Phyo K Myint1, Ben Carter2, Fenella Barlow-Pay3, Roxanna Short2, Alice G Einarsson4, Eilidh Bruce1, Kathryn McCarthy5, Alessia Verduri6, Jemima Collins7, James Hesford5, Frances Rickard5, Emma Mitchell5, Mark Holloway5, Aine McGovern8, Arturo Vilches-Moraga9, Philip Braude5, Lyndsay Pearce9, Michael Stechman10, Angeline Price11, Terence J Quinn12, Enrico Clini6, Susan Moug13, Jonathan Hewitt14. 1. Institute of Applied Health Science, University of Aberdeen, Aberdeen, Scotland. 2. Department of Biostatistics & Health Informatics, King's College London, England. 3. Royal Alexandra Hospital, Paisley, Scotland. 4. Department of Medicine for the Elderly, NHS Grampian, Aberdeen, Scotland. 5. North Bristol NHS Trust, Bristol, England. 6. University of Modena and Reggio Emilia - Hospital Policlinico, Modena, Emilia-Romagna, Italy. 7. Ysbyty Ystrad Fawr, Aneurin Bevan University Health Board, Wales, Newport, UK. 8. Glasgow Royal Infirmary, Glasgow, Scotland. 9. Salford Royal NHS Trust and, Salford, UK. 10. University Hospital of Wales, Cardiff, Wales, UK. 11. Manchester University, Manchester, England. 12. Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland. 13. University of Glasgow, Glasgow, Scotland. 14. Department of Geriatric Medicine, 3rd Floor Academic Centre, Llandough Hospital, Penlan Road, Penarth, CF64 2XX.
Abstract
BACKGROUND: Whilst there is literature on the impact of SARS viruses in the severely immunosuppressed, less is known about the link between routine immunosuppressant use and outcome in COVID-19. Consequently, guidelines on their use vary depending on specific patient populations. METHODS: The study population was drawn from the COPE Study (COVID-19 in Older People), a multicentre observational cohort study, across the UK and Italy. Data were collected between 27 February and 28 April 2020 by trained data-collectors and included all unselected consecutive admissions with COVID-19. Load (name/number of medications) and dosage of immunosuppressant were collected along with other covariate data. Primary outcome was time-to-mortality from the date of admission (or) date of diagnosis, if diagnosis was five or more days after admission. Secondary outcomes were Day-14 mortality and time-to-discharge. Data were analysed with mixed-effects, Cox proportional hazards and logistic regression models using non-users of immunosuppressants as the reference group. RESULTS: In total 1184 patients were eligible for inclusion. The median (IQR) age was 74 (62-83), 676 (57%) were male, and 299 (25.3%) died in hospital (total person follow-up 15,540 days). Most patients exhibited at least one comorbidity, and 113 (~10%) were on immunosuppressants. Any immunosuppressant use was associated with increased mortality: aHR 1.87, 95% CI: 1.30, 2.69 (time to mortality) and aOR 1.71, 95% CI: 1.01-2.88 (14-day mortality). There also appeared to be a dose-response relationship. CONCLUSION: Despite possible indication bias, until further evidence emerges we recommend adhering to public health measures, a low threshold to seek medical advice and close monitoring of symptoms in those who take immunosuppressants routinely regardless of their indication. However, it should be noted that the inability to control for the underlying condition requiring immunosuppressants is a major limitation, and hence caution should be exercised in interpretation of the results. PLAIN LANGUAGE SUMMARY: Regular Use of Immune Suppressing Drugs is Associated with Increased Risk of Death in Hospitalised Patients with COVID-19 Background: We do not have much information on how the COVID-19 virus affects patients who use immunosuppressants, drugs which inhibit or reduce the activity of the immune system. There are various conflicting views on whether immune-suppressing drugs are beneficial or detrimental in patients with the disease. Methods: This study collected data from 10 hospitals in the UK and one in Italy between February and April 2020 in order to identify any association between the regular use of immunosuppressant medicines and survival in patients who were admitted to hospital with COVID-19. Results: 1184 patients were included in the study, and 10% of them were using immunosuppressants. Any immunosuppressant use was associated with increased risk of death, and the risk appeared to increase if the dose of the medicine was higher. Conclusion: We therefore recommend that patients who take immunosuppressant medicines routinely should carefully adhere to social distancing measures, and seek medical attention early during the COVID-19 pandemic.
BACKGROUND: Whilst there is literature on the impact of SARS viruses in the severely immunosuppressed, less is known about the link between routine immunosuppressant use and outcome in COVID-19. Consequently, guidelines on their use vary depending on specific patient populations. METHODS: The study population was drawn from the COPE Study (COVID-19 in Older People), a multicentre observational cohort study, across the UK and Italy. Data were collected between 27 February and 28 April 2020 by trained data-collectors and included all unselected consecutive admissions with COVID-19. Load (name/number of medications) and dosage of immunosuppressant were collected along with other covariate data. Primary outcome was time-to-mortality from the date of admission (or) date of diagnosis, if diagnosis was five or more days after admission. Secondary outcomes were Day-14 mortality and time-to-discharge. Data were analysed with mixed-effects, Cox proportional hazards and logistic regression models using non-users of immunosuppressants as the reference group. RESULTS: In total 1184 patients were eligible for inclusion. The median (IQR) age was 74 (62-83), 676 (57%) were male, and 299 (25.3%) died in hospital (total person follow-up 15,540 days). Most patients exhibited at least one comorbidity, and 113 (~10%) were on immunosuppressants. Any immunosuppressant use was associated with increased mortality: aHR 1.87, 95% CI: 1.30, 2.69 (time to mortality) and aOR 1.71, 95% CI: 1.01-2.88 (14-day mortality). There also appeared to be a dose-response relationship. CONCLUSION: Despite possible indication bias, until further evidence emerges we recommend adhering to public health measures, a low threshold to seek medical advice and close monitoring of symptoms in those who take immunosuppressants routinely regardless of their indication. However, it should be noted that the inability to control for the underlying condition requiring immunosuppressants is a major limitation, and hence caution should be exercised in interpretation of the results. PLAIN LANGUAGE SUMMARY: Regular Use of Immune Suppressing Drugs is Associated with Increased Risk of Death in Hospitalised Patients with COVID-19 Background: We do not have much information on how the COVID-19 virus affects patients who use immunosuppressants, drugs which inhibit or reduce the activity of the immune system. There are various conflicting views on whether immune-suppressing drugs are beneficial or detrimental in patients with the disease. Methods: This study collected data from 10 hospitals in the UK and one in Italy between February and April 2020 in order to identify any association between the regular use of immunosuppressant medicines and survival in patients who were admitted to hospital with COVID-19. Results: 1184 patients were included in the study, and 10% of them were using immunosuppressants. Any immunosuppressant use was associated with increased risk of death, and the risk appeared to increase if the dose of the medicine was higher. Conclusion: We therefore recommend that patients who take immunosuppressant medicines routinely should carefully adhere to social distancing measures, and seek medical attention early during the COVID-19 pandemic.
Authors: Jonathan Hewitt; Ben Carter; Arturo Vilches-Moraga; Terence J Quinn; Philip Braude; Alessia Verduri; Lyndsay Pearce; Michael Stechman; Roxanna Short; Angeline Price; Jemima T Collins; Eilidh Bruce; Alice Einarsson; Frances Rickard; Emma Mitchell; Mark Holloway; James Hesford; Fenella Barlow-Pay; Enrico Clini; Phyo K Myint; Susan J Moug; Kathryn McCarthy Journal: Lancet Public Health Date: 2020-06-30
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