%0 Journal Article
%@ 2589-7500
%A Thygesen, Johan H
%A Zhang, Huayu
%A Issa, Hanane
%A Wu, Jinge
%A Hama, Tuankasfee
%A Phiho-Gomes, Ana-Caterina
%A Groza, Tudor
%A Khalid, Sara
%A Lumbers, Thomas R
%A Hocaoglu, Mevhibe
%A Khunti, Kamlesh
%A Priedon, Rouven
%A Banerjee, Amitava
%A Pontikos, Nikolas
%A Tomlinson, Chris
%A Torralbo, Ana
%A Taylor, Paul
%A Sudlow, Cathie
%A Denaxas, Spiros
%A Hemingway, Harry
%A Wu, Honghan
%D 2025
%F discovery:10204223
%I Elsevier BV
%J The Lancet Digital Health
%N 2
%P e145-e156
%T Prevalence and demographics of 331 rare diseases and associated COVID-19-related mortality among 58 million individuals: a nationwide retrospective observational study
%U https://discovery.ucl.ac.uk/id/eprint/10204223/
%V 7
%X Background The Global Burden of Disease Study has provided key evidence to inform clinicians, researchers, and  policy makers across common diseases, but no similar effort with a single-study design exists for hundreds of rare  diseases. Consequently, for many rare conditions there is little population-level evidence, including prevalence and  clinical vulnerability, resulting in an absence of evidence-based care that was prominent during the COVID-19 pandemic.  We aimed to inform rare disease care by providing key descriptors from national data and explore the impact of rare  diseases during the COVID-19 pandemic.  Methods In this nationwide retrospective observational cohort study, we used the electronic health records (EHRs) of  more than 58 million people in England, linking nine National Health Service datasets spanning health-care settings  for people who were alive on Jan 23, 2020. Starting with all rare diseases listed in Orphanet (an extensive online  resource for rare diseases), we quality assured and filtered down to analyse 331 conditions mapped to ICD-10 or  Systemized Nomenclature of Medicine–Clinical Terms that were clinically validated in our dataset. For all 331 rare  diseases, we calculated population prevalences, analysed patients’ clinical and demographic details, and investigated  mortality with SARS-CoV-2. We assessed COVID-19-related mortality by comparing cohorts of patients for each rare  disease and rare disease category with controls matched for age group, sex, ethnicity, and vaccination status, at a ratio  of two controls per individual with a rare disease.  Findings Of 58 162316 individuals, we identified 894 396 with at least one rare disease and assessed COVID-19-related  mortality between Sept 1, 2020, and Nov 30, 2021. We calculated reproducible estimates, adjusted for age and sex, for  all 331 rare diseases, including for 186 (56·2%) conditions without existing prevalence estimates in Orphanet. 49 rare  diseases were significantly more frequent in female individuals than in male individuals, and 62 were significantly  more frequent in male individuals than in female individuals; 47 were significantly more frequent in Asian or British  Asian individuals than in White individuals; and 22 were significantly more frequent in Black or Black British  individuals than in White individuals. 37 rare diseases were significantly more frequent in the White population  compared with either the Black or Asian population. 7965 (0·9%) of 894 396 patients with a rare disease died from  COVID-19, compared with 141 287 (0·2%) of 58 162316 in the full study population. In fully vaccinated individuals,  the risk of COVID-19-related mortality was significantly higher for eight rare diseases, with patients with bullous  pemphigoid (hazard ratio 8·07, 95% CI 3·01–21·62) being at highest risk.  Interpretation Our study highlights that national-scale EHRs provide a unique resource to estimate detailed  prevalence, clinical, and demographic data for rare diseases. Using COVID-19-related mortality analysis, we showed  the power of large-scale EHRs in providing insights to inform public health decision making for these often neglected  patient populations.  Funding British Heart Foundation Data Science Centre, led by Health Data Research UK.
%Z Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0  license.