Rutter, Megan
(2023)
Health outcomes in people with rare autoimmune rheumatic diseases before and during the COVID-19 pandemic and the effect of corticosteroids: whole population data from England.
PhD thesis, University of Nottingham.
Abstract
Introduction:
Rare autoimmune rheumatic diseases (RAIRD) are a heterogenous group of immune-mediated inflammatory diseases. They are chronic and often require immunosuppression.
At the onset of the COVID-19 pandemic, it was unclear whether people with RAIRD were at increased risk of severe COVID-19 outcomes, whether some conditions were associated with greater risk than others and whether immunosuppressive treatments, such as corticosteroids, conferred an increased risk of severe disease.
RAIRD have long been associated with increased morbidity and mortality, with poor outcomes attributable both to the effects of treatment and the underlying disease. Severe infections, including with atypical pathogens, are of concern. Previous studies have found that mortality is approximately 1.2-10-fold higher among people with RAIRD compared with the general population, however there is variability within and between diseases, reflecting lack of statistical power, selection bias and variations in ascertainment of the underlying diseases. There have been few population-based studies and contemporary data regarding cause of death in RAIRD remain scarce.
Methods:
I used linked national datasets of routinely collected healthcare data (demographic, death certificate, hospital, PCR testing and prescription data) to describe health outcomes in people with RAIRD.
The specific objectives of the studies were to:
1) Calculate the age-standardised rates of laboratory confirmed COVID-19 infection and death among people with RAIRD in England during the first and second waves of the COVID-19 pandemic (1st March 2020 – 31st July 2020 and 1st August 2020 – 30th April 2021) and compare these rates to those in the general population. Describe hospital and intensive care admissions related to COVID-19 infection, and all-cause mortality during each wave.
2) Assess the relationship between corticosteroid treatment and COVID-19-related death among people with RAIRD during the second wave of the COVID-19 pandemic.
3) Describe all-cause mortality in people with RAIRD during the years 2013-2020, including the calculation of all-cause and cause-specific age-sex-standardised mortality rates and comparison with the general population in England.
Results:
1) Of the 168,680 people with RAIRD alive at the start of the first COVID-19 wave, 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardised infection rate was 1.54 (95% CI 1.50-1.59) times higher than in the general population. 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardised mortality rate for COVID-19-related death was 2.41 (2.30 – 2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population.
2) Of the 168,330 people with RAIRD alive at the start of the second COVID-19 wave, 9,961 (5.92%) had a positive COVID-19 PCR test. The age-standardised infection rate ratio between RAIRD and the general population was 0.99 (95% CI 0.97-1.00). 1,342 (0.80%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardised mortality rate for COVID-19-related death was 2.76 (2.63–2.89) times higher than in the general population. There was a dose-dependent relationship between 30-day corticosteroid usage and COVID-19-related death. There was no increase in deaths due to other causes.
3) There were 108,593 people with RAIRD in 2013 and 180,083 in 2020. The majority were female (annual minimum 69.9%, maximum 70.9%). Median age increased from 61.5 to 62.5 years, compared to 39.7 to 40.2 years in the general population. Crude and age-sex-standardised all-cause mortality gradually reduced between 2013-2019, increasing again in 2020 (during COVID-19). Age-sex-standardised mortality in 2013 was 2,324.5 per 100,000 person/years (95% CI 2,261.5-2,387.6) and in 2020 2,332.8 (2,283.3-2,382.2; rate ratio 2.4 (2.3-2.4) compared to general population). Risk of death due to infection (rate ratio 4.11 (3.82-4.40)), cardiovascular disease (2.51 (2.47–2.56)), COVID-19 (2.77 (2.62–2.92)), and respiratory disease (2.92 (2.84–2.99)) were particularly raised. Intra-disease comparison showed higher all-cause mortality in scleroderma, myositis, microscopic polyangiitis and unspecified arteritis. Only 28/53,166 deaths were secondary to cytomegalovirus, 35 Pneumocystis jirovecii pneumonia and 8 progressive multifocal leukoencephalopathy.
Conclusions:
1) During the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared to the general population. These increases were seen despite shielding policies.
2) During the second wave of COVID-19 in England, people with RAIRD had the same risk of COVID-19 infection but a 2.76-fold increased risk of COVID-19-related death compared to the general population, with corticosteroids associated with increased risk.
3) Adjusting for age and sex, mortality in people with RAIRD was increased across all causes except dementia. Risk of death due to infection, COVID-19 and respiratory disease was particularly raised. Deaths due to infections associated with immunosuppression were rare.
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