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Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, belonging to the genus beta-CoV, have caused outbreaks or pandemics. SARS-CoV-2 has evolved into many variants with increased resistance to the current vaccines. Spike (S) protein and its receptor-binding domain (RBD) fragment of these CoVs are important vaccine targets; however, the RBD of the SARS-CoV-2 Omicron variant is highly mutated, rending neutralizing antibodies elicited by ancestral-based vaccines targeting this region ineffective, emphasizing the need for effective vaccines with broad-spectrum efficacy against SARS-CoV-2 variants and other CoVs with pandemic potential. This study describes a pan-beta-CoV subunit vaccine, Om-S-MERS-RBD, by fusing the conserved and highly potent RBD of MERS-CoV into an RBD-truncated SARS-CoV-2 Omicron S protein, and evaluates its neutralizing immunogenicity and protective efficacy in mouse models. Om-S-MERS-RBD formed a conformational structure, maintained effective functionality and antigenicity, and bind efficiently to MERS-CoV receptor, human dipeptidyl peptidase 4, and MERS-CoV RBD or SARS-CoV-2 S-specific antibodies. Immunization of mice with Om-S-MERS-RBD and adjuvants (Alum plus monophosphoryl lipid A) induced broadly neutralizing antibodies against pseudotyped MERS-CoV, SARS-CoV, and SARS-CoV-2 original strain, as well as T-cell responses specific to RBD-truncated Omicron S protein. Moreover, the neutralizing activity against SARS-CoV-2 Omicron subvariants was effectively improved after priming with an Omicron-S-RBD protein. Adjuvanted Om-S-MERS-RBD protein protected mice against challenge with SARS-CoV-2 Omicron variant, MERS-CoV, and SARS-CoV, significantly reducing viral titers in the lungs. Overall, these findings indicated that Om-S-MERS-RBD protein could develop as an effective universal subunit vaccine to prevent infections with MERS-CoV, SARS-CoV, SARS-CoV-2, and its variants., Importance: Coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, the respective causative agents of coronavirus disease 2019, SARS, and MERS, continually threaten human health. The spike (S) protein and its receptor-binding domain (RBD) fragment of these CoVs are critical vaccine targets. Nevertheless, the highly mutated RBD of SARS-CoV-2 variants, especially Omicron, significantly reduces the efficacy of current vaccines against SARS-CoV-2 variants. Here a protein-based pan-beta-CoV subunit vaccine is designed by fusing the potent and conserved RBD of MERS-CoV into an RBD-truncated Omicron S protein. The resulting vaccine maintained effective functionality and antigenicity, induced broadly neutralizing antibodies against all of these highly pathogenic human CoVs, and elicited Omicron S-specific cellular immune responses, protecting immunized mice from SARS-CoV-2 Omicron, SARS-CoV, and MERS-CoV infections. Taken together, this study rationally designed a pan-beta-CoV subunit vaccine with broad-spectrum efficacy, which has the potential for development as an effective universal vaccine against SARS-CoV-2 variants and other CoVs with pandemic potential., Competing Interests: The authors declare no financial interests. The authors have filed a patent application related to this study, with L.D., G.W., and F.L. as inventors.

Grasping the roles of epitopes in viral glycoproteins is essential for unraveling the structure and function of these proteins. Up to now, all identified epitopes have been found to either neutralize, have no effect on, or enhance viral entry into cells. Here, we used nanobodies (single-domain antibodies) as probes to investigate a unique epitope on the SARS-CoV-2 spike protein, located outside the protein's receptor-binding domain. Nanobody binding to this epitope enhances the cell entry of prototypic SARS-CoV-2, while neutralizing the cell entry of SARS-CoV-2 Omicron variant. Moreover, nanobody binding to this epitope promotes both receptor binding activity and post-attachment activity of prototypic spike, explaining the enhanced viral entry. The opposite occurs with Omicron spike, explaining the neutralized viral entry. This study reveals a unique epitope that can both enhance and neutralize viral entry across distinct viral variants, suggesting that epitopes may vary their roles depending on the viral context. Consequently, antibody therapies should be assessed across different viral variants to confirm their efficacy and safety., Competing Interests: The University of Minnesota has filed a patent on Nanosota-5, -6, and -7 with F.L., G.Y., F.B., and B.L. as inventors., (Copyright: © 2024 Ye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Since the COVID-19 outbreak, raccoon dogs have been suggested as a potential intermediary in transmitting SARS-CoV-2 to humans. To understand their role in the COVID-19 pandemic and the species barrier for SARS-CoV-2 transmission to humans, we analyzed how their ACE2 protein interacts with SARS-CoV-2 spike protein. Biochemical data showed that raccoon dog ACE2 is an effective receptor for SARS-CoV-2 spike protein, though not as effective as human ACE2. Structural comparisons highlighted differences in the virus-binding residues of raccoon dog ACE2 compared to human ACE2 (L24Q, Y34H, E38D, T82M, R353K), explaining their varied effectiveness as receptors for SARS-CoV-2. These variations contribute to the species barrier that exists between raccoon dogs and humans regarding SARS-CoV-2 transmission. Identifying these barriers can help assess the susceptibility of other mammals to SARS-CoV-2. Our research underscores the potential of raccoon dogs as SARS-CoV-2 carriers and identifies molecular barriers that affect the virus's ability to jump between species., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hsueh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: The COVID-19 pandemic exposed limitations of conventional antibodies as therapeutics, including high cost, limited potency, ineffectiveness against new viral variants, and primary reliance on injection-only delivery. Nanobodies are single-domain antibodies with therapeutic potentials. We discovered three anti-SARS-CoV-2 nanobodies, named Nanosota-2, -3, and -4, from an immunized alpaca. Nanosota-2 is super potent against prototypic SARS-CoV-2, Nanosota-3 is highly potent against the omicron variant, and Nanosota-4 is effective against both SARS-CoV-1 and SARS-CoV-2. In addition to their super potency and combined broad antiviral spectrum, these nanobodies are cost-effective, can be easily adapted to new viral variants through phage display, and can potentially be administered as inhalers. The Nanosota series are powerful therapeutic candidates to combat circulating SARS-CoV-2 and prepare for possible future coronavirus pandemics., Competing Interests: The University of Minnesota has filed a patent on Nanosota-2, -3 and -4 with F.L, G.Y., and B.L. as inventors. B.S. and B.E.W. are co-founders of Turkey Creek Biotechnology.

SARS-CoV-2 spike protein plays a key role in mediating viral entry and inducing host immune responses. It can adopt either an open or closed conformation based on the position of its receptor-binding domain (RBD). It is yet unclear what causes these conformational changes or how they influence the spike's functions. Here, we show that Lys417 in the RBD plays dual roles in the spike's structure: it stabilizes the closed conformation of the trimeric spike by mediating inter-spike-subunit interactions; it also directly interacts with ACE2 receptor. Hence, a K417V mutation has opposing effects on the spike's function: it opens up the spike for better ACE2 binding while weakening the RBD's direct binding to ACE2. The net outcomes of this mutation are to allow the spike to bind ACE2 with higher probability and mediate viral entry more efficiently, but become more exposed to neutralizing antibodies. Given that residue 417 has been a viral mutational hotspot, SARS-CoV-2 may have been evolving to strike a balance between infection potency and immune evasion, contributing to its pandemic spread., Competing Interests: QG, YW, FH, JS, GY, FB, MH, RW, BL, FL No competing interests declared, (© 2023, Geng, Wan et al.)

Aims: Due to a prolonged period of national and regional lockdown measures during the coronavirus (COVID-19) pandemic, there has been an increase reliance on informal care for informal carers. In light of this, the current study compared the experiences of carers and non-carers on various mental health and wellbeing measures across six key time points during the pandemic., Methods: Data analysed were from the University College London (UCL) COVID -19 Social Study. Our study focused on six time points in England: (1) the first national lockdown (March-April 2020); (2) the beginning of first lockdown rules easing (May 2020); (3) the second national lockdown (November 2020); (4) the third national lockdown (January 2021); (5) the easing of the third lockdown (March 2021); and (6) the end of restrictions (July-August 2021). We considered five mental health and wellbeing measures: depressive symptoms, anxiety symptoms, loneliness, life satisfaction, and sense of being worthwhile. Propensity score matching was applied for the analyses., Results: We found that informal carers experienced higher levels of depressive and anxiety symptoms than non-carers across much of the pandemic. During the first national lockdown, carers also experienced a higher sense of life being worthwhile. No association was found between informal caring responsibilities and levels of loneliness and life satisfaction., Conclusion: Given that carers are an essential national healthcare support, especially during a pandemic, it is crucial to integrate carers' needs into healthcare planning and delivery. These results highlight that there is a pressing need to provide adequate and targeted mental health support for carers during and following this pandemic., Competing Interests: Conflict Of InterestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The coronavirus disease 2019 (COVID-19) pandemic has brought about significant behavioural changes, one of which is increased time spent at home. This could have important public health implications. This study aimed to explore longitudinal patterns of 'home confinement' (defined as not leaving the house/garden) during the COVID-19 pandemic, and the associated predictors and mental health outcomes., Methods: Data were from the UCL COVID-19 Social Study. The analytical sample consisted of 25 390 adults in England who were followed up for 17 months (March 2020-July 2021). Data were analysed using growth mixture models., Results: Our analyses identified three classes of growth trajectories, including one class showing a high level of persistent home confinement (the home-confined, 24.8%), one changing class with clear alignment with national containment measures (the adaptive, 32.0%), and one class with a persistently low level of confinement (the unconfined, 43.1%). A range of factors were associated with the class membership of home-confinement trajectories, such as age, gender, income, employment status, social relationships and health. The home-confined class had the highest number of depressive (diff = 1.34-1.68, p < 0.001) and anxiety symptoms (diff = 0.84-1.05, p < 0.001) at the end of the follow-up than the other two classes., Conclusions: There was substantial heterogeneity in longitudinal patterns of home confinement during the COVID-19 pandemic. People with a persistent high level of confinement had the worst mental health outcomes, calling for special attention in mental health action plans, in particular targeted interventions for at-risk groups.

Introduction: We investigated whether changes in engagement in home-based creative activities were associated with changes in depressive symptoms, anxiety symptoms and life satisfaction during the COVID-19 pandemic, aiming to replicate findings from the UK in a USA sample., Methods: 3725 adults were included from the COVID-19 Social Study in the USA, a panel study collecting data weekly during the COVID-19 pandemic. We measured engagement in eight types of creative leisure activities on the previous weekday between April and September 2020. Data were analysed using fixed effects regression models., Results: Increased time spent gardening was associated with reductions in depressive and anxiety symptoms and enhanced life satisfaction. Spending more time doing woodwork/DIY and arts/crafts were also associated with enhanced life satisfaction. However, more time watching television, films or other similar media (not for information on COVID-19) was associated with increased depressive symptoms. Other creative activities were not associated with mental health or well-being., Conclusion: Some findings differ from evidence obtained in the UK, demonstrating the importance of replicating research across countries. Our findings should also be considered when formulating guidelines for future stay-at-home directives, enabling individuals to stay well despite the closure of public resources., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: There has been much research into the mental health impact of the Coronavirus Disease 2019 (COVID-19) pandemic and how it is related to time-invariant individual characteristics. However, there is still a lack of research showing long-term trajectories of mental health across different stages of the pandemic. And little is known regarding the longitudinal association of time-varying factors with mental health outcomes. This study aimed to provide a longitudinal profile of how mental health in adults changed across different stages of the COVID-19 pandemic and to examine their longitudinal associations with time-varying contextual (e.g., COVID-19 policy response and pandemic intensity) and individual level factors., Methods and Findings: This study used data from a large panel study of over 57,000 adults living in England, who were followed up regularly for 2 years between March 2020 and April 2022. Mental health outcomes were depressive and anxiety symptoms. Depressive symptoms were assessed by the Patient Health Questionnaire (PHQ-9) and anxiety symptoms by the Generalized Anxiety Disorder assessment (GAD-7). Entropy balancing weights were applied to restore sample representativeness. After weighting, approximately 50% of participants were female, 14% from ethnic minority backgrounds, with a mean age of 48 years. Descriptive analyses showed that mental health changes were largely in line with changes in COVID-19 policy response and pandemic intensity. Further, data were analysed using fixed-effects (FE) models, which controlled for all time-invariant confounders (observed or not). FE models were fitted separately across 3 stages of the COVID-19 pandemic, including the first national lockdown (21/03/2020-23/08/2020), second and third national lockdowns (21/09/2020-11/04/2021), and "freedom" period (12/04/2021-14/11/2021). We found that more stringent policy response (measured by stringency index) was associated with increased depressive symptoms, in particular, during lockdown periods (β = 0.23, 95% confidence interval (CI) = [0.18 to 0.28], p < 0.001; β = 0.30, 95% CI = [0.21 to 0.39], p < 0.001; β = 0.04, 95% CI = [-0.03 to 0.12], p = 0.262). Higher COVID-19 deaths were also associated with increased depressive symptoms, but this association weakened over time (β = 0.29, 95% CI = [0.25 to 0.32], p < 0.001; β = 0.09, 95% CI = [0.05 to 0.13], p < 0.001; β = -0.06, 95% CI = [-0.30 to 0.19], p = 0.655). Similar results were also found for anxiety symptoms, for example, stringency index (β = 0.17, 95% CI = [0.12 to 0.21], p < 0.001; β = 0.13, 95% CI = [0.06 to 0.21], p = 0.001; β = 0.10, 95% CI = [0.03 to 0.17], p = 0.005), COVID-19 deaths (β = 0.07, 95% CI = [0.04 to 0.10], p < 0.001; β = 0.04, 95% CI = [0.00 to 0.07], p = 0.03; β = 0.16, 95% CI = [-0.08 to 0.39], p = 0.192). Finally, there was also evidence for the longitudinal association of mental health with individual level factors, including confidence in government/healthcare/essentials, COVID-19 knowledge, COVID-19 stress, COVID-19 infection, and social support. However, it is worth noting that the magnitudes of these longitudinal associations were generally small. The main limitation of the study was its non-probability sample design., Conclusions: Our results provided empirical evidence on how changes in contextual and individual level factors were related to changes in depressive and anxiety symptoms. While some factors (e.g., confidence in healthcare, social support) clearly acted as consistent predictors of depressive and/or anxiety symptoms, other factors (e.g., stringency index, COVID-19 knowledge) were dependent on the specific situations occurring within society. This could provide important implications for policy making and for a better understanding of mental health of the general public during a national or global health crisis., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DF is a Guest Editor on PLOS Medicine’s COVID-19 Pandemic and Global Mental Health Special Issue., (Copyright: © 2023 Bu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: There is a growing global awareness of the psychological consequences of long COVID, supported by emerging empirical evidence. However, the emergence and long-term trajectories of psychological symptoms following the infection are still unclear., Aims: To examine when psychological symptoms first emerge following infection with SARS-CoV-2 and the long-term trajectories of psychological symptoms comparing long- and short-COVID groups., Method: We analysed longitudinal data from the UCL COVID-19 Social Study (March 2020 to November 2021). We included data from adults living in England who reported contracting SARS-CoV-2 by November 2021 ( n = 3115). Of these, 15.9% reported having had long COVID ( n = 495). They were matched to participants who had short COVID using propensity score matching on a variety of demographic, socioeconomic and health covariates ( n = 962 individuals with 13 325 observations) and data were further analysed using growth curve modelling., Results: Depressive and anxiety symptoms increased immediately following the onset of infection in both long- and short-COVID groups. But the long-COVID group had substantially greater initial increases in depressive symptoms and heightened levels over 22 months follow-up. Initial increases in anxiety were not significantly different between groups, but only the short-COVID group experienced an improvement in anxiety over follow-up, leading to widening differences between groups., Conclusions: The findings support work on the psychobiological pathways involved in the development of psychological symptoms relating to long COVID. The results highlight the need for monitoring of mental health and provision of adequate support to be interwoven with diagnosis and treatment of the physical consequences of long COVID.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease (COVID-19), has been devastated by COVID-19 in an increasing number of countries and health care systems around the world since its announcement of a global pandemic on 11 March 2020. During the pandemic, emerging novel viral mutant variants have caused multiple outbreaks of COVID-19 around the world and are prone to genetic evolution, causing serious damage to human health. As confirmed cases of COVID-19 spread rapidly, there is evidence that SARS-CoV-2 infection involves the central nervous system (CNS) and peripheral nervous system (PNS), directly or indirectly damaging neurons and further leading to neurodegenerative diseases (ND), but the molecular mechanisms of ND and CVOID-19 are unknown. We employed transcriptomic profiling to detect several major diseases of ND: Alzheimer 's disease (AD), Parkinson' s disease (PD), and multiple sclerosis (MS) common pathways and molecular biomarkers in association with COVID-19, helping to understand the link between ND and COVID-19. There were 14, 30 and 19 differentially expressed genes (DEGs) between COVID-19 and Alzheimer 's disease (AD), Parkinson' s disease (PD) and multiple sclerosis (MS), respectively; enrichment analysis showed that MAPK, IL-17, PI3K-Akt and other signaling pathways were significantly expressed; the hub genes (HGs) of DEGs between ND and COVID-19 were CRH, SST, TAC1, SLC32A1, GAD2, GAD1, VIP and SYP. Analysis of transcriptome data suggests multiple co-morbid mechanisms between COVID-19 and AD, PD, and MS, providing new ideas and therapeutic strategies for clinical prevention and treatment of COVID-19 and ND., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Government enforced restrictions on movement during the COVID-19 pandemic are likely to have had profound impacts on the daily behaviours of many individuals, including physical activity (PA). Given the associations between PA and other health behaviours, changes in PA during the pandemic may have been detrimental for other health behaviours. This study aimed to evaluate whether changes in PA during and after the first national lockdown in the United Kingdom (UK) were associated with concurrent changes in alcohol consumption, sleep, nutrition quality, diet quantity and sedentary time. Data were derived from the UCL COVID-19 Social Study, in which 52,784 adults were followed weekly across 22 weeks of the pandemic from 23rd March to 23rd August 2020. Fixed effects regression models showed that greater PA was positively associated with improved sleep and nutrition quality. However, increases in PA also showed modest associations with increased alcohol consumption and sedentary time. Encouraging people to engage in PA may lead to wider changes in other health behaviours in times of adversity. These associations could be a result of increases in available leisure time for many people during COVID-19 restrictions and are of ongoing importance given the emerging long-term changes to lifestyle and working patterns., (© 2022. The Author(s).)

This study examined the association between greenspace and the growth trajectories of anxiety symptoms during the COVID-19 pandemic. Using data from 19,848 urban residents in England who were followed for 20 months between March 2020 and October 2021, we found that living in an area with higher greenspace coverage (exposure) was associated with fewer anxiety symptoms independent of population density, area deprivation levels, socio-demographics, and health profiles. There was limited evidence that greenspace was related to the change of anxiety symptoms over time. No association with anxiety trajectories was found when considering distance to nearest greenspace (proximity), highlighting potentially differential mental health effects of simply having access to local parks and recreation areas versus living in areas of greater natural environment land cover. These findings have important implications for mental health intervention and policymaking., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Between March 2020 and March 2021, the United Kingdom (UK) experienced three lockdowns due to the COVID-19 pandemic. Given the evident association between arts engagement and wellbeing, this study was designed to compare the predictors and patterns of home-based arts engagement during these lockdowns. Data analysed in this study were from the UK COVID-19 Social Study run by University College London. Multinomial logistic regression was used to identify predictors of arts engagement and compare (i) respondents' engagement levels during the first lockdown in April/May 2020 and their levels in pre-pandemic times (N = 23,086), (ii) their engagement levels during the second lockdown in November/December 2020 with their levels during the first lockdown (N = 11,481), and (iii) their engagement levels during the third lockdown in January/February 2021 with their levels during the first lockdown (N = 13,270). During first lockdown, 1 in 4 increased their arts engagement and 1 in 6 decreased it. Of those who increased, 2 in 5 maintained or further increased their engagement in subsequent lockdowns, but just 7% of those who had decreased their engagement increased it. Younger adults (aged 18-29) showed initial increases in first lockdown, whilst people who were not employed and those with a physical health condition showed decreases and people with a mental health condition showed changes during the first lockdown (both increases and decreases). Females and people with higher education showed continuous changes across the three lockdowns, with women being more likely to increase their engagement and those with higher education being less likely to decrease. People of ethnic minorities and those with higher income declined their engagement in the third lockdown. This study provides insight into levels of arts engagement across the three national lockdowns in the UK and suggests that the pandemic may have affected long-term cultural behaviours for some groups., Competing Interests: The authors have declared that no competing interests exist.

The COVID-19 pandemic led to national lockdowns in countries around the world. Whilst lockdowns were shown to be effective in reducing the spread of disease, they were also associated with adverse effects on people's mental health and wellbeing. Previous studies have suggested that time spent outside may have played a role in mitigating these negative effects, but research on this topic remains limited. Therefore, this study was designed to explore the longitudinal associations between going outdoors and people's mental health and wellbeing during the first national lockdown (March-May 2020) in the UK. Data from 35,301 participants from the COVID-19 Social Study were analysed. Fixed effects regression was used to explore the longitudinal association between changes in going outdoors (the number of days spent outside) and changes in depressive symptoms, anxiety symptoms, life satisfaction and loneliness. A range of household and neighbourhood moderators were examined. Results show that an increase in the number of days spent outside was associated with decreases in depressive and anxiety symptoms and an increase in life satisfaction. Associations were more salient amongst people living with others, and those with greater satisfaction with their neighbourhood walkability and green spaces. No longitudinal association was found with loneliness. Overall, our analyses showed a positive association between going outdoors and improved mental health and wellbeing during the first COVID-19 lockdown in the UK. These findings are important for formulating guidance for people to stay well at home during pandemics and for the on-going nature-based social prescribing scheme., (© 2022. The Author(s).)

Many studies have investigated the impact of the COVID-19 pandemic on mental health. Throughout the pandemic, time spent at home increased to a great extent due to restrictive measures. Here we set out to investigate the relationship between housing conditions and the mental health of populations across European countries. We analyzed survey data collected during spring 2020 from 69,136 individuals from four cohorts from Denmark, France, and the UK. The investigated housing conditions included household density, composition, and crowding, access to outdoor facilities, dwelling type, and urbanicity. The outcomes were loneliness, anxiety, and life satisfaction. Logistic regression models were used, and results were pooled using random-effects meta-analysis. In the meta-analysis, living alone was associated with higher levels of loneliness (OR = 3.08, 95% CI 1.87-5.07), and lower life satisfaction (OR = 1.27, 95% CI 1.05-0.55), compared to living with others. Not having access to an outdoor space and household crowding were suggestively associated with worse outcomes. Living in crowded households, living alone, or lacking access to outdoor facilities may be particularly important in contributing to poor mental health during a lockdown. Addressing the observed fundamental issues related to housing conditions within society will likely have positive effects in reducing social inequalities, as well as improving preparedness for future pandemics., (© 2022. The Author(s).)

Aims: This study aimed to examine potential heterogeneity in longitudinal changes in home-based arts engagement during the first national lockdown and following gradual easing of restrictions in the UK. Furthermore, it sought to explore factors that were associated with patterns of longitudinal changes in home-based arts engagement., Method: Data were from the UCL COVID-19 Social Study. The analytical sample consisted of 29,147 adults in the UK who were followed up for 22 weeks from 21 March to 21 August 2020. Data were analysed using growth mixture models., Results: Our analyses identified five classes of growth trajectories. There were two stable classes showing little change in arts engagement over time (64.4% in total), two classes showing initial increases in arts engagement followed by declines as restrictions were eased (29.8%), and one class showing slight declines during strict lockdown followed by an increase in arts engagement after the easing of restrictions (5.9%). A range of factors were found to be associated with class membership of these arts engagement trajectories, such as age, gender, education, income, employment status, and health., Conclusion: There is substantial heterogeneity in longitudinal changes in home-based arts engagement. For participants whose engagement changed over time, growth trajectories of arts engagement were related to changes in lockdown measures. These findings suggest that some individuals may have drawn on the arts when they needed them the most, such as during the strict lockdown period, even if they usually had lower levels of arts engagement before the pandemic. Overall, our results indicate the importance of promoting arts engagement during pandemics and periods of lockdown as part of public health campaigns.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has put a great strain on people's mental health. A growing number of studies have shown worsening mental health measures globally during the pandemic. However, there is a lack of empirical study on how people support their mental health during the COVID-19 pandemic. This study aimed to examine a number of formal and informal mental health support. Further, it explored factors that might be associated with the use of different types mental health support., Methods: Data from 26,720 adults in the UCL COVID-19 Social Study were analysed between 13th April 2020 and 3rd July 2020. Data were analysed using logistic and Poisson regression models., Results: About 45% of people reported talking to friends or family members to support their mental health, 43% engaging in self-care activities, 20% taking medication, 9% speaking to mental health professionals, 8% talking to a GP or other health professional, and another 8% using helpline or online services. Gender, education, living status, loneliness, pre-existing mental health conditions, general depression and anxiety, coping and personality were found to be associated with the use of mental health support., Conclusion: While the negative impacts caused by the COVID-19 pandemic are inevitable, people can play an active role in managing their mental health. Understanding the patterns and predictors of various kinds of mental health support during the pandemic is crucial for future service planning and delivery through recognising potential barriers to mental health care faced by certain groups., (© 2021. The Author(s).)

Background: There is currently major concern about the impact of the global COVID-19 outbreak on mental health. But it remains unclear how individual behaviours could exacerbate or protect against adverse changes in mental health., Aims: To examine the associations between specific activities (or time use) and mental health and well-being among people during the COVID-19 pandemic., Method: Data were from the UCL COVID-19 Social Study, a panel study collecting data weekly during the COVID-19 pandemic. The analytical sample consisted of 55 204 adults living in the UK who were followed up for the 11-week strict lockdown period from 21 March to 31 May 2020. Data were analysed using fixed-effects and Arellano-Bond models., Results: Changes in time spent on a range of activities were associated with changes in mental health and well-being. After controlling for bidirectionality, behaviours involving outdoor activities such as gardening and exercising predicted subsequent improvements in mental health and well-being, whereas increased time spent following news about COVID-19 predicted declines in mental health and well-being., Conclusions: These results are relevant to the formulation of guidance for people obliged to spend extended periods in isolation during health emergencies and may help the public to maintain well-being during future lockdowns and pandemics.

Recent studies have shown reduced physical activity at early stages of the COVID-19 pandemic. However, there is a lack of investigation on longitudinal changes in physical activity beyond lockdowns and stay-at-home orders. Moreover, it is unclear if there is heterogeneity in physical activity growth trajectories. This study aimed to explore longitudinal patterns of physical activity and factors associated with them. Data were from the UCL COVID-19 Social Study. The analytical sample consisted of 35,915 adults in England who were followed up for 22 weeks from 24th March to 23rd August 2020. Data were analysed using growth mixture models. Our analyses identified six classes of growth trajectories, including three stable classes showing little change over time (62.4% in total), two classes showing decreasing physical activity (28.6%), and one class showing increasing physical activity over time (9%). A range of factors were found to be associated the class membership of physical activity trajectories, such as age, gender, education, income, employment status, and health. There is substantial heterogeneity in longitudinal changes in physical activity during the COVID-19 pandemic. However, a substantial proportion of our sample showed persistent physical inactivity or decreasing physical activity. Given the well-established link between physical activity and health, persistent or increased physical inactivity is likely to have both immediate and long-term implications for people's physical and mental health, as well as general wellbeing. More efforts are needed to promote physical activity during the pandemic and beyond., (© 2021. The Author(s).)

Rationale: The negative impact of the COVID-19 pandemic on mental health is well evidenced. However, there is little research on how individuals' coping strategies were related to changes in mental health over time., Methods: The current study used data from the COVID-19 Social Study in the United Kingdom (N = 26,505) to explore whether coping strategies (problem-focused, emotion-focused, avoidant, and socially-supportive) were associated with (i) better mental health as lockdown was introduced, and (ii) faster recovery over time., Results: People with greater use of problem-focused, avoidant, and supportive coping displayed more mental health symptoms, while greater use of emotion-focused coping was associated with fewer mental health symptoms. Symptoms decreased over time for all coping strategies, but only socially-supportive coping was associated with a faster decrease in anxiety and depressive symptoms, indicating a potential protective effect of social support on psychological distress., Conclusions: Problem-, avoidant- and emotion-focused coping strategies were not associated with faster improvements in mental health. Suggesting the adoption of one of these coping styles in itself is not necessarily a driver of improvements in mental health; rather, specific attributes of the behaviours expressed as part of this coping style appear to be important in and of themselves., (Copyright © 2021. Published by Elsevier Ltd.)

Background & Aims: The COVID-19 pandemic has led to the implementation of stay-at-home and lockdown measures. It is currently unknown if the experience of lockdown leads to long term changes in individual's eating behaviors. The objectives of this study were: i) to derive longitudinal trajectories of change in eating during UK lockdown, and ii) to identify risk factors associated with eating behavior trajectories., Method: Data from 22,374 UK adults from the UCL COVID-19 Social study (a panel study collecting weekly data during the pandemic) were analyzed from 28th March to 29th May 2020. Latent Class Growth Analysis was used to derive trajectories of change in eating. These were then associated with prior socio-economic, health-related and psychological factors using multinomial regression models., Results: Analyses suggested five trajectories, with the majority (64%) showing no change in eating. In contrast, one trajectory was marked by persistently eating more, whereas another by persistently eating less. Overall, participants with greater depressive symptoms were more likely to report any change in eating. Loneliness was linked to persistently eating more (OR = 1.07), whereas being single or divorced, as well as stressful life events, were associated with consistently eating less (OR = 1.69). Overall, higher education status was linked to lower odds of changing eating behavior (OR = 0.54-0.77). Secondary exploratory analyses suggest that participants self-reported to have overweight were more commonly categorised into the group consistently eating more, whereas participants with underweigh persistently ate less., Conclusion: In this study, we found that one third of the sample report changes in quantities eaten throughout the first UK lockdown period. Findings highlight the importance of adjusting public health programs to support eating behaviors in future lockdowns both in this and potential future pandemics. This is particularly important as part of on-going preventive efforts to prevent nutrition-related chronic diseases., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: COVID-19 is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed. This is the second edition of a living systematic review of randomized clinical trials assessing the effects of all treatment interventions for participants in all age groups with COVID-19., Methods and Findings: We planned to conduct aggregate data meta-analyses, trial sequential analyses, network meta-analysis, and individual patient data meta-analyses. Our systematic review was based on PRISMA and Cochrane guidelines, and our eight-step procedure for better validation of clinical significance of meta-analysis results. We performed both fixed-effect and random-effects meta-analyses. Primary outcomes were all-cause mortality and serious adverse events. Secondary outcomes were admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and non-serious adverse events. According to the number of outcome comparisons, we adjusted our threshold for significance to p = 0.033. We used GRADE to assess the certainty of evidence. We searched relevant databases and websites for published and unpublished trials until November 2, 2020. Two reviewers independently extracted data and assessed trial methodology. We included 82 randomized clinical trials enrolling a total of 40,249 participants. 81 out of 82 trials were at overall high risk of bias. Meta-analyses showed no evidence of a difference between corticosteroids versus control on all-cause mortality (risk ratio [RR] 0.89; 95% confidence interval [CI] 0.79 to 1.00; p = 0.05; I2 = 23.1%; eight trials; very low certainty), on serious adverse events (RR 0.89; 95% CI 0.80 to 0.99; p = 0.04; I2 = 39.1%; eight trials; very low certainty), and on mechanical ventilation (RR 0.86; 95% CI 0.55 to 1.33; p = 0.49; I2 = 55.3%; two trials; very low certainty). The fixed-effect meta-analyses showed indications of beneficial effects. Trial sequential analyses showed that the required information size for all three analyses was not reached. Meta-analysis (RR 0.93; 95% CI 0.82 to 1.07; p = 0.31; I2 = 0%; four trials; moderate certainty) and trial sequential analysis (boundary for futility crossed) showed that we could reject that remdesivir versus control reduced the risk of death by 20%. Meta-analysis (RR 0.82; 95% CI 0.68 to 1.00; p = 0.05; I2 = 38.9%; four trials; very low certainty) and trial sequential analysis (required information size not reached) showed no evidence of difference between remdesivir versus control on serious adverse events. Fixed-effect meta-analysis showed indications of a beneficial effect of remdesivir on serious adverse events. Meta-analysis (RR 0.40; 95% CI 0.19 to 0.87; p = 0.02; I2 = 0%; two trials; very low certainty) showed evidence of a beneficial effect of intravenous immunoglobulin versus control on all-cause mortality, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm or reject realistic intervention effects. Meta-analysis (RR 0.63; 95% CI 0.35 to 1.14; p = 0.12; I2 = 77.4%; five trials; very low certainty) and trial sequential analysis (required information size not reached) showed no evidence of a difference between tocilizumab versus control on serious adverse events. Fixed-effect meta-analysis showed indications of a beneficial effect of tocilizumab on serious adverse events. Meta-analysis (RR 0.70; 95% CI 0.51 to 0.96; p = 0.02; I2 = 0%; three trials; very low certainty) showed evidence of a beneficial effect of tocilizumab versus control on mechanical ventilation, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm of reject realistic intervention effects. Meta-analysis (RR 0.32; 95% CI 0.15 to 0.69; p < 0.00; I2 = 0%; two trials; very low certainty) showed evidence of a beneficial effect of bromhexine versus standard care on non-serious adverse events, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm or reject realistic intervention effects. Meta-analyses and trial sequential analyses (boundary for futility crossed) showed that we could reject that hydroxychloroquine versus control reduced the risk of death and serious adverse events by 20%. Meta-analyses and trial sequential analyses (boundary for futility crossed) showed that we could reject that lopinavir-ritonavir versus control reduced the risk of death, serious adverse events, and mechanical ventilation by 20%. All remaining outcome comparisons showed that we did not have enough information to confirm or reject realistic intervention effects. Nine single trials showed statistically significant results on our outcomes, but were underpowered to confirm or reject realistic intervention effects. Due to lack of data, it was not relevant to perform network meta-analysis or possible to perform individual patient data meta-analyses., Conclusions: No evidence-based treatment for COVID-19 currently exists. Very low certainty evidence indicates that corticosteroids might reduce the risk of death, serious adverse events, and mechanical ventilation; that remdesivir might reduce the risk of serious adverse events; that intravenous immunoglobin might reduce the risk of death and serious adverse events; that tocilizumab might reduce the risk of serious adverse events and mechanical ventilation; and that bromhexine might reduce the risk of non-serious adverse events. More trials with low risks of bias and random errors are urgently needed. This review will continuously inform best practice in treatment and clinical research of COVID-19., Systematic Review Registration: PROSPERO CRD42020178787., Competing Interests: The authors have declared that no competing interests exist.

Background: There is major concern about the impact of the global COVID-19 outbreak on mental health. Several studies suggest that mental health deteriorated in many countries before and during enforced isolation (ie, lockdown), but it remains unknown how mental health has changed week by week over the course of the COVID-19 pandemic. This study aimed to explore the trajectories of anxiety and depression over the 20 weeks after lockdown was announced in England, and compare the growth trajectories by individual characteristics., Methods: In this prospective longitudinal observational study, we analysed data from the UCL COVID-19 Social Study, a panel study weighted to population proportions, which collects information on anxiety (using the Generalised Anxiety Disorder assessment) and depressive symptoms (using the Patient Health Questionnaire) weekly in the UK since March 21, 2020. We included data from adults living in England who had at least three repeated measures between March 23 and Aug 9, 2020. Analyses were done using latent growth models, which were fitted to account for sociodemographic and health covariates., Findings: Between March 23, and Aug 9, data from over 70 000 adults were collected in the UCL COVID-19 Social Study. When including participants living in England with three follow-up measures and no missing values, our analytic sample consisted of 36 520 participants. The average depression score was 6·6 (SD=6·0, range 0-27) and the average anxiety score 5·7 (SD=5·6, range 0-21) in week 1. Anxiety and depression levels both declined across the first 20 weeks following the introduction of lockdown in England (b=-1·93, SE=0·26, p<0·0001 for anxiety; b=-2·52, SE=0·28, p<0·0001 for depressive symptoms). The fastest decreases were seen across the strict lockdown period (between weeks 2 and 5), with symptoms plateauing as further lockdown easing measures were introduced (between weeks 16 and 20). Being a woman or younger, having lower educational attainment, lower income, or pre-existing mental health conditions, and living alone or with children were all risk factors for higher levels of anxiety and depression at the start of lockdown. Many of these inequalities in experiences were reduced as lockdown continued, but differences were still evident 20 weeks after the start of lockdown., Interpretation: These data suggest that the highest levels of depression and anxiety occurred in the early stages of lockdown but declined fairly rapidly, possibly because individuals adapted to circumstances. Our findings emphasise the importance of supporting individuals in the lead-up to future lockdowns to try to reduce distress, and highlight that groups already at risk for poor mental health before the pandemic have remained at risk throughout lockdown and its aftermath., Funding: Nuffield Foundation, UK Research and Innovation, Wellcome Trust., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC-BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19., Methods/design: We will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; "active placebo;" no intervention; standard care; an "active" intervention; another vaccine for COVID-19) for participants in all age groups. Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, trial sequential analyses, network meta-analyses, and individual patient data meta-analyses. Within-study bias will be assessed using Cochrane risk of bias tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and Confidence in Network Meta-Analysis (CINeMA) approaches will be used to assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and described and analyzed separately., Discussion: COVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease., Systematic Review Registration: PROSPERO CRD42020196492.

Rationale: There are increasing worries that lockdowns and 'stay-at-home' orders due to the COVID-19 pandemic could lead to a rise in loneliness, which is recognised as a major public health concern. But profiles of loneliness during the pandemic and risk factors remain unclear., Objective: The current study aimed to examine if and how loneliness levels changed during the strict lockdown and to explore the clustering of loneliness growth trajectories., Methods: Data from 38,217 UK adults in the UCL COVID -19 Social Study (a panel study collecting data weekly during the pandemic) were analysed during the strict lockdown period in the UK (23/03/2020-10/05/2020). The sample was well-stratified and weighted to population proportions of gender, age, ethnicity, education and geographical location. Growth mixture modelling was used to identify the latent classes of loneliness growth trajectories and their predictors., Results: Analyses revealed four classes, with the baseline loneliness level ranging from low to high. In the first a few weeks of lockdown, loneliness levels increased in the highest loneliness group, decreased in the lowest loneliness group, and stayed relatively constant in the middle two groups. Younger adults (OR = 2.17-6.81), women (OR = 1.59), people with low income (OR = 1.3), the economically inactive (OR = 1.3-2.04) and people with mental health conditions (OR = 5.32) were more likely to be in highest loneliness class relative to the lowest. Further, living with others or in a rural area, and having more close friends or greater social support were protective., Conclusions: Perceived levels of loneliness under strict lockdown measures due to COVID-19 were relatively stable in the UK, but for many people these levels were high with no signs of improvement. Results suggest that more efforts are needed to address loneliness., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

There are concerns internationally that lockdown measures taken during the coronavirus disease 2019 (COVID-19) pandemic could lead to a rise in loneliness. As loneliness is recognised as a major public health concern, it is therefore vital that research considers the impact of the current COVID-19 pandemic on loneliness to provide necessary support. But it remains unclear, who is lonely in lockdown? This study compared sociodemographic predictors of loneliness before and during the COVID-19 pandemic using cross-cohort analyses of data from UK adults captured before the pandemic (UK Household Longitudinal Study, n = 31,064) and during the pandemic (UCL (University College London) COVID-19 Social Study, n = 60,341). Risk factors for loneliness were near identical before and during the pandemic. Young adults, women, people with lower education or income, the economically inactive, people living alone and urban residents had a higher risk of being lonely. Some people who were already at risk of being lonely (e.g. young adults aged 18–30 years, people with low household income and adults living alone) experienced a heightened risk during the COVID-19 pandemic compared with people living before COVID-19 emerged. Furthermore, being a student emerged as a higher risk factor during lockdown than usual. Findings suggest that interventions to reduce or prevent loneliness during COVID-19 should be targeted at those sociodemographic groups already identified as high risk in previous research. These groups are likely not just to experience loneliness during the pandemic but potentially to have an even higher risk than normal of experiencing loneliness relative to low-risk groups. • We compared data from 31,000 UK adults during 2017-2019 with 60,000 UK adults during the COVID-19 pandemic. • Some risk factors for loneliness were the same as in ordinary circumstances (e.g. women and people living alone). • Other groups experienced even greater risk of loneliness than usual (e.g. younger people and people of low income). • Some groups were at risk of loneliness who are not usually considered high risk (e.g. students). [ABSTRACT FROM AUTHOR]