Simple hyperinflammation scores predict mortality in hospitalized patients with COVID-19 and offer a personalized medicine approach to dexamethasone intervention
Simple hyperinflammation scores predict mortality in hospitalized patients with COVID-19 and offer a personalized medicine approach to dexamethasone intervention
Background Dexamethasone is recommended for use in all patients with COVID-19 requiring supplemental oxygen, however, only some patients develop hyperinflammation (COV-HI) potentially influencing their response to corticosteroids. This study tested the ability of criteria defining COV-HI to predict response to dexamethasone. Methods A retrospective, multicentre, observational cohort study of 1313-patients with PCR-confirmed COVID-19 during first and second waves of community-acquired infection including 212 patients who received dexamethasone monotherapy. Demographic data, laboratory tests and clinical status were recorded from admission until death or discharge, with minimum 28-days follow-up. Patients were stratified at admission as COV-HI-YES/COV-HI-NO based on three published COV-HI definitions. Results Patients with COV-HI shared a biological phenotype of hypoalbuminemia/anemia, and elevated D -dimer/lactate dehydrogenase/alanine transaminase/respiratory rates. Combining these features predicted 28-day mortality and stratified COV-HI-YES from COV-HI-NO more effectively compared to individual markers/demographic features alone. In COV-HI-YES patients, dexamethasone treatment halved mortality-risk (relative risk = 0.50) compared to untreated patients. However, in COV-HI-NO patients mortality-risk was 3.03x higher (CI = 1.3-7.0) in treated versus untreated patients during a 28-day admission period. Conclusions We present a framework for a new machine-learning based scoring system for COV-HI combining clinical assessment with laboratory markers for prediction of mortality and targeting glucocorticoids in hospitalized COVID-19 patients.
COVID-19 hyperinflammation, Dexamethasone, Mortality risk
Oppong, Alexandra E.
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Coelewij, Leda
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Hutchinson, Matthew
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Carpenter, Ben
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Robinson, George A.
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Liddle, Trevor
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Hawkins, Ellie
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Cox, Miriam F.
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Ciurtin, Coziana
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Venkatachalam, Srinivasan
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Collin, Matthew
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Tattersall, Rachel S.
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Ardern-Jones, Michael
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Duncombe, Andrew S.
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Jury, Elizabeth C.
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Manson, Jessica J.
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December 2025
Oppong, Alexandra E.
580e58a1-8107-46e8-8dcf-ec31f398f82e
Coelewij, Leda
ae2a2f6a-4c29-480f-bf9d-a77c676fae39
Hutchinson, Matthew
7ac9a548-354d-457d-8a7b-cdb02851db4e
Carpenter, Ben
677cca6a-9581-48a7-bbe0-48c2a3b57c6b
Robinson, George A.
33a59eab-756a-4ada-b393-3d92fa556360
Liddle, Trevor
633a4adc-6aa4-4582-94f9-edc4b4986f6a
Hawkins, Ellie
ef717c42-e8fd-4a9a-ad8c-100d268e34dc
Cox, Miriam F.
0177e9ac-f02b-4e10-87a5-6117674c3b03
Ciurtin, Coziana
293fc6a8-70f4-45a5-8ccb-04decbd12ce2
Venkatachalam, Srinivasan
ca9b6331-2bc4-4caa-8805-edbba7fd2b76
Collin, Matthew
1007a158-59e1-4575-8ec6-85e686d0bcc9
Tattersall, Rachel S.
1cb88b99-581e-4114-9da4-9ce48de2599d
Ardern-Jones, Michael
7ac43c24-94ab-4d19-ba69-afaa546bec90
Duncombe, Andrew S.
ce7cb7e9-5aec-4801-ab3c-18b4de474fef
Jury, Elizabeth C.
31671c93-466f-4c37-87b8-91d588e69c49
Manson, Jessica J.
8c15425f-1c2e-4506-a2d9-221146780f2a
Oppong, Alexandra E., Coelewij, Leda, Hutchinson, Matthew, Carpenter, Ben, Robinson, George A., Liddle, Trevor, Hawkins, Ellie, Cox, Miriam F., Ciurtin, Coziana, Venkatachalam, Srinivasan, Collin, Matthew, Tattersall, Rachel S., Ardern-Jones, Michael, Duncombe, Andrew S., Jury, Elizabeth C. and Manson, Jessica J.
(2025)
Simple hyperinflammation scores predict mortality in hospitalized patients with COVID-19 and offer a personalized medicine approach to dexamethasone intervention.
International Journal of Infectious Diseases, 161, [108119].
(doi:10.1016/j.ijid.2025.108119).
Abstract
Background Dexamethasone is recommended for use in all patients with COVID-19 requiring supplemental oxygen, however, only some patients develop hyperinflammation (COV-HI) potentially influencing their response to corticosteroids. This study tested the ability of criteria defining COV-HI to predict response to dexamethasone. Methods A retrospective, multicentre, observational cohort study of 1313-patients with PCR-confirmed COVID-19 during first and second waves of community-acquired infection including 212 patients who received dexamethasone monotherapy. Demographic data, laboratory tests and clinical status were recorded from admission until death or discharge, with minimum 28-days follow-up. Patients were stratified at admission as COV-HI-YES/COV-HI-NO based on three published COV-HI definitions. Results Patients with COV-HI shared a biological phenotype of hypoalbuminemia/anemia, and elevated D -dimer/lactate dehydrogenase/alanine transaminase/respiratory rates. Combining these features predicted 28-day mortality and stratified COV-HI-YES from COV-HI-NO more effectively compared to individual markers/demographic features alone. In COV-HI-YES patients, dexamethasone treatment halved mortality-risk (relative risk = 0.50) compared to untreated patients. However, in COV-HI-NO patients mortality-risk was 3.03x higher (CI = 1.3-7.0) in treated versus untreated patients during a 28-day admission period. Conclusions We present a framework for a new machine-learning based scoring system for COV-HI combining clinical assessment with laboratory markers for prediction of mortality and targeting glucocorticoids in hospitalized COVID-19 patients.
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PIIS1201971225003418
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Accepted/In Press date: 9 October 2025
Published date: December 2025
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© 2025 The Authors.
Keywords:
COVID-19 hyperinflammation, Dexamethasone, Mortality risk
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Local EPrints ID: 509243
URI: http://eprints.soton.ac.uk/id/eprint/509243
ISSN: 1201-9712
PURE UUID: 257ce231-7db6-4bf4-a1a0-6c2483e0b853
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Date deposited: 13 Feb 2026 18:07
Last modified: 14 Feb 2026 02:43
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Contributors
Author:
Alexandra E. Oppong
Author:
Leda Coelewij
Author:
Matthew Hutchinson
Author:
Ben Carpenter
Author:
George A. Robinson
Author:
Trevor Liddle
Author:
Ellie Hawkins
Author:
Miriam F. Cox
Author:
Coziana Ciurtin
Author:
Srinivasan Venkatachalam
Author:
Matthew Collin
Author:
Rachel S. Tattersall
Author:
Andrew S. Duncombe
Author:
Elizabeth C. Jury
Author:
Jessica J. Manson
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