Natural history of long-COVID in a nationwide, population cohort study.

Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test. Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection.

Diet-Related Inflammation Is Associated with Worse COVID-19 Outcomes in the UK Biobank Cohort.

Diet, the most important modulator of inflammatory and immune responses, may affect COVID-19 incidence and disease severity. Data from 196,154 members of the UK biobank had at least one 24 h dietary recall. COVID-19 outcomes were based on PCR testing, hospital admissions, and death certificates. Adjusted Poisson regression analyses were performed to estimate the risk ratios (RR) and their 95% confidence intervals (CI) for dietary inflammatory index (DII)/energy-adjusted DII (E-DII) scores. Models were adjusted for sociodemographic factors, comorbidities, smoking status, physical activity, and sleep duration. Between January 2020 and March 2021, there were 11,288 incident COVID-19 cases, 1270 COVID-19-related hospitalizations, and 315 COVID-19-related deaths. The fully adjusted model showed that participants in the highest (vs. lowest) DII/E-DII quintile were at 10-17% increased risk of COVID-19 (DII: RR Q5 vs. Q1 = 1.10, 95% CI 1.04-1.17, Ptrend < 0.001; E-DII: RR Q5 vs. Q1 = 1.17, 95% CI 1.10-1.24, Ptrend < 0.001) and ≈40% higher risk was observed for disease severity (DII: RR Q5 vs. Q1 = 1.40, 95% CI 1.18-1.67, Ptrend < 0.001; E-DII: RR Q5 vs. Q1 = 1.39, 95% CI 1.16-1.66, Ptrend < 0.001). There was a 43% increased risk of COVID-19-related death in the highest DII quintile (RR Q5 vs. Q1 = 1.43, 95% CI 1.01-2.01, Ptrend = 0.04). About one-quarter of the observed positive associations between DII and COVID-19-related outcomes were mediated by body mass index (25.8% for incidence, 21.6% for severity, and 19.8% for death). Diet-associated inflammation increased the risk of COVID-19 infection, severe disease, and death.

Chronic pain and COVID-19 hospitalisation and mortality: a UK Biobank cohort study.

ABSTRACT: The risk of COVID-19 in those with chronic pain is unknown. We investigated whether self-reported chronic pain was associated with COVID-19 hospitalisation or mortality. UK Biobank recruited 502,624 participants aged 37 to 73 years between 2006 and 2010. Baseline exposure data, including chronic pain (>3 months, in at least 1 of 7 prespecified body sites) and chronic widespread pain (>3 months, all over body), were linked to COVID-19 hospitalisations or mortality. Univariable or multivariable Poisson regression analyses were performed on the association between chronic pain and COVID-19 hospitalisation and Cox regression analyses of the associations with COVID-19 mortality. Multivariable analyses adjusted incrementally for sociodemographic confounders, then lifestyle risk factors, and finally long-term condition count. Of 441,403 UK Biobank participants with complete data, 3180 (0.7%) were hospitalised for COVID-19 and 1040 (0.2%) died from COVID-19. Chronic pain was associated with hospital admission for COVID-19 even after adjustment for all covariates (incidence rate ratio 1.16; 95% confidence interval [CI] 1.08-1.24; P < 0.001), as was chronic widespread pain (incidence rate ratio 1.33; 95% CI 1.06-1.66; P = 0.012). There was clear evidence of a dose-response relationship with number of pain sites (fully adjusted global P-value < 0.001). After adjustment for all covariates, there was no association between chronic pain (HR 1.01; 95% CI 0.89-1.15; P = 0.834) but attenuated association with chronic widespread pain (HR 1.50, 95% CI 1.04-2.16, P-value = 0.032) and COVID-19 mortality. Chronic pain is associated with higher risk of hospitalisation for COVID-19, but the association with mortality is unclear. Future research is required to investigate these findings further and determine whether pain is associated with long COVID.

Development and optimisation of a multi-component workplace intervention to increase cycling for the Cycle Nation Project.

The Cycle Nation Project (CNP) aimed to develop, test the feasibility of and optimize a multi-component individual-/social-level workplace-based intervention to increase cycling among office staff at a multinational bank (HSBC UK). To do this, we first explored barriers to cycling in a nationally-representative survey of UK adults, then undertook focus groups with bank employees to understand any context-specific barriers and ways in which these might be overcome. These activities led to identification of 10 individual-level, two social-level, and five organizational-level modifiable factors, which were mapped to candidate intervention components previously identified in a scoping review of cycling initiatives. Interviews with HSBC UK managers then explored the practicality of implementing the candidate intervention components in bank offices. The resultant pilot CNP intervention included 32 core components across six intervention functions (education, persuasion, incentivisation, training, environmental restructuring, enablement). Participants received a loan bike for 12-weeks (or their own bike serviced), and a 9-week cycle training course (condensed to 6 weeks for those already confident in basic cycling skills), including interactive information sharing activities, behavior change techniques (e.g., weekly goal setting), bike maintenance training, practical off-road cycling skill games and on-road group rides. Sessions were delivered by trained bank staff members who were experienced cyclists. The CNP pilot intervention was delivered across three sites with 68 participants. It was completed in two sites (the third site was stopped due to COVID-19) and was feasible and acceptable to both women and men and across different ethnicities. In addition, the CNP intervention was successful (at least in the short term) in increasing cycling by 3 rides/week on average, and improving perceptions of safety, vitality, confidence, and motivation to cycle. Following minor modifications, the long-term effectiveness and cost-effectiveness of the CNP intervention should be tested in a full-scale randomized controlled trial.

Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study.

With increasing numbers infected by SARS-CoV-2, understanding long-COVID is essential to inform health and social care support. A Scottish population cohort of 33,281 laboratory-confirmed SARS-CoV-2 infections and 62,957 never-infected individuals were followed-up via 6, 12 and 18-month questionnaires and linkage to hospitalization and death records. Of the 31,486 symptomatic infections,1,856 (6%) had not recovered and 13,350 (42%) only partially. No recovery was associated with hospitalized infection, age, female sex, deprivation, respiratory disease, depression and multimorbidity. Previous symptomatic infection was associated with poorer quality of life, impairment across all daily activities and 24 persistent symptoms including breathlessness (OR 3.43, 95% CI 3.29-3.58), palpitations (OR 2.51, OR 2.36-2.66), chest pain (OR 2.09, 95% CI 1.96-2.23), and confusion (OR 2.92, 95% CI 2.78-3.07). Asymptomatic infection was not associated with adverse outcomes. Vaccination was associated with reduced risk of seven symptoms. Here we describe the nature of long-COVID and the factors associated with it.

The association between a lifestyle score, socioeconomic status, and COVID-19 outcomes within the UK Biobank cohort.

BACKGROUND: Infection with SARS-CoV-2 virus (COVID-19) impacts disadvantaged groups most. Lifestyle factors are also associated with adverse COVID-19 outcomes. To inform COVID-19 policy and interventions, we explored effect modification of socioeconomic-status (SES) on associations between lifestyle and COVID-19 outcomes. METHODS: Using data from UK-Biobank, a large prospective cohort of 502,536 participants aged 37-73 years recruited between 2006 and 2010, we assigned participants a lifestyle score comprising nine factors. Poisson regression models with penalised splines were used to analyse associations between lifestyle score, deprivation (Townsend), and COVID-19 mortality and severe COVID-19. Associations between each exposure and outcome were examined independently before participants were dichotomised by deprivation to examine exposures jointly. Models were adjusted for sociodemographic/health factors. RESULTS: Of 343,850 participants (mean age > 60 years) with complete data, 707 (0.21%) died from COVID-19 and 2506 (0.76%) had severe COVID-19. There was evidence of a nonlinear association between lifestyle score and COVID-19 mortality but limited evidence for nonlinearity between lifestyle score and severe COVID-19 and between deprivation and COVID-19 outcomes. Compared with low deprivation, participants in the high deprivation group had higher risk of COVID-19 outcomes across the lifestyle score. There was evidence for an additive interaction between lifestyle score and deprivation. Compared with participants with the healthiest lifestyle score in the low deprivation group, COVID-19 mortality risk ratios (95% CIs) for those with less healthy scores in low versus high deprivation groups were 5.09 (1.39-25.20) and 9.60 (4.70-21.44), respectively. Equivalent figures for severe COVID-19 were 5.17 (2.46-12.01) and 6.02 (4.72-7.71). Alternative SES measures produced similar results. CONCLUSIONS: Unhealthy lifestyles are associated with higher risk of adverse COVID-19, but risks are highest in the most disadvantaged, suggesting an additive influence between SES and lifestyle. COVID-19 policy and interventions should consider both lifestyle and SES. The greatest public health benefit from lifestyle focussed COVID-19 policy and interventions is likely to be seen when greatest support for healthy living is provided to the most disadvantaged groups.

COVID-19 infection and outcomes in a population-based cohort of 17 203 adults with intellectual disabilities compared with the general population.

BACKGROUND: Adults with intellectual disabilities (ID) may be at higher risk of COVID-19 death. We compared COVID-19 infection, severe infection, mortality, case fatality and excess deaths, among adults with, and without, ID. METHODS: Adults with ID in Scotland's Census, 2011, and a 5% sample of other adults, were linked to COVID-19 test results, hospitalisation data and deaths (24 January 2020-15 August 2020). We report crude rates of COVID-19 infection, severe infection (hospitalisation/death), mortality, case fatality; age-standardised, sex-standardised and deprivation-standardised severe infection and mortality ratios; and annual all-cause mortality for 2020 and 2015-2019. FINDINGS: Successful linkage of 94.9% provided data on 17 203 adults with, and 188 634 without, ID. Adults with ID had more infection (905/100 000 vs 521/100 000); severe infection (538/100 000 vs 242/100 000); mortality (258/100 000 vs 116/100 000) and case fatality (30% vs 24%). Poorer outcomes remained after standardisation: standardised severe infection ratio 2.61 (95% CI 1.81 to 3.40) and mortality ratio 3.26 (95% CI 2.19 to 4.32). These were higher at ages 55-64: 7.39 (95% CI 3.88 to 10.91) and 19.05 (95% CI 9.07 to 29.02), respectively, and in men, and less deprived neighbourhoods. All-cause mortality was slightly higher in 2020 than 2015-2019 for people with ID: standardised mortality ratio 2.50 (95% CI 2.18 to 2.82) and 2.39 (95% CI 2.28 to 2.51), respectively. CONCLUSION: Adults with ID had more COVID-19 infections, and worse outcomes once infected, particularly adults under 65 years. Non-pharmaceutical interventions directed at formal and informal carers are essential to reduce transmission. All adults with ID should be prioritised for vaccination and boosters regardless of age.

Thromboembolic Risk in Hospitalized and Nonhospitalized COVID-19 Patients: A Self-Controlled Case Series Analysis of a Nationwide Cohort.

OBJECTIVE: To assess the associations between coronavirus disease 2019 (COVID-19) infection and thromboembolism including myocardial infarction (MI), ischemic stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE). PATIENTS AND METHODS: A self-controlled case-series study was conducted covering the whole of Scotland's general population. The study population comprised individuals with confirmed (positive test) COVID-19 and at least one thromboembolic event between March 2018 and October 2020. Their incidence rates during the risk interval (5 days before to 56 days after the positive test) and the control interval (the remaining periods) were compared intrapersonally. RESULTS: Across Scotland, 1449 individuals tested positive for COVID-19 and experienced a thromboembolic event. The risk of thromboembolism was significantly elevated over the whole risk period but highest in the 7 days following the positive test (incidence rate ratio, 12.01; 95% CI, 9.91 to 14.56) in all included individuals. The association was also present in individuals not originally hospitalized for COVID-19 (incidence rate ratio, 4.07; 95% CI, 2.83 to 5.85). Risk of MI, stroke, PE, and DVT were all significantly higher in the week following a positive test. The risk of PE and DVT was particularly high and remained significantly elevated even 56 days following the test. CONCLUSION: Confirmed COVID-19 infection was associated with early elevations in risk with MI, ischemic stroke, and substantially stronger and prolonged elevations with DVT and PE both in hospital and community settings. Clinicians should consider thromboembolism, especially PE, among people with COVID-19 in the community.

Ethnic and socioeconomic differences in SARS-CoV-2 infection: prospective cohort study using UK Biobank.

BACKGROUND: Understanding of the role of ethnicity and socioeconomic position in the risk of developing SARS-CoV-2 infection is limited. We investigated this in the UK Biobank study. METHODS: The UK Biobank study recruited 40-70-year-olds in 2006-2010 from the general population, collecting information about self-defined ethnicity and socioeconomic variables (including area-level socioeconomic deprivation and educational attainment). SARS-CoV-2 test results from Public Health England were linked to baseline UK Biobank data. Poisson regression with robust standard errors was used to assess risk ratios (RRs) between the exposures and dichotomous variables for being tested, having a positive test and testing positive in hospital. We also investigated whether ethnicity and socioeconomic position were associated with having a positive test amongst those tested. We adjusted for covariates including age, sex, social variables (including healthcare work and household size), behavioural risk factors and baseline health. RESULTS: Amongst 392,116 participants in England, 2658 had been tested for SARS-CoV-2 and 948 tested positive (726 in hospital) between 16 March and 3 May 2020. Black and south Asian groups were more likely to test positive (RR 3.35 (95% CI 2.48-4.53) and RR 2.42 (95% CI 1.75-3.36) respectively), with Pakistani ethnicity at highest risk within the south Asian group (RR 3.24 (95% CI 1.73-6.07)). These ethnic groups were more likely to be hospital cases compared to the white British. Adjustment for baseline health and behavioural risk factors led to little change, with only modest attenuation when accounting for socioeconomic variables. Socioeconomic deprivation and having no qualifications were consistently associated with a higher risk of confirmed infection (RR 2.19 for most deprived quartile vs least (95% CI 1.80-2.66) and RR 2.00 for no qualifications vs degree (95% CI 1.66-2.42)). CONCLUSIONS: Some minority ethnic groups have a higher risk of confirmed SARS-CoV-2 infection in the UK Biobank study, which was not accounted for by differences in socioeconomic conditions, baseline self-reported health or behavioural risk factors. An urgent response to addressing these elevated risks is required.

Comparison of COVID-19 outcomes among shielded and non-shielded populations.

Many western countries used shielding (extended self-isolation) of people presumed to be at high-risk from COVID-19 to protect them and reduce healthcare demand. To investigate the effectiveness of this strategy, we linked family practitioner, prescribing, laboratory, hospital and death records and compared COVID-19 outcomes among shielded and non-shielded individuals in the West of Scotland. Of the 1.3 million population, 27,747 (2.03%) were advised to shield, and 353,085 (26.85%) were classified a priori as moderate risk. COVID-19 testing was more common in the shielded (7.01%) and moderate risk (2.03%) groups, than low risk (0.73%). Referent to low-risk, the shielded group had higher confirmed infections (RR 8.45, 95% 7.44-9.59), case-fatality (RR 5.62, 95% CI 4.47-7.07) and population mortality (RR 57.56, 95% 44.06-75.19). The moderate-risk had intermediate confirmed infections (RR 4.11, 95% CI 3.82-4.42) and population mortality (RR 25.41, 95% CI 20.36-31.71) but, due to their higher prevalence, made the largest contribution to deaths (PAF 75.30%). Age ≥ 70 years accounted for 49.55% of deaths. In conclusion, in spite of the shielding strategy, high risk individuals were at increased risk of death. Furthermore, to be effective as a population strategy, shielding criteria would have needed to be widely expanded to include other criteria, such as the elderly.

Correction: Multimorbidity, polypharmacy, and COVID-19 infection within the UK Biobank cohort.

[This corrects the article DOI: 10.1371/journal.pone.0238091.].

Family history of diabetes and risk of SARS-COV-2 in UK Biobank: A prospective cohort study.

INTRODUCTION: The aim of this study was to determine risk of being SARS-CoV-2 positive and severe infection (associated with hospitalization/mortality) in those with family history of diabetes. METHODS: We used UK Biobank, an observational cohort recruited between 2006 and 2010. We compared the risk of being SARS-CoV-2 positive and severe infection for those with family history of diabetes (mother/father/sibling) against those without. RESULTS: Of 401,268 participants in total, 13,331 tested positive for SARS-CoV-2 and 2282 had severe infection by end of January 2021. In unadjusted models, participants with ≥2 family members with diabetes were more likely to be SARS-CoV-2 positive (risk ratio-RR 1.35; 95% confidence interval-CI 1.24-1.47) and severe infection (RR 1.30; 95% CI 1.04-1.59), compared to those without. The excess risk of being tested positive for SARS-CoV-2 was attenuated but significant after adjusting for demographics, lifestyle factors, multimorbidity and presence of cardiometabolic conditions. The excess risk for severe infection was no longer significant after adjusting for demographics, lifestyle factors, multimorbidity and presence of cardiometabolic conditions, and was absent when excluding incident diabetes. CONCLUSION: The totality of the results suggests that good lifestyle and not developing incident diabetes may lessen risks of severe infections in people with a strong family of diabetes.

Remote history of VTE is associated with severe COVID-19 in middle and older age: UK Biobank cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a common, life-threatening complication of COVID-19 infection. COVID-19 risk-prediction models include a history of VTE. However, it is unclear whether remote history (>9 years previously) of VTE also confers increased risk of COVID-19. OBJECTIVES: To investigate possible association between VTE and COVID-19 severity, independent of other risk factors. METHODS: Cohort study of UK Biobank participants recruited between 2006 and 2010. Baseline data, including history of VTE, were linked to COVID-19 test results, COVID-19-related hospital admissions, and COVID-19 deaths. The risk of COVID-19 hospitalization or death was compared for participants with a remote history VTE versus without. Poisson regression models were run univariately then adjusted stepwise for sociodemographic, lifestyle, and comorbid covariates. RESULTS: After adjustment for sociodemographic and lifestyle confounders and comorbid conditions, remote history of VTE was associated with nonfatal community (RR 1.61, 95% CI 1.02-2.54, p = .039), nonfatal hospitalized (RR 1.52, 95% CI 1.06-2.17, p = .024) and severe (hospitalized or fatal) (RR 1.40, 95% CI 1.04-1.89, p = .025) COVID-19. Associations with remote history of VTE were stronger among men (severe COVID-19: RR 1.68, 95% CI 1.14-2.42, p = .009) than for women (severe COVID-19: RR 1.07, 95% CI 0.66-1.74, p = .786). CONCLUSION: Our findings support inclusion of remote history of VTE in COVID-19 risk-prediction scores, and consideration of sex-specific risk scores.

Occupation and risk of severe COVID-19: prospective cohort study of 120 075 UK Biobank participants.

OBJECTIVES: To investigate severe COVID-19 risk by occupational group. METHODS: Baseline UK Biobank data (2006-10) for England were linked to SARS-CoV-2 test results from Public Health England (16 March to 26 July 2020). Included participants were employed or self-employed at baseline, alive and aged <65 years in 2020. Poisson regression models were adjusted sequentially for baseline demographic, socioeconomic, work-related, health, and lifestyle-related risk factors to assess risk ratios (RRs) for testing positive in hospital or death due to COVID-19 by three occupational classification schemes (including Standard Occupation Classification (SOC) 2000). RESULTS: Of 120 075 participants, 271 had severe COVID-19. Relative to non-essential workers, healthcare workers (RR 7.43, 95% CI 5.52 to 10.00), social and education workers (RR 1.84, 95% CI 1.21 to 2.82) and other essential workers (RR 1.60, 95% CI 1.05 to 2.45) had a higher risk of severe COVID-19. Using more detailed groupings, medical support staff (RR 8.70, 95% CI 4.87 to 15.55), social care (RR 2.46, 95% CI 1.47 to 4.14) and transport workers (RR 2.20, 95% CI 1.21 to 4.00) had the highest risk within the broader groups. Compared with white non-essential workers, non-white non-essential workers had a higher risk (RR 3.27, 95% CI 1.90 to 5.62) and non-white essential workers had the highest risk (RR 8.34, 95% CI 5.17 to 13.47). Using SOC 2000 major groups, associate professional and technical occupations, personal service occupations and plant and machine operatives had a higher risk, compared with managers and senior officials. CONCLUSIONS: Essential workers have a higher risk of severe COVID-19. These findings underscore the need for national and organisational policies and practices that protect and support workers with an elevated risk of severe COVID-19.

COVID-19 Surveillance in a Primary Care Sentinel Network: In-Pandemic Development of an Application Ontology.

BACKGROUND: Creating an ontology for COVID-19 surveillance should help ensure transparency and consistency. Ontologies formalize conceptualizations at either the domain or application level. Application ontologies cross domains and are specified through testable use cases. Our use case was an extension of the role of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) to monitor the current pandemic and become an in-pandemic research platform. OBJECTIVE: This study aimed to develop an application ontology for COVID-19 that can be deployed across the various use-case domains of the RCGP RSC research and surveillance activities. METHODS: We described our domain-specific use case. The actor was the RCGP RSC sentinel network, the system was the course of the COVID-19 pandemic, and the outcomes were the spread and effect of mitigation measures. We used our established 3-step method to develop the ontology, separating ontological concept development from code mapping and data extract validation. We developed a coding system-independent COVID-19 case identification algorithm. As there were no gold-standard pandemic surveillance ontologies, we conducted a rapid Delphi consensus exercise through the International Medical Informatics Association Primary Health Care Informatics working group and extended networks. RESULTS: Our use-case domains included primary care, public health, virology, clinical research, and clinical informatics. Our ontology supported (1) case identification, microbiological sampling, and health outcomes at an individual practice and at the national level; (2) feedback through a dashboard; (3) a national observatory; (4) regular updates for Public Health England; and (5) transformation of a sentinel network into a trial platform. We have identified a total of 19,115 people with a definite COVID-19 status, 5226 probable cases, and 74,293 people with possible COVID-19, within the RCGP RSC network (N=5,370,225). CONCLUSIONS: The underpinning structure of our ontological approach has coped with multiple clinical coding challenges. At a time when there is uncertainty about international comparisons, clarity about the basis on which case definitions and outcomes are made from routine data is essential.