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Every three months, the 51������ Impact Committee considers dozens of articles and selects the most impactful examples, ranked against core pillars of the 51������ ethos: research quality, team science, scale, open science, patient and public involvement, patient impact and diversity.

In May 2025, the committee chose the paper ‘Prevalence and demographics of 331 rare diseases and associated COVID-19-related mortality among 58 million individuals: a nationwide retrospective observational study’, by Thygesen et al, as their winning publication in the Partner category.

Overview

An England-wide study, covering more than 58 million people, identified eight rare diseases that carry significantly increased risks for COVID-19-related mortality in fully vaccinated people.  The paper was published in , and highlights the importance of including rare diseases in public health strategies.

The challenge

For many rare conditions, there is little population-level evidence about the burden of disease to help inform clinical care and policy-making.  The rarity of some diseases also leads to lengthy waits for diagnosis, aggravating the problem of data gaps.  Even data on the prevalence of rare conditions, or how many people are vulnerable to them, are often missing for many of these diseases – resulting in an absence of evidence-based care. The challenges of the COVID-19 pandemic prominently highlighted the dearth of this important evidence.

The solution

Researchers, supported by the at 51������, set out to help plug such knowledge gaps, and discover new insights into rare diseases, by employing the power of large-scale linked data.  Using linked electronic health records (EHRs) in a nationwide retrospective observational cohort study, they investigated the prevalence of rare diseases across the population in England, and the risks that COVID-19 may pose to people with these conditions.

The study revealed eight rare diseases linked with an increased risk of dying from COVID-19.  It found that people with rare diseases were nearly five times more likely to die from COVID-19 than the general population – and that conditions carrying the highest risk were infertility disorders and kidney diseases.

The study period spanned two ‘waves’ of the pandemic – presenting researchers with particular difficulties in untangling the effects of different COVID-19 variants, as well as overlapping symptoms in multiple illnesses.  However, they were able to overcome such issues by taking advantage of the population-wide, highly detailed data provided by EHRs – which also allowed them to explore the diversity of patients with rare diseases, and identify communities particularly affected by the pandemic.

The impact

The study represents the first time an analysis has been performed on so many rare diseases, and the impact of COVID-19 on people with such conditions – making this work a landmark achievement.

Analysis of diversity data was particularly important because it highlighted significant health inequalities among specific ethnic groups, in which some rare diseases are disproportionately common.

Living with a rare disease can be extremely challenging.  But these findings fill a critical knowledge gap – and emphasise the power of electronic health record data to reveal the prevalence and outcomes of rare diseases.  The study also highlights the need for better inclusion of rare diseases in public health strategies, including future pandemic planning, vaccination policies, and NHS service provision.

Lead author Dr Johan Thygesen, UCL Institute of Health Informatics, said:

“So much fundamental population-level information about rare diseases – such as general prevalence and gender and ethnicity differences – remains unknown. This lack of data was especially problematic during the pandemic, as it is crucial for healthcare planning. Our paper helps bridge this gap for 331 rare diseases, and really showcases the great research potential of our national data.”

Co-author Professor Honghan Wu, University of Glasgow and formerly UCL, said:

“Early detection means earlier intervention and better treatment and support. The ability to link data gives us deeper understanding, and allows us to spot individuals who would otherwise have slipped through the net. Research harnessing NHS data through linking EHRs has enormous potential to inform care and public health, especially for patient populations that are far too often neglected.”