Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study.

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.
Competing Interests: 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.
(© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)