Fewer COVID-19 neurological complications with dexamethasone and remdesivir
Fewer COVID-19 neurological complications with dexamethasone and remdesivir
Objective: the objective of this study was to assess the impact of treatment with dexamethasone, remdesivir or both on neurological complications in acute coronavirus diease 2019 (COVID-19).
Methods: we used observational data from the International Severe Acute and emerging Respiratory Infection Consortium World Health Organization (WHO) Clinical Characterization Protocol, United Kingdom. Hospital inpatients aged ≥18 years with laboratory-confirmed severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection admitted between January 31, 2020, and June 29, 2021, were included. Treatment allocation was non-blinded and performed by reporting clinicians. A propensity scoring methodology was used to minimize confounding. Treatment with remdesivir, dexamethasone, or both was assessed against the standard of care. The primary outcome was a neurological complication occurring at the point of death, discharge, or resolution of the COVID-19 clinical episode.
Results: out of 89,297 hospital inpatients, 64,088 had severe COVID-19 and 25,209 had non-hypoxic COVID-19. Neurological complications developed in 4.8% and 4.5%, respectively. In both groups, neurological complications were associated with increased mortality, intensive care unit (ICU) admission, worse self-care on discharge, and time to recovery. In patients with severe COVID-19, treatment with dexamethasone (n = 21,129), remdesivir (n = 1,428), and both combined (n = 10,846) were associated with a lower frequency of neurological complications: OR = 0.76 (95% confidence interval [CI] = 0.69-0.83), OR = 0.69 (95% CI = 0.51-0.90), and OR = 0.54 (95% CI = 0.47-0.61), respectively. In patients with non-hypoxic COVID-19, dexamethasone (n = 2,580) was associated with less neurological complications (OR = 0.78, 95% CI = 0.62-0.97), whereas the dexamethasone/remdesivir combination (n = 460) showed a similar trend (OR = 0.63, 95% CI = 0.31-1.15).
Interpretation: treatment with dexamethasone, remdesivir, or both in patients hospitalized with COVID-19 was associated with a lower frequency of neurological complications in an additive manner, such that the greatest benefit was observed in patients who received both drugs together.
Grundmann, Alexander
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Wu, Chieh-Hsi
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Hardwick, Marc
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Baillie, John Kenneth
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Openshaw, Peter J.M.
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Semple, Malcolm G.
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Böhning, Dankmar
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Pett, Sarah
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Michael, Benedict D
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Thomas, Rhys H
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Galea, Ian
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19 October 2022
Grundmann, Alexander
d8b102e1-88ad-4246-b10a-b2fd489bb49d
Wu, Chieh-Hsi
ace630c6-2095-4ade-b657-241692f6b4d3
Hardwick, Marc
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Baillie, John Kenneth
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Openshaw, Peter J.M.
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Semple, Malcolm G.
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Böhning, Dankmar
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Pett, Sarah
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Michael, Benedict D
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Thomas, Rhys H
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Galea, Ian
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Grundmann, Alexander, Wu, Chieh-Hsi, Hardwick, Marc, Baillie, John Kenneth, Openshaw, Peter J.M., Semple, Malcolm G., Böhning, Dankmar, Pett, Sarah, Michael, Benedict D, Thomas, Rhys H and Galea, Ian
(2022)
Fewer COVID-19 neurological complications with dexamethasone and remdesivir.
Annals of Neurology.
(doi:10.1002/ana.26536).
Abstract
Objective: the objective of this study was to assess the impact of treatment with dexamethasone, remdesivir or both on neurological complications in acute coronavirus diease 2019 (COVID-19).
Methods: we used observational data from the International Severe Acute and emerging Respiratory Infection Consortium World Health Organization (WHO) Clinical Characterization Protocol, United Kingdom. Hospital inpatients aged ≥18 years with laboratory-confirmed severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection admitted between January 31, 2020, and June 29, 2021, were included. Treatment allocation was non-blinded and performed by reporting clinicians. A propensity scoring methodology was used to minimize confounding. Treatment with remdesivir, dexamethasone, or both was assessed against the standard of care. The primary outcome was a neurological complication occurring at the point of death, discharge, or resolution of the COVID-19 clinical episode.
Results: out of 89,297 hospital inpatients, 64,088 had severe COVID-19 and 25,209 had non-hypoxic COVID-19. Neurological complications developed in 4.8% and 4.5%, respectively. In both groups, neurological complications were associated with increased mortality, intensive care unit (ICU) admission, worse self-care on discharge, and time to recovery. In patients with severe COVID-19, treatment with dexamethasone (n = 21,129), remdesivir (n = 1,428), and both combined (n = 10,846) were associated with a lower frequency of neurological complications: OR = 0.76 (95% confidence interval [CI] = 0.69-0.83), OR = 0.69 (95% CI = 0.51-0.90), and OR = 0.54 (95% CI = 0.47-0.61), respectively. In patients with non-hypoxic COVID-19, dexamethasone (n = 2,580) was associated with less neurological complications (OR = 0.78, 95% CI = 0.62-0.97), whereas the dexamethasone/remdesivir combination (n = 460) showed a similar trend (OR = 0.63, 95% CI = 0.31-1.15).
Interpretation: treatment with dexamethasone, remdesivir, or both in patients hospitalized with COVID-19 was associated with a lower frequency of neurological complications in an additive manner, such that the greatest benefit was observed in patients who received both drugs together.
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Grundmann et al 2022
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Published date: 19 October 2022
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Funding Information:
This work uses data provided by patients and collected by the National Health Service (NHS) as part of their care and support #DataSavesLives. We are extremely grateful to the 2,648 frontline NHS clinical and research staff and volunteer medical students who collected these data in challenging circumstances; and the generosity of the participants and their families for their individual contributions in these difficult times. I.G. was supported by Gilead Sciences (IN‐UK‐540‐6109) and the National Institute for Health Research (NIHR). The ISARIC WHO CCP‐UK study was registered at https://www.isrctn.com/ISRCTN66726260 (Reference ISRCTN66726260) and designated an Urgent Public Health Research Study by the NIHR. This research used data assets made available by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (research which commenced between October 1, 2020, and March 31, 2021, grant ref MC_PC_20029; April 1, 2021 to September 30, 2022, grant ref MC_PC_20058). B.D.M. is supported to conduct COVID‐19 neuroscience research by the UKRI/MRC (MR/V03605X/1). B.D.M. is also supported for additional neurological inflammation research due to viral infection by grants from the NIHR (award CO‐CIN‐01), the Medical Research Council (MC_PC_19059) and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), the MRC/UKRI (MR/V007181/1), MRC (MR/T028750/1), and Wellcome (ISSF201902/3).
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© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
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Local EPrints ID: 472899
URI: http://eprints.soton.ac.uk/id/eprint/472899
ISSN: 0364-5134
PURE UUID: 4015d996-1b69-49e0-ac4a-688cf9b5c0b9
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Date deposited: 05 Jan 2023 18:01
Last modified: 17 Mar 2024 04:00
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Author:
Alexander Grundmann
Author:
Marc Hardwick
Author:
John Kenneth Baillie
Author:
Peter J.M. Openshaw
Author:
Malcolm G. Semple
Author:
Sarah Pett
Author:
Benedict D Michael
Author:
Rhys H Thomas
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