Journal article
Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, 4.1MB, Terms of use)
-
- Publisher copy:
- 10.1371/journal.ppat.1009804
Authors
- Publisher:
- Public Library of Science
- Journal:
- PLoS Pathogens More from this journal
- Volume:
- 17
- Issue:
- 9
- Article number:
- e1009804
- Place of publication:
- United States
- Publication date:
- 2021-09-16
- Acceptance date:
- 2021-07-16
- DOI:
- EISSN:
-
1553-7374
- ISSN:
-
1553-7366
- Pmid:
-
34529726
- Language:
-
English
- Keywords:
- Pubs id:
-
1195912
- Local pid:
-
pubs:1195912
- Deposit date:
-
2021-11-09
Terms of use
- Copyright holder:
- Youngs et al.
- Copyright date:
- 2021
- Rights statement:
- ©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.
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record