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Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions

View ORCID ProfileDivij Mathew, Josephine R. Giles, View ORCID ProfileAmy E. Baxter, View ORCID ProfileAllison R. Greenplate, Jennifer E. Wu, View ORCID ProfileCécile Alanio, View ORCID ProfileDerek A. Oldridge, View ORCID ProfileLeticia 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, View ORCID ProfileSigrid Gouma, Claudia P. Arevalo, Marcus J. Bolton, Fang Chen, Simon F. Lacey, View ORCID ProfileScott E. Hensley, View ORCID ProfileSokratis Apostolidis, Alexander C. Huang, Laura A. Vella, The UPenn COVID Processing Unit, View ORCID ProfileMichael R. Betts, View ORCID ProfileNuala J. Meyer, View ORCID ProfileE. John Wherry
doi: https://doi.org/10.1101/2020.05.20.106401
Divij Mathew
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
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  • ORCID record for Divij Mathew
Josephine R. Giles
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
13Parker Institute for Cancer Immunotherapy at University of Pennsylvania Perelman School of Medicine
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Amy E. Baxter
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
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  • ORCID record for Amy E. Baxter
Allison R. Greenplate
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
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Jennifer E. Wu
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
13Parker Institute for Cancer Immunotherapy at University of Pennsylvania Perelman School of Medicine
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Cécile Alanio
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
13Parker Institute for Cancer Immunotherapy at University of Pennsylvania Perelman School of Medicine
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  • ORCID record for Cécile Alanio
Derek A. Oldridge
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
3Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine
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  • ORCID record for Derek A. Oldridge
Leticia Kuri-Cervantes
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
4Department of Microbiology, University of Pennsylvania Perelman School of Medicine
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  • ORCID record for Leticia Kuri-Cervantes
M. Betina Pampena
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
4Department of Microbiology, University of Pennsylvania Perelman School of Medicine
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Kurt D’Andrea
5Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania
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Sasikanth Manne
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
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Zeyu Chen
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
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Yinghui Jane Huang
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
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John P. Reilly
12Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine
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Ariel R Weisman
12Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine
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Caroline A.G. Ittner
12Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine
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Oliva Kuthuru
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
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Jeanette Dougherty
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
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Kito Nzingha
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
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Nicholas Han
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
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Justin Kim
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
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Ajinkya Pattekar
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
6Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine
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Eileen C. Goodwin
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
4Department of Microbiology, University of Pennsylvania Perelman School of Medicine
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Elizabeth M. Anderson
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
4Department of Microbiology, University of Pennsylvania Perelman School of Medicine
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Madison E. Weirick
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
4Department of Microbiology, University of Pennsylvania Perelman School of Medicine
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Sigrid Gouma
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
4Department of Microbiology, University of Pennsylvania Perelman School of Medicine
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Claudia P. Arevalo
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
4Department of Microbiology, University of Pennsylvania Perelman School of Medicine
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Marcus J. Bolton
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
4Department of Microbiology, University of Pennsylvania Perelman School of Medicine
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Fang Chen
7Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine
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Simon F. Lacey
7Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine
8Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine
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Scott E. Hensley
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
4Department of Microbiology, University of Pennsylvania Perelman School of Medicine
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Sokratis Apostolidis
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
9Division of Rheumatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine
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Alexander C. Huang
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
10Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine
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Laura A. Vella
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
11Division of Infectious Disease, Department of Pediatrics, Children’s Hospital of Philadelphia
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Michael R. Betts
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
4Department of Microbiology, University of Pennsylvania Perelman School of Medicine
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  • For correspondence: Nuala.Meyer@pennmedicine.upenn.edu betts@pennmedicine.upenn.edu wherry@pennmedicine.upenn.edu
Nuala J. Meyer
12Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine
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  • For correspondence: Nuala.Meyer@pennmedicine.upenn.edu betts@pennmedicine.upenn.edu wherry@pennmedicine.upenn.edu
E. John Wherry
1Institute for Immunology, University of Pennsylvania Perelman School of Medicine
2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine
13Parker Institute for Cancer Immunotherapy at University of Pennsylvania Perelman School of Medicine
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  • For correspondence: Nuala.Meyer@pennmedicine.upenn.edu betts@pennmedicine.upenn.edu wherry@pennmedicine.upenn.edu
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Abstract

COVID-19 has become a global pandemic. Immune dysregulation has been implicated, but immune responses remain poorly understood. We analyzed 71 COVID-19 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ∼200 immune and >30 clinical features revealed activation of T cell and B cell subsets, but only in some patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses could reach >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three “immunotypes” associated with poor clinical trajectories versus improving health. These immunotypes may have implications for therapeutics and vaccines.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted May 23, 2020.
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Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions
Divij Mathew, Josephine R. Giles, Amy E. Baxter, Allison R. Greenplate, Jennifer E. Wu, Cécile Alanio, Derek A. Oldridge, 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, Scott E. Hensley, Sokratis Apostolidis, Alexander C. Huang, Laura A. Vella, The UPenn COVID Processing Unit, Michael R. Betts, Nuala J. Meyer, E. John Wherry
bioRxiv 2020.05.20.106401; doi: https://doi.org/10.1101/2020.05.20.106401
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Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions
Divij Mathew, Josephine R. Giles, Amy E. Baxter, Allison R. Greenplate, Jennifer E. Wu, Cécile Alanio, Derek A. Oldridge, 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, Scott E. Hensley, Sokratis Apostolidis, Alexander C. Huang, Laura A. Vella, The UPenn COVID Processing Unit, Michael R. Betts, Nuala J. Meyer, E. John Wherry
bioRxiv 2020.05.20.106401; doi: https://doi.org/10.1101/2020.05.20.106401

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