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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients
PLoS Pathogens, Volume 17, No. 9, Article e1009804, Year 2021
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Description
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. Copyright: © 2021 Youngs et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Authors & Co-Authors
Lim, Nicholas
United Kingdom, Oxford
University of Oxford
Sharpe, Hannah R.
United Kingdom, Oxford
The Jenner Institute
Amini, Ali
United Kingdom, Oxford
University of Oxford
Edmans, Matthew D.
United Kingdom, Oxford
University of Oxford
Zacharopoulou, Panagiota
United Kingdom, Oxford
University of Oxford
Sampson, Oliver L.
United Kingdom, Oxford
University of Oxford
Paton, Robert S.
United Kingdom, Oxford
University of Oxford
Hurt, William James
United Kingdom, London
St George’s, University of London
United Kingdom, London
St George's University Hospitals Nhs Foundation Trust
Duncan, David A.
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
United Kingdom, Didcot
Diamond Light Source
McNaughton, Anna L.
United Kingdom, Oxford
University of Oxford
Miao, Vincent N.
United States, Cambridge
Massachusetts Institute of Technology
United States, Boston
Massachusetts General Hospital
Leaver, Susannah K.
United Kingdom, London
St George's University Hospitals Nhs Foundation Trust
Ball, Jonathan A.S.
United Kingdom, London
St George's University Hospitals Nhs Foundation Trust
Skelly, Dónal Thomas
United Kingdom, Oxford
University of Oxford
Barnes, Eleanor J.
United Kingdom, Oxford
University of Oxford
United Kingdom, Oxford
The Jenner Institute
Dunachie, Susanna J.
United Kingdom, Oxford
University of Oxford
Ogg, Graham Stuart
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
Lambe, Teresa
United Kingdom, Oxford
The Jenner Institute
Pavord, Ian Douglas
United Kingdom, Oxford
Nihr Oxford Biomedical Research Centre
Shalek, Alex K.
United States, Cambridge
Massachusetts Institute of Technology
United States, Boston
Massachusetts General Hospital
Thompson, Craig Peter
United Kingdom, Oxford
University of Oxford
Macallan, Derek Clive
United Kingdom, London
St George’s, University of London
United Kingdom, London
St George's University Hospitals Nhs Foundation Trust
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
University of Oxford
Klenerman, Paul
United Kingdom, Oxford
University of Oxford
Bicanic, Tihana A.
United Kingdom, London
St George’s, University of London
United Kingdom, London
St George's University Hospitals Nhs Foundation Trust
Statistics
Citations: 31
Authors: 25
Affiliations: 11
Identifiers
Doi:
10.1371/journal.ppat.1009804
ISSN:
15537366
Research Areas
Covid
Health System And Policy
Study Design
Randomised Control Trial
Case Study
Study Approach
Qualitative