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Risk of death among people with rare autoimmune diseases compared to the
general population in England during the 2020 COVID-19 pandemic.
Emily Peach, Research Fellow, Division of Epidemiology and Public Health, University of
Nottingham UK Emily.peach@nottingham.ac.uk
Megan Rutter, Clinical Research Fellow, Division of Epidemiology and Public Health,
University of Nottingham UK Megan.Rutter@nottingham.ac.uk
Peter Lanyon, Consultant Rheumatologist and Honorary Clinical Associate Professor,
Nottingham University Hospitals NHS Trust, Nottingham, UK
Peter.Lanyon@nottingham.ac.uk
Matthew J Grainge, Associate Professor in Medical Statistics, Division of Epidemiology and
Public Health, University of Nottingham UK Matthew.Grainge@nottingham.ac.uk
Richard Hubbard, Professor of Epidemiology and Honorary Respiratory Consultant, Division
of Epidemiology and Public Health, University of Nottingham UK
Richard.Hubbard@nottingham.ac.uk
Jeanette Aston, NCARDRS rare disease data liaison, National Disease Registration Service,
Public Health England Jeanette.Aston@phe.gov.uk
Mary Bythell, NCARDRS Head of Rare Disease, National Disease Registration Service,
Public Health England Mary.Bythell@phe.gov.uk
Sarah Stevens, Interim Deputy Director, National Disease Registration Service, Public
Health England Sarah.Stevens@phe.gov.uk
Fiona Pearce, Clinical Associate Professor of Rheumatology Epidemiology, Division of
Epidemiology and Public Health, University of Nottingham UK
Fiona.Pearce@nottingham.ac.uk
Correspondence to: Fiona Pearce, Clinical Sciences Building, City Hospital campus,
Hucknall Road, Nottingham, NG5 1PB, Fiona.Pearce@nottingham.ac.uk
Key words
COVID-19
Rare autoimmune rheumatic diseases
Lupus
Vasculitis
Scleroderma
Myositis
Juvenile idiopathic arthritis
Epidemiology
Mortality
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NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
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Key messages:
• People with RAIRD had an increased risk of dying during COVID-19 from age 35
years onwards, whereas in the general population it increased from the age of 55
onwards.
• Women had a greater increase in their risk of death during COVID-19 compared to
men.
• The risk of working age people with RAIRD dying during COVID-19 was similar to
that of someone 20 years older in the general population.
. CC-BY-NC-ND 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)preprint
The copyright holder for thisthis version posted November 22, 2020. ; https://doi.org/10.1101/2020.10.09.20210237doi: medRxiv preprint
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Abstract (max 250 words)
Objectives To quantify the risk of death among people with rare autoimmune rheumatic
diseases (RAIRD) during the UK 2020 COVID-19 pandemic compared to the general
population, and compared to their pre-COVID risk.
Methods We conducted a cohort study in Hospital Episode Statistics for England 2003
onwards, and linked data from the NHS Personal Demographics Service. We used ONS
published data for general population mortality rates.
Results We included 168,691 people with a recorded diagnosis of RAIRD alive on
01/03/2020. Their median age was 61.7 (IQR 41.5-75.4) years, and 118,379 (70.2%) were
female. Our case ascertainment methods had a positive predictive value of 85%. 1,815
(1.1%) participants died during March and April 2020. The age-standardised mortality rate
(ASMR) among people with RAIRD (3669.3, 95% CI 3500.4-3838.1 per 100,000 person-
years) was 1.44 (95% CI 1.42-1.45) times higher than the average ASMR during the same
months of the previous 5 years, whereas in the general population of England it was 1.38
times higher. Age-specific mortality rates in people with RAIRD compared to the pre-COVID
rates were higher from the age of 35 upwards, whereas in the general population the
increased risk began from age 55 upwards. Women had a greater increase in mortality rates
during COVID-19 compared to men.
Conclusion The risk of all-cause death is more prominently raised during COVID-19 among
people with RAIRD than among the general population. We urgently need to quantify how
much risk is due to COVID-19 infection and how much is due to disruption to healthcare
services.
. CC-BY-NC-ND 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)preprint
The copyright holder for thisthis version posted November 22, 2020. ; https://doi.org/10.1101/2020.10.09.20210237doi: medRxiv preprint
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Introduction
There are limited data, and no whole population studies, on the impact of COVID 19 on
people with rare diseases. This is important to inform shielding advice for people with rare
diseases, and also to communicate realistic levels of risk as they apply to different groups
and allow informed personal choices (1). There is also a risk that the known discrepancy in
outcomes and access to treatment between rare and common diseases will widen, leading
to more health inequality(2).
We have studied the risk of death during the 2020 UK COVID-19 epidemic across rare
autoimmune rheumatic diseases (RAIRD) because they are an exemplar group of rare
diseases requiring treatment with immunosuppression. People with these conditions have
slightly increased mortality compared to the general population, and they may be at
increased risk both due to COVID-19 infection and from their disease when healthcare
services are disrupted. However, their risk during COVID-19 has not been quantified. Using
linked national health records for the whole population of England we have estimated the
risk of death among people with rare autoimmune rheumatic diseases during March and
April 2020, at the beginning of the COVID-19 pandemic in the UK, and compared this to 1)
their risk before COVID-19 and 2) the risk of death in the general population during COVID-
19.
Methods
The Registration of Complex Rare Diseases Exemplars in Rheumatology (RECORDER)
project is a collaboration between the University of Nottingham, and the National Congenital
Anomaly and Rare Disease Registration Service (NCARDRS) within Public Health England.
NCARDRS registers people with congenital abnormalities and rare diseases across the
whole of England. Currently there is no routine notification to NCARDRS by healthcare
providers of people with rare diseases that are non-genetic and occur after infancy(3,4).
RECORDER has established the methodologies for identification, validation and registration
with NCARDRS of people who have later onset, non-genetic rare diseases, using rare
autoimmune rheumatic diseases as an exemplar group of conditions. This has been enabled
through NCARDRS access to national routinely collected healthcare datasets, such as
Hospital Episode Statistics (HES). HES contains every episode of admitted NHS patient care
in England (in-patient and day-case), with all prevalent diagnoses coded according to ICD-
10. Importantly, each of the rare autoimmune rheumatic diseases maps to a unique ICD-10
code that does not also include other conditions, and patients with these conditions also
have frequent in-patient or day-case activity, making them ideal for identification in HES.
We have previously validated ascertaining diagnoses of vasculitis (ANCA-associated
vasculitis, Takayasu arteritis and Kawasaki disease) in HES, with positive predictive values
(PPV) over 85%(5). For this study we have used NCARDRS legal permissions and data
sharing agreements with NHS Trusts in England to validate additional diagnoses, confirming
diagnoses of randomly selected people with coded diagnoses of systemic lupus
erythematosus, scleroderma, idiopathic inflammatory myositis, Behcet’s disease, giant cell
arteritis and juvenile idiopathic arthritis in two hospital Trusts.
We included people who had a diagnostic code for a rare autoimmune rheumatic disease in
in-patient HES from 2003 onwards, were resident in England, and who were alive on 1
March 2020. We used data from the NHS Personal Demographics Service, linked by NHS
number and date of birth, to ascertain whether people were alive or dead, and their date of
death(6). Authors extracted data from the whole HES dataset themselves. A data flow
diagram is shown in figure 1. The data did not require further cleaning after building the
. CC-BY-NC-ND 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)preprint
The copyright holder for thisthis version posted November 22, 2020. ; https://doi.org/10.1101/2020.10.09.20210237doi: medRxiv preprint
5
cohort. We calculated the mortality rate during March and April 2020, using the cohort of
people with rare autoimmune rheumatic conditions as the denominator population. We
repeated the calculation for mortality rates during March and April for each of the 5 previous
years for comparison. We converted all rates into age-standardised mortality rates (ASMRs)
per 100,000 population, standardised to the 2013 European Standard Population. We
calculated sex-specific mortality rates, including ASMRs however it should be noted that the
European standard population is not disaggregated by sex, meaning it assumes equal
numbers of males and females, and identical distributions by age for males and for females.
The World Health Organisation and the Office for National Statistics (ONS) therefore advise
focusing on age-standardised rates rather than age-sex standardised rates for headline
measures. Age-specific mortality rates per 100,000 people were calculated in 10-year age
bands for comparison to data on the whole population of England.
We accessed publicly available data from the ONS statistical bulletin on “Deaths involving
COVID-19, UK: deaths occurring between 1 March and 30 April 2020” to compare our crude,
age-standardised and age-specific mortality rates to the whole population of England during
the same time period(7).
This study received a favourable opinion from the Camden and Kings Cross Research
Ethics Committee, study reference 20/HRA/2076, on 18 June 2020. Data were accessed
and processed under section 251 permission granted to NCARDRS CAG 10-02(d)/2015).
For quality assurance the data extraction and analysis were re-conducted by an independent
analyst from the National Cancer Registration and Analysis Service (NCRAS).
Patient and public involvement: This project was discussed with and the aims supported by
the Rare Autoimmune Rheumatic Disease Alliance of patient charities(8). A lay summary is
available as an online supplement, and the results are being discussed with patients and
representatives of the RAIRDA charities and disseminated to patients via their networks.
. CC-BY-NC-ND 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)preprint
The copyright holder for thisthis version posted November 22, 2020. ; https://doi.org/10.1101/2020.10.09.20210237doi: medRxiv preprint
