One year health outcomes associated with systemic corticosteroids for COVID-19: a longitudinal cohort study

Background In patients with COVID-19 requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) one year after discharge. Methods Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies. HRQoL, assessed by EQ-5D-5L utility index, pre-hospital and one year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias. Findings In 1,888 participants included in the primary analysis, 1,149 received corticosteroids. There was no between-group difference in EQ-5D-5L utility index at one year (mean difference 0.004, 95% CI: -0.026 to 0.034, p = 0.77). A similar reduction in EQ-5D-5L was seen at one year between corticosteroid exposed and non-exposed groups (mean (SD) change -0.12 (0.22) vs -0.11 (0.22), p = 0.32). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a larger cohort of 109,318 patients admitted to hospital with COVID-19, EQ-5D-5L utility index at one year remained similar between the two groups. Interpretation Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL one year after hospital discharge. Treatments to address this are urgently needed. ### Competing Interest Statement AART declares that their institute was awarded a fellowship from British Heart Foundation and grant funding from Heart Research UK and National Institute for Health and Care Research; payment for lectures and presentations received from Janssen-Cilag Ltd; support for attending meetings from Janssen-Cilag Ltd. AH​ declares that their institute was awarded funding from UK Research and Innovation (MR/V027859/1), National Institute of Health Research (COV0319) and NIHR Manchester BRC; leadership or fiduciary role as Chair for NIHR Translational Research Collaboration. AS declares that their institute was awarded joint funding from UKRI & NIHR (MR/V027859/1 and COV0319) to complete this work. AB declares consulting fees from Roche, Merck, Sanofi and GSK. ABD​ declares that they were awarded funding from Wellcome Clinical Research Career Development Fellowship (216606/Z/19/Z) to complete this work. ADS​ declares that their institute was awarded grant funding from AstraZeneca, Bayer, GSK, Chiesi, Novartis, Pfizer outside the submitted manuscript; consulting fees from AstraZeneca, Bayer, GSK, Chiesi, Novartis, Pfizer, Insmed, Gilead; payment for lectures and presentations received by AstraZeneca, Bayer, GSK, Chiesi, Novartis, Pfizer, Insmed, Gilead, 30T; participation on a Data Safety Monitoring Board or Advisory Board for Bayer; receipt of drugs from GSK outside the submitted manuscript. AShe declares that their institute was awarded grant funding from NIHR and UKRI to complete this work; participation on a Data Safety Monitoring Board or Advisory Board for Astra-Zenecas Thrombotic Thrombocytopenic Taskforce; leadership or fiduciary role for UK and Scottish Government COVID-19 advisory groups. CE declares a grant from GSK. CEB declares that their institute received grant funding from NIHR/UKRI and NIHR to complete this work; their institute received grant funding from Nottingham Hospitals Charity and University of Nottingham. CEBr declares that their institute received grant funding from MRC/NIHR and NIHR to complete this work; their institute received grant funding from GSK, AZ, Sanofi, Regeneron, Roche, Genentech, BI, Novartis, Chiesi, 4Dpharma, Mologic; consulting fees from GSK, AZ, Sanofi, Regeneron, Roche, Genentech, BI, Novartis, Chiesi, 4Dpharma, Mologic, Areteia. DP declares funding from NIHR and MRC; leadership or fiduciary role for Faculty of Intensive Care Medicine Board. GPM declares funding from NIHR (RP-2017-ST2-007) to complete this work; funding from British Heart Foundation, Wellcome Trust and NIHR; research support from Resonance Health, Circle CVi and Perspectum. RGJ declares that their institute received funding from Astra Zeneca, Biogen, Galecto, GlaxoSmithKline, Nordic Biosciences, RedX and Pliant; consulting fees from AstraZeneca, Brainomix, Bristol Myers Squibb, Chiesi, Cohbar, Daewoong, GlaxoSmithKline, Veracyte, Resolution Therapeutics and Pliant; payment for lectures and presentations received from Boehringer Ingelheim, Chiesi, Roche, PatientMPower, AstraZeneca; payment for expert testimony from Pinsent Masons LLP; participation on a Data Safety Monitoring Board or Advisory Board for Boehringer Ingelheim, Galapagos, Vicore; leadership or fiduciary role for NuMedii and president for Action for Pulmonary Fibrosis. GC declares funding from GlaxoSmithKline and AstraZeneca; received honoraria for delivering talks from GSK, AZ, Chiesi, BI; participation on a Data Safety Monitoring Board or Advisory Board as Chair on the Act on COPD Programme for AZ in Scotland; leadership or fiduciary role as Chair for the Lothian Respiratory Managed Clinical Network. JDC declares funding from AstraZeneca, Boehringer Ingelheim, Grifols, Gilead sciences, Insmed, Genentech, Glaxosmithkline; consulting fees from AstraZeneca, Boehringer Ingelheim, Grifols, Gilead sciences, Insmed, Genentech, Glaxosmithkline, Antabio, Zambon, Trudell; leadership or fiduciary roles as Chief Editor of European Respiratory Journal, Chair of British Thoracic Society Science and Research Committee and Trustee of the British Thoracic Society. JTS declares funding from UKRI. JKQ declares that their institute received funding from Industrial Strategy Challenge Fund, the Medical Research Council, Health Data Research, GSK, BI, asthma+lung UK, AZ; consulting fees from GlaxoSmithKline, Evidera, Chiesi, AstraZeneca, Insmed. JP declares funding from Breathing Matters and UCL/H BRC (NIHR); consulting fees from The Limbic. JJ declares funding from Gilead, Microsoft Research, GlaxoSmithKline; consulting fees from Boehringer Ingelheim, Roche, GlaxoSmithKline, NHSX; payment for lectures and presentations received from Boehringer Ingelheim, Roche, GlaxoSmithKline, Takeda; support for attending meetings and/or travel from Boehringer Ingelheim; patents planned, issued or pending (UK patent application number 2113765.8 and UK patent application number GB2211487.0); participation on a Data Safety Monitoring Board or Advisory Board for Boehringer Ingelheim and Roche. JRH declares funding from AstraZeneca; consulting fees from AstraZeneca and GSK; payment for lectures and presentations received from AstraZeneca, Boehringer Ingelheim, Chiesi, Sanofi, Takeda; support for attending meetings and/or travel from AstraZeneca; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca; Receipt of equipment from Nonin. LGH declares that their institute received funding from GSK, Astra Zeneca, Roche/Genentech; payment for lectures received from Astra Zeneca, Novartis, Roche / Genentech, Sanofi, Circassia, GlaxoSmithKline, Chiesi, Teva; support to travel to meetings from AstraZeneca and GSK; participation on a Data Safety Monitoring Board or Advisory Board for Novartis, Roche/Genentech, GSK, Teva and Celltrion. LH-W declares funding from NIHR (RfPB grant PB-PG-0317-20032). LVW declares funding from UK Research and Innovation (MR/V027859/1), GSK/Asthma + Lung UK (Professorship (C17-1)) and National Institute of Health Research (COV0319) to complete this work; funding from Orion Pharma, GSK, Genentech, AstraZeneca, Nordic Bioscience, Sysmex (OGT); Consulting fees Galapagos, Boehringer Ingelheim, GSK; support for attending meetings and/or travel Genentech; participation on Advisory Board for Galapagos; leadership or fiduciary roles as Associate Editor for European Respiratory Journal and Medical Research Council Board member and Deputy Chair. MGS declares grant funding from National Institute of Health Research UK, Medical Research Council UK and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool to complete this work; participation on a Data Safety Monitoring Board or Advisory Board for Pfizer; leadership or fiduciary roles as Chair of Infectious Disease Scientific Advisory Board Integrum Scientific LLC and Director of MedEx Solutions Ltd; Stock or stock options as minority owner of Integrum Scientific LLC and majority owner of MedEx Solutions Ltd; receipt of equipment, materials, drugs, medical writing, gifts or other services from Chiesi Farmaceutici S.p.A.; non-remunerated independent member of HMG UK Scientific Advisory Group for Emergencies (SAGE), COVID-19 Response (March 2020 to March 2022) and non-remunerated independent member of HMG UK New Emerging Respiratory Virus Threats Advisory Group (NERVTAG) (2014 to July 2023). MJ declares funding from MRC to complete this work; funding from MRC, British Lung Foundation and Boehringher Ingelheim; consulting fees from Skyhawk therapeutics; leadership or fiduciary role in AAIR Charity Scientific Committee. MT declares grant funding from NIHR Cambridge BRC and NIHR HTA to complete this work; consulting fees from Jansen; support for attending meetings and/or travel from GSK, Jansen; participation on a Data Safety Monitoring Board or Advisory Board for ComCov and FluCov. MJR declares support for attending meetings and/or travel from Novartis Pharmaceuticals; stock or stock options from Novartis Pharmaceuticals and Roche Pharmaceuticals; employed full time as a Senior Clinical Development Medical Director at Novartis Pharmaceuticals. MJD declares grant funding from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, AstraZeneca and Janssen; consulting fees from Eli Lilly, Boehringer Ingelheim, Novo Nordisk and Sanofi; payment for speaking for Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, AstraZeneca, Amgen, Napp Pharmaceuticals and Novartis; advisory Board Member for Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, Lexicon, Pfizer, Medtronic and ShouTi Pharma Inc., Zealand Pharma. MM declares that their institute received joint funding from UKRI & NIHR to complete this work. NDB declares they have received non-restrictive educational grants from Chiesi, AZ, and Teva for attending conferences; honoraria from TEVA, AZ, and GSK; support for attending meetings and/or travel from Chiesi and AZ; participation on a Data Safety Monitoring Board or Advisory Board for TEVA. NE declares receipt of equipment from Global Access Diagnostics (previously Mologic Inc). OCL declares that their institute received joint funding from UKRI & NIHR- grant (MR/V027859/1 and COV0319) to complete this work. PEP declares funding from NIHR. PJMO declares funding from UKRI-MRC/DHSC NIHR and UKRI-BEIS. RAE declares funding from UKRI/MRC/NIHR to complete this work; funding from Wolfson Foundation and Genentech/Roche; consulting fees from AstraZeneca/Evidera; payment for speaking fees from Boeringher and Moderna; support for attending meetings from Chiesi; leadership or fiduciary role as ERS Group 01.02 Pulmonary Rehabilitation and Chronic Care Secretary and ATS Pulmonary Rehabilitation Assembly Chair. RA declares lecture fees from Boehringer Ingelheim; support for attending meeting from Boehringer Ingelheim. SJS declares grants or contracts from NIHR (programme Grant (NIHR 202020)_, Wellcome Doctoral Training Programme, HTA Project Grant (NIHR: 131015), NIHR DHSC/UKRI COVID-19 Rapid Response Initiative, NIHR Global Research Group (NIHR 17/63/20), Actegy Limited and NIHR Senior Investigator; payment for presentations for GSK, Ministry of Justice, CIPLA, Sherbourne Gibbs; participation on NICE Expert Adviser Panel (long COVID), Wales Long COVID Advisory Board and NHS-E Long Covid Your Covid Recovery working group; leadership or fiduciary role as ATS Pulmonary Rehabilitation Assembly Chair, Clinical Lead RCP Pulmonary Rehabilitation Accreditation Scheme and Clinical Lead NACAP Audit for Pulmonary Rehabilitation. SR-J declares that their institute received funding from UKRI to complete this work; their institute received funding from NIHR Sheffield Biomedical Research centre, Bill & Melinda Gates Foundation, UKRI (MRC) and EDCTP. SH declares consulting fees from NovoNordisk; participation on a Data Safety Monitoring Board or Advisory Board for Eli Lilly with payments made Institution. SN declares grant funding from Oxford NIHR Biomedical Research centre. WD-CM declares that their institute received funding from National Institute for Health Research and NHS Accelerated Access Collaborative; leadership or fiduciary role as Honorary President of the Association for Respiratory Technology and Physiology. ### Clinical Protocols ### Funding Statement PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: PHOSP-COVID was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry ([ISRCTN10980107][1]). ISARIC was approved by the South Central - Oxford C Research Ethics Committee in England and the Scotland A Research Ethics Committee. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The PHOSP-COVID study website (https://www.phosp.org) contains an overview of the study, resources, information about people involved, and publications. Research activity using the study is organised across a series of Working Groups. These were established at the outset of the study to coordinate research, minimise duplication of efforts, and facilitate communication across research and clinical specialties. Researchers interested in undertaking research using PHOSP-COVID are encouraged to contact the relevant Working Group leads (https://www.phosp.org/working-group/) in the first instance. The data are currently held in the Outbreak Data Analysis Platform (ODAP, https://odap.ac.uk/). Researchers seeking to access these data are directed to https://www.phosp.org/resource/ for information and forms. Correspondence to be directed to Dr Rachael A Evans, the Co-Principal Investigator of PHOSP-COVID study phosp@leicester.ac.uk. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN10980107