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

Understanding of the role of ethnicity and socioeconomic position in the risk of developing SARS - CoV-2 in fection is limited. We investig ated this in the UK Biobank study.

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 resul ts from Public Health England were linked to baseline UK Biobank data. Poisson regression with robust standard errors was used to a ssess 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 a ssociated with having a positive te st amongst those tested. We adjusted for covariates including age, sex, social variables (including healthcare work and household size ), behavioural risk factors and base line health.

Among 428,225 participants in England, 1,474 had been tested and 669 tested positive between 16 March and 13 April 2020. Black, south Asian and white Irish people were more likely to have . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 3 confirmed infec tion (RR 4.01 (95%CI 2.92-5.12); RR 2.11 (95%CI 1.43-3.10); and RR 1.60 (95% CI 1.08- 2.38) re spectively) and were more likely to be hospital cases compared to the White British. While they were more likely to be tested, they were also more likely to test positive. Adjustment for baseline health and behavioural risk factors l ed to little change, with only modest attenuation when accounting for socioeconomic variables. Socioeconomic deprivation and having no qualifications were consiste ntly associated with a higher risk of confirmed infec tion (RR 2.26 (95%CI 1.76-2.90); and RR 1.91 (95%CI 1.53-2.38) respectively).

Some minority e thnic groups have a higher risk of confirmed S ARS -CoV-2 infection in the UK Biobank study which was not accounted for by difference s in socioeconomic conditions, measured baseline health or behavioural risk fac tors. An urgent response to addressing these elevated risks is required. Keyw ords Ethnicity; inequality; coronavirus, COVID-19, SARS-CoV-2, heal th inequality, infectious dise ase, social factors, pandemic . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 4 Bac kground The Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) and its resulting disease (COVID-19) is spreading rapidly worldwide. 1 A better understanding of the predic tors of developing infection is essential for heal th service pl anning (e.g. ensuring adequate faciliti es for those most at risk), targeting prevention e fforts (e.g. targeted shielding or surveillance) and for informing future modelling efforts. Age, male sex and pre-existing medical conditions are established predictors of adverse COVID-19 outcomes, as is excess adiposity, 2 but the role of social determinants is poorly understood. 3,4 Ethnicity and socioeconomic position strongly influence health outcomes for both infectious and non-communicable di sea ses. Previous pandemics have often disproportiona tely impacted e thnic minorities and socioeconomically disadvantaged populations. 5,6 Early evidence suggests that the same may be occurring in the current SARS-CoV-2 pandemic but empirical research remains highly limited. 7 It is highly plausible that infection risk will vary across these social groups. For example, socioeconomic disadvantage is linked to living in overcrowded housing and some ethnic groups are more likely to live in larger households 8 – both of which potentially predispose to increased risk of infection, and to greater viral load. Establishing the risk of developing infection across different social groups is challenging. A major issue is th at information about ethnicity and socioeconomic position are often not well collected within routine health data. Furthermore, the size of the different social groups in the general population is also often not accurately known. The ideal approach to estimating infection risk across different social groups is to analyse data from a cohort study, but most existing cohort studie s which include detailed informa tion about ethnicity and socioeconomic position are subject to long delays in data being available for analysis and are too small to provide useful e stimates of infection risk. The UK Biobank study has carried out data linkage between its study pa rticipants and SARS-CoV-2 test results held by Public Health England. We therefore aimed to investiga te the relationship . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 5 between ethnicity, socioeconomic position and the risk of having confirmed SARS-CoV-2 infection in the population-based UK Biobank study.

Study design and participants Data were obtained from UK Biobank ( https://www.ukbiobank.ac.uk/ ), with the methods de scrib ed in detail previously. 9 In brief, over 502 000 community-dwelling individuals aged 37 to 73 years were recruited to the study during 2006 to 2010. Participants attended one of 22 assessment centres across England, Scotland and Wales. Data were collected on a range of topic s including social and demographic factors, health and behavioural risk fac tors, using standardised questionnaires administered by trained interviewers and self-completion by computer.

of COVID-19 tests for UK Biobank participants, including confirmed cases, were provided by the Public Health England (PHE) microbiology database S econd Generation Surveillance System and linked to UK Biobank ba seline data. 10 Data provided by PHE included the specimen date, specimen type (e.g. upper respiratory tract), l aboratory, origin (whether there was evidence from microbiological record that the participant was an inpatient or not) and result (positive or negative). Data were available for th e period 16 March 2020 to 14 April 2020. Since data on test re sults were only available for England, we restricted the study population to people who atte nded UK Biobank baseline asse ssment centres in England. Particip ants who were identified as having died prior to 14 February 2018 from the linked mortality records provided by the NHS Information Centre and those who requested to withdraw from the study (N=26) were also excluded from the analysis. In addition to the analyses of the overall population, we also investigated positive test results among those who had bee n tested only. This allowed us to investigate the potential for bias due to differential testing betwe en ethnic and socioeconomic . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 6 groups. UK Biobank received ethical approval from the NHS National Research Ethics Service North West ( 11/ NW/ 0382). Assess ment of ethnicit y and socioeconomic pos ition All exposures were derived from the baseline assessment centre da ta collection. Ethnicity was self- reported based on pre-defined categories into: white British, white Irish, other w hite background, south Asian, black (Caribbean or African), Chinese, mixed or other. Due to small numbers, analyses of the Mixed and Chinese groups were limited. In line with previous research, we also do not report

for the other group due to problems with interpretation of this highly heterogenous group. 11 Socioeconomic positi on was a ssessed using two different mea sures recorded at the baseline visit. Area-level socioeconomic deprivation was assessed by the Townsend index (including measures of unemployment, n on-car ownership, non-home ownership and household overcrowding) corresponding to the output area in which the respondent’s home postcode wa s recorded. 12 Quartiles were derived from the index, where the lowest quartile represents the most advantage d and the highe st the least advantag ed. Highest education level usually remains stable throughout the adult life course and was assessed a s 1) university or college degree, 2) A-level s or equivalent, 3) O- levels, General Ce rtificate of Secondary Education (GCSE), vocational Certificate of Secondary Education (CSE) or equivalent, 4) other (e.g. National Vocational Qualifications or other profe ssional qualifications), or 5) none of the above. 13 Ascertainment of SARS-CoV-2 outcomes We defined our primary outcome a s having a positive test within the Public Health England database available through linkage. 10 This re flects confirmed infection but does not include symptomatic individuals who have not presented to the health service or not been tested, or asymptomatic case s. Some sy stemic differences exist in testing threshold. For example, healthcare workers may be more likely to be tested and therefore observed differences may reflect differences in testing practices. To . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 7 investigate whe the r diffe rential ascertainment was bia sing our results, we studi ed three further outcomes. We identified positive cases that had their test taken while attending hospital (i.e . either Emergency Departments or as inpatients – hereafter referred to as hospital cases). This group is likely to reflect more severe illness and therefore is less likely to be subject to ascertainment bias. In addition, we investigated outcomes related to testing practice by a ssessing the risk of being tested in the overall population and testing positive amongst only those who had been tested. Higher levels of confirmed SARS-CoV-2 infection could arise from higher rates of testing amongst some population subgroups. However, if this were to occur, the likeli hood of having a positive test would be lower amongst groups experiencing high rates of testing. Potential confounders and mediators Age group (5-year age bands), sex and a ssessment centre were included as potential confounder variables in all sta ti stical model s. Country of birth (UK and Ireland) versus elsewhere was also included, given its influence on cultural practices. 14 We also included several variables which could reflect potential confounding or mediation. Participa nts were asked about the title of their current or most recent job at baseline and these were converted to the Standa rd Occupational Cla ssificati on (SOC 2000) by UK Biobank. Healthcare (and related) workers were identified from the SOC 2000 codes 22 (Health Professionals), 32 (Health and Social Welfare Associate Professionals), 118 (Health and Social Service s Managers), 611 (Healthcare and Related Personal Services) and 9221 (Hospital porters). Baseline health status was asse ssed using self-reported long-standing illne ss, health, disability or infirmity (yes or no) and the number of chronic health conditions self-reported from a pre-de fined list of 43 conditions and top-coded at 4 or more, ba sed on a previously published approach. 15 Lifestyle factors included smoking (neve r, previous, current); body mass index (BMI) (weight/height 2 derived from physical mea surements and classified into underweight, normal we ight, overweight, . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 8 obese); and alcohol consumption (categorised into daily or almost daily, 3-4 times a week, onc e or twice a week, 1-3 times per month, special occasions, former drink er or never). Other social variables were also considered. Employment status distinguished those in paid employment or self-employment, retired, looking after home and/or family, unabl e to work because of sickness or disability, unemployment or other. For those in work, manual versus non-manual occupation was asse ssed by asking participants to report whether their job involved heavy manual or physical work (never/rarely/sometimes versus usually/always). Housing tenure was categorised into owner-occupier or renter/other (including those who live in accommodation rent free, in a care home or shel tered accommodation). Urban/rural sta tus was derived from da ta on the home area population density; UK Bio bank combined each participant’s home postcode with data generated from the 2001 census from the Office of National Statistics. The number of people within a household was categorised into three groups: single person, two people and three or more people (which included those living in institutions, such as care homes). Statistical analys es The association between the exposures (ethnicity and socioeconomic position) and the outcomes of interest (confirmed infection, hospital case, being tested and having a positive test amongst those tested) were explored using Poisson regression. Poisson regression was preferred over logistic regression to allow relative risk s to be presented, rather than odds ratios which are often misinterpreted. 16 Robust standard errors were used to ensure accurate e stimation of 95% confidence intervals and p values. Missing data were excluded from the analysis. Sensi tivity analyses were conducted running the key models for those with complete data on all vari ables. Statistical analysis was conducted using Stata/MP 15.1 To investigate e thnicity, we initially adjusted for age, sex and assessment centre (model 1) and then added country of birth (model 2). Subsequent models a dditionally adjusted for variables which we hypothe sised were likely to be at least partially mediating rather than confoundi ng variables. Model . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 9 3 adjusted for model 2 variable s and for being a healthcare worker. Model 4 additionally adjuste d for social variables (n amely urbanicity, number of people per household, highest education level, deprivation, tenure status, employment status, manual work); model 5 was adju sted for model 2 plus health status varia bles (self-rated health, number of chronic conditions and limiting longstanding illness or disability); model 6 was adjusted for mod el 2 plus behavioural risk factors (smoking, alc ohol consumption and BMI); and model 7 was adjusted for all aforementioned covariates. We followed a similar approach to explore the role of deprivation and education l evel. Model 1 was adjusted for age, sex and assessment centre; model 2 added ethnicity and country of birth; model 3 also a djusted for the social variables (as above); model 4 adjusted for model 2 plus he alth status variables; model 5 was adjusted for model 2 plus behavioural risk factors; and model 6 was adjusted for all pr evious covariates.

Most of the baseline UK Biobank sample in England was white British, with the ne xt largest groups being other white, white Irish and then south Asian and black (Table 1). Approximately one-third (32.6%) of the sample had a degree a nd 16.5% had no formal qualifications. [Table 1 he re] Data for 1474 participants who had been tested for SARS-CoV-2 be tween 16 March and 13 April 2020 were linked to UK Biobank baseline data and available for analysis (N=428,225) (Addi tonal file Figure S1 for flowchart). Of these, 669 participants received a positive test result from a total of 2724 tests. 572 received a positive test while attending hospital , suggesting more severe illness. The geometric mean number of tests performed per participant tested was 1.63 (95% CI: 1.59 to 1.67), with relatively small differences in the numbers of tests by ethnicity and socioeconomic position. . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 10 In comparison to the white British majority ethnic group, several ethnic minority groups had a higher risk of testing positive for SARS-CoV-2 infection and also testing positive while a ttending hospital (Figure 1 and Additonal file: Table S3a). Black participants had the highest risk (RR 4.01 (95%CI 2.92- 5.52)), with adjustment for country of birth resulting in little attenuation (RR 3.70 (95%CI 2.50 -5.48)); adjustment for a history of being a healthcare worker (RR 3.35 (95%CI 2.24-5.00)) and for social factors (including measures of socioeconomic position) did additionally attenuate the risk (RR 2.45 (95%CI 1.57-3.81)). South Asians also had an elevated risk (RR 2.11 (95%CI 1.43-3 .10) in model 1), with a similar pattern of a ttenuation as for the black ethnic group. In contrast, the white Irish group had a consistent modestly elevated risk of having a positive test (RR 1.60 (95% CI 1.08-2.38)) which did not change with adjustment for cova riates. The Chinese group had imprecisely estimated risk ratios due to smalle r numbers. The pattern of findings for hospital ca ses was similar, suggesting that the higher testing rates amongst certain ethnic groups in the community were not skewing the results. Similarly, analyses of the likelihood of testing positive amongst those who had been tested was often higher or the same in these ethnic groups (Table 2), wherea s a lower risk would have suggested differentially high testing. [Table 2 he re] In comparison to the most socioeconomically advantaged quartile, living in a disadvantaged area (according to the Townsend deprivation score) was associated with a higher risk of confirmed infection, particularly for the most disadvantaged quartile (RR 2.48 (95%CI 1.95-3.16)) (Figure 2 and Additonal file: Table S4a). Differences in ethnicity and country of birth, social fac tors, baselin e heal th and behavioural risk fac tors all moderately attenuated the a ssociation in the most disadvantaged quartile. Socioeconomic deprivation was also associated with hospital cases. While testi ng was again more likely, the risk of being diagnosed positive amongst those tested also tended to be higher, rather than lower (Table 2). . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 11 Analyses by education also showed a hig her risk of confirme d SARS-CoV-2 infection with lower level s of education (RR 1.95 (95% CI 1.56 -2.43) for no qualifications compared to degree level educated) (Figure 3 and Additional file: Table S5 a). While adjustment for e thnicity and country of birth made little difference to the association, adjustment for social factors, baseline health a nd behavioural risk factors all attenuated the a ssociation somewhat (RR 1.41 (95%CI 1.09-1.82) in fully adjusted model). We again observed a similar pa ttern in hospital ca ses and found little evidence of increased testing amongst the less educated group s (Figure 3 and Table 2). We repea ted analyses for those who had complete data on all variables (N= 392,116), but this made little differe nce to the substantive results (Additional file 1: Figures S2-S4). Dis c us sion Several e thnic minority groups had a higher risk of both being diagnosed and testing positive in a hospital setting with laboratory-c onfirmed SARS-CoV-2 infection in the UK Biobank study. The black, south Asian and white Irish ethnic groups were found to be at greatest risk. Similarly, measures of socioeconomic disadvantage (a rea-based deprivation and lower education) were also associated with an increased risk of having confirmed infection and being a hospital case. For both ethnicity and socioeconomic position, we did not find evidence that these patterns were likely to be due to differential ascertainment, since although the likelihood of testing was increased, the likelihood of a positive test was, if anything, higher among ethnic minoriti es who had been tested. Ethnic differences in infection risk did no t appear to be fully accounted for by differences in pre-existing health, behavioural risk fac tors or country of birth measured at ba seline. Furthermore, socioeconomic differences appeared to make a modest contribution to these ethnic differences. Our s tudy has s everal impor tant str engths . First, by using a well characteris ed cohort st udy, we can identify a clearly defined population at risk of experiencing SARS-CoV-2 infection. By combining data linkage with a large sample size, thi s ha s allowed us to provide empirical data from this pandemic in a timely fashion. Ethnici ty was collec ted using self-report which is widely considered to be a gold- . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 12 standard approach 17 and the availability of a larg e dataset has allowed us to provide empirical data on this crucial policy priority in a timely fashion, including a more nuanced appreciation of the risks of infection within different members of the white majority population, as well as minority ethnic populations. Our investigation of socioeconomic position ha s similarly ben efited from being able to study different mea sures and assess the pattern of findings acro ss these. The detailed data collected in this cohort has also allowed us to investigate the extent to which observed inequalitie s a re potentially mediated by a wide range of factors, including behavioural risk factors, pre-existing health status and other social variables. However, several potential limitations should be noted. Ascertainment bias is potentially problema tic and could arise in several ways, including differential healthcare seeking, differential testing and differential prognosis. Even so, we have been unable to find any evidence to suggest that differential healthcare seeking or testing would explain the ob served pattern of findings. Increased ascertainment amongst ethnic minorities would be expected to re sult in a lower proportion of confirmed ca ses amongst those tested wherea s we observed the opposite . One possibility that remains is that some ethnic and socioeconomic groups have a poorer prognosis and are there fo re more likely to be admitted to hospital and therefore to be tested. However, if this were the case, the issue of more adverse outcomes among these groups remains concerning. Other li mitations include the non-representativeness of the UK Biobank study population, with those who were more advantaged being more likely to pa rticipate and ethnic minorities less well represented. There is therefore the potential that the findings in our study may not reflect the broader UK population. 18 However, empirical research has found that this does not result in substantial bias in measures of association in the UK Biobank study. 19 We have also been unable to fully exclude all deaths that occurred prior to the pandemic, due to lack of up-to-da te linkage to mortality records at present. Our exposure data were collec ted some years ago and it is therefore likely that pre-existing health, risk factors and some social variables have changed, although generally most risk factors track throughout life. Being a healthcare worker was also ascertained at base line, although many who . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 13 stopped employment in thi s a rea have now returned to work. Lastly, we have not explored the role of speci fic health conditions such as asthma, diabetes and high blood pressure, which have been shown to be associated with a higher risk of severe outcomes 3,20 and are more prevalent amongst socioeconomically disadvantaged groups and some ethnic minority groups. 21,22 However, these are likely to operate as mediato rs rather than confounders. Administrative data from health services has recently suggested an increased risk of severe COVID- 19 disease within e thnic minority groups. The UK’s Intensive Care National Audit & Research Centre (ICNARC) analy sed data on 5,578 pa tients admitted to critical care up to 16 th April 2020 and found black and Asian people compri sed a high proportion of total patients (11.2% and 14.9% respectively), although it wa s unclear whether these higher percentages were bia sed by most cases being initially seen in areas with high BME proportions. 23 Similarly, data from the US Centers for Disease Control and Prevention also suggest a higher risk amongst Black or African American people, but information on race was missing for approximately two-thirds of those diagno sed. 24 Academic research on this topic has been limited to date. An ecological study of US counties has suggested that more socially vulnerable a reas (which included grea te r numbers of people with socioeconomic disadvantage and ethnic minorities) were associated with higher COVID-19 ca se fatality rates. 25 O ur study adds substantially to the evidence by finding that ethnicity appe ars to be an important predictor of labora tory-confirmed SARS -CoV-2 infec tion that is only partly attenuated by a large range of potential mediators (such as socioeconomic position), as well as addressing concerns about numerator-denominator bias. Our results suggest th ere is an urgent ne ed for furthe r research on how SARS-CoV-2 infection a ffects different ethnic and socioeconomic groups. Our findings warrant replic ation in other datasets, ideally including representative samples and across different countries. As the pandemic evolves, there is a need to monitor infection and disease outcome s by ethnicity and socioeconomic position. However, data to allow thi s disaggregation is often not available – record linkage could potentially . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 14 help address this gap, particularly in settings where administrative register data are available. Given the differenc es in health risks across occupational groups 26 , understanding the risks that the full range of key workers experience is also required. Lastly, other social groups, such as homeless people, prisoners and undocumented migrants, experience severe disadvantage and research is necessary to study the se highly vulnera ble populations too. 27,28 Conc lus ions The limited evidenc e available sugge sts that some ethnic minority groups, particularly black and south Asian people , are particularly vulnerable to SARS-CoV-2 infection. Socioeconomic disadvantage and poorer pre-existing health do not explain all this elevated risk. There i s therefore a need to determine exactly why this increased risk occurs. An immediate policy re sponse is required to ensure the health system is responsive to the needs of ethnic minority groups. This should include ensuring that health and care workforces, which often rely on workers from minority ethnic populations, have access to the necessary protective personal equipment (PPE) to ensure they can work sa fely. Timely communication of guidelines to reduce the risk of being exposed to the virus is also required in a range of la nguages. 29 Previous evidence suggests ethnic minorities in the UK tend to receive rea sonably equitable care in many, but not all, are as. 30 However, this is not the case in many other countries (such a s the US ) where the adverse consequences of SARS -CoV-2 infection may be even worse. SARS-CoV-2 therefore has the potential to substantially exac erbate ethnic and socioeconomic inequalities in health 31 , unless steps are taken to mitiga te these inequalities. The data from this study may be helpful to inform allocation of more aggressive therapies in people with severe di sease, or targeting preventative vaccination to at risk groups, once evide nce for such approaches becomes available. Li s t of abbrevi at i ons BMI Body Mass Index . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 15 CI Confidence interval COVID-19 Coronavirus-19 CSE Certificate of Secondary Education GCSE Gene ral Certifica te of Secondary Education ICNARC Intensive Care National Audi t & Research Centre NHS National Health Service UK United Kingdom PPE Personal protective equipment RR Risk ratio SARS-COV-2 Severe acute respiratory syndrome coronavirus 2 SOC Standard Occupational Classification D e c l ar at i o n s Ethics Approval UK Biobank received ethical approval from the NHS National Research Ethic s Service North West (11/NW/0382). Al l particip ants provided written informed consent before enrolment in the study, which was conducted in accordarce with the Declaration of Helsinki. The study protocol is available online ( https://www.ukbiobank.ac .uk/wp-content/uploads/2011/11/UK-Biobank-Protoc ol.pdf ). Consent for publication Not applic able Availability of data and materials . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 16 The data that support the finding s of this study are available from UK Biobank ( https://www.ukbiobank.ac.uk/ ) but restrictions apply to their availability. These data were used under licence for the current study, and so are not publicly available. The data are available from the authors upon reasonabl e request and with permission of UK Biobank. Competing interests JPP is a member of the UK Biobank Steering Committee. Apart from the funding acknowledged below, we declare no other competing interests. Funding CLN acknowledges funding from a Medical Research Council Fellowship (MR/R024774/1). ED and SVK acknowledge funding from the Medical Research Council (MC_UU_12017/13) and Scottish Government Chief Scientist Office (SPHSU13). SVK also acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02). The funder of the study had no role in study design, data collec tion, data analysis, data interpre tation, or writing of the report. Authors' contributions SVK, KOD and JPP conceived the idea for the paper. CLN conducted the analy sis. All authors contributed to the interpretation of the findings. CLN and SVK jointly wrote the first draft. All authors critically revised the paper for intellec tual content and approved the final version of the manuscript. The corresponding authors (SVK and CLN) had full access to all the da ta in the study and had final responsibility for the decision to submit for publication.

We are grateful to UK Biobank participants. This re sea rch has been conducted using the UK Biobank resource under Application 41686. . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 17 Fig ur e 1: Risk r atios f o r associations bet ween et hni city (White Britis h a s referen ce categ or y ) and SARS-CoV -2 M o d e l 1 : Ag e , s ex a n d a sse ss m en t ce n tr e Mode l 2: Model 1 + country of b irth Mode l 3: Model 2 + he a lthcare worke r Mode l 4: Model 3 + socia l varia b les ( urbani c i t y , number of p eop le per hous e ho ld , h ig he s t e duc a tion lev el, dep r ivation, tenure s tatus, e mp loyment status, ma n ual w ork ) Mode l 5: Model 4 + he a lth status varia ble s (s el f- ra t e d health, number of c hron i c condit i ons and l im iting longs ta nd in g i ll n ess ) + be ha vio u r a l ris k fa c tors (s m o ki ng, al c ohol consu mptio n and BMI) Fig ur e 2: Risk r atios associa t ions betwee n Townsend depriv ation s c ore quartile (most a dvantage d as refe rence c ategory) and SARS-CoV-2 M o d e l 1 : Ag e , s ex a n d a sse ss m en t ce n tr e Mode l 2: Model 1 + e t h n icity + c oun t ry of birth Mode l 3: Model 2 + socia l varia b les ( hea lth care worker, urba nicity, n um ber of peop l e per h ouseh ol d, hi g hest education leve l, te nure status, em pl o yment st a tus , manual work) Mode l 4: Model 3 + he a lth s tatus varia ble s (s el f- ra t e d health, number of c hron i c condit i ons and l im iting longs ta nd in g i ll n ess ) + be ha vio u r a l ris k fa c tors (s m o ki ng, al c ohol consu mptio n and BMI) Fig ur e 3: Risk r atios f o r associations bet ween highest edu cational level (degree educ ated as

category) a nd SARS-CoV-2 M o d e l 1 : Ag e , s ex a n d a sse ss m en t ce n tr e Mode l 2: Model 1 + e t h n icity + c oun t ry of birth Mode l 3: Model 2 + socia l varia b les ( hea lth care worker, urba nicity, n um ber of peop l e per h ouseh ol d, dep r ivation, tenure s tatus, e mp loyment status, ma n ual w ork ) . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 18 Mode l 4: Model 3 + he a lth s tatus varia ble s (s el f- ra t e d health, number of c hron i c condit i ons and l im iting longs ta nd in g i ll n ess ) + be ha vio u r a l ris k fa c tors (s m o ki ng, al c ohol consu mptio n and BMI) . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 19 Tabl e 1 Description of the st udy populat ion Ag e gr o u p N % 3 7 - 44 4 5, 633 1 0 . 66 4 5 - 49 5 7, 353 1 3 . 39 5 0 - 54 6 5, 746 1 5 . 35 5 5 - 59 7 7, 370 1 8 . 07 60 -6 4 103 , 4 93 24 .1 7 6 5 - 69 7 6, 634 1 7 . 90 70 + 1 ,99 6 0 . 47 Se x N % F e ma l e 235 , 1 49 54 .9 1 Ma le 193 , 0 76 45 .0 9 Ethn ic i t y N % W hi te B r i t i sh 375 , 3 66 88 .1 6 Wh i t e Iris h 1 0, 822 2.5 4 Wh i t e Ot h er 1 4, 365 3.3 7 Mi x ed 2 ,66 1 0 . 62 S o u th A s i a n 9 ,24 6 2 . 17 B l a c k 7 ,72 6 1 . 81 C h i ne s e 1 ,40 2 0 . 33 O t he r 4 ,20 4 0 . 99 C ou ntr y o f b irth N % UK & I re l an d 390 , 2 62 91 .4 8 El s e w he re 3 6, 358 8.5 2 Num ber in h ous eh o l d N % 1 7 7, 080 1 8 . 12 2 198 , 0 98 46 .5 7 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 20 3 + 150 , 2 39 35 .3 2 Ed uc a ti on L e vel N % Colle g e or U ni ve rs it y degree 136 , 8 66 32 .6 4 A l ev e ls /AS le v e l s o r eq u iv a le n t 4 7, 381 1 1 . 30 O lev el s /GCSE s/ C S E s o r e qui va l ent 115 , 7 89 27 .6 2 Oth er 4 9, 689 1 1 . 85 N on e o f th e a bov e 6 9, 552 1 6 . 59 D e p riv a t ion ( qua rt i l e) N % 1 107 , 6 25 25 .1 6 2 107 , 3 94 25 .1 1 3 107 , 0 22 25 .0 2 4 105 , 6 83 24 .7 1 Housi ng t enu r e N % O wn e r 377 , 3 94 88 .9 6 Rent/ O th e r 4 6, 847 1 1 . 04 Urb an/ Rur al N % U r b an 363 , 5 63 85 .7 2 R ura l 6 0, 569 1 4 . 28 E m pl o ym ent s tatus N % In pa id e mpl o y m e n t or s el f - emp l oy e d 248 , 6 02 58 .4 1 R e ti re d 138 , 9 55 32 .6 5 Loo k i n g after ho me a nd/ o r fa mi l y 1 2, 131 2.8 5 Un a b le t o w ork b eca use of s ick ne s s or d 1 2, 870 3.0 2 U ne m p lo y ed 7 ,36 7 1 . 73 O t he r 5 ,67 5 1 . 33 Man u al oc cupa t i on N % N on - m a nu a l 214 , 4 43 50 .4 2 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 21 Ma nu a l 33 ,8 5 0 7 . 96 N o t in e mp loy me n t 176 , 9 98 41 .6 2 He a lth c ar e w or k e r N % N o 221 , 6 79 52 .1 1 Yes 2 6, 713 6.2 8 N o t in e mp loy me n t 176 , 9 98 41 .6 1 Lon g-stand i ng il lnes s, dis abi l ity or in fir m ity N % N o 284 , 7 06 68 .3 1 Y e s 132 , 0 78 31 .6 9 Num ber o f lon g-te r m c o nd iti on s N % 0 159 , 4 76 37 .4 6 1 141 , 1 21 33 .1 5 2 7 5, 814 1 7 . 81 3 31 ,8 0 8 7 . 47 4+ 17 ,5 3 6 4 . 12 Se l f -r ep ort ed h e a lth N % Excell e n t 6 9, 282 1 6 . 29 G o od 249 , 3 82 58 .6 4 Fa ir 8 9, 048 2 0 . 94 P o o r 17 ,5 8 0 4 . 13 Bo d y Ma ss I n dex (B MI) N % U nde r w e i gh t ( = 30. 0) 1 0 2,43 0 2 4 . 06 Sm o k i n g s t a t u s N % N e v e r 235 , 7 11 55 .3 7 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 22 P r e v iou s 147 , 2 35 34 .5 9 Current 4 2, 745 1 0 . 04 A l co ho l c o n s ump t io n N % Dail y or alm ost da i ly 8 7, 430 2 0 . 48 Th re e o r fou r ti m e s a w e ek 99 ,0 5 8 23 .2 0 O n c e o r tw i c e a w e ek 109 , 5 62 25 .6 6 O n e to th r e e t ime s a mon th 47 ,7 2 0 11 .1 8 Special occ a s io ns o nly 4 9, 165 1 1 . 52 Fo rm er dr i n k e r 1 4, 842 3.4 8 Never 1 9, 144 4.4 8 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 23 Tabl e 2 Risk ra tios for te sting positive for SARS- CoV-2 a mon gs t those tes ted (N= 1,474 ) in UK Biobank M o d e l 1 Mo de l 2 Mo de l 3 Mo de l 4 Mo de l 5 Mo d e l 6 R R [ 95% CI] RR [9 5% CI] RR [9 5 % CI] RR [ 95% CI] RR [9 5% CI] RR [9 5 % C I] Ethn ic i t y: Whi t e Briti sh 1. 000 - 1 . 00 0 - 1 . 0 00 - 1 .00 0 - 1. 000 - 1 . 0 00 - Wh i t e Iris h 1. 119 [ 0 .8 46 ,1 .48 1 ] 1 . 12 0 [ 0 . 8 46 ,1 .4 81 ] 1 . 1 80 [0. 888, 1.5 6 9] 1 .13 2 [ 0 .8 50 ,1 .507 ] 1. 162 [ 0 . 8 88 ,1 .5 21 ] 1 . 2 39 [0. 933, 1.6 4 5] Wh i t e Ot h er 0. 975 [ 0 .7 11 ,1 .33 5 ] 1 . 00 6 [ 0 . 7 03 ,1 .4 41 ] 1 . 1 08 [0. 761, 1.6 1 3] 0 .98 6 [ 0 .6 84 ,1 .422 ] 1. 000 [ 0 . 6 94 ,1 .4 39 ] 1 . 0 32 [0. 699, 1.5 2 4] Mixe d 1. 068 [ 0 .5 30 ,2 .15 4 ] 1 . 09 2 [ 0 . 5 36 ,2 .2 25 ] 1 . 0 69 [0. 538, 2.1 2 5] 1 .08 2 [ 0 .5 19 ,2 .256 ] 1. 101 [ 0 . 5 60 ,2 .1 64 ] 1 . 0 82 [0. 547, 2.1 4 2] Sout h Asian 1. 122 [ 0 .8 57 ,1 .46 8 ] 1 . 18 7 [ 0 . 8 04 ,1 .7 53 ] 1 . 2 98 [0. 859, 1.9 6 2] 1 .19 6 [ 0 .8 09 ,1 .766 ] 1. 196 [ 0 . 7 87 ,1 .8 16 ] 1 . 2 78 [0. 819, 1.9 9 5] Bla c k 1. 380 ** [ 1 .1 26 ,1 .69 1 ] 1. 4 3 2 * [ 1 . 0 74 ,1 .9 09 ] 1. 423 * [1. 046, 1.9 3 5] 1 .31 9 [ 0 .9 88 ,1 .762 ] 1. 3 8 8 * [ 1 . 0 33 ,1 .8 64 ] 1 . 3 08 [0. 952, 1.7 9 7] Chin ese 2 . 0 36 *** [ 1 .7 01 ,2 .43 8 ] 2. 1 4 3 *** [ 1 . 5 33 ,2 .9 98 ] 2. 400 *** [1. 522, 3.7 8 5] 2. 0 4 5 *** [ 1 .4 40 ,2 .903 ] 2. 0 1 3 *** [ 1 . 3 92 ,2 .9 10 ] 2. 125 * [1. 195, 3.7 7 8] Oth er 1. 060 [ 0 .7 48 ,1 .50 1 ] 1 . 10 9 [ 0 . 7 19 ,1 .7 11 ] 1 . 1 64 [0. 693, 1.9 5 4] 1 .23 4 [ 0 .8 12 ,1 .874 ] 1. 160 [ 0 . 7 41 ,1 .8 16 ] 1 . 1 70 [0. 671, 2.0 3 8] So cio e co nomi c depri vatio n: Qu artile 1 (m os t adv a n ta ged) 1. 000 - 1 . 00 0 - 1 . 0 00 - 1 .00 0 - 1. 000 - 1 . 0 00 - . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 24 Qu artile 2 1. 063 [ 0 .8 75 ,1 .29 0 ] 1 . 07 2 [ 0 . 8 82 ,1 .3 03 ] 1 . 0 56 [0. 866, 1.2 8 7] 1 .08 7 [ 0 .8 90 ,1 .327 ] 1. 092 [ 0 . 8 97 ,1 .3 28 ] 1 . 0 83 [0. 882, 1.3 3 0] Qu artile 3 1. 090 [ 0 .9 05 ,1 .31 3 ] 1 . 10 4 [ 0 . 9 15 ,1 .3 32 ] 1 . 1 06 [0. 914, 1.3 3 8] 1 .15 9 [ 0 .9 57 ,1 .403 ] 1. 126 [ 0 . 9 33 ,1 .3 59 ] 1 . 1 73 [0. 966, 1.4 2 5] Qu artile 4 (le a s t adv a n ta ged) 1. 092 [ 0 .9 15 ,1 .30 2 ] 1 . 07 8 [ 0 . 9 00 ,1 .2 90 ] 1 . 1 17 [0. 919, 1.3 5 8] 1 .11 8 [ 0 .9 29 ,1 .346 ] 1. 090 [ 0 . 9 08 ,1 .3 09 ] 1 . 1 59 [0. 948, 1.4 1 8] Ed uc a ti on le v e l : Colle g e or Uni versit y degree 1. 000 - 1 . 00 0 - 1 . 0 00 - 1 .00 0 - 1. 000 - 1 . 0 00 - A l e ve l s/ A S level s or equi valent 1. 023 [ 0 .8 25 ,1 .27 0 ] 1 . 03 0 [ 0 . 8 27 ,1 .2 83 ] 1 . 0 42 [0. 836, 1.3 0 0] 1 .01 3 [ 0 .8 10 ,1 .266 ] 1. 044 [ 0 . 8 39 ,1 .3 00 ] 1 . 0 31 [0. 825, 1.2 8 8] O level s /GC SEs/ C S E s o r eq ui v a le nt 1. 084 [ 0 .9 24 ,1 .27 3 ] 1 . 10 1 [ 0 . 9 37 ,1 .2 95 ] 1 . 0 89 [0. 921, 1.2 8 9] 1 .12 3 [ 0 .9 52 ,1 .324 ] 1. 084 [ 0 . 9 21 ,1 .2 76 ] 1 . 0 92 [0. 919, 1.2 9 8] Oth er 1. 157 [ 0 .9 60 ,1 .39 5 ] 1 . 17 7 [ 0 . 9 74 ,1 .4 24 ] 1 . 1 30 [0. 929, 1.3 7 6] 1 .20 3 [ 0 .9 90 ,1 .461 ] 1. 178 [ 0 . 9 69 ,1 .4 31 ] 1 . 1 49 [0. 937, 1.4 0 9] No ne of t h e abo ve 1. 078 [ 0 .9 17 ,1 .26 9 ] 1 . 08 8 [ 0 . 9 20 ,1 .2 86 ] 1 . 0 83 [0. 907, 1.2 9 4] 1 .10 2 [ 0 .9 26 ,1 .312 ] 1. 084 [ 0 . 9 10 ,1 .2 91 ] 1 . 0 88 [0. 902, 1.3 1 3] R R= ris k ra tio; 95% c onfi denc e in te r vals i n b r ac k ets * p < 0 . 0 5, ** p < 0. 01, *** p < 0. 0 01 Not e: R Rs s ho wn a re f or t h e rel a ti ons h i p bet w e e n each v ariabl e sh ow n an d t h e ris k of te s tin g po sitiv e am on gst th os e w ho hav e ha d a t es t. Co e ffic i e nt s f or t he co va ria tes inc lud ed are no t s h o w n . Model 1 : Ad j u s ted fo r ag e , se x , a ss es smen t ce nt r e Mo de l 2 : 1 + e t h nicit y, c ou ntr y of bi r t h . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 25 Mo d e l 3 : 2 + educati on l evel , hous eho l d siz e, soci oe c on o mi c d e pri v at ion, h o us in g t en u r e , urban icit y , e m p loy me nt s t atu s , m a nu a l o cc u pa ti on , he a lt h c a r e wo r k e r Mo de l 4 : 2 + limit ing i ll n e s s/ d isa bilit y , n u m b e r of chro nic c on di ti o ns, s e lf-ra te d h ea l th Mo de l 5 : 2 + B od y Mas s I n dex , s mo k i n g s tat u s, a l c ohol co n s um pti o n Mo de l 6 : A ll of t h e abo ve co v a riat e s . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint 26

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(which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint White Irish White Other Mixed South Asian Black 0.0 2.0 4.0 6.0 Risk Ratio (95% CI) Risk of being tested for SARS-CoV2 White Irish White Other Mixed South Asian Black 0.0 2.0 4.0 6.0 Risk Ratio (95% CI) Risk of testing positive for SARS-CoV2 White Irish White Other Mixed South Asian Black 0.0 2.0 4.0 6.0 Risk Ratio (95% CI) Risk of testing positive for SARS-CoV2 in a hospital setting Ethnicity age + sex + asessment centre + ethnicity + country of birth + health care worker + social factors + health + behavioural risk factors . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint Quartile 2 Quartile 3 Quartile 4 (least advantaged) 1.0 1.5 2.0 2.5 3.0 3.5 Risk Ratio (95% CI) Risk of being tested for SARS-CoV2 Quartile 2 Quartile 3 Quartile 4 (least advantaged) 1.0 1.5 2.0 2.5 3.0 3.5 Risk Ratio (95% CI) Risk of testing positive for SARS-CoV2 Quartile 2 Quartile 3 Quartile 4 (least advantaged) 1.0 1.5 2.0 2.5 3.0 3.5 Risk Ratio (95% CI) Risk of testing positive for SARS-CoV2 in a hospital setting Socioeconomic deprivation age + sex + asessment centre + deprivation + ethnicity + country of birth + social factors + health + behavioural risk factors . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint A levels/AS levels O levels/GCSEs/CSEs None of the above 0.5 1.0 1.5 2.0 2.5 3.0 Risk Ratio (95% CI) Risk of being tested for SARS-CoV2 A levels/AS levels O levels/GCSEs/CSEs None of the above 0.5 1.0 1.5 2.0 2.5 3.0 Risk Ratio (95% CI) Risk of testing positive for SARS-CoV2 A levels/AS levels O levels/GCSEs/CSEs None of the above 0.5 1.0 1.5 2.0 2.5 3.0 Risk Ratio (95% CI) Risk of testing positive for SARS-CoV2 in a hospital setting Education level age + sex + asessment centre + education + ethnicity + country of birth + social factors + health + behavioural risk factors . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 30, 2020. ; https://doi.org/10.1101/2020.04.22.20075663doi: medRxiv preprint