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Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients
DOI:
10.1371/journal.ppat.1009804
Authors:
Jonathan
Youngs
(University of London; St. George’s Hospital NHS Trust)
,
Nicholas M.
Provine
(University of Oxford)
,
Nicholas
Lim
(University of Oxford)
,
Hannah R.
Sharpe
(Jenner Institute, University of Oxford)
,
Ali
Amini
(University of Oxford)
,
Yi-Ling
Chen
(University of Oxford)
,
Jian
Luo
(University of Oxford)
,
Matthew D.
Edmans
(University of Oxford)
,
Panagiota
Zacharopoulou
(University of Oxford)
,
Wentao
Chen
(University of Oxford)
,
Oliver
Sampson
(University of Oxford)
,
Robert
Paton
(University of Oxford)
,
William J.
Hurt
(St. George’s University of London)
,
David A.
Duncan
(University of Oxford; Diamond Light Source)
,
Anna L.
Mcnaughton
(University of Oxford)
,
Vincent N.
Miao
(Massachusetts Institute of Technology)
,
Susannah
Leaver
(St George’s University Hospital NHS Foundation Trust,)
,
Duncan L. A.
Wyncoll
(Guy’s and St Thomas’ Hospital NHS Foundation Trust)
,
Jonathan
Ball
(St George’s University Hospital NHS Foundation Trust)
,
Philip
Hopkins
(King’s College, London)
,
Donal T.
Skelly
(University of Oxford)
,
Eleanor
Barnes
(University of Oxford)
,
Susanna
Dunachie
(University of Oxford)
,
Graham
Ogg
(University of Oxford)
,
Teresa
Lambe
(University of Oxford)
,
Ian
Pavord
(University of Oxford)
,
Alex K.
Shalek
(Massachusetts Institute of Technology; Broad Institute of MIT and Harvard, Cambridge)
,
Craig P.
Thompson
(University of Oxford)
,
Luzheng
Xue
(University of Oxford)
,
Derek C.
Macallan
(St. George’s University of London; St. George’s Hospital NHS Trust)
,
Philip
Goulder
(University of Oxford)
,
Paul
Klenerman
(University of Oxford)
,
Tihana
Bicanic
(St. George’s University of London; St. George’s Hospital NHS Trust)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Plos Pathogens
, VOL 17
State:
Published (Approved)
Published:
September 2021

Abstract: Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.92, 95% CI = 2.49–14.1). MAIT cell activation correlates with several other mortality-associated immunologic measures including broad activation of CD8+ T cells and non-Vδ2 γδT cells, and elevated levels of cytokines and chemokines, including GM-CSF, CXCL10, CCL2, and IL-6. MAIT cell activation is also a predictor of disease severity in influenza (ECMO/death HR = 4.43, 95% CI = 1.08–18.2). Single-cell RNA-sequencing reveals a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 –a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
Journal Keywords: COVID 19; Influenza; Cytokines; T helper cells; Cytotoxic T cells; Intensive care units; Virus testing; Serum proteins
Diamond Keywords: COVID-19; Viruses
Subject Areas:
Biology and Bio-materials
Technical Areas:
Added On:
21/09/2021 14:24
Documents:
journal.ppat.1009804.pdf
Discipline Tags:
Pathogens
Infectious Diseases
Health & Wellbeing
Life Sciences & Biotech
Technical Tags: