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

Qin Xu; Pedro Milanez-Almeida; Andrew J Martins; Andrea J Radtke; Kenneth B Hoehn; Cihan Oguz; Jinguo Chen; Can Liu; Juanjie Tang; Gabrielle Grubbs; Sydney Stein; Sabrina Ramelli; Juraj Kabat; Hengameh Behzadpour; Maria Karkanitsa; Jacquelyn Spathies; Heather Kalish; Lela Kardava; Martha Kirby; Foo Cheung; Silvia Preite; Patrick C Duncker; Moses M Kitakule; Nahir Romero; Diego Preciado; Lyuba Gitman; Galina Koroleva; Grace Smith; Arthur Shaffer; Ian T McBain; Peter J McGuire; Stefania Pittaluga; Ronald N Germain; Richard Apps; Daniella M Schwartz; Kaitlyn Sadtler; Susan Moir; Daniel S Chertow; Steven H Kleinstein; Surender Khurana; John S Tsang; Pamela Mudd; Pamela L Schwartzberg; Kalpana Manthiram

doi:10.1038/s41590-022-01367-z

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

Nat Immunol. 2023 Jan;24(1):186-199. doi: 10.1038/s41590-022-01367-z. Epub 2022 Dec 19.

Authors

Qin Xu¹, Pedro Milanez-Almeida^#², Andrew J Martins^#³, Andrea J Radtke^#⁴, Kenneth B Hoehn^#⁵, Cihan Oguz^{6

7}, Jinguo Chen², Can Liu³, Juanjie Tang⁸, Gabrielle Grubbs⁸, Sydney Stein^{9

10}, Sabrina Ramelli⁹, Juraj Kabat⁴, Hengameh Behzadpour¹¹, Maria Karkanitsa¹², Jacquelyn Spathies¹³, Heather Kalish¹³, Lela Kardava¹⁴, Martha Kirby¹⁵, Foo Cheung², Silvia Preite¹, Patrick C Duncker¹⁶, Moses M Kitakule¹⁷, Nahir Romero¹⁸, Diego Preciado^{11

18}, Lyuba Gitman^{11

18}, Galina Koroleva², Grace Smith¹⁹, Arthur Shaffer²⁰, Ian T McBain¹, Peter J McGuire¹⁵, Stefania Pittaluga¹⁹, Ronald N Germain^{4

21}, Richard Apps², Daniella M Schwartz¹⁷, Kaitlyn Sadtler¹², Susan Moir¹⁴, Daniel S Chertow^{9

10}, Steven H Kleinstein^{5

22

23}, Surender Khurana⁸, John S Tsang^{2

3}, Pamela Mudd^{11

18}, Pamela L Schwartzberg^{24

25}, Kalpana Manthiram²⁶

Affiliations

¹ 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.
² Center for Human Immunology, NIAID, NIH, Bethesda, MD, USA.
³ Multiscale Systems Biology Section, LISB, NIAID, NIH, Bethesda, MD, USA.
⁴ Center for Advanced Tissue Imaging, LISB, NIAID, NIH, Bethesda, MD, USA.
⁵ Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
⁶ NIAID Collaborative Bioinformatics Resource (NCBR), NIAID, NIH, Bethesda, MD, USA.
⁷ Axle Informatics, Bethesda, MD, USA.
⁸ Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, USA.
⁹ Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center (CC), NIH, Bethesda, MD, USA.
¹⁰ Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA.
¹¹ Division of Pediatric Otolaryngology, Children's National Hospital, Washington, DC, USA.
¹² Laboratory of Immuno-Engineering, National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH, Bethesda, MD, USA.
¹³ Trans-NIH Shared Resource on Biomedical Engineering and Physical Science, NIBIB, NIH, Bethesda, MD, USA.
¹⁴ B-cell Immunology Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA.
¹⁵ National Human Genome Research Institute (NHGRI), NIH, Bethesda, MD, USA.
¹⁶ Cytek Biosciences, Fremont, CA, USA.
¹⁷ Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, MD, USA.
¹⁸ Division of Otolaryngology, Department of Surgery, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
¹⁹ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, MD, USA.
²⁰ Lymphoid Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA.
²¹ Lymphocyte Biology Section, LISB, NIAID, NIH, Bethesda, MD, USA.
²² Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.
²³ Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
²⁴ 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. [email protected].
²⁵ National Human Genome Research Institute (NHGRI), NIH, Bethesda, MD, USA. [email protected].
²⁶ 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. [email protected].

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adaptive Immunity
Antibodies, Viral
COVID-19*
Child
Humans
Palatine Tonsil
Pandemics
SARS-CoV-2*

Substances

Antibodies, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding