Adjudicated myocarditis and multisystem illness trajectory in healthcare workers post-COVID-19.

BACKGROUND: We investigated the associations of healthcare worker status with multisystem illness trajectory in hospitalised post-COVID-19 individuals. METHODS AND RESULTS: One hundred and sixty-eight patients were evaluated 28-60 days after the last episode of hospital care. Thirty-six (21%) were healthcare workers. Compared with non-healthcare workers, healthcare workers were of similar age (51.3 (8.7) years vs 55.0 (12.4) years; p=0.09) more often women (26 (72%) vs 48 (38%); p<0.01) and had lower 10-year cardiovascular risk (%) (8.1 (7.9) vs 15.0 (11.5); p<0.01) and Coronavirus Clinical Characterisation Consortium in-hospital mortality risk (7.3 (10.2) vs 12.7 (9.8); p<0.01). Healthcare worker status associated with less acute inflammation (peak C reactive protein 48 mg/L (IQR: 14-165) vs 112 mg/L (52-181)), milder illness reflected by WHO clinical severity score distribution (p=0.04) and shorter duration of admission (4 days (IQR: 2-6) vs 6 days (3-12)).In adjusted multivariate logistic regression analysis, healthcare worker status associated with a binary classification (probable/very likely vs not present/unlikely) of adjudicated myocarditis (OR: 2.99; 95% CI (1.01 to 8.89) by 28-60 days postdischarge).After a mean (SD, range) duration of follow-up after hospital discharge of 450 (88) days (range 290, 627 days), fewer healthcare workers died or were rehospitalised (1 (3%) vs 22 (17%); p=0.038) and secondary care referrals for post-COVID-19 syndrome were common (42%) and similar to non-healthcare workers (38%; p=0.934). CONCLUSION: Healthcare worker status was independently associated with the likelihood of adjudicated myocarditis, despite better antecedent health. Two in five healthcare workers had a secondary care referral for post-COVID-19 syndrome. TRIAL REGISTRATION NUMBER: NCT04403607.

Multi-system investigation of covid-19 illness

IntroductionThe pathophysiology and trajectory of multiorgan involvement in post-COVID-19 syndrome is uncertain. We aimed to adjudicate the likelihood of myocarditis in post-COVID-19 patients.MethodsA prospective, longitudinal, cohort study involving post-COVID-19 patients enrolled in-hospital or early post-discharge (visit 1) and re-evaluated 28–60 days post-discharge (visit 2). Serial research blood tests (biomarkers), digital electrocardiography, and patient reported outcome measures were obtained at both visits. Chest computed tomography with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging, were acquired at visit 2.Results159 patients (mean age 55 years, 43% female) and 27 controls with similar age, sex, ethnicity, and vascular risk factors were enrolled from 22 May 2020 to 2 July 2021 and had a primary outcome evaluation. Adjudicated likelihood of myocarditis was not (n=17;11%), unlikely (n=56;35%), probably (n=65;41%) or very likely (n=21;13%). Healthcare worker status (odds ratio, 95% confidence interval: 2.99 (1.01, 8.89);p=0.048), acute kidney injury (3.26 (1.00, 10.64);p=0.050) and HbA1c(0.64 (0.42, 0.99);p=0.044) were multivariable associates of adjudicated myocarditis. During convalescence, COVID-19 was associated with worse health-related quality of life (EQ5D-5L) (p<0.001), illness perception (p<0.001), anxiety and depression (p<0.001), physical activity (p<0.001) and predicted maximal oxygen utilization (ml/kg/min) (p<0.001). These measures were associated with adjudicated myocarditis.ConclusionThe illness trajectory of COVID-19 includes persisting cardio-renal inflammation, lung damage and hemostasis activation. Adjudicated myocarditis occurred in one in eight hospitalized patients and was associated with impairments in health status, physical and psychological wellbeing during community convalescence.Conflict of InterestNil

A multisystem, cardio-renal investigation of post-COVID-19 illness.

The pathophysiology and trajectory of post-Coronavirus Disease 2019 (COVID-19) syndrome is uncertain. To clarify multisystem involvement, we undertook a prospective cohort study including patients who had been hospitalized with COVID-19 (ClinicalTrials.gov ID NCT04403607 ). Serial blood biomarkers, digital electrocardiography and patient-reported outcome measures were obtained in-hospital and at 28-60 days post-discharge when multisystem imaging using chest computed tomography with pulmonary and coronary angiography and cardio-renal magnetic resonance imaging was also obtained. Longer-term clinical outcomes were assessed using electronic health records. Compared to controls (n = 29), at 28-60 days post-discharge, people with COVID-19 (n = 159; mean age, 55 years; 43% female) had persisting evidence of cardio-renal involvement and hemostasis pathway activation. The adjudicated likelihood of myocarditis was 'very likely' in 21 (13%) patients, 'probable' in 65 (41%) patients, 'unlikely' in 56 (35%) patients and 'not present' in 17 (11%) patients. At 28-60 days post-discharge, COVID-19 was associated with worse health-related quality of life (EQ-5D-5L score 0.77 (0.23) versus 0.87 (0.20)), anxiety and depression (PHQ-4 total score 3.59 (3.71) versus 1.28 (2.67)) and aerobic exercise capacity reflected by predicted maximal oxygen utilization (20.0 (7.6) versus 29.5 (8.0) ml/kg/min) (all P < 0.01). During follow-up (mean, 450 days), 24 (15%) patients and two (7%) controls died or were rehospitalized, and 108 (68%) patients and seven (26%) controls received outpatient secondary care (P = 0.017). The illness trajectory of patients after hospitalization with COVID-19 includes persisting multisystem abnormalities and health impairments that could lead to substantial demand on healthcare services in the future.

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.

Risk of mortality among inpatients with COVID-19 and type 2 diabetes: National data from Kuwait.

INTRODUCTION: To investigate type 2 diabetes as a risk factor for COVID-19 death following hospital admission in Kuwait. METHODS: A retrospective cohort study using data from a central hospital that cared for all hospitalized COVID-19 patients in Kuwait. We investigated the association between type 2 diabetes, with COVID-19 mortality using multiply imputed logistic regression and calculated the population attributable fraction. RESULTS: A total of 5333 patients were admitted with COVID-19, of whom 244 died (4.6%). Diabetes prevalence was 24.8%, but 53.7% of those who died had diabetes. After adjusting for age, sex, ethnicity and other comorbidities, diabetes was associated with death (OR 1.70 [95% CI 1.23, 2.34]) and admission to the intensive care unit more than 3 days after initial admission (OR 1.78 [95% CI 1.17, 2.70]). Assuming causality, the population attributable fraction for type 2 diabetes in COVID-19 death was 19.6% (95% CI 10.8, 35.6). CONCLUSION: Type 2 diabetes is a strong risk factor for COVID-19 death in the Middle East. Given the high prevalence of type 2 diabetes in the Middle East, as well as many Western countries, the public health implications are considerable.

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.

Modifiable and non-modifiable risk factors for COVID-19, and comparison to risk factors for influenza and pneumonia: results from a UK Biobank prospective cohort study.

OBJECTIVES: We aimed to investigate demographic, lifestyle, socioeconomic and clinical risk factors for COVID-19, and compared them to risk factors for pneumonia and influenza in UK Biobank. DESIGN: Cohort study. SETTING: UK Biobank. PARTICIPANTS: 49-83 year olds (in 2020) from a general population study. MAIN OUTCOME MEASURES: Confirmed COVID-19 infection (positive SARS-CoV-2 test). Incident influenza and pneumonia were obtained from primary care data. Poisson regression was used to study the association of exposure variables with outcomes. RESULTS: Among 235 928 participants, 397 had confirmed COVID-19. After multivariable adjustment, modifiable risk factors were higher body mass index and higher glycated haemoglobin (HbA1C) (RR 1.28 and RR 1.14 per SD increase, respectively), smoking (RR 1.39), slow walking pace as a proxy for physical fitness (RR 1.53), and use of blood pressure medications as a proxy for hypertension (RR 1.33). Higher forced expiratory volume in 1 s (FEV1) and high-density lipoprotein (HDL) cholesterol were both associated with lower risk (RR 0.84 and RR 0.83 per SD increase, respectively). Non-modifiable risk factors included male sex (RR 1.72), black ethnicity (RR 2.00), socioeconomic deprivation (RR 1.17 per SD increase in Townsend Index), and high cystatin C (RR 1.13 per SD increase). The risk factors overlapped with pneumonia somewhat, less so for influenza. The associations with modifiable risk factors were generally stronger for COVID-19, than pneumonia or influenza. CONCLUSION: These findings suggest that modification of lifestyle may help to reduce the risk of COVID-19 and could be a useful adjunct to other interventions, such as social distancing and shielding of high risk.

Comparison of two different frailty measurements and risk of hospitalisation or death from COVID-19: findings from UK Biobank.

BACKGROUND: Frailty has been associated with worse prognosis following COVID-19 infection. While several studies have reported the association between frailty and COVID-19 mortality or length of hospital stay, there have been no community-based studies on the association between frailty and risk of severe infection. Considering that different definitions have been identified to assess frailty, this study aimed to compare the association between frailty and severe COVID-19 infection in UK Biobank using two frailty classifications: the frailty phenotype and the frailty index. METHODS: A total of 383,845 UK Biobank participants recruited 2006-2010 in England (211,310 [55.1%] women, baseline age 37-73 years) were included. COVID-19 test data were provided by Public Health England (available up to 28 June 2020). An adapted version of the frailty phenotype derived by Fried et al. was used to define frailty phenotype (robust, pre-frail, or frail). A previously validated frailty index was derived from 49 self-reported questionnaire items related to health, disease and disability, and mental wellbeing (robust, mild frailty, and moderate/severe frailty). Both classifications were derived from baseline data (2006-2010). Poisson regression models with robust standard errors were used to analyse the associations between both frailty classifications and severe COVID-19 infection (resulting in hospital admission or death), adjusted for sociodemographic and lifestyle factors. RESULTS: Of UK Biobank participants included, 802 were admitted to hospital with and/or died from COVID19 (323 deaths and 479 hospitalisations). After analyses were adjusted for sociodemographic and lifestyle factors, a higher risk of COVID-19 was observed for pre-frail (risk ratio (RR) 1.47 [95% CI 1.26; 1.71]) and frail (RR 2.66 [95% CI 2.04; 3.47]) individuals compared to those classified as robust using the frailty phenotype. Similar results were observed when the frailty index was used (RR mildly frail 1.46 [95% CI 1.26; 1.71] and RR moderate/severe frailty 2.43 [95% CI 1.91; 3.10]). CONCLUSIONS: Frailty was associated with a higher risk of severe COVID-19 infection resulting in hospital admission or death, irrespective of how it was measured and independent of sociodemographic and lifestyle factors. Public health strategies need to consider the additional risk that COVID-19 poses in individuals with frailty, including which additional preventive measures might be required.

Is older age associated with COVID-19 mortality in the absence of other risk factors? General population cohort study of 470,034 participants.

INTRODUCTION: Older people have been reported to be at higher risk of COVID-19 mortality. This study explored the factors mediating this association and whether older age was associated with increased mortality risk in the absence of other risk factors. METHODS: In UK Biobank, a population cohort study, baseline data were linked to COVID-19 deaths. Poisson regression was used to study the association between current age and COVID-19 mortality. RESULTS: Among eligible participants, 438 (0.09%) died of COVID-19. Current age was associated exponentially with COVID-19 mortality. Overall, participants aged ≥75 years were at 13-fold (95% CI 9.13-17.85) mortality risk compared with those <65 years. Low forced expiratory volume in 1 second, high systolic blood pressure, low handgrip strength, and multiple long-term conditions were significant mediators, and collectively explained 39.3% of their excess risk. The associations between these risk factors and COVID-19 mortality were stronger among older participants. Participants aged ≥75 without additional risk factors were at 4-fold risk (95% CI 1.57-9.96, P = 0.004) compared with all participants aged <65 years. CONCLUSIONS: Higher COVID-19 mortality among older adults was partially explained by other risk factors. 'Healthy' older adults were at much lower risk. Nonetheless, older age was an independent risk factor for COVID-19 mortality.

Correction to: Protocol for a randomised controlled trial to investigate the effect of home- and gym-based resistance exercise training on glycaemic control, body composition and muscle strength.

An amendment to this paper has been published and can be accessed via the original article.

Protocol for a randomised controlled trial to investigate the effect of home- and gym-based resistance exercise training on glycaemic control, body composition and muscle strength.

BACKGROUND: Resistance exercise is known to be effective in reducing glycated haemoglobin (HbA1c) in people with type 2 diabetes. However, studies, so far, have employed supervised resistance exercise in a laboratory or gym facility which limits the future translation of such exercise in to clinical practice and recommendations. Our primary aim, therefore, is to test the hypothesis, in a randomized controlled trial, that home-based resistance exercise training and gym-based resistance exercise training both reduce HbA1c levels in people with type 2 diabetes compared to control. We will also investigate the effects of home- and gym-based resistance exercise training on muscle strength and body composition. METHODS: The current study is a three-arm randomised controlled trial which will be conducted with 150 eligible people with type 2 diabetes to compare home-and gym-based resistance exercise training with usual care in Kuwait. The interventions will be delivered by exercise specialists and last for 32 weeks. The primary outcomes are HbA1c with secondary outcomes measuring muscle function, body composition, physical activity and quality of life. DISCUSSION: Ethical approval has been granted by the Dasman Diabetes Institute ethical review committee (RA/197/2019). Study findings will be disseminated through presentation at scientific conferences and in scientific journals. TRIAL REGISTRATION: NCT04136730: Retrospectively registered on 21 October 2019.

BMI and future risk for COVID-19 infection and death across sex, age and ethnicity: Preliminary findings from UK biobank.

AIMS: We examined the link between BMI and risk of a positive test for SARS-CoV-2 and risk of COVID-19-related death among UK Biobank participants. METHODS: Among 4855 participants tested for SARS-CoV-2 in hospital, 839 were positive and of these 189 died from COVID-19. Poisson models with penalised thin plate splines were run relating exposures of interest to test positivity and case-fatality, adjusting for confounding factors. RESULTS: BMI was associated strongly with positive test, and risk of death related to COVID-19. The gradient of risk in relation to BMI was steeper in those under 70, compared with those aged 70 years or older for COVID-19 related death (Pinteraction = 0.03). BMI was more strongly related to test positivity (Pinteraction = 0.010) and death (Pinteraction = 0.002) in non-whites (predominantly South Asians and Afro-Caribbeans), compared with whites. CONCLUSIONS: These data add support for adiposity being more strongly linked to COVID-19-related deaths in younger people and non-white ethnicities. If future studies confirm causality, lifestyle interventions to improve adiposity status may be important to reduce the risk of COVID-19 in all, but perhaps particularly, non-white communities.