Early antiviral CD4+ and CD8+ T cells are associated with upper airway clearance of SARS-CoV-2

Research ArticleImmunologyInfectious disease Open Access | 10.1172/jci.insight.186078

Sydney I. Ramirez,1,2 Paul G. Lopez,1 Farhoud Faraji,1,3 Urvi M. Parikh,4 Amy Heaps,4 Justin Ritz,5 Carlee Moser,5 Joseph J. Eron,6 David Wohl,7 Judith Currier,7 Eric S. Daar,8 Alex Greninger,9 Paul Klekotka,10 Alba Grifoni,1 Daniela Weiskopf,1,2 Alessandro Sette,1,2 Bjoern Peters,1,2 Michael D. Hughes,5 Kara W. Chew,7 Davey M. Smith,2 Shane Crotty,1,2 and for the Accelerating COVID-19 Therapeutic Interventions and Vaccines-2 (ACTIV-2)/A5401 Study Team11

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

Find articles by Lopez, P. in: JCI | PubMed | Google Scholar

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

Find articles by Faraji, F. in: JCI | PubMed | Google Scholar |

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

Find articles by Parikh, U. in: JCI | PubMed | Google Scholar |

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

Find articles by Daar, E. in: JCI | PubMed | Google Scholar

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

Find articles by Klekotka, P. in: JCI | PubMed | Google Scholar

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

Find articles by Peters, B. in: JCI | PubMed | Google Scholar |

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

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

1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.

2Division of Infectious Diseases and Global Public Health, Department of Medicine, and

3Department of Otolaryngology-Head and Neck Surgery, UCSD, La Jolla, California, USA.

4Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

5Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

6Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

7Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

8Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

9Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA.

10Eli Lilly and Company, San Diego, California, USA.

11The ACTIV-2/A5401 Study Team is detailed in Supplemental Acknowledgments.

Address correspondence to: Shane Crotty, 9420 Athena Circle, La Jolla, California, 92037, USA. Phone: 858.752.6500; Email: shane@lji.org. Or to: Davey M. Smith, 9500 Gilman Drive #0679, La Jolla, California, 92093, USA. Phone: 858.642.1620; Email: d13smith@health.ucsd.edu.

Published December 20, 2024 - More info

Published in Volume 9, Issue 24 on December 20, 2024
JCI Insight. 2024;9(24):e186078. https://doi.org/10.1172/jci.insight.186078.
© 2024 Ramirez 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 December 20, 2024 - Version history
Received: August 19, 2024; Accepted: October 25, 2024 View PDF Abstract

T cells are involved in protective immunity against numerous viral infections. Data regarding functional roles of human T cells in SARS-CoV-2 (SARS2) viral clearance in primary COVID-19 are limited. To address this knowledge gap, we assessed samples for associations between SARS2 upper respiratory tract viral RNA levels and early virus-specific adaptive immune responses for 95 unvaccinated clinical trial participants with acute primary COVID-19 aged 18–86 years old, approximately half of whom were considered at high risk for progression to severe COVID-19. Functionality and magnitude of acute SARS2-specific CD4+ and CD8+ T cell responses were evaluated, in addition to antibody responses. Most individuals with acute COVID-19 developed SARS2-specific T cell responses within 6 days of COVID-19 symptom onset. Early CD4+ T cell and CD8+ T cell responses were polyfunctional, and both strongly associated with reduced upper respiratory tract SARS2 viral RNA, independent of neutralizing antibody titers. Overall, these findings provide evidence for protective roles for circulating SARS2-specific CD4+ and CD8+ T cells during acute COVID-19.

Introduction

Since the emergence of SARS-CoV-2 (SARS2) as a novel human pathogen, much has been learned about protective immunity to SARS2 in the contexts of infection and COVID-19 vaccines. Serologic correlates of protection have been established for vaccines (18). In the context of prophylaxis, virus neutralization by monoclonal antibodies (mAbs) has been demonstrated as one mechanism of protective immunity (912). In contrast, in the context of infection, the relative importance of immune system compartments may diff

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