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

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 ~5...

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Published in:	Science (American Association for the Advancement of Science) Vol. 369; no. 6508
Main Authors:	Mathew, Divij, Giles, Josephine R, Baxter, Amy E, Oldridge, Derek A, Greenplate, Allison R, Wu, Jennifer E, Alanio, Cécile, Kuri-Cervantes, Leticia, Pampena, M Betina, D'Andrea, Kurt, Manne, Sasikanth, Chen, Zeyu, Huang, Yinghui Jane, Reilly, John P, Weisman, Ariel R, Ittner, Caroline A G, Kuthuru, Oliva, Dougherty, Jeanette, Nzingha, Kito, Han, Nicholas, Kim, Justin, Pattekar, Ajinkya, Goodwin, Eileen C, Anderson, Elizabeth M, Weirick, Madison E, Gouma, Sigrid, Arevalo, Claudia P, Bolton, Marcus J, Chen, Fang, Lacey, Simon F, Ramage, Holly, Cherry, Sara, Hensley, Scott E, Apostolidis, Sokratis A, Huang, Alexander C, Vella, Laura A, Betts, Michael R, Meyer, Nuala J, Wherry, E John
Format:	Journal Article
Language:	English
Published:	United States 04.09.2020
Subjects:	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 Coronavirus Infections - immunology COVID-19 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
ISSN:	1095-9203, 1095-9203
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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.
AbstractList	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. 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.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.
Author	Hensley, Scott E Greenplate, Allison R Chen, Zeyu Pampena, M Betina Vella, Laura A Kuri-Cervantes, Leticia Arevalo, Claudia P Huang, Yinghui Jane Wherry, E John Betts, Michael R Baxter, Amy E Gouma, Sigrid Meyer, Nuala J Weirick, Madison E Dougherty, Jeanette Goodwin, Eileen C Manne, Sasikanth Huang, Alexander C D'Andrea, Kurt Anderson, Elizabeth M Reilly, John P Bolton, Marcus J Ittner, Caroline A G Pattekar, Ajinkya Apostolidis, Sokratis A Oldridge, Derek A Ramage, Holly Weisman, Ariel R Chen, Fang Lacey, Simon F Nzingha, Kito Kuthuru, Oliva Giles, Josephine R Han, Nicholas Cherry, Sara Mathew, Divij Wu, Jennifer E Alanio, Cécile Kim, Justin
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Medicine, Philadelphia, PA, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/32669297$$D View this record in MEDLINE/PubMed
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ContentType	Journal Article
Contributor	Chandra, Aditi Byrne, Katelyn T Kaminskiy, Yaroslav Shah, Jennifer B Alam, Zahidul Addison, Mary M Prager, Elizabeth M Hamilton, Jacob T Perkey, Eric Descamps, Hélène C Noll, Julia Han Omran, Dalia K Shilan, Jake S Pueschl, Dana Vanderbeck, Ashley N
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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.
Copyright_xml	– notice: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
CorporateAuthor	UPenn COVID Processing Unit
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References	32511371 - bioRxiv. 2020 May 23:2020.05.20.106401. doi: 10.1101/2020.05.20.106401
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Snippet	Coronavirus disease 2019 (COVID-19) is currently a global pandemic, but human immune responses to the virus remain poorly understood. We used high-dimensional...
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SubjectTerms	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 Coronavirus Infections - immunology COVID-19 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
Title	Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications
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