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

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

doi:10.1172/jci.insight.146242

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

Find articles by Layton, E. 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 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

Find articles by Loos, 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 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

Find articles by Lauffenburger, 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 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

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

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

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.

Version 1 (February 23, 2021): In-Press Preview

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

Article tools

Related posts

Metrics

Go to

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

Article tools

Related posts

Metrics

Go to

Sign up for email alerts