Risk of death among people with rare autoimmune diseases compared with the general population in England during the 2020 COVID-19 pandemic

  1. Emily Peach
  2. Megan Rutter
  3. Peter Lanyon
  4. Matthew J Grainge
  5. Richard Hubbard
  6. Jeanette Aston
  7. Mary Bythell
  8. Sarah Stevens
  9. Fiona Pearce

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Abstract

Objectives

To quantify the risk of death among people with rare autoimmune rheumatic diseases (RAIRD) during the UK 2020 COVID-19 pandemic compared with the general population, and compared with their pre-COVID risk.

Methods

We conducted a cohort study in Hospital Episode Statistics for England from 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 1 March 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%. A total of 1815 (1.1%) participants died during March and April 2020. The age-standardized 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 with 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 with 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 health-care services.

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    SciScore for 10.1101/2020.10.09.20210237: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study received a favourable opinion from the Camden and Kings Cross Research Ethics Committee, study reference 20/HRA/2076, on 18 June 2020.
    RandomizationFor 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.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableWe 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.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Other weaknesses are that by identifying cases using in-patient data we may miss patients only treated as outpatients, which are not routinely coded in HES. We have included primary and co-morbid diagnoses to maximise sensitivity, and prevalence estimates based on our findings for AAV, systemic lupus erythematosus and scleroderma, are similar to reported population estimates(12–14). Recently the European League Against Rheumatism (EULAR) reported “no evidence that people with rheumatic musculoskeletal disorders face more risk of contracting SARS-CoV-2 than individuals without rheumatic musculoskeletal disorders, nor that they have a worse prognosis when they contract it.” (15) No evidence was presented on the risk to people with RAIRD compared to the general population. Our study provides the first evidence of this risk, and suggests that people with rare autoimmune rheumatic diseases are at higher risk of death during COVID-19 than the general population. The recent OPENSAFELY study, reported on the risk of in-hospital death due to COVID-19 among >17 million community based adults(16). The analysis included “common autoimmune diseases” reporting the combined risk for people with rheumatoid arthritis, lupus or psoriasis. However, because it does not have whole population coverage, even the large OPENSAFELY study does not have a sufficiently large cohort to study rare diseases. The adjusted hazard ratio for common autoimmune diseases was 1.23 (95% CI 1.12-1.35) compared to our...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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  2. Version published to 10.1093/rheumatology/keaa855
  3. Version published to 10.1101/2020.10.09.20210237v3 on medRxiv
  4. Version published to 10.1101/2020.10.09.20210237v2 on medRxiv
  5. Version published to 10.1101/2020.10.09.20210237v1 on medRxiv