Evaluating the immune response in treatment-naive hospitalised patients with influenza and COVID-19
Evaluating the immune response in treatment-naive hospitalised patients with influenza and COVID-19
The worldwide COVID-19 pandemic has claimed millions of lives and has had a profound effect on global life. Understanding the body's immune response to SARS-CoV-2 infection is crucial in improving patient management and prognosis. In this study we compared influenza and SARS-CoV-2 infected patient cohorts to identify distinct blood transcript abundances and cellular composition to better understand the natural immune response associated with COVID-19, compared to another viral infection being influenza, and identify a prognostic signature of COVID-19 patient outcome. Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of 88 patients infected with influenza and a cohort of 80 patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines. Gene transcript abundances, enriched pathways and cellular composition were compared between cohorts using RNA-seq. A genetic signature between COVID-19 survivors and non-survivors was assessed as a prognostic predictor of COVID-19 outcome. Contrasting immune responses were detected with an innate response elevated in influenza and an adaptive response elevated in COVID-19. Additionally ribosomal, mitochondrial oxidative stress and interferon signalling pathways differentiated the cohorts. An adaptive immune response was associated with COVID-19 survival, while an inflammatory response predicted death. A prognostic transcript signature, associated with circulating immunoglobulins, nucleosome assembly, cytokine production and T cell activation, was able to stratify COVID-19 patients likely to survive or die. This study provides a unique insight into the immune responses of treatment naïve patients with influenza or COVID-19. The comparison of immune response between COVID-19 survivors and non-survivors enables prognostication of COVID-19 patients and may suggest potential therapeutic strategies to improve survival.
Adaptive Immunity, COVID-19, Humans, Influenza Vaccines, Influenza, Human, Pandemics, SARS-CoV-2
Legebeke, Jelmer
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Lord, Jenny
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Penrice-Randal, Rebekah
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Vallejo, Andres F.
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Poole, Stephen
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Brendish, Nathan J.
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Dong, Xiaofeng
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Hartley, Catherine
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Holloway, John W.
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Lucas, Jane S.
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Williams, Anthony P.
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Wheway, Gabrielle
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Strazzeri, Fabio
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Gardner, Aaron
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Schofield, James P.R.
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Skipp, Paul J.
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Hiscox, Julian A.
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Polak, Marta E.
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Clark, Tristan W.
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Baralle, Diana
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19 May 2022
Legebeke, Jelmer
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Lord, Jenny
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Penrice-Randal, Rebekah
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Vallejo, Andres F.
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Poole, Stephen
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Brendish, Nathan J.
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Dong, Xiaofeng
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Hartley, Catherine
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Holloway, John W.
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Lucas, Jane S.
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Williams, Anthony P.
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Wheway, Gabrielle
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Strazzeri, Fabio
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Gardner, Aaron
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Schofield, James P.R.
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Skipp, Paul J.
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Hiscox, Julian A.
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Polak, Marta E.
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Clark, Tristan W.
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Baralle, Diana
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Legebeke, Jelmer, Lord, Jenny, Penrice-Randal, Rebekah, Vallejo, Andres F., Poole, Stephen, Brendish, Nathan J., Dong, Xiaofeng, Hartley, Catherine, Holloway, John W., Lucas, Jane S., Williams, Anthony P., Wheway, Gabrielle, Strazzeri, Fabio, Gardner, Aaron, Schofield, James P.R., Skipp, Paul J., Hiscox, Julian A., Polak, Marta E., Clark, Tristan W. and Baralle, Diana
(2022)
Evaluating the immune response in treatment-naive hospitalised patients with influenza and COVID-19.
Frontiers in Immunology, 13, [853265].
(doi:10.3389/fimmu.2022.853265).
Abstract
The worldwide COVID-19 pandemic has claimed millions of lives and has had a profound effect on global life. Understanding the body's immune response to SARS-CoV-2 infection is crucial in improving patient management and prognosis. In this study we compared influenza and SARS-CoV-2 infected patient cohorts to identify distinct blood transcript abundances and cellular composition to better understand the natural immune response associated with COVID-19, compared to another viral infection being influenza, and identify a prognostic signature of COVID-19 patient outcome. Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of 88 patients infected with influenza and a cohort of 80 patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines. Gene transcript abundances, enriched pathways and cellular composition were compared between cohorts using RNA-seq. A genetic signature between COVID-19 survivors and non-survivors was assessed as a prognostic predictor of COVID-19 outcome. Contrasting immune responses were detected with an innate response elevated in influenza and an adaptive response elevated in COVID-19. Additionally ribosomal, mitochondrial oxidative stress and interferon signalling pathways differentiated the cohorts. An adaptive immune response was associated with COVID-19 survival, while an inflammatory response predicted death. A prognostic transcript signature, associated with circulating immunoglobulins, nucleosome assembly, cytokine production and T cell activation, was able to stratify COVID-19 patients likely to survive or die. This study provides a unique insight into the immune responses of treatment naïve patients with influenza or COVID-19. The comparison of immune response between COVID-19 survivors and non-survivors enables prognostication of COVID-19 patients and may suggest potential therapeutic strategies to improve survival.
Text
fimmu-13-853265
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More information
Accepted/In Press date: 13 April 2022
Published date: 19 May 2022
Additional Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: the CoV-19POC trial was funded by University Hospital Southampton Foundation Trust (UHSFT) and the FluPOC trial by the National Institute for Health Research (NIHR) Post-Doctoral Fellowship Programme. In addition, the CoV-19POC and FluPOC trials were supported by the NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research Centre (BRC). JLe was supported by a PhD studentship from the NIHR Southampton BRC (no. NIHR-INF-0932). RP-R was supported by a PhD studentship from the Medical Research Council Discovery Medicine North Doctoral Training Partnership (no. MR/N013840/1). NB was supported by the NIHR Clinical Lecturer scheme. JHi, CH and XD were supported by the US Food and Drug Administration (no. 75F40120C00085), and this work was partly supported by U.S. Food and Drug Administration Medical Countermeasures Initiative (no 75F40120C00085) awarded to JHi. MP was supported by a Sir Henry Dale Fellowship from Welcome Trust and The Royal Society (no. 109377/Z/15/Z). TC was supported by a NIHR Post-Doctoral Fellowship (no. 2016-09-061). DB and her laboratory are supported by a NIHR Research Professorship (no. RP-2016-07-011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords:
Adaptive Immunity, COVID-19, Humans, Influenza Vaccines, Influenza, Human, Pandemics, SARS-CoV-2
Identifiers
Local EPrints ID: 506361
URI: http://eprints.soton.ac.uk/id/eprint/506361
ISSN: 1664-3224
PURE UUID: 2cc8485a-c142-4353-ad56-22cecf6f0f05
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Date deposited: 05 Nov 2025 17:35
Last modified: 19 Nov 2025 02:57
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Contributors
Author:
Jelmer Legebeke
Author:
Jenny Lord
Author:
Rebekah Penrice-Randal
Author:
Andres F. Vallejo
Author:
Stephen Poole
Author:
Nathan J. Brendish
Author:
Xiaofeng Dong
Author:
Catherine Hartley
Author:
Fabio Strazzeri
Author:
Aaron Gardner
Author:
James P.R. Schofield
Author:
Paul J. Skipp
Author:
Julian A. Hiscox
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