Nottingham was initially under a Human Tissue Authority licence in Nottingham (Licence number: 11035) and subsequently also North West – Greater Manchester South Research Ethics Committee, reference 20/NW/0395. not other ethnicities) more than doubled HCWs likelihood of seropositivity, independent of age, sex, measured socio-economic factors and hospital role. strong class=”kwd-title” Keywords: Covid-19, seropositivity, Healthcare workers, ethnicity Research in context Evidence before this study We searched PubMed for articles published between Jan 1 and December 18, 2020, with the terms Covid-19, healthcare workers, and ethnicity. We did not restrict our search by language or type of publication. Patients from many Black and minority ethnic (BAME) groups have been shown to have higher rates of hospitalisation and worse outcomes with SARS-CoV-2 infection, with differences in co-morbidities and socio-economic factors considered Itga4 important causes. Healthcare workers (HCWs) have increased rates of SARS-CoV-2 infection compared with the general population due at least in part to high levels of occupational exposure. Understanding true differences in infection rates between ethnic groups also requires data from surveillance screening across asymptomatic populations and adjustment for socio-economic and exposure levels. Our PubMed search yielded no investigations carrying out separate analyses of the various ethnicities that are categorised as BAME in the UK. Added value of this study We carried out a longitudinal serological study among 1364 healthcare workers in 5 hospitals in England adjusting for surrogates of socioeconomic status, hospital role, access to PPE, age and sex and presence of Covid-19 symptoms and analysed the role of the various ethnicities categorised as BAME in the UK with regards to overall seropositivity. Implications of all available evidence Our study suggests that HCWs of Black ethnicity (but not other minority ethnic groups) have higher overall rates of SARS-CoV-2 seropositivity than their White counterparts, even after adjustment for demographics, socio-economic status, presence of Covid-19 symptoms and exposure, suggesting a higher ability to mount an antibody response to the virus. HCWs working on ITU had lower rates of SARS-CoV-2 infection during the first wave of the COVID-19 pandemic compared with other front-line HCWs. Alt-text: Unlabelled box Introduction Ethnic differences in severe disease hospitalisation [1] and mortality [2] emerged early in the SARS-CoV-2 pandemic. Proposed explanations include the impact of comorbidities, genetic and socio-economic factors, including access to healthcare, personal protective (PPE) equipment, behavioural and occupational influences [3]. However, most SARS-CoV-2 infections are non-hospitalised with approximately one-third asymptomatic [4]. Large-scale community cross-sectional epidemiological studies BI 1467335 (PXS 4728A) have reported higher infection prevalence in certain ethnic minority populations [5]. These studies however typically report PCR tests in symptomatic individuals or single time point community surveillance [6], underestimating true case ascertainment. Even for population serology studies at scale, limitations remain including recall bias (for symptoms), reduced test sensitivity or specificity (PCR/antigen testing especially at point-of-care), variable/inappropriate timing of tests (prior to sero-conversion; after sero-reversion) and challenges with adjusting for exposure and socio-economic status. Frontline healthcare workers (HCWs) are at higher SARS-CoV-2 infection risk [7,8,9] with reported estimates from 3.4 to 18 times higher than the general population [[8], [9], [10]]. Understanding HCW infection is important. Nosocomial transmission can make hospitals pandemic amplifiers/sustainers [11] and lessons from the first wave are swiftly needed as subsequent waves emerge. HCWs are also work-force representative, easier BI 1467335 (PXS 4728A) to study (e.g. during lock-down), have good ethnic minority representation [5,12] and have many societal socio-economic and behavioural confounders removed or measurable (by NHS role), making them useful to explore ethnic differences in SARS-CoV-2 transmission dynamics. Finally, working in an environment where there is substantial risk of sustained exposure, HCW cohort studies allow an assessment of the impact of mitigation strategies such as PPE [13]. Using best available technology to define SARS-CoV-2 infection and symptoms (longitudinal data collection, multi-timepoint accurate lab-based antibody assays for two antigens), this study assessed differences in symptomatology, serological prevalence and infection severity in HCWs by ethnicity across five hospitals, correcting for demographic BI 1467335 (PXS 4728A) and socio-economic differences where feasible. Methods Healthcare worker cohorts A five hospital HCW longitudinal study (n=1,364) of UK first wave SARS-CoV-2 infection consisting of two initially independent studies (PANTHER, Nottingham: Nottingham City Hospital and Queen’s Medical Centre – both Nottingham University Hospital NHS trust; COVIDsortium, London: St Bartholomew’s, Nightingale and Royal Free Hospitals) that were methodologically aligned for scale in April 2020 (“type”:”clinical-trial”,”attrs”:”text”:”NCT04318314″,”term_id”:”NCT04318314″NCT04318314). London ethical approval was South Central – Oxford A Research Ethics Committee,.