Health outcome priorities of people with multiple long-term conditions before and during the COVID-19 pandemic: Survey data from the UK (preprint)

Background The outcome prioritisation tool (OPT) is a simple tool to ascertain the health outcome priorities of people with MLTC. Use of this tool in people aged under 65 years with MLTC has not previously been investigated. This study investigated the feasibility of using the OPT in people with MLTC aged 45 years or above, in a multi-ethnic primary-care setting, to describe the health outcome priorities of people with MLTC by age, clusters of long-term conditions and demographic factors, and to investigate any differences in prioritisation in light of the COVID-19 pandemic. Methods This was a multi-centre cross-sectional study using a questionnaire for online self-completion by people aged 45 years or above with MLTC in 19 primary care settings across the East Midlands, UK. Participants were asked to complete the OPT twice, first from their current perspective and second from their recollection of their priorities prior to COVID-19. Results The questionnaire was completed by 2,454 people with MLTC. The majority of participants agreed or strongly agreed that the OPT was easy to complete, relevant to their healthcare and will be useful in communicating priorities to their doctor. Summary scores for the whole cohort of participants showed Keeping Alive and Maintaining Independence receiving the highest scores. Statistically significant differences in prioritisation by age, clusters of long-term conditions and employment status were observed, with respondents aged over 65 most likely to prioritise Maintaining independence, and respondents aged under 65 most likely to prioritise Keeping alive. There were no differences before or after COVID-19, or by ethnicity. Conclusions The OPT is feasible and acceptable for use to elicit the health outcome priorities of people with MLTC across both middle-aged and older age groups and in a UK setting. Individual factors could influence the priorities of people with MLTC and must be considered by clinicians during consultations.

Employment outcomes of people with Long Covid symptoms: community-based cohort study (preprint)

Background: Evidence on the long-term employment consequences of SARS-CoV-2 infection is lacking. We used data from a large, community-based sample in the UK to estimate associations between Long Covid and subsequent employment outcomes. Methods: This was an observational, longitudinal study using a pre-post design. We included UK COVID-19 Infection Survey participants who completed questionnaires on Long Covid from 3 February 2021 to 30 September 2022 when they were aged 16 to 64 years and not in full-time education. We used conditional logit modelling to explore the time-varying relationship between Long Covid status [≥]12 weeks after a first test-confirmed SARS-CoV-2 infection (reference: pre-infection) and labour market inactivity (neither working nor looking for work) or workplace absence lasting [≥]4 weeks. Results: Of 206,299 included participants (mean age 45 years, 54% female, 92% white), 15% were ever inactive in the labour market and 10% were ever long-term absent during follow-up. Compared with pre-infection, inactivity was higher in participants reporting Long Covid 30 to <40 weeks (adjusted odds ratio (aOR): 1.45; 95% CI: 1.17 to 1.81) or 40 to <52 weeks (1.34; 1.05 to 1.72) post-infection. Compared with pre-infection, reporting Long Covid was also associated with increased odds of long-term absence 18 to <24 weeks (1.40; 1.04 to 1.90) and 24 to <30 weeks (1.45; 1.03 to 2.04) post-infection, but not beyond 30 weeks. Combining with official statistics on Long Covid prevalence, our estimates translate to 27,000 (95% CI: 6,000 to 47,000) working-age adults in the UK being inactive because of their Long Covid symptoms in July 2022. Conclusions: Long Covid is likely to have contributed to reduced levels of participation in the UK labour market, though it is unlikely to be the sole driver. Further research is required to quantify the contribution of other factors, such as indirect health effects of the pandemic.

Antipsychotic prescribing and mortality in people with dementia before and during the COVID-19 pandemic: retrospective cohort study (preprint)

Background: Antipsychotic drugs have been associated with increased mortality, stroke and myocardial infarction in people with dementia. Concerns have been raised that antipsychotic prescribing may have increased during the COVID-19 pandemic due to social restrictions imposed to limit the spread of the virus. We used multisource, routinely-collected healthcare data from Wales, UK, to investigate prescribing and mortality trends in people with dementia before and during the COVID-19 pandemic. Methods: We used individual-level, anonymised, population-scale linked health data to identify adults aged >=60 years with a diagnosis of dementia in Wales, UK. We explored antipsychotic prescribing trends over 67 months between 1st January 2016 and 1st August 2021, overall and stratified by age and dementia subtype. We used time series analyses to examine all-cause, myocardial infarction (MI) and stroke mortality over the study period and identified the leading causes of death in people with dementia. Findings: Of 57,396 people with dementia, 11,929 (21%) were prescribed an antipsychotic at any point during follow-up. Accounting for seasonality, antipsychotic prescribing increased during the second half of 2019 and throughout 2020. However, the absolute difference in prescribing rates was small, ranging from 1253 to 1305 per 10,000 person-months. Prescribing in the 60-64 age group and those with Alzheimer's disease increased throughout the 5-year period. All-cause and stroke mortality increased in the second half of 2019 and throughout 2020 but MI mortality declined. From January 2020, COVID-19 was the second commonest underlying cause of death in people with dementia. Interpretation: During the COVID-19 pandemic there was a small increase in antipsychotic prescribing in people with dementia. The long-term increase in antipsychotic prescribing in younger people and in those with Alzheimer's disease warrants further investigation. Funding: British Heart Foundation (BHF) (SP/19/3/34678) via the BHF Data Science Centre led by HDR UK, and the Scottish Neurological Research Fund.

Socioeconomic inequalities of Long COVID: findings from a population-based survey in the United Kingdom (preprint)

Objective To estimate the risk of Long COVID by socioeconomic deprivation and to further examine the socioeconomic inequalities in Long COVID by sex and occupational groups. Design We analysed data from the COVID-19 Infection Survey conducted by the Office for National Statistics between 26/04/2020 and 31/01/2022. This is the largest and nationally representative survey of COVID-19 in the UK and provides uniquely rich, contemporaneous, and longitudinal data on occupation, health status, COVID-19 exposure, and Long COVID symptoms. Setting Community-based longitudinal survey of COVID-19 in the UK. Participants We included 201,799 participants in our analysis who were aged between 16 and 64 years and had a confirmed SARS-CoV-2 infection. Main outcome measures We used multivariable logistic regression models to estimate the risk of Long COVID at least 4 weeks after acute SARS-CoV-2 infection by deciles of index of multiple deprivation (IMD) and adjusted for a range of demographic and spatiotemporal factors. We further examined the modifying effects of socioeconomic deprivation by sex and occupational groups. Results A total of 19,315 (9.6%) participants reported having Long COVID symptoms. Compared to the least deprived IMD decile, participants in the most deprived decile had a higher adjusted risk of Long COVID (11.4% vs 8.2%; adjusted OR: 1.45; 95% confidence interval [CI]: 1.33, 1.57). There were particularly significantly higher inequalities (most vs least deprived decile) of Long COVID in healthcare and patient facing roles (aOR: 1.76; 1.27, 2.44), and in the education sector (aOR: 1.62; 1.26, 2.08). The inequality of Long COVID was higher in females (aOR: 1.54; 1.38, 1.71) than males (OR: 1.32; 1.15, 1.51). Conclusions Participants living in the most socioeconomically deprived areas had a higher risk of Long COVID. The inequality gap was wider in females and certain public facing occupations (e.g., healthcare and education). These findings will help inform public health policies and interventions in adopting a social justice and health inequality lens.

Vaccine effectiveness for preventing COVID-19 hospital admission during pregnancy: a population-based cohort study in England during the Alpha and Delta waves of the SARS-CoV-2 pandemic (preprint)

Objective: To estimate vaccine effectiveness (VE) for preventing COVID-19 hospital admission in women first infected with SARS-CoV-2 during pregnancy, and assess how this compares to VE among women of reproductive age who were not pregnant when first infected. Design: Population-based cohort study using national, linked Census and administrative data. Setting: England, United Kingdom, from 8th December 2020 to 31st August 2021. Participants: 815,4777 women aged 18 to 45 years (mean age, 30.4 years) who had documented evidence of a first SARS-CoV-2 infection in NHS Test and Trace data or Hospital Episode Statistics. Main outcome measures: A hospital inpatient episode where COVID-19 was recorded as the primary diagnosis. Cox proportional hazards models, adjusted for calendar time of infection and sociodemographic factors related to vaccine uptake and risk of severe COVID-19, were used to estimate VE as the complement of the hazard ratio for COVID-19 hospital admission. Results: Compared with unvaccinated pregnant women, the adjusted rate of COVID-19 hospital admission was 76% (95% confidence interval 69% to 82%) lower for single-vaccinated pregnant women and 83% (75% to 88%) lower for double-vaccinated pregnant women. These estimates were similar to those found for non-pregnant women: 79% (76% to 81%) for single-vaccinated and 82% (80% to 83%) for double-vaccinated. Among those vaccinated more than 90 days before infection, being double-vaccinated was associated with a greater reduction in risk than being single-vaccinated. Conclusions: COVID-19 vaccination is associated with reduced rates of severe illness in pregnant women infected with SARS-CoV-2, and the reduction in risk is similar to that for non-pregnant women. Waning of vaccine effectiveness occurs more quickly after one dose of a vaccine than two doses.

Risk of death following SARS-CoV-2 infection or COVID-19 vaccination in young people in England: a self-controlled case series study (preprint)

Objectives: To assess whether there is a change in the incidence of cardiac and all-cause death in young people following COVID-19 vaccination or SARS-CoV-2 infection in unvaccinated individuals. Design: Self-controlled case series. Setting: National, linked electronic health record data in England. Study population: Individuals aged 12-29 who had received at least one dose of COVID-19 vaccination and died between 8 December 2020 and 2 February 2022 and registered by 16 February 2022 within 12 weeks of COVID-19 vaccination; Individuals aged 12-29 who died within 12 weeks of testing positive for SARS-CoV-2. Main outcome measures: Cardiac and all-cause deaths occurring within 12 weeks of vaccination or SARS-CoV-2 infection. Results: Compared to the baseline period, there was no evidence of a change in the incidence of cardiac death in the six weeks after vaccination, whether for each of weeks 1 to 6 or the whole six-week period. There was a decrease in the risk of all-cause death in the first week after vaccination and no change in each of weeks 2 to 6 after vaccination or whole six-week period after vaccination. Subgroup analyses by sex, age, vaccine type, and last dose also showed no change in the risk of death in the first six weeks after vaccination. There was a large increase in the incidence of cardiac and all-cause death in the overall risk period after SARS-CoV-2 infection among the unvaccinated. Conclusion: There is no evidence of an association between COVID-19 vaccination and an increased risk of death in young people. By contrast, SARS-CoV-2 infection was associated with substantially higher risk of cardiac related death and all-cause death.

Risk of Long Covid in people infected with SARS-CoV-2 after two doses of a COVID-19 vaccine: community-based, matched cohort study (preprint)

Background: It is unclear whether receiving two COVID-19 vaccinations before SARS-CoV-2 infection reduces the risk of developing Long Covid symptoms. We examined whether the likelihood of symptoms 12 weeks after infection differed by vaccination status. Methods: We included COVID-19 Infection Survey participants aged 18-69 years who tested positive for SARS-CoV-2 between 26 April 2020 and 30 November 2021; we excluded participants who, before their first test-confirmed infection, had suspected COVID-19 or Long Covid symptoms, or were single-vaccinated. Participants who were double-vaccinated [≥]14 days before infection were 1:1 propensity-score matched, based on socio-demographic characteristics and time from infection to follow-up for Long Covid, to those unvaccinated at time of infection. We estimated adjusted odds ratios (aOR) of Long Covid symptoms [≥]12 weeks post-infection, comparing double-vaccinated with unvaccinated (reference group) participants. Results: The study sample comprised 3,090 double-vaccinated participants (mean age 49 years, 54% female, 92% white, median follow-up from infection 96 days) and matched control participants. Long Covid symptoms were reported by 294 double-vaccinated participants (prevalence 9.5%) compared with 452 unvaccinated participants (14.6%), corresponding to an aOR for Long Covid symptoms of 0.59 (95% CI: 0.50 to 0.69). There was no evidence of heterogeneity by adenovirus vector versus messenger ribonucleic acid vaccines (p=0.25). Conclusions: COVID-19 vaccination is associated with reduced risk of Long Covid, emphasising the need for public health initiatives to increase population-level vaccine uptake. Longer follow-up is needed, as is the assessment of further vaccine doses and the Omicron variant.

Risk of myocarditis following sequential COVID-19 vaccinations by age and sex (preprint)

ABSTRACT In an updated self-controlled case series analysis of 42,200,614 people aged 13 years or more, we evaluate the association between COVID-19 vaccination and myocarditis, stratified by age and sex, including 10,978,507 people receiving a third vaccine dose. Myocarditis risk was increased during 1-28 days following a third dose of BNT162b2 (IRR 2.02, 95%CI 1.40, 2.91). Associations were strongest in males younger than 40 years for all vaccine types with an additional 3 (95%CI 1, 5) and 12 (95% CI 1,17) events per million estimated in the 1-28 days following a first dose of BNT162b2 and mRNA-1273, respectively; 14 (95%CI 8, 17), 12 (95%CI 1, 7) and 101 (95%CI 95, 104) additional events following a second dose of ChAdOx1, BNT162b2 and mRNA-1273, respectively; and 13 (95%CI 7, 15) additional events following a third dose of BNT162b2, compared with 7 (95%CI 2, 11) additional events following COVID-19 infection. An association between COVID-19 infection and myocarditis was observed in all ages for both sexes but was substantially higher in those older than 40 years. These findings have important implications for public health and vaccination policy. Funding Health Data Research UK.

Changes in the trajectory of Long Covid symptoms following COVID-19 vaccination: community-based cohort study (preprint)

ObjectiveTo estimate associations between COVID-19 vaccination and Long Covid symptoms in adults who were infected with SARS-CoV-2 prior to vaccination. DesignObservational cohort study using individual-level interrupted time series analysis. SettingRandom sample from the community population of the UK. Participants28,356 COVID-19 Infection Survey participants (mean age 46 years, 56% female, 89% white) aged 18 to 69 years who received at least their first vaccination after test-confirmed infection. Main outcome measuresPresence of long Covid symptoms at least 12 weeks after infection over the follow-up period 3 February to 5 September 2021. ResultsMedian follow-up was 141 days from first vaccination (among all participants) and 67 days from second vaccination (84% of participants). First vaccination was associated with an initial 12.8% decrease (95% confidence interval: -18.6% to -6.6%) in the odds of Long Covid, but increasing by 0.3% (-0.6% to +1.2%) per week after the first dose. Second vaccination was associated with an 8.8% decrease (-14.1% to -3.1%) in the odds of Long Covid, with the odds subsequently decreasing by 0.8% (-1.2% to -0.4%) per week. There was no statistical evidence of heterogeneity in associations between vaccination and Long Covid by socio-demographic characteristics, health status, whether hospitalised with acute COVID-19, vaccine type (adenovirus vector or mRNA), or duration from infection to vaccination. ConclusionsThe likelihood of Long Covid symptoms reduced after COVID-19 vaccination, and the improvement was sustained over the follow-up period after the second dose. Vaccination may contribute to a reduction in the population health burden of Long Covid, though longer follow-up time is needed. Summary boxWhat is already known on this topic O_LICOVID-19 vaccines are effective at reducing rates of SARS-CoV-2 infection, transmission, hospitalisation, and death C_LIO_LIThe incidence of Long Covid may be reduced if infected after vaccination, but the relationship between vaccination and pre-existing long COVID symptoms is unclear, as published studies are generally small and with self-selected participants C_LI What this study adds O_LIThe likelihood of Long Covid symptoms reduced after COVID-19 vaccination, and the improvement was sustained over the follow-up period after the second dose C_LIO_LIThere was no evidence of differences in this relationship by socio-demographic characteristics, health-related factors, vaccine type, or duration from infection to vaccination C_LIO_LIAlthough causality cannot be inferred from this observational evidence, vaccination may contribute to a reduction in the population health burden of Long Covid; further research is needed to understand the biological mechanisms that may ultimately contribute to the development of therapeutics for Long Covid C_LI

Association of chronic kidney disease, ethnicity and socioeconomic status with COVID-19 hospitalisation and mortality: a UK Biobank study (preprint)

O_LIIn individuals with chronic kidney disease (CKD), Black and South Asian ethnic groups are twice as likely to have severe COVID-19 compared to White participants, whilst the most socially deprived groups are at a 50-60% increased risk of severe COVID-19. C_LIO_LIThis study is the first to highlight the association between ethnicity and socioeconomic deprivation and the risk of severe COVID-19 among those with CKD in the UK. C_LIO_LIInterventions to reduce morbidity and mortality amongst these groups and policy and practice improvements are needed to address the broad disparity among CKD patients. C_LI

Obesity, Ethnicity, and Covid-19 Mortality: A population-based cohort study of 12.6 Million Adults in England (preprint)

Abstract Importance: Obesity and ethnicity are well characterised risk factors for severe COVID-19 outcomes, but the differential effects of obesity on COVID-19 outcomes by race/ethnicity has not been examined robustly in the general population. Objective: To investigate the association between body mass index (BMI) and COVID-19 mortality across different ethnic groups. Design, Setting, and Participants: This is a retrospective cohort study using linked national Census, electronic health records and mortality data for English adults aged 40 years or older who were alive at the start of pandemic (24th January 2020). Exposures: BMI obtained from electronic health records. Self-reported ethnicity (white, black, South Asian, other) was the effect-modifying variable. Main Outcomes and Measures: COVID-19 related death identified by ICD-10 codes U07.1 or U07.2 mentioned on the death certificate from 24th January 2020 until December 28th 2020. Results: The analysis included white (n = 11,074,708; mean age 61.9 [13.4] years; 54% women), black (n = 416,542; 56.4 [11.7] years; 57% women), South Asian (621,691; 55.7 [12.4] years; 51% women) and other (n = 478,196; 55.3 [11.6] years; 55% women) ethnicities with linked BMI data. The association between BMI and COVID-19 mortality was stronger in ethnic minority groups. Compared to a BMI of 22.5 kg/m2 in white ethnicities, the adjusted HR for COVID-19 mortality at a BMI of 30 kg/m2 in white, black, South Asian and other ethnicities was 0.95 (95% CI: 0.87-1.03), 1.72 (1.52-1.94), 2.00 (1.78-2.25) and 1.39 (1.21-1.61), respectively. The estimated risk of COVID-19 mortality at a BMI of 40 kg/m2 in white ethnicities (HR = 1.73) was equivalent to the risk observed at a BMI of 30.1 kg/m2, 27.0 kg/m2, and 32.2 kg/m2 in black, South Asian and other ethnic groups, respectively. 5 Conclusions: This population-based study using linked Census and electronic health care records demonstrates that the risk of COVID-19 mortality associated with obesity is greater in ethnic minority groups compared to white populations.

Sarcopenic obesity and the risk of hospitalisation or death from COVID-19: findings from UK Biobank (preprint)

BackgroundCoronavirus disease{square}2019 (COVID{square}19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS{square}CoV{square}2 virus). The role of skeletal muscle mass in modulating immune response is well documented. Whilst obesity is well-established as a key factor in COVID-19 infection and outcome, no study has examined the influence of both sarcopenia (low muscle mass) and obesity, termed sarcopenic obesity on COVID-19 risk. MethodsThis study uses data from UK Biobank. Probable sarcopenia was defined as low handgrip strength. Sarcopenic obesity was mutually exclusively defined as the presence of obesity and low muscle mass (based on two established criteria: appendicular lean mass (ALM) adjusted for either: 1) height and 2) body mass index (BMI)). Severe COVID-19 was defined by a positive test result in a hospital setting or death with a primary cause reported as COVID-19. Fully adjusted logistic regression models were used to analyse the associations between sarcopenic status and severe COVID-19. This work was conducted under UK Biobank application number 52553. ResultsWe analysed data from 490,301 UK Biobank participants. 2203 (0.4%) had severe COVID-19 infection. Individuals with probable sarcopenia were 64% more likely to have had severe COVID-19 infection (odds ratio (OR) 1.638; P<.001). Obesity increased the likelihood of severe COVID-19 infection by 76% (P<.001). Using either ALM index and ALM/BMI index to define low muscle mass, those with sarcopenic obesity were 2.6 times more likely to have severe COVID-19 (OR: 2.619; P<.001). Sarcopenia alone did not increase the risk of COVID-19. ConclusionsSarcopenic obesity may increase the risk of severe COVID-19 infection, over that of obesity alone. The mechanisms for this are complex but could be a result of a reduction in respiratory functioning, immune response, and ability to respond to metabolic stress.

Influenza, Shingles and Pneumococcal Vaccine Uptake, Offer and Refusal in Adult Populations at High-Risk for COVID-19: A UK Population-Based Cohort Study (preprint)

Background: As COVID-19 vaccination programs are being rolled out globally, we studied the ethnic, deprivation, household size and comorbidity ‘patterning’ of existing vaccination programs in populations at high-risk for COVID-19, to inform risk-stratified vaccination strategies and mitigate health inequalities. Methods: A population-level cohort study of UK adults aged 65 years or older, using a large primary care database. We used multivariable logistic regression to assess uptake of influenza, pneumococcal and shingles vaccination across ethnic groups, deprivation quintile, household size, and comorbidities, computing odds ratios (OR) adjusted for age, sex, demographics, body mass index and smoking. Offers and refusals of each vaccination type were analysed in those not receiving them. Findings: The cohort comprised 2,054,463 patients from 1,318 general practices. 1,452,014 (70.7%) patients received influenza vaccine, 1,391,228 (67.7%) received pneumococcal vaccine, and 690,783 (53.4%) received shingles vaccine. Compared to Whites, influenza vaccination uptake was lower in Pakistani (adjusted odds ratio (OR) 0.82; 99% confidence interval: 0.74-0.90), Black Caribbean (OR 0.46; 0.43-0.48), Black African (OR 0.63; 0.58-0.68), Chinese (OR 0.70; 0.64-0.76) and ‘Other ethnic group’ (OR 0.65; 0.63-0.69). The Black Caribbean group had higher vaccination refusal than the White group for influenza vaccination (OR 1.17; 1.05-1.30). Vaccination uptake was lower among the more deprived and those living in household sizes above 3 or more persons, with some significant interactions between ethnicity and comorbidities. Uptake of all three vaccines was higher in those with asthma, COPD, type 2 diabetes, hypertension and learning disability, whilst lower in those with dementia. Interpretation: Whilst uptake and refusal of influenza, shingles and pneumococcal vaccination are patterned by ethnicity, deprivation, household size and comorbidities, vaccination offer is mostly patterned by comorbidities. This information can inform national policies to ensure equitable implementation of COVID-19 vaccination programs to avoid exacerbating health inequalities.Funding Statement: This project was funded by the Medical Research Council (Grant Ref: MR/V027778/1).Declaration of Interests: PST reports previous consultation with AstraZeneca and Duke-NUS outside the submitted work. KK is a Member of the Scientific Advisory Group for Emergencies (SAGE), Member of Independent SAGE, Director of the University of Leicester Centre for Black Minority Health and Trustee of the south Asian Health Foundation. JHC is a member of several SAGE committees and chair of the risk stratification subgroup of the NERVTAG. She is unpaid director of QResearch and founder and former medical director of ClinRisk Ltd (outside the submitted work). MP, AKC, HDM, DS, TAR, FZ, BRS, SJG, CC, CG have no interests to declare.

Association of working shifts, inside and outside of healthcare, with risk of severe COVID-19: An observational study (preprint)

BackgroundHealth and key workers are at an increased risk of developing severe COVID-19; it is not known, however, if this risk is exacerbated in those with irregular work patterns. We aimed to investigate the risk of severe COVID-19 in health and shift workers. MethodsWe included UK Biobank participants in employment or self-employed at baseline and with linked COVID-19 data to 31st August 2020. Participants were grouped as neither a health worker nor shift worker (reference category), health worker only, shift worker only, or both and associations with severe COVID-19 investigated in logistic regressions. FindingsOf 235,685 participants (81{middle dot}5% neither health nor shift worker, 1{middle dot}4% health worker only, 16{middle dot}9% shift worker only, and 0{middle dot}3% both), there were 580 (0{middle dot}25%) cases of severe COVID-19. The risk of severe COVID-19 was higher in health workers (adjusted odds ratio: 2.32 [95% CI: 1{middle dot}33, 4{middle dot}05]; shift workers (2{middle dot}06 [1{middle dot}72, 2{middle dot}47]); and in health workers who worked shifts (7{middle dot}56 [3{middle dot}86, 14{middle dot}79]). Being both a health worker and a shift worker had a possible greater impact on the risk severe COVID-19 in South Asian and Black and African Caribbean ethnicities compared to White individuals. InterpretationBoth health and shift work were independently associated with over twice the risk of severe COVID-19; the risk was over seven times higher in health workers who work shifts. Vaccinations, therapeutic and preventative options should take into consideration not only health and key worker status but also shift worker status. FundingNational Institute for Health Research, UK Research and Innovation. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe risk of developing severe COVID-19 is greater in occupational groups with higher levels of viral exposure, e.g. health and key workers. We searched PubMed and medRxiv up to December 8, 2020 for papers on shift work patterns, health work and incidence of COVID-19 using the keywords "COVID-19", "SARS-CoV-2", "shift work" "health worker". Recent evidence suggests shift workers are also at increased risk of severe COVID-19 but it is not clear if the risk is exacerbated in those who work shifts in healthcare. Added value of this studyThis study uses data from UK Biobank, a prospective cohort of >500,000 adults aged 40-69 years with baseline assessments between March 2006 and July 2010. Participants occupation was categorised according to whether or not they were health workers and/or shift workers at baseline. Results showed that being a health worker, or working shifts, were similarly and independently associated with over twice the population level risk of severe COVID-19 independent of age, sex, ethnicity, deprivation and co-morbidities. The risk was seven times higher in health workers with shift working patterns. The impact of health and shift work tended to be higher in males and in minority ethnic groups, who are already at an increased risk of severe COVID-19. In people over the age of retirement, the risk of developing severe COVID-19 associated with baseline health worker status was no longer apparent, suggesting the risk is likely explained by exposure to the virus. However, the elevated risk associated with baseline shift worker status persisted, albeit attenuated. Implications of all the available evidenceShift workers are at elevated risk of developing severe COVID-19. The persistence of an elevated risk in people who are now over retirement age, but had a shift worker status at baseline, suggests the risk may not be fully explained by increased exposure to the virus. Vaccination, therapeutic and prevention programmes are being prioritised for health care workers. Our data suggests that shift workers should also be prioritised for these preventive measures.

Patterns of Multimorbidity and Risk of Severe SARS-CoV-2 Infection: an observational study in the U.K. (preprint)

Background Pre-existing comorbidities have been linked to SARS-CoV-2 infection but evidence is sparse on the importance and pattern of multimorbidity (2 or more conditions) and severity of infection indicated by hospitalisation or mortality. We aimed to use a multimorbidity index developed specifically for COVID-19 to investigate the association between multimorbidity and risk of severe SARS-CoV-2 infection. Methods We used data from the UK Biobank linked to laboratory confirmed test results for SARS-CoV-2 infection and mortality data from Public Health England between March 16 and July 26, 2020. By reviewing the current literature on COVID-19 we derived a multimorbidity index including: 1) angina; 2) asthma; 3) atrial fibrillation; 4) cancer; 5) chronic kidney disease; 6) chronic obstructive pulmonary disease; 7) diabetes mellitus; 8) heart failure; 9) hypertension; 10) myocardial infarction; 11) peripheral vascular disease; 12) stroke. Adjusted logistic regression models were used to assess the association between multimorbidity and risk of severe SARS-CoV-2 infection (hospitalisation or death). Potential effect modifiers of the association were assessed: age, sex, ethnicity, deprivation, smoking status, body mass index, air pollution, 25-hydroxyvitamin D, cardiorespiratory fitness, high sensitivity C-reactive protein. Results Among 360,283 participants, the median age was 68 [range, 48-85] years, most were White (94.5%), and 1,706 had severe SARS-CoV-2 infection. The prevalence of multimorbidity was more than double in those with severe SARS-CoV-2 infection (25%) compared to those without (11%), and clusters of several multimorbidities were more common in those with severe SARS-CoV-2 infection. The most common clusters with severe SARS-CoV-2 infection were stroke with hypertension (79% of those with stroke had hypertension); diabetes and hypertension (72%); and chronic kidney disease and hypertension (68%). Multimorbidity was independently associated with a greater risk of severe SARS-CoV-2 infection (adjusted odds ratio 1.91 [95% confidence interval 1.70, 2.15] compared to no multimorbidity). The risk remained consistent across potential effect modifiers, except for greater risk among men. Conclusion The risk of severe SARS-CoV-2 infection is higher in individuals with multimorbidity, indicating the need to target research and resources in people with SARS-CoV-2 infection and multimorbidity.

Obesity, walking pace and risk of severe COVID-19: Analysis of UK Biobank (preprint)

Unstructured abstractObesity is an emerging risk factor for coronavirus disease-2019 (COVID-19). Simple measures of physical fitness, such as self-reported walking pace, could also be important risk factors, but have not been well documented. This analysis includes 414,201 UK Biobank participants with complete covariate and linked COVID-19 data. We analysed the risk of severe (in-hospital) COVID-19 across categories of obesity status and walking pace. As of June 20th 2020 there were 972 cases of severe COVID-19 that had occurred within the cohort. Compared to normal weight individuals, the adjusted odds ratio (OR) for severe COVID-9 in those with obesity was 1.49 (1.24, 1.78). Compared to those with a brisk walking pace, the OR in slow walkers was 1.84 (1.49, 2.27). Slow walkers had the highest risk of severe COVID-19 regardless of obesity status. For example, compared to normal weight brisk walkers, the odds of severe COVID-19 in obese brisk walkers was 1.39 (0.99, 1.98), whereas the odds in normal weight slow walkers was 2.48 (1.56, 3.93). Self-reported walking pace, a simple measure of functional fitness, appears to be a risk factor for severe COVID-19 that is independent of obesity. This may help inform simple pragmatic public health risk stratification and preventative strategies.