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ResearchIn-Press PreviewCOVID-19Immunology Open Access | 10.1172/jci.insight.146242

Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2

Krystle K.Q. Yu,1 Stephanie Fischinger,2 Malisa T. Smith,1 Caroline Atyeo,3 Deniz Cizmeci,4 Caitlin R. Wolf,1 Erik D. Layton,1 Jennifer K. Logue,1 Melissa S. Aguilar,1 Kiel Shuey,1 Carolin Loos,3 Jingyou Yu,5 Nicholas M. Franko,1 Robert Y. Choi,6 Anna Wald,1 Dan H. Barouch,5 David M. Koelle,1 Douglas Lauffenburger,7 Helen Y. Chu,1 Galit Alter,3 and Chetan Seshadri1

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Yu, K. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Fischinger, S. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Smith, M. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Atyeo, C. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Cizmeci, D. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Wolf, C. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

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1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Logue, J. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Aguilar, M. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Shuey, K. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

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1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Yu, J. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Franko, N. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Choi, R. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Wald, A. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Barouch, D. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Koelle, D. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

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1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Chu, H. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

Find articles by Alter, G. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Washington School of Medicine, Seattle, United States of America

2Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

3Ragon Institute of MGH, MIT and Harvard, Boston, United States of America

4Department of Biological Engineering, Ragon Institute of MGH, MIT, and Harvard, Boston, United States of America

5Virology and Vaccine Research, Harvard Medical School, Boston, United States of America

6Department of Infectious Diseases, Providence Medical Group, Everett, United States of America

7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America

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Published February 23, 2021 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.146242.
Copyright © 2021, Yu et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 23, 2021 - Version history
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Abstract

Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multi-parameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins in a convalescent cohort of COVID-19 subjects who were either hospitalized (n=20) or not hospitalized (n=40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virus-specific CD4 T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4 T-cells and antibodies targeting the S1 domain of spike among subjects that were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2, which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19.

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