TY - JOUR
T1 - Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK
T2 - prospective, cohort study
AU - ISARIC4C Investigators
AU - Narhi, Fiina
AU - Moonesinghe, Ramani
AU - Shenkin, Susan Deborah
AU - Drake, Thomas M
AU - Mulholland, Rachel
AU - Donegan, Cara
AU - Dunning , Jake
AU - Fairfield, Cameron
AU - Girvan, Michelle
AU - Hardwick, Hayley E
AU - Ho, Antonia
AU - Leeming, Gary
AU - Nguyen-Van-Tam, Jonathan S.
AU - Pius, Riinu
AU - Russell, Clark D
AU - Shaw, Catherine A
AU - Spencer, Rebecca G.
AU - Turtle, Lance
AU - Openshaw, Peter J M
AU - Baillie, Kenneth
AU - Harrison, Ewen M
AU - Semple, Malcolm G
AU - Docherty, Annemarie B
A2 - Macgillivray, Louise
N1 - Funding Information:
This study is 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 HPRU in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at the University of Liverpool, both in partnership with Public Health England (NIHR award 200907), the Wellcome Trust and the UK Department for International Development (215091/Z/18/Z), the Bill & Melinda Gates Foundation (OPP1209135), the Liverpool Experimental Cancer Medicine Centre (grant reference C18616/A25153), and the EU Platform for European Preparedness Against (Re-)emerging Epidemics 1 (FP7 project 602525). The NIHR Clinical Research Network provided infrastructure support for this research. This research was funded, in part, by the Wellcome Trust. RHM reports grants from BREATHE, the health data research hub for respiratory health (MC_PC_19004). BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and is delivered by Health Data Research UK. ABD acknowledges funding from the Wellcome Trust (216606/Z/19/Z0). LT is supported by a Wellcome Trust fellowship (205228/Z/16/Z). PJMO is supported by a NIHR Senior Investigator Award (award 201385). The views expressed are those of the authors and not necessarily those of the DHSC, the Department for International Development, the NIHR, the MRC, the Wellcome Trust, or Public Health England. Investigators were independent from funders. ISARIC4C CCP-UK data are provided by patients and collected by the UK National Health Service as part of their care. Although there was no direct involvement from patients or the public, quality improvement is paramount in ensuring the reliability of the health-care system that aims to maximise benefit and minimise harm to patients. This research was conducted as part of an urgent public health study in response to an emergency, meaning there was insufficient time for public involvement before data collection commenced. We are extremely grateful to the 2648 front-line NHS clinical and research staff and volunteer medical students who collected these data under 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 (Wellcome Trust, London, UK) and Nahoko Shindo (WHO, Geneva, Switzerland).
Funding Information:
ABD reports grants from the UK Department of Health and Social Care (DHSC) during the conduct of the study, and grants from the Wellcome Trust outside the submitted work. JSN-V-T reports grants from the DHSC during the conduct of the study, and is seconded to the DHSC. PJMO reports personal fees from consultancies and from the European Respiratory Society; grants from the UK Medical Research Council (MRC), the MRC Global Challenge Research Fund, the EU, the NIHR Biomedical Research Centre, MRC–GSK, the Wellcome Trust, and the NIHR (Health Protection Research Unit in Respiratory Infections at Imperial College London); and is an NIHR senior investigator outside the submitted work; his role as President of the British Society for Immunology was unpaid but travel and accommodation at some meetings was provided by the society. JKB reports grants from the MRC. MGS reports grants from DHSC, NIHR UK, MRC UK, HPRU in Emerging and Zoonotic Infections, and University of Liverpool, during the conduct of the study; and is chair of the Infectious Diseases Science Advisory Board and minority shareholder of Integrum Scientific, Greensboro NC, and Independent external and non-remunerated member of Pfizer's External Data Monitoring Committee for their mRNA vaccine program(s) outside the submitted work. All other authors declare no competing interests.
Funding Information:
This study is 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 HPRU in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at the University of Liverpool, both in partnership with Public Health England (NIHR award 200907), the Wellcome Trust and the UK Department for International Development (215091/Z/18/Z), the Bill & Melinda Gates Foundation (OPP1209135), the Liverpool Experimental Cancer Medicine Centre (grant reference C18616/A25153), and the EU Platform for European Preparedness Against (Re-)emerging Epidemics 1 (FP7 project 602525). The NIHR Clinical Research Network provided infrastructure support for this research. This research was funded, in part, by the Wellcome Trust. RHM reports grants from BREATHE, the health data research hub for respiratory health (MC_PC_19004). BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and is delivered by Health Data Research UK. ABD acknowledges funding from the Wellcome Trust (216606/Z/19/Z0). LT is supported by a Wellcome Trust fellowship (205228/Z/16/Z). PJMO is supported by a NIHR Senior Investigator Award (award 201385). The views expressed are those of the authors and not necessarily those of the DHSC, the Department for International Development, the NIHR, the MRC, the Wellcome Trust, or Public Health England. Investigators were independent from funders. ISARIC4C CCP-UK data are provided by patients and collected by the UK National Health Service as part of their care. Although there was no direct involvement from patients or the public, quality improvement is paramount in ensuring the reliability of the health-care system that aims to maximise benefit and minimise harm to patients. This research was conducted as part of an urgent public health study in response to an emergency, meaning there was insufficient time for public involvement before data collection commenced. We are extremely grateful to the 2648 front-line NHS clinical and research staff and volunteer medical students who collected these data under 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 (Wellcome Trust, London, UK) and Nahoko Shindo (WHO, Geneva, Switzerland).
Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2022/3/22
Y1 - 2022/3/22
N2 - BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care.METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260.FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70-0·89], p=0·0001, for 70-79 years; 0·52 [0·46-0·58], p<0·0001, for >80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75-80% in January, 2021.INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered.FUNDING: UK National Institute for Health Research and UK Medical Research Council.
AB - BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care.METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260.FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70-0·89], p=0·0001, for 70-79 years; 0·52 [0·46-0·58], p<0·0001, for >80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75-80% in January, 2021.INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered.FUNDING: UK National Institute for Health Research and UK Medical Research Council.
KW - Adolescent
KW - Adrenal Cortex Hormones/therapeutic use
KW - COVID-19/drug therapy
KW - Cohort Studies
KW - Female
KW - Humans
KW - Pregnancy
KW - Prospective Studies
KW - United Kingdom
KW - World Health Organization
U2 - 10.1016/S2589-7500(22)00018-8
DO - 10.1016/S2589-7500(22)00018-8
M3 - Article
C2 - 35337642
SN - 2589-7500
VL - 4
SP - e220-e234
JO - The Lancet Digital Health
JF - The Lancet Digital Health
IS - 4
ER -
