Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

Determinants of Change in Physical Activity in Children During the Transition from Elementary to High School.

INTRODUCTION: Effective public health interventions targeting factors that influence physical activity are urgently needed to reduce the age-related decline in physical activity in youth. The purpose of this study was to identify associations between physical activity and a set of potential influences on physical activity in children as they transition from elementary to high school. METHODS: Participants were 951 children from South Carolina school districts who completed outcome and independent variable measures on at least two time points from the 5th through 11th grades in 2010 - 2017. The primary outcome variable was physical activity, measured by accelerometry. Independent variables included a comprehensive set of variables in the child, parent/home, school, and community domains. Children, parents and school administrators, and staff completed questionnaires to assess psychosocial and home, school, and neighborhood environmental influences. Growth curve analyses identified independent variables associated with physical activity over time, either as a main effect or as an interaction with age. RESULTS: As main effects, self-efficacy, self-schema, sport participation, weekday outdoor hours, importance of child participating in sports and physical activity, safe to play outside, and Physical Activity Resource Assessment weighted score were positively associated with physical activity. The associations between physical activity and enjoyment motivation, appearance motivation, weekend outdoor time, and home equipment exhibited significant interactions with age. Enjoyment motivation influenced physical activity during the earlier years, whereas the remaining three variables influenced physical activity in the later years. CONCLUSIONS: Interventions should target multiple domains of influences that may vary by age.

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury.

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury.

Plasma steroid concentrations reflect acute disease severity and normalise during recovery in people hospitalised with COVID-19.

OBJECTIVE: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies. DESIGN/PATIENTS: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study). MEASUREMENTS: Plasma steroids were quantified by liquid chromatography-mass spectrometry. Steroid concentrations were compared against disease severity (WHO ordinal scale) and validated symptom scores. Data are presented as geometric mean (SD). RESULTS: In the acute cohort (n = 239, 66.5% male), plasma cortisol concentration increased with disease severity (cortisol 753.3 [1.6] vs. 429.2 [1.7] nmol/L in fatal vs. least severe, p < .001). In males, testosterone concentrations decreased with severity (testosterone 1.2 [2.2] vs. 6.9 [1.9] nmol/L in fatal vs. least severe, p < .001). In the follow-up cohort (n = 198, 62.1% male, 68.9% ongoing symptoms, 165 [121-192] days postdischarge), plasma cortisol concentrations (275.6 [1.5] nmol/L) did not differ with in-hospital severity, perception of recovery, or patient-reported symptoms. Male testosterone concentrations (12.6 [1.5] nmol/L) were not related to in-hospital severity, perception of recovery or symptom scores. CONCLUSIONS: Circulating glucocorticoids in patients hospitalised with COVID-19 reflect acute illness, with a marked rise in cortisol and fall in male testosterone. These findings are not observed 5 months from discharge. The lack of association between hormone concentrations and common post-COVID symptoms suggests steroid insufficiency does not play a causal role in this condition.

Association of physical activity, sedentary behavior, diet quality with adiposity: a longitudinal analysis in children categorized by baseline weight status.

BACKGROUND/OBJECTIVES: Childhood obesity rates have increased in recent years. The effectiveness of future public health interventions to reduce childhood obesity will be enhanced by a better understanding of behavioral factors that influence adiposity in children as they transition from childhood to adolescence. The purpose of this study was to examine whether initial weight status modifies the longitudinal associations of physical activity, sedentary behavior, and diet quality with changes in adiposity over time. SUBJECTS/METHODS: A total of 658 children (45% boys) were stratified into 3 groups based on 5th grade BMI percentiles ( < 85th, 85-95th, > 95th) and followed from 5th grade to 6th and/or 7th grade. Study variables, including fat-mass-index (FMI), moderate-to-vigorous physical activity (MVPA), diet quality, and sedentary behavior, were measured at 5th, 6th, and/or 7th grades. Separate growth curve models were conducted within each weight status group to examine the associations between MVPA, sedentary behavior, diet quality and adiposity, operationalized as FMI. All models controlled for sex, maturity offset, race, and parent education. RESULTS: Of the 658 children, 53% were classified with normal weight at baseline, 18% with overweight, and 29% with obesity. Associations between MVPA, sedentary behavior, diet quality and FMI varied within each weight status group. MVPA was negatively associated with adiposity (FMI) for all weight status groups. Diet quality and sedentary behavior were associated with adiposity only in children with obesity at baseline; neither diet quality nor sedentary behavior was associated with FMI for those with overweight. CONCLUSIONS: MVPA was negatively associated with adiposity (FMI) in all weight status groups, suggesting that MVPA may protect against higher adiposity. Sedentary behavior and diet quality were associated with adiposity only in children with obesity at baseline; neither sedentary behavior nor diet quality was associated with FMI for children with overweight.

Understanding Commitment of Local Food Banks, Faith-Based Organizations, and Schools to Provide Nongovernment Food Programs.

Background: Nongovernment food assistance is typically provided to families by faith-based organizations, schools, and food banks. Community organizations appear to be strongly committed to these programs, but little is known about the basis for this commitment. Objectives: The aim of this study was to examine the values and identities of community organizations to understand the reasons for their commitment to providing nongovernment food assistance. Methods: Thirty-three in-depth interviews were conducted with 36 leaders at faith-based organizations (19 participants), schools (14 participants), and a local food bank (3 participants) in South Carolina. Observations were made, and informational documents (e.g., flyers and pamphlets) were reviewed. Thematic coding using the constant comparative method was guided by the policy concepts of organizational perspectives, values, and identities. Results: Nongovernment food programs offered participants volunteering opportunities to become involved with community organizations, which in turn increased financial support for the sustainability of these programs. School participants regarded themselves as a mechanism through which food programs were provided because of their commitment to students and believed they have limited capacity to make proposals to influence the food programs. Seeking to improve the well-being of the community by ending hunger was not the primary value on which organizations focused; instead, it was the process of fulfilling other values (e.g., forming or maintaining relationships within the community), maintaining identity, and appealing to their participants that strengthened their commitment to nongovernment food programs. Conclusion: Nongovernment programs are meant to be a solution to food insecurity complementary to government programs. Commitment to nongovernment programs fulfills organizational identities, wants, and assumptions, but a consequence of commitment to food programs, derived from fulfilling other values, is that the roots of hunger in a community become obscured and alternative solutions are ignored or rejected.

Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization.

Post-COVID cognitive deficits, including 'brain fog', are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized with COVID-19, we identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19. A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety. Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits.

Prevalence of swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19: the PHOSP-COVID analysis.

OBJECTIVE: Identify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19. DESIGN: Multicentre prospective observational cohort study using questionnaire data at visit 1 (2-7 months post discharge) and visit 2 (10-14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations. SETTING: 64 UK acute hospital Trusts. PARTICIPANTS: Adults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19. MAIN OUTCOME MEASURES: Self-reported swallow, communication, voice and cognitive compromise. RESULTS: Compromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p<0.001) or non-invasive ventilation (p=0.001) and to have been proned (p<0.001). Communication compromise was reported in 23% (527/2275) univariable analysis identified associations with younger age (p<0.001), female sex (p<0.001), social deprivation (p<0.001) and being a healthcare worker (p=0.010). Cognitive issues were reported by 70% (1598/2275), consistent at both visits, at visit 1 respondents were more likely to have higher baseline comorbidities and at visit 2 were associated with greater social deprivation (p<0.001). CONCLUSION: Swallow, communication, voice and cognitive problems were prevalent post hospitalisation for COVID-19, alongside whole system compromise including reduced mobility and overall health scores. Research and testing of rehabilitation interventions are required at pace to explore these issues.

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls.

Background: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings: We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01-1.03), male (1.54, 1.16-2.04), neither obese nor severely obese (1.82, 1.06-3.13 and 4.19, 2.14-8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09-2.22) or cardiovascular disease (1.33, 1.00-1.79), and shorter hospital admission (1.01 per day, 1.00-1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation: Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding: PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care.COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders.

Longitudinal changes in domains of physical activity during the transition from elementary school to high school in the U.S.

OBJECTIVES: To describe patterns of age-related change in self-reported physical activity domains within a heterogeneous sample of boys and girls in the U.S. transitioning from elementary to high school. DESIGN: Prospective cohort study. METHODS: Participants included n = 644 children recruited in 5th grade (10.5 ±â€¯0.5 years old, 45 % female) who completed the Physical Activity Choices survey at least twice over 5 time points (5th, 6th, 7th, 9th and 11th grade). Participants' self-reported physical activities were categorized into organized and non-organized activities, and a comprehensive variable was created as the product of the total number of physical activities reported in the past 5 days, the number of days spent in each activity, and the total time spent in each activity. Descriptive statistics and growth curve models (controlling for covariates) for the total sample and by sex were examined for total, organized, and non-organized physical activities from ages 10 to 17. RESULTS: There was a significant age by gender interaction (p < 0.05) for time spent in non-organized physical activities. Specifically, both sexes had similar patterns of decline before age 13, while boys increased after age 13 and girls declined and then maintained. In contrast, boys and girls declined in organized physical activities from ages 10 to 17 (p < 0.001). CONCLUSIONS: We observed stark differences in the age-related change between organized and non-organized physical activities and marked differences in the patterns of non-organized physical activities between boys and girls. Future research should examine physical activity interventions that consider age-, sex-, and domain-specific physical activity options for youth.

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study.

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.

Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study.

Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group-robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)-at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

A process for converting an in-person training to increase church capacity to implement physical activity and healthy eating practices and policies to an online format.

The implementation of evidence-based public health programs into practice is critical for improving health, but trainings for organizational change agents are often not scalable. To describe the process of converting a training that targets faith-based organizational capacity development from an in-person to an online format. We engaged in an iterative process to convert the training delivery mode from in-person to online that included assessing stakeholder support, consulting the literature on best practices, seeking a design team, consolidating content, designing engaging lessons, and building an online site. Feedback from end-users and other audiences was incorporated throughout. Pilot participants with characteristics like intended training users were then recruited via community and faith-based partner networks. They rated their agreement with statements about the effectiveness as well as design and functionality of each lesson and the overall training (1 = strongly disagree, 5 = strongly agree) and participated in a structured follow-up interview. Nine pilot participants (representing 9 churches in 7 states; 6 African American, 5 with health ministries) rated the online lessons favorably (all ratings ≥ 4.5). Most (90.4%) perceived the lesson duration to be "just right" and spent 52.5 ± 9.9 minutes/lesson. Participants evaluated the overall training positively (all ratings ≥ 4.7). Lesson content, resources, multimedia, and program ideas were most-liked aspects of lessons, while content, staff responsiveness, discussion board, and pace were most-liked aspects of the overall training in open-ended and interview responses. This paper shares a replicable process for converting training modalities from in-person to online with the goal of increased scalability.

The effect of COVID rehabilitation for ongoing symptoms Post HOSPitalisation with COVID-19 (PHOSP-R): protocol for a randomised parallel group controlled trial on behalf of the PHOSP consortium.

INTRODUCTION: Many adults hospitalised with COVID-19 have persistent symptoms such as fatigue, breathlessness and brain fog that limit day-to-day activities. These symptoms can last over 2 years. Whilst there is limited controlled studies on interventions that can support those with ongoing symptoms, there has been some promise in rehabilitation interventions in improving function and symptoms either using face-to-face or digital methods, but evidence remains limited and these studies often lack a control group. METHODS AND ANALYSIS: This is a nested single-blind, parallel group, randomised control trial with embedded qualitative evaluation comparing rehabilitation (face-to-face or digital) to usual care and conducted within the PHOSP-COVID study. The aim of this study is to determine the effectiveness of rehabilitation interventions on exercise capacity, quality of life and symptoms such as breathlessness and fatigue. The primary outcome is the Incremental Shuttle Walking Test following the eight week intervention phase. Secondary outcomes include measures of function, strength and subjective assessment of symptoms. Blood inflammatory markers and muscle biopsies are an exploratory outcome. The interventions last eight weeks and combine symptom-titrated exercise therapy, symptom management and education delivered either in a face-to-face setting or through a digital platform ( www.yourcovidrecovery.nhs.uk ). The proposed sample size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care. ETHICS AND DISSEMINATION: Ethical approval was gained as part of the PHOSP-COVID study by Yorkshire and the Humber Leeds West Research NHS Ethics Committee, and the study was prospectively registered on the ISRCTN trial registry (ISRCTN13293865). Results will be disseminated to stakeholders, including patients and members of the public, and published in appropriate journals. Strengths and limitations of this study • This protocol utilises two interventions to support those with ongoing symptoms of COVID-19 • This is a two-centre parallel-group randomised controlled trial • The protocol has been supported by patient and public involvement groups who identified treatments of symptoms and activity limitation as a top priority.

A Summary of One Research Team's Contributions to Understanding Physical Activity Behavior in Children and Youth.

Schools are well-positioned to provide physical activity opportunities to help youth achieve the recommended 60 or more daily minutes of moderate-to-vigorous physical activity. The Children's Physical Activity Research Group (CPARG) at the University of South Carolina has focused on understanding physical activity in school-aged youth for 30+ years. The purpose of this article was to critically review (CPARG) contributions to the field in school settings and school-age youth. We reviewed 127 published CPARG articles from six research projects conducted between 1993-2019. The review was guided by questions in five categories: measurement of physical activity and its determinants, characteristics of physical activity behavior, correlates/determinants of physical activity, physical activity interventions, and race/ethnicity and physical activity. Results were summarized by question and synthesized across categories. CPARG contributions included assessing physical activity levels, patterns, forms, and contexts; identifying and measuring physical activity correlates/determinants; and conducting school-based physical activity interventions. Identifying multiple domains of physical activity determinants enables researchers and practitioners to select/design age-appropriate, valid, and reliable instruments to assess determinants. Focusing on determinants enables them to create effective physical activity interventions, environments, programs, and policies in schools. These efforts must address race/ethnicity differences, ensuring that measurement instruments and intervention strategies are culturally appropriate.

Influence of implementation strategies on implementation outcomes in a statewide dissemination of Faith, Activity, and Nutrition (FAN).

Faith-based organizations are promising settings for implementation science because they can reach populations bearing a disproportionate burden of chronic disease. This study examined how implementation strategies influenced implementation outcomes in Faith, Activity, and Nutrition (FAN) statewide dissemination. Ninety-three (9%) of 985 invited churches enrolled; 91 (98%) and 83 (89%) completed baseline and 12-month assessments. Community Health Advisors trained and provided phone technical assistance to church committees, led by a FAN coordinator. Church committees were charged with developing plans and installing healthy eating (HE) and physical activity (PA) policies, opportunities, messages and pastor support (implementation outcomes). Structural equation modeling examined how implementation strategies influenced implementation outcomes. Nearly all (99%) FAN coordinators and 60% of pastors attended training, 57% of committees submitted program plans and 51%/54% (HE/PA) of committees met 'every few months'. Statistically significant (P < 0.05) model paths showed positive influences of strategies on implementation outcomes: pastor training on HE and PA pastor support; plan completion on HE and PA messages, PA policies and opportunities as well as FAN committee meetings and committee meetings on HE pastor support, HE policies, PA opportunities and HE and PA messages. This study advances implementation science and provides a model applicable to organizations such as worksites and schools.

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.

BACKGROUND: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms. METHODS: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators. RESULTS: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. CONCLUSIONS: Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.

Stressed out - The role of oxidative stress in airway smooth muscle dysfunction in asthma and COPD.

The airway smooth muscle (ASM) surrounding the airways is dysfunctional in both asthma and chronic obstructive pulmonary disease (COPD), exhibiting; increased contraction, increased mass, increased inflammatory mediator release and decreased corticosteroid responsiveness. Due to this dysfunction, ASM is a key contributor to symptoms in patients that remain symptomatic despite optimal provision of currently available treatments. There is a significant body of research investigating the effects of oxidative stress/ROS on ASM behaviour, falling into the following categories; cigarette smoke and associated compounds, air pollutants, aero-allergens, asthma and COPD relevant mediators, and the anti-oxidant Nrf2/HO-1 signalling pathway. However, despite a number of recent reviews addressing the role of oxidative stress/ROS in asthma and COPD, the potential contribution of oxidative stress/ROS-related ASM dysfunction to asthma and COPD pathophysiology has not been comprehensively reviewed. We provide a thorough review of studies that have used primary airway, bronchial or tracheal smooth muscle cells to investigate the role of oxidative stress/ROS in ASM dysfunction and consider how they could contribute to the pathophysiology of asthma and COPD. We summarise the current state of play with regards to clinical trials/development of agents targeting oxidative stress and associated limitations, and the adverse effects of oxidative stress on the efficacy of current therapies, with reference to ASM related studies where appropriate. We also identify limitations in the current knowledge of the role of oxidative stress/ROS in ASM dysfunction and identify areas for future research.

The Faith, Activity, and Nutrition (FAN) dissemination and implementation study: changes in and maintenance of organizational practices over 24 months in a statewide initiative.

BACKGROUND: Few studies have examined the impact of ecological health promotion interventions on organizational practices over time, especially in faith-based settings. This statewide dissemination and implementation study examined change in organizational practices and their predictors across a 24-month period, as well as maintenance of change. METHODS: Using a pre-post quasi-experimental design, church coordinators from 92 United Methodist Churches in South Carolina (42% predominantly African American congregations) completed surveys at baseline, and immediate, 12-, and 24-months post-training regarding physical activity (PA) and healthy eating (HE) organizational practices consistent with the Faith, Activity, and Nutrition (FAN) program (opportunities, policies, pastor support, messages) and possible predictors. The study was guided by the RE-AIM framework and the Consolidated Framework for Implementation Research (CFIR). Mixed model repeated measures analyses examined change in organizational practices over time. Regression models examined CFIR predictors of 24-month PA and HE organizational practices, controlling for baseline practices. Churches were also classified as maintainers (implemented at 12 and 24 months), non-sustained implementers (implemented at 12 but not 24 months), delayed implementers (implemented at 24 but not 12 months), and low implementers (implemented at neither 12 nor 24 months) for each FAN component. RESULTS: PA and HE organizational practices increased over time (p < .0001). CFIR domains (and constructs within) of intervention characteristics (adaptability, relative advantage, cost/time), inner setting (relative priority, organizational rewards, readiness, congregant needs), characteristics of the implementer (self-efficacy, perceived benefits), and implementation process (engaging opinion leaders, engaging champions) were important predictors of 24-month PA and HE organizational practices. Over half of churches implementing PA policies, PA messages, HE policies, and HE opportunities at 12 months were maintainers at 24 months, and one-third were maintainers for PA opportunities, HE messages, and PA and HE pastor support. Furthermore, 16% of 12-month non-implementers were delayed implementers at 24 months for PA policies and 31% were delayed implementers for HE policies. CONCLUSIONS: This study makes important contributions to the faith-based health promotion literature by including a large sample of churches, testing an ecological intervention approach, and assessing organizational practices over a 24-month period. Study findings can guide technical assistance and program adaptations over time. TRIAL REGISTRATION: This study was registered in clinicaltrials.gov NCT02868866 on August 16, 2016.