to support PA advice provision within primary care to elicit patient behavior change and increase PA.

The Role of Diet Quality in Mediating the Association between Ultra-Processed Food Intake, Obesity and Health-Related Outcomes: A Review of Prospective Cohort Studies.

Prospective cohort studies show that higher intakes of ultra-processed food (UPF) increase the risk of obesity and obesity-related outcomes, including cardiovascular disease, cancer and type 2 diabetes. Whether ultra-processing itself is detrimental, or whether UPFs just have a lower nutritional quality, is debated. Higher UPF intakes are inversely associated with fruit, vegetables, legumes and seafood consumption. Therefore, the association between UPFs and poor health could simply be from excess nutrient intake or from a less healthful dietary pattern. If so, adjustment for dietary quality or pattern should explain or greatly reduce the size of the significant associations between UPFs and health-related outcomes. Here, we provide an overview of the literature and by using a novel approach, review the relative impact of adjusting for diet quality/patterns on the reported associations between UPF intake and health-related outcomes in prospective cohort studies. We find that the majority of the associations between UPFs, obesity and health-related outcomes remain significant and unchanged in magnitude after adjustment for diet quality or pattern. Our findings suggest that the adverse consequences of UPFs are independent of dietary quality or pattern, questioning the utility of reformulation to mitigate against the obesity pandemic and wider negative health outcomes of UPFs.

Impact of the COVID-19 Pandemic on Diet Behaviour Among UK Adults: A Longitudinal Analysis of the HEBECO Study.

COVID-19 pandemic restrictions impacted dietary habits during the initial months of the pandemic, but long-term effects are unclear. In this longitudinal study, self-selected UK adults (n = 1,733, 71.1% female, 95.7% white ethnicity) completed three online surveys (May-June, August-September, and November-December 2020, with a retrospective pre-pandemic component in the baseline survey), self-reporting sociodemographics, lifestyle, and behaviours, including high fat, salt, and sugar (HFSS) snacks, HFSS meals, and fruit and vegetable (FV) intake. Data were analysed using generalised estimating equations. Monthly HFSS snacks portion intake increased from pre-pandemic levels (48.3) in May-June (57.6, p < 0.001), decreased in August-September (43.7, p < 0.001), before increasing back to pre-pandemic levels in November-December (49.2, p < 0.001). A total of 48.5% self-reported increased [25.9 (95% confidence interval: 24.1, 27.8)] and 47.7% self-reported decreased [24.1 (22.4, 26.0)] monthly HFSS snacks portion intakes in November-December compared with pre-pandemic levels. Monthly HFSS meals portion intake decreased from pre-pandemic levels (7.1) in May-June (5.9, p < 0.001), was maintained in August-September (5.9, p = 0.897), and then increased again in November-December (6.6, p < 0.001) to intakes that remained lower than pre-pandemic levels (p = 0.007). A total of 35.2% self-reported increased [4.8 (4.3, 5.3)] and 44.5% self-reported decreased [5.1 (4.6, 5.6)] monthly HFSS meals portion intakes in November-December compared with pre-pandemic levels. The proportion meeting FV intake recommendations was stable from pre-pandemic through to August-September (70%), but decreased in November-December 2020 (67%, p = 0.034). Increased monthly HFSS snacks intake was associated with female gender, lower quality of life, and - in a time - varying manner - older age and higher HFSS meals intake. Increased monthly HFSS meals intake was associated with female gender, living with adults only, and higher HFSS snacks intake. Reduced FV intake was associated with higher body mass index (BMI) and lower physical activity. These results suggest large interindividual variability in dietary change during the first year of the pandemic, with important public health implications in individuals experiencing persistent increases in unhealthy diet choices, associated with BMI, gender, quality of life, living conditions, physical activity, and other dietary behaviours.

Impact of COVID-19 Pandemic on Weight and BMI among UK Adults: A Longitudinal Analysis of Data from the HEBECO Study.

COVID-19-related restrictions impacted weight and weight-related factors during the initial months of the pandemic. However, longitudinal analyses are scarce. An online, longitudinal study was conducted among self-selected UK adults (n = 1818), involving three surveys (May-June, August-September, November-December 2020), covering anthropometric, sociodemographic, COVID-19-related and behavioural measures. Data were analysed using generalised estimating equations. Self-reported average weight/body mass index (BMI) significantly increased between the May-June period and the August-September period (74.95 to 75.33 kg/26.22 kg/m2 to 26.36kg/m2, p < 0.001, respectively), and then significantly decreased to November-December (to 75.06 kg/26.27 kg/m2, p < 0.01), comparable to May-June levels (p = 0.274/0.204). However, there was great interindividual variation, 37.0%/26.7% increased (average 3.64 kg (95% confidence interval: 3.32, 3.97)/1.64 kg/m2 (1.49, 1.79)), and 34.5%/26.3% decreased (average 3.59 kg (3.34, 3.85)/1.53 kg/m2 (1.42, 1.63)) weight/BMI between May-June and November-December. Weight/BMI increase was significantly negatively associated with initial BMI, and positively associated with monthly high fat, salt and sugar (HFSS) snacks intake and alcohol consumption, and for BMI only, older age. Associations were time-varying; lower initial BMI, higher HFSS snacks intake and high-risk alcohol consumption were associated with maintaining weight/BMI increases between August-September and November-December. The average weight/BMI of UK adults fluctuated between May-June and November-December 2020. However, the substantial interindividual variation in weight/BMI trajectories indicates long-term health impacts from the pandemic, associated with food and alcohol consumption.

Characterisation of B.1.1.7 and Pangolin coronavirus spike provides insights on the evolutionary trajectory of SARS-CoV-2.

The recent emergence of SARS-CoV-2 variants with increased transmission, pathogenesis and immune resistance has jeopardised the global response to the COVID-19 pandemic. Determining the fundamental biology of viral variants and understanding their evolutionary trajectories will guide current mitigation measures, future genetic surveillance and vaccination strategies. Here we examine virus entry by the B.1.1.7 lineage, commonly referred to as the UK/Kent variant. Pseudovirus infection of model cell lines demonstrate that B.1.1.7 entry is enhanced relative to the Wuhan-Hu-1 reference strain, particularly under low expression of receptor ACE2. Moreover, the entry characteristics of B.1.1.7 were distinct from that of its predecessor strain containing the D614G mutation. These data suggest evolutionary tuning of spike protein function. Additionally, we found that amino acid deletions within the N-terminal domain (NTD) of spike were important for efficient entry by B.1.1.7. The NTD is a hotspot of diversity across sarbecoviruses, therefore, we further investigated this region by examining the entry of closely related CoVs. Surprisingly, Pangolin CoV spike entry was 50-100 fold enhanced relative to SARS-CoV-2; suggesting there may be evolutionary pathways by which SARSCoV-2 may further optimise entry. Swapping the NTD between Pangolin CoV and SARS-CoV-2 demonstrates that changes in this region alone have the capacity to enhance virus entry. Thus, the NTD plays a hitherto unrecognised role in modulating spike activity, warranting further investigation and surveillance of NTD mutations.