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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
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
1201-9712
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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Oppong, Alexandra E.
580e58a1-8107-46e8-8dcf-ec31f398f82e
Coelewij, Leda
ae2a2f6a-4c29-480f-bf9d-a77c676fae39
Hutchinson, Matthew
7ac9a548-354d-457d-8a7b-cdb02851db4e
Carpenter, Ben
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Robinson, George A.
33a59eab-756a-4ada-b393-3d92fa556360
Liddle, Trevor
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Hawkins, Ellie
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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.
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Ardern-Jones, Michael
7ac43c24-94ab-4d19-ba69-afaa546bec90
Duncombe, Andrew S.
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Jury, Elizabeth C.
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Manson, Jessica J.
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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).

Record type: Article

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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Accepted/In Press date: 9 October 2025
Published date: December 2025
Additional Information: Publisher Copyright: © 2025 The Authors.
Keywords: COVID-19 hyperinflammation, Dexamethasone, Mortality risk

Identifiers

Local EPrints ID: 509243
URI: http://eprints.soton.ac.uk/id/eprint/509243
ISSN: 1201-9712
PURE UUID: 257ce231-7db6-4bf4-a1a0-6c2483e0b853
ORCID for Michael Ardern-Jones: ORCID iD orcid.org/0000-0003-1466-2016

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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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