The University of Southampton
University of Southampton Institutional Repository

Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19

Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19
Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19

While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways that drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral lung diseases remain poorly characterized. We analyzed plasma samples from 471 hospitalized patients recruited through the prospective multicenter ISARIC4C study and 39 outpatients with mild disease, enabling extensive characterization of responses across a full spectrum of COVID-19 severity. Progressive elevation of levels of numerous inflammatory cytokines and chemokines (including IL-6, CXCL10, and GM-CSF) were associated with severity and accompanied by elevated markers of endothelial injury and thrombosis. Principal component and network analyses demonstrated central roles for IL-6 and GM-CSF in COVID-19 pathogenesis. Comparing these profiles to archived samples from patients with fatal influenza, IL-6 was equally elevated in both conditions whereas GM-CSF was prominent only in COVID-19. These findings further identify the key inflammatory, thrombotic, and vascular factors that characterize and distinguish severe and fatal COVID-19.

2470-9468
Thwaites, Ryan S
0cf76282-a7ed-4361-8a93-78ca5e7127fc
Sanchez Sevilla Uruchurtu, Ashley
6063d5e3-a3dd-4b35-899f-5d12a3931d36
Siggins, Matthew K
92337ac7-6072-480e-b915-26a6449d9599
Liew, Felicity
e49e3c8f-853a-4876-8cd8-739f39d8b74d
Russell, Clark D
80352f5e-cda1-4635-b0ca-c3c920c67590
Moore, Shona C
b2fd0970-e2be-4d9f-a31c-ed29cc8762b5
Fairfield, Cameron
dda58852-a5ae-4539-b70e-3fa2c38a5680
Carter, Edwin
7ac60db0-3e90-407c-9d7c-a3ef811256c7
Abrams, Simon
8c25b3de-1f59-4c44-b7b5-eb3a193fac8d
Short, Charlotte-Eve
cd9d97c0-4c2e-42a7-ac08-9c0a55d6e784
Thaventhiran, Thilipan
4891f173-80e1-4521-9f28-9e1f235e08a7
Bergstrom, Emma
5a6bfe8b-96f7-4184-8faf-31bccc6597f9
Gardener, Zoe
b1c2fbb4-13f6-41f4-94fe-ded9a55de832
Ascough, Stephanie
54d7cdee-6e0d-4d24-b933-d54e3d619cb9
Chiu, Christopher
1bd7076d-c8f5-4968-bd72-6f35cc0c20e8
Docherty, Annemarie B
0b579461-1b7a-456a-aa13-09f229c7a9d8
Hunt, David
5867549e-0e44-4f07-9a42-93aaf092fd4d
Crow, Yanick J
5d673b40-d640-46ff-93fa-b4081a1a9b34
Solomon, Tom
3311a8fe-fc3d-42ab-8c99-cacc179f1f77
Taylor, Graham P
aacd657b-fb42-4c1f-8b18-bd0bdea2c178
Turtle, Lance
46a79918-7fd1-4002-84d5-bc3bd0b26632
Harrison, Ewen M
6e9fdc8e-928d-4135-b8d1-9547783025f1
Dunning, Jake
a311288a-ef83-4475-bf56-b36d9a3525b3
Semple, Malcolm G
15b207df-e044-4078-9b40-1af17b800ab1
Baillie, J Kenneth
a08f7c7f-62a3-44ea-af0e-aa5f1ffde00c
Openshaw, Peter JM
1b26f033-26d6-4e75-a337-7e877a809ec1
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751
ISARIC4C Investigators
Thwaites, Ryan S
0cf76282-a7ed-4361-8a93-78ca5e7127fc
Sanchez Sevilla Uruchurtu, Ashley
6063d5e3-a3dd-4b35-899f-5d12a3931d36
Siggins, Matthew K
92337ac7-6072-480e-b915-26a6449d9599
Liew, Felicity
e49e3c8f-853a-4876-8cd8-739f39d8b74d
Russell, Clark D
80352f5e-cda1-4635-b0ca-c3c920c67590
Moore, Shona C
b2fd0970-e2be-4d9f-a31c-ed29cc8762b5
Fairfield, Cameron
dda58852-a5ae-4539-b70e-3fa2c38a5680
Carter, Edwin
7ac60db0-3e90-407c-9d7c-a3ef811256c7
Abrams, Simon
8c25b3de-1f59-4c44-b7b5-eb3a193fac8d
Short, Charlotte-Eve
cd9d97c0-4c2e-42a7-ac08-9c0a55d6e784
Thaventhiran, Thilipan
4891f173-80e1-4521-9f28-9e1f235e08a7
Bergstrom, Emma
5a6bfe8b-96f7-4184-8faf-31bccc6597f9
Gardener, Zoe
b1c2fbb4-13f6-41f4-94fe-ded9a55de832
Ascough, Stephanie
54d7cdee-6e0d-4d24-b933-d54e3d619cb9
Chiu, Christopher
1bd7076d-c8f5-4968-bd72-6f35cc0c20e8
Docherty, Annemarie B
0b579461-1b7a-456a-aa13-09f229c7a9d8
Hunt, David
5867549e-0e44-4f07-9a42-93aaf092fd4d
Crow, Yanick J
5d673b40-d640-46ff-93fa-b4081a1a9b34
Solomon, Tom
3311a8fe-fc3d-42ab-8c99-cacc179f1f77
Taylor, Graham P
aacd657b-fb42-4c1f-8b18-bd0bdea2c178
Turtle, Lance
46a79918-7fd1-4002-84d5-bc3bd0b26632
Harrison, Ewen M
6e9fdc8e-928d-4135-b8d1-9547783025f1
Dunning, Jake
a311288a-ef83-4475-bf56-b36d9a3525b3
Semple, Malcolm G
15b207df-e044-4078-9b40-1af17b800ab1
Baillie, J Kenneth
a08f7c7f-62a3-44ea-af0e-aa5f1ffde00c
Openshaw, Peter JM
1b26f033-26d6-4e75-a337-7e877a809ec1
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751

Thwaites, Ryan S, Sanchez Sevilla Uruchurtu, Ashley, Siggins, Matthew K, Liew, Felicity, Russell, Clark D, Moore, Shona C, Fairfield, Cameron, Carter, Edwin, Abrams, Simon, Short, Charlotte-Eve, Thaventhiran, Thilipan, Bergstrom, Emma, Gardener, Zoe, Ascough, Stephanie, Chiu, Christopher, Docherty, Annemarie B, Hunt, David, Crow, Yanick J, Solomon, Tom, Taylor, Graham P, Turtle, Lance, Harrison, Ewen M, Dunning, Jake, Semple, Malcolm G, Baillie, J Kenneth and Openshaw, Peter JM , ISARIC4C Investigators (2021) Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Science immunology, 6 (57), [eabg9873]. (doi:10.1126/sciimmunol.abg9873).

Record type: Article

Abstract

While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways that drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral lung diseases remain poorly characterized. We analyzed plasma samples from 471 hospitalized patients recruited through the prospective multicenter ISARIC4C study and 39 outpatients with mild disease, enabling extensive characterization of responses across a full spectrum of COVID-19 severity. Progressive elevation of levels of numerous inflammatory cytokines and chemokines (including IL-6, CXCL10, and GM-CSF) were associated with severity and accompanied by elevated markers of endothelial injury and thrombosis. Principal component and network analyses demonstrated central roles for IL-6 and GM-CSF in COVID-19 pathogenesis. Comparing these profiles to archived samples from patients with fatal influenza, IL-6 was equally elevated in both conditions whereas GM-CSF was prominent only in COVID-19. These findings further identify the key inflammatory, thrombotic, and vascular factors that characterize and distinguish severe and fatal COVID-19.

This record has no associated files available for download.

More information

Published date: 10 March 2021

Identifiers

Local EPrints ID: 449163
URI: http://eprints.soton.ac.uk/id/eprint/449163
ISSN: 2470-9468
PURE UUID: 01aff133-3b0f-466f-9dee-36b29637c14a
ORCID for Ahilanandan Dushianthan: ORCID iD orcid.org/0000-0002-0165-3359

Catalogue record

Date deposited: 18 May 2021 16:33
Last modified: 17 Mar 2024 03:51

Export record

Altmetrics

Contributors

Author: Ryan S Thwaites
Author: Ashley Sanchez Sevilla Uruchurtu
Author: Matthew K Siggins
Author: Felicity Liew
Author: Clark D Russell
Author: Shona C Moore
Author: Cameron Fairfield
Author: Edwin Carter
Author: Simon Abrams
Author: Charlotte-Eve Short
Author: Thilipan Thaventhiran
Author: Emma Bergstrom
Author: Zoe Gardener
Author: Stephanie Ascough
Author: Christopher Chiu
Author: Annemarie B Docherty
Author: David Hunt
Author: Yanick J Crow
Author: Tom Solomon
Author: Graham P Taylor
Author: Lance Turtle
Author: Ewen M Harrison
Author: Jake Dunning
Author: Malcolm G Semple
Author: J Kenneth Baillie
Author: Peter JM Openshaw
Author: Ahilanandan Dushianthan ORCID iD
Corporate Author: ISARIC4C Investigators

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×