Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

Leticia Kuri-Cervantes, M. Betina Pampena, Wenzhao Meng, Aaron M. Rosenfeld, Caroline A.G. Ittner, Ariel R. Weisman, Roseline Agyekum, Divij Mathew, Amy E. Baxter, Laura Vella, Oliva Kuthuru, Sokratis Apostolidis, Luanne Bershaw, Jeannete Dougherty, Allison R. Greenplate, Ajinkya Pattekar, Justin Kim, Nicholas Han, View ORCID ProfileSigrid Gouma, Madison E. Weirick, Claudia P. Arevalo, Marcus J. Bolton, Eileen C. Goodwin, Elizabeth M. Anderson, View ORCID ProfileScott E. Hensley, Tiffanie K. Jones, Nilam S. Mangalmurti, Eline T. Luning Prak, E. John Wherry, Nuala J. Meyer, Michael R. Betts
doi: https://doi.org/10.1101/2020.05.18.101717
Leticia Kuri-Cervantes
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Betina Pampena
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wenzhao Meng
3Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, PA19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aaron M. Rosenfeld
3Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, PA19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Caroline A.G. Ittner
4Division of Pulmonary, Allergy and Critical Care, Center for Translational Lung Biology, Lung Biology Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ariel R. Weisman
4Division of Pulmonary, Allergy and Critical Care, Center for Translational Lung Biology, Lung Biology Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roseline Agyekum
4Division of Pulmonary, Allergy and Critical Care, Center for Translational Lung Biology, Lung Biology Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Divij Mathew
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amy E. Baxter
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laura Vella
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Oliva Kuthuru
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sokratis Apostolidis
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
7Division of Rheumatology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luanne Bershaw
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeannete Dougherty
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Allison R. Greenplate
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ajinkya Pattekar
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Justin Kim
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicholas Han
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sigrid Gouma
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sigrid Gouma
Madison E. Weirick
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Claudia P. Arevalo
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marcus J. Bolton
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eileen C. Goodwin
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elizabeth M. Anderson
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott E. Hensley
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Scott E. Hensley
Tiffanie K. Jones
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nilam S. Mangalmurti
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eline T. Luning Prak
3Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, PA19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E. John Wherry
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
8Parker Institute for Cancer Immunotherapy at the University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: betts@pennmedicine.upenn.edu nuala.meyer@pennmedicine.upenn.edu wherry@pennmedicine.upenn.edu
Nuala J. Meyer
5Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: betts@pennmedicine.upenn.edu nuala.meyer@pennmedicine.upenn.edu wherry@pennmedicine.upenn.edu
Michael R. Betts
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: betts@pennmedicine.upenn.edu nuala.meyer@pennmedicine.upenn.edu wherry@pennmedicine.upenn.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified broad changes in neutrophils, NK cells, and monocytes during severe COVID-19, suggesting excessive mobilization of innate lineages. We found marked activation within T and B cells, highly oligoclonal B cell populations, profound plasmablast expansion, and SARS-CoV-2-specific antibodies in many, but not all, severe COVID-19 cases. Despite this heterogeneity, we found selective clustering of severe COVID-19 cases through unbiased analysis of the aggregated immunological phenotypes. Our findings demonstrate broad immune perturbations spanning both innate and adaptive leukocytes that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.

One Sentence Summary Broad immune perturbations in severe COVID-19

Competing Interest Statement

NJM reports funding to her institution from Athersys, Inc, Biomarck Inc, and the Marcus Foundation for research unrelated to the work under consideration. She has no other conflicts of interest. EJW is a member of the Parker Institute for Cancer Immunotherapy. EJW has consulting agreements with and/or is on the scientific advisory board for Merck, Roche, Pieris, Elstar, and Surface Oncology. EJW is a founder of Surface Oncology and Arsenal Biosciences. EJW has a patent licensing agreement on the PD-1 pathway with Roche/Genentech. SEH has received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck for work unrelated to this report. ETLP is currently receiving funding from Janssen Pharmaceuticals, and is part of a scientific advisory panel for Roche Diagnostics Corporation for work unrelated to this publication

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted May 18, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection
Leticia Kuri-Cervantes, M. Betina Pampena, Wenzhao Meng, Aaron M. Rosenfeld, Caroline A.G. Ittner, Ariel R. Weisman, Roseline Agyekum, Divij Mathew, Amy E. Baxter, Laura Vella, Oliva Kuthuru, Sokratis Apostolidis, Luanne Bershaw, Jeannete Dougherty, Allison R. Greenplate, Ajinkya Pattekar, Justin Kim, Nicholas Han, Sigrid Gouma, Madison E. Weirick, Claudia P. Arevalo, Marcus J. Bolton, Eileen C. Goodwin, Elizabeth M. Anderson, Scott E. Hensley, Tiffanie K. Jones, Nilam S. Mangalmurti, Eline T. Luning Prak, E. John Wherry, Nuala J. Meyer, Michael R. Betts
bioRxiv 2020.05.18.101717; doi: https://doi.org/10.1101/2020.05.18.101717
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection
Leticia Kuri-Cervantes, M. Betina Pampena, Wenzhao Meng, Aaron M. Rosenfeld, Caroline A.G. Ittner, Ariel R. Weisman, Roseline Agyekum, Divij Mathew, Amy E. Baxter, Laura Vella, Oliva Kuthuru, Sokratis Apostolidis, Luanne Bershaw, Jeannete Dougherty, Allison R. Greenplate, Ajinkya Pattekar, Justin Kim, Nicholas Han, Sigrid Gouma, Madison E. Weirick, Claudia P. Arevalo, Marcus J. Bolton, Eileen C. Goodwin, Elizabeth M. Anderson, Scott E. Hensley, Tiffanie K. Jones, Nilam S. Mangalmurti, Eline T. Luning Prak, E. John Wherry, Nuala J. Meyer, Michael R. Betts
bioRxiv 2020.05.18.101717; doi: https://doi.org/10.1101/2020.05.18.101717

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3602)
  • Biochemistry (7567)
  • Bioengineering (5522)
  • Bioinformatics (20782)
  • Biophysics (10325)
  • Cancer Biology (7978)
  • Cell Biology (11635)
  • Clinical Trials (138)
  • Developmental Biology (6602)
  • Ecology (10200)
  • Epidemiology (2065)
  • Evolutionary Biology (13611)
  • Genetics (9539)
  • Genomics (12844)
  • Immunology (7919)
  • Microbiology (19538)
  • Molecular Biology (7657)
  • Neuroscience (42081)
  • Paleontology (308)
  • Pathology (1257)
  • Pharmacology and Toxicology (2201)
  • Physiology (3267)
  • Plant Biology (7038)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1951)
  • Systems Biology (5426)
  • Zoology (1116)