ResearchIn-Press PreviewCOVID-19Immunology
Open Access | 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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Yu, J.
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Published February 23, 2021 - More info
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.