Prevalence of 406 rare diseases by ethnicity and their associated COVID-19 infection burden: A national cross-sectional study of 62.5 million people in England

Abstract Background The COVID-19 pandemic disproportionately affected vulnerable populations, including individuals with rare diseases (RDs) and, in the general population, those from ethnic minority backgrounds. However, the intersectional risk, and how these vulnerabilities combine, is poorly understood. A comprehensive baseline map of RD prevalence by granular ethnicity is required to investigate the pandemic’s true impact on these complex patient groups. Methods This study had two aims: (1) to generate the national scale prevalence estimates for 406 rare diseases stratified by 19 ethnicity groupings; and (2) to describe the burden of recorded COVID-19 infection across these distinct populations. We conducted a cross-sectional study within the National Health Service (NHS) England Secure Data Environment, accessed via the BHF Data Science Centre’s CVD-COVID-UK/COVID-IMPACT Consortium, linking primary care, hospital, and mortality records for individuals alive on 31 July 2023. We calculated age- and sex-standardised prevalence for 406 RD and calculated COVID-19 infection rates for the overall cohort, for each RD, and by the six-group Office for National Statistics (ONS) and the 19-group NHS ethnicity classifications. Results We observed a higher burden of COVID-19 infection in the RD cohort (1.7% of the total population) compared to the non-RD population (32.8% vs. 29.0%). The burden varied significantly by ethnicity (e.g., 27.7% in the Pakistani 23.8% in the Black African groups, vs. 33.7% in the White British group) and by specific RD (24.6%–41.2% among the top 25 diseases). This highlights the importance of this ethnicity-stratified prevalence map, which revealed significant underlying ethnic disparities in the RDs themselves. For example, the Pakistani population had markedly elevated odds for certain metabolic disorders (e.g., medium-chain acyl-CoA dehydrogenase deficiency, OR=4.46[4.07–4.90]), and Black Caribbean individuals showed increased odds of autoimmune conditions (e.g., discoid lupus erythematosus, OR=3.34[3.06–3.64]). Conclusions The burden of the COVID-19 pandemic disproportionately affected individuals with rare diseases. However, the patterning of this risk by ethnicity is complex and runs contrary to general population trends, likely reflecting the deep-seated ethnic disparities in the prevalence of specific RDs. Our foundational map of 406 rare diseases by granular ethnicity is essential for understanding these factors and identifying which specific patient-ethnic subgroups face the greatest intersectional risk.