Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children

Qin Xu, Cell Signaling and Immunity Section, Laboratory of Immune System Biology (LISB), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Pedro Milanez-Almeida, Center for Human Immunology, NIAID, NIH, Bethesda, MD, USA.
Andrew J. Martins, Multiscale Systems Biology Section, LISB, NIAID, NIH, Bethesda, MD, USA.
Andrea J. Radtke, Center for Advanced Tissue Imaging, LISB, NIAID, NIH, Bethesda, MD, USA.
Kenneth B. Hoehn, Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Cihan Oguz, NIAID Collaborative Bioinformatics Resource (NCBR), NIAID, NIH, Bethesda, MD, USA.
Jinguo Chen, Center for Human Immunology, NIAID, NIH, Bethesda, MD, USA.
Can Liu, Multiscale Systems Biology Section, LISB, NIAID, NIH, Bethesda, MD, USA.
Juanjie Tang, Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, USA.
Gabrielle Grubbs, Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, USA.
Sydney Stein, Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center (CC), NIH, Bethesda, MD, USA.
Sabrina Ramelli, Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center (CC), NIH, Bethesda, MD, USA.
Juraj Kabat, Center for Advanced Tissue Imaging, LISB, NIAID, NIH, Bethesda, MD, USA.
Hengameh Behzadpour, Division of Pediatric Otolaryngology, Children's National Hospital, Washington, DC, USA.
Maria Karkanitsa, Laboratory of Immuno-Engineering, National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH, Bethesda, MD, USA.
Jacquelyn Spathies, Trans-NIH Shared Resource on Biomedical Engineering and Physical Science, NIBIB, NIH, Bethesda, MD, USA.
Heather Kalish, Trans-NIH Shared Resource on Biomedical Engineering and Physical Science, NIBIB, NIH, Bethesda, MD, USA.
Lela Kardava, B-cell Immunology Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA.
Martha Kirby, National Human Genome Research Institute (NHGRI), NIH, Bethesda, MD, USA.
Foo Cheung, Center for Human Immunology, NIAID, NIH, Bethesda, MD, USA.
Silvia Preite, Cell Signaling and Immunity Section, Laboratory of Immune System Biology (LISB), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Patrick C. Duncker, Cytek Biosciences, Fremont, CA, USA.
Moses M. Kitakule, Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, MD, USA.
Nahir Romero, Division of Otolaryngology, Department of Surgery, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Diego Preciado, Division of Pediatric Otolaryngology, Children's National Hospital, Washington, DC, USA.
Lyuba Gitman, Division of Pediatric Otolaryngology, Children's National Hospital, Washington, DC, USA.
Galina Koroleva, Center for Human Immunology, NIAID, NIH, Bethesda, MD, USA.
Grace Smith, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, MD, USA.
Arthur Shaffer, Lymphoid Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA.
Ian T. McBain, Cell Signaling and Immunity Section, Laboratory of Immune System Biology (LISB), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Peter J. McGuire, National Human Genome Research Institute (NHGRI), NIH, Bethesda, MD, USA.
Stefania Pittaluga, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, MD, USA.

Document Type

Journal Article

Publication Date

12-19-2022

Journal

Nature immunology

DOI

10.1038/s41590-022-01367-z

Abstract

Most studies of adaptive immunity to SARS-CoV-2 infection focus on peripheral blood, which may not fully reflect immune responses at the site of infection. Using samples from 110 children undergoing tonsillectomy and adenoidectomy during the COVID-19 pandemic, we identified 24 samples with evidence of previous SARS-CoV-2 infection, including neutralizing antibodies in serum and SARS-CoV-2-specific germinal center and memory B cells in the tonsils and adenoids. Single-cell B cell receptor (BCR) sequencing indicated virus-specific BCRs were class-switched and somatically hypermutated, with overlapping clones in the two tissues. Expanded T cell clonotypes were found in tonsils, adenoids and blood post-COVID-19, some with CDR3 sequences identical to previously reported SARS-CoV-2-reactive T cell receptors (TCRs). Pharyngeal tissues from COVID-19-convalescent children showed persistent expansion of germinal center and antiviral lymphocyte populations associated with interferon (IFN)-γ-type responses, particularly in the adenoids, and viral RNA in both tissues. Our results provide evidence for persistent tissue-specific immunity to SARS-CoV-2 in the upper respiratory tract of children after infection.

Department

Surgery

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