TY - JOUR
T1 - Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study.
AU - Investigators, ISARIC4C
AU - Dark, Paul
N1 - Funding Information:
This work was funded by the National Institute for Health Research (NIHR) and the UK Medical Research Council (MRC). This study uses data provided by patients and collected by the Uk National Health Service (NHS) as part of their care and support #DataSavesLives. We are grateful to the 2648 frontline NHS clinical and research staff and volunteer medical students and the NIHR Clinical Research Network, who collected these data in challenging circumstances, and the generosity of the participants and their families for their individual contributions in these difficult times. We also acknowledge the support of Jeremy J Farrar and Nahoko Shindo. This study was supported by grants from the NIHR (award CO-CIN-01), the MRC (grant MC_PC_19059), the NIHR Imperial Biomedical Research Centre (grants P45058 and IS-BRC-1215-20013), the NIHR Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England (PHE; NIHR award 200907), the Wellcome Trust and UK Department for International Development (215091/Z/18/Z), the Bill & Melinda Gates Foundation (OPP1209135), and Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), EU Platform for European Preparedness Against (Re-)emerging Epidemics (FP7 project 602525), and NIHR Clinical Research Network. PJMO is supported by a NIHR Senior Investigator Award (201385). The views expressed are those of the authors and not necessarily those of the UK Department of Health and Social Care, UK Department for International Development, NIHR, MRC, Wellcome Trust, or PHE.
Funding Information:
This work was funded by the National Institute for Health Research (NIHR) and the UK Medical Research Council (MRC). This study uses data provided by patients and collected by the Uk National Health Service (NHS) as part of their care and support #DataSavesLives. We are grateful to the 2648 frontline NHS clinical and research staff and volunteer medical students and the NIHR Clinical Research Network, who collected these data in challenging circumstances, and the generosity of the participants and their families for their individual contributions in these difficult times. We also acknowledge the support of Jeremy J Farrar and Nahoko Shindo. This study was supported by grants from the NIHR (award CO-CIN-01), the MRC (grant MC_PC_19059), the NIHR Imperial Biomedical Research Centre (grants P45058 and IS-BRC-1215-20013), the NIHR Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England (PHE; NIHR award 200907), the Wellcome Trust and UK Department for International Development (215091/Z/18/Z), the Bill & Melinda Gates Foundation (OPP1209135), and Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), EU Platform for European Preparedness Against (Re-)emerging Epidemics (FP7 project 602525), and NIHR Clinical Research Network. PJMO is supported by a NIHR Senior Investigator Award (201385). The views expressed are those of the authors and not necessarily those of the UK Department of Health and Social Care, UK Department for International Development, NIHR, MRC, Wellcome Trust, or PHE.
Funding Information:
All authors declare support from the National Institute for Health Research (NIHR), the Medical Research Council (MRC), the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London, NIHR Biomedical Research Centre (BRC) at Imperial College London, and NIHR Clinical Research Network for the submitted work. ABD reports grants from the UK Department of Health and Social Care (DHSC), during the conduct of the study, and grants from Wellcome Trust, outside the submitted work. PJMO reports personal fees from consultancies and from the European Respiratory Society, grants from MRC, MRC Global Challenge Research Fund, EU, NIHR BRC, MRC, GSK, Wellcome Trust, NIHR (Health Protection Research Unit [HPRU] in Respiratory Infection), and is NIHR senior investigator outside the submitted work. PJMO's role as President of the British Society for Immunology was unpaid but travel and accommodation at some meetings was provided. JKB reports grants from MRC. MGS reports grants from DHSC NIHR, MRC, and HPRU in Emerging and Zoonotic Infections, University of Liverpool, during the conduct of the study, and honoraria from Integrum Scientific, outside the submitted work. All other authors declare no support from any organisation for the submitted work, no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work.
Publisher Copyright:
© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2021/5/7
Y1 - 2021/5/7
N2 - Background: Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evidence from community studies, administrative data, and small studies of hospitalised patients suggest NSAIDs are not associated with poorer COVID-19 outcomes. We aimed to characterise the safety of NSAIDs and identify whether pre-existing NSAID use was associated with increased severity of COVID-19 disease. Methods: This prospective, multicentre cohort study included patients of any age admitted to hospital with a confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 between Jan 17 and Aug 10, 2020. The primary outcome was in-hospital mortality, and secondary outcomes were disease severity at presentation, admission to critical care, receipt of invasive ventilation, receipt of non-invasive ventilation, use of supplementary oxygen, and acute kidney injury. NSAID use was required to be within the 2 weeks before hospital admission. We used logistic regression to estimate the effects of NSAIDs and adjust for confounding variables. We used propensity score matching to further estimate effects of NSAIDS while accounting for covariate differences in populations. Results: Between Jan 17 and Aug 10, 2020, we enrolled 78 674 patients across 255 health-care facilities in England, Scotland, and Wales. 72 179 patients had death outcomes available for matching; 40 406 (56·2%) of 71 915 were men, 31 509 (43·8%) were women. In this cohort, 4211 (5·8%) patients were recorded as taking systemic NSAIDs before admission to hospital. Following propensity score matching, balanced groups of NSAIDs users and NSAIDs non-users were obtained (4205 patients in each group). At hospital admission, we observed no significant differences in severity between exposure groups. After adjusting for explanatory variables, NSAID use was not associated with worse in-hospital mortality (matched OR 0·95, 95% CI 0·84–1·07; p=0·35), critical care admission (1·01, 0·87–1·17; p=0·89), requirement for invasive ventilation (0·96, 0·80–1·17; p=0·69), requirement for non-invasive ventilation (1·12, 0·96–1·32; p=0·14), requirement for oxygen (1·00, 0·89–1·12; p=0·97), or occurrence of acute kidney injury (1·08, 0·92–1·26; p=0·33). Interpretation: NSAID use is not associated with higher mortality or increased severity of COVID-19. Policy makers should consider reviewing issued advice around NSAID prescribing and COVID-19 severity. Funding: National Institute for Health Research and Medical Research Council.
AB - Background: Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evidence from community studies, administrative data, and small studies of hospitalised patients suggest NSAIDs are not associated with poorer COVID-19 outcomes. We aimed to characterise the safety of NSAIDs and identify whether pre-existing NSAID use was associated with increased severity of COVID-19 disease. Methods: This prospective, multicentre cohort study included patients of any age admitted to hospital with a confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 between Jan 17 and Aug 10, 2020. The primary outcome was in-hospital mortality, and secondary outcomes were disease severity at presentation, admission to critical care, receipt of invasive ventilation, receipt of non-invasive ventilation, use of supplementary oxygen, and acute kidney injury. NSAID use was required to be within the 2 weeks before hospital admission. We used logistic regression to estimate the effects of NSAIDs and adjust for confounding variables. We used propensity score matching to further estimate effects of NSAIDS while accounting for covariate differences in populations. Results: Between Jan 17 and Aug 10, 2020, we enrolled 78 674 patients across 255 health-care facilities in England, Scotland, and Wales. 72 179 patients had death outcomes available for matching; 40 406 (56·2%) of 71 915 were men, 31 509 (43·8%) were women. In this cohort, 4211 (5·8%) patients were recorded as taking systemic NSAIDs before admission to hospital. Following propensity score matching, balanced groups of NSAIDs users and NSAIDs non-users were obtained (4205 patients in each group). At hospital admission, we observed no significant differences in severity between exposure groups. After adjusting for explanatory variables, NSAID use was not associated with worse in-hospital mortality (matched OR 0·95, 95% CI 0·84–1·07; p=0·35), critical care admission (1·01, 0·87–1·17; p=0·89), requirement for invasive ventilation (0·96, 0·80–1·17; p=0·69), requirement for non-invasive ventilation (1·12, 0·96–1·32; p=0·14), requirement for oxygen (1·00, 0·89–1·12; p=0·97), or occurrence of acute kidney injury (1·08, 0·92–1·26; p=0·33). Interpretation: NSAID use is not associated with higher mortality or increased severity of COVID-19. Policy makers should consider reviewing issued advice around NSAID prescribing and COVID-19 severity. Funding: National Institute for Health Research and Medical Research Council.
UR - http://europepmc.org/abstract/med/33997800
U2 - 10.1016/S2665-9913(21)00104-1
DO - 10.1016/S2665-9913(21)00104-1
M3 - Article
C2 - 33997800
VL - 3
SP - e498-e506
JO - The Lancet. Rheumatology
JF - The Lancet. Rheumatology
IS - 7
ER -
