Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications.

Abstract

Coronavirus disease 2019 (COVID-19) is currently a global pandemic, but human immune responses to the virus remain poorly understood. We used high-dimensional cytometry to analyze 125 COVID-19 patients and compare them with recovered and healthy individuals. Integrated analysis of ~200 immune and ~50 clinical features revealed activation of T cell and B cell subsets in a proportion of patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses reaching >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable with that in uninfected individuals. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. Our analyses identified three immunotypes associated with poor clinical trajectories versus improving health. These immunotypes may have implications for the design of therapeutics and vaccines for COVID-19.

• Authors: Divij Mathew, Josephine R Giles, Amy E Baxter, Derek A Oldridge, Allison R Greenplate, Jennifer E Wu, Cécile Alanio, Leticia Kuri-Cervantes, M Betina Pampena, Kurt D'Andrea, Sasikanth Manne, Zeyu Chen, Yinghui Jane Huang, John P Reilly, Ariel R Weisman, Caroline A G Ittner, Oliva Kuthuru, Jeanette Dougherty, Kito Nzingha, Nicholas Han, Justin Kim, Ajinkya Pattekar, Eileen C Goodwin, Elizabeth M Anderson, Madison E Weirick, Sigrid Gouma, Claudia P Arevalo, Marcus J Bolton, Fang Chen, Simon F Lacey, Holly Ramage, Sara Cherry, Scott E Hensley, Sokratis A Apostolidis, Alexander C Huang, Laura A Vella, UPenn COVID Processing Unit, Michael R Betts, Nuala J Meyer, E John Wherry
• Journal: Science (New York, N.Y.) (Science) Vol. 369 Issue 6508 (09 04 2020) ISSN: 1095-9203 [Electronic] United States
• PMID: 32669297 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemical References

• Antibodies, Viral
• Cytokines

Topics

• Adaptive Immunity
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Viral (blood)
• B-Lymphocyte Subsets (immunology)
• B-Lymphocytes (immunology)
• Betacoronavirus (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• COVID-19
• Coronavirus Infections (immunology)
• Cytokines (blood)
• Female
• Humans
• Immunologic Memory
• Lymphocyte Activation
• Male
• Middle Aged
• Pandemics
• Plasma Cells (immunology)
• Pneumonia, Viral (immunology)
• SARS-CoV-2
• Severity of Illness Index
• T-Lymphocyte Subsets (immunology)
• T-Lymphocytes (immunology)
• T-Lymphocytes, Helper-Inducer (immunology)
• Time Factors
• Young Adult