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ResearchIn-Press PreviewImmunologyInfectious disease Free access | 10.1172/JCI145516

Durable SARS-CoV-2 B cell immunity after mild or severe disease

Clinton O. Ogega,1 Nicole E. Skinner,1 Paul W. Blair,1 Han-Sol Park,2 Kirsten Littlefield,2 Abhinaya Ganesan,2 Santosh Dhakal,2 Pranay Ladiwala,3 Annukka A.R. Antar,1 Stuart C. Ray,1 Michael J. Betenbaugh,4 Andrew Pekosz,2 Sabra L. Klein,5 Yukari C. Manabe,1 Andrea L. Cox,1 and Justin R. Bailey1

1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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

1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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

1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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

1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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

1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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

1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

Find articles by Manabe, Y. in: JCI | PubMed | Google Scholar |

1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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

1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America

3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, United States of America

4Department of Chemical and Biomolecular Engineering, Johns Hopkins Univeristy, Baltimore, United States of America

5Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States of America

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Published February 11, 2021 - More info

J Clin Invest. https://doi.org/10.1172/JCI145516.
Copyright © 2021, American Society for Clinical Investigation
Published February 11, 2021 - Version history
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Abstract

Multiple studies have shown loss of SARS-CoV-2 specific antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from COVID-19. However, memory B cells (MBC) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multi-dimensional flow cytometric analysis of S protein receptor binding domain (S-RBD)-specific MBC in cohorts of ambulatory COVID-19 patients with mild disease (n = 7), and hospitalized patients with moderate to severe disease (n = 7), at a median of 54 (39-104) days after symptom onset. We detected S-RBD-specific class-switched MBC in 13 of 14 participants, failing only in the individual with lowest plasma levels of anti-S-RBD IgG and neutralizing antibodies. Resting MBC (rMBC) made up the largest proportion of S-RBD-specific MBC in both cohorts. FCRL5, a marker of functional memory on rMBC, was more dramatically upregulated on S-RBD-specific rMBC after mild infection than after severe infection. These data indicate that most SARS-CoV-2-infected individuals develop S-RBD-specific, class-switched rMBC that resemble germinal center-derived B cells induced by effective vaccination against other pathogens, providing evidence for durable B cell-mediated immunity against SARS-CoV-2 after mild or severe disease.

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