Evidence map›Paper›PMID 36536106›Full record

ArticleNature immunology2023

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 and 34 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Nature immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05656365 (Evaluating the Genetics and Immunology of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis), which is not on this map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
6.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05656365 recruitingnot on this map

Evaluating the Genetics and Immunology of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome and Other Tonsil Disorders

TypeobservationalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2023 to 2038Enrolled1,500ConditionsPeriodic Fever, Aphthous Stomatitis, Pharyngitis, And Cervical Adenitis (Pfapa), Obstructive Sleep Apnea, Tonsillitis, Tonsil Disorder
3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.

  1. Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025
    Pooled it
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  3. Distinct CD8iScience · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

44 authors at 14 institutions in 1 country.

Qin XuCell 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.ORCID http://orcid.org/0000-0003-1812-3108
Pedro Milanez-Almeida *Center for Human Immunology, NIAID, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8285-957X
Andrew J Martins *Multiscale Systems Biology Section, LISB, NIAID, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-1832-1924
Andrea J Radtke *Center for Advanced Tissue Imaging, LISB, NIAID, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-4379-8967
Kenneth B Hoehn *Department of Pathology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0411-4307
Cihan OguzNIAID Collaborative Bioinformatics Resource (NCBR), NIAID, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2860-3546
Jinguo ChenCenter for Human Immunology, NIAID, NIH, Bethesda, MD, USA.
Can LiuMultiscale Systems Biology Section, LISB, NIAID, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8411-3891
Juanjie TangDivision of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, USA.
Gabrielle GrubbsDivision of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, USA.ORCID http://orcid.org/0000-0003-4302-9535
Sydney SteinEmerging Pathogens Section, Critical Care Medicine Department, Clinical Center (CC), NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-0259-4485
Sabrina RamelliEmerging Pathogens Section, Critical Care Medicine Department, Clinical Center (CC), NIH, Bethesda, MD, USA.
Juraj KabatCenter for Advanced Tissue Imaging, LISB, NIAID, NIH, Bethesda, MD, USA.
Hengameh BehzadpourDivision of Pediatric Otolaryngology, Children's National Hospital, Washington, DC, USA.ORCID http://orcid.org/0000-0002-0050-8336
Maria KarkanitsaLaboratory of Immuno-Engineering, National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3474-2371
Jacquelyn SpathiesTrans-NIH Shared Resource on Biomedical Engineering and Physical Science, NIBIB, NIH, Bethesda, MD, USA.
Heather KalishTrans-NIH Shared Resource on Biomedical Engineering and Physical Science, NIBIB, NIH, Bethesda, MD, USA.
Lela KardavaB-cell Immunology Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-9135-6026
Martha KirbyNational Human Genome Research Institute (NHGRI), NIH, Bethesda, MD, USA.
Foo CheungCenter for Human Immunology, NIAID, NIH, Bethesda, MD, USA.
Silvia PreiteCell 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 DunckerCytek Biosciences, Fremont, CA, USA.
Moses M KitakuleLaboratory of Allergic Diseases, NIAID, NIH, Bethesda, MD, USA.
Nahir RomeroDivision of Otolaryngology, Department of Surgery, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Diego PreciadoDivision of Pediatric Otolaryngology, Children's National Hospital, Washington, DC, USA.
Lyuba GitmanDivision of Pediatric Otolaryngology, Children's National Hospital, Washington, DC, USA.
Galina KorolevaCenter for Human Immunology, NIAID, NIH, Bethesda, MD, USA.
Grace SmithLaboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-6381-0391
Arthur ShafferLymphoid Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA.
Ian T McBainCell 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 McGuireNational Human Genome Research Institute (NHGRI), NIH, Bethesda, MD, USA.
Stefania PittalugaLaboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-7688-1439
Ronald N GermainCenter for Advanced Tissue Imaging, LISB, NIAID, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1495-9143
Richard AppsCenter for Human Immunology, NIAID, NIH, Bethesda, MD, USA.
Daniella M SchwartzLaboratory of Allergic Diseases, NIAID, NIH, Bethesda, MD, USA.
Kaitlyn SadtlerLaboratory of Immuno-Engineering, National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH, Bethesda, MD, USA.
Susan MoirB-cell Immunology Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA.
Daniel S ChertowEmerging Pathogens Section, Critical Care Medicine Department, Clinical Center (CC), NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-1675-1728
Steven H KleinsteinDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-4957-1544
Surender KhuranaDivision of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, USA.ORCID http://orcid.org/0000-0002-0593-7965
John S TsangCenter for Human Immunology, NIAID, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3186-3047
Pamela MuddDivision of Pediatric Otolaryngology, Children's National Hospital, Washington, DC, USA.
Pamela L SchwartzbergCell 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. pams@nih.gov.ORCID http://orcid.org/0000-0001-6318-9187
Kalpana ManthiramCell 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. kalpana.manthiram@nih.gov.ORCID http://orcid.org/0000-0001-6451-8173
National Institutes of Health · USChildren's National · USNational Institute of Allergy and Infectious Diseases · USAdvanced Tissue (United States) · USCenter for Biologics Evaluation and Research · USLocal Initiatives Support Corporation · USNational Human Genome Research Institute · USNational Cancer Institute · USNational Institute of Biomedical Imaging and Bioengineering · USYale University · USAmerican Axle & Manufacturing (United States) · USCenter for Cancer Research · USGeorge Washington University · USNational Institutes of Health Clinical Center · US

Funding

Infectious Diseases Research Technologies Core - BethesdaZICAI001051 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2009 to 2025
$226.1M
Metabolism, infection and immunity in inborn errors of mitochondrial metabolismZIAHG200381 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI MCGUIRE, PETER · 2012 to 2025
$21.7M
Genetic and Biochemical Approaches to Tyrosine Kinase and Lymphocyte SignalingZIAAI001240 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SCHWARTZBERG, PAMELA · 2019 to 2025
$18.8M
Lymphoma Disease Discovery and DefintionZIASC000550 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI JAFFE, ELAINE · 2009 to 2025
$16.9M
Functional Biology Of T CellsZIAAI000758 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI GERMAIN, RONALD N · 2009 to 2025
$15.4M
ImmunoengineeringZIAEB000093 · NIBIB · NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING · PI SADTLER, KAITLYN · 2020 to 2025
$5.5M
COMPUTATIONAL TOOLS FOR THE ANALYSIS OF HIGH-THROUGHPUT IMMUNOGLOBULIN SEQUENCING EXPERIMENTSR01AI104739 · NIAID · YALE UNIVERSITY · PI KLEINSTEIN, STEVEN H. · 2014 to 2022
$3.6M
COVID-19 Instrumentation in the RTBZICAI001313 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2020 to 2023
$2.6M
Evaluation of Oropharyngeal responses to SARS-CoV-2ZIAAI001345 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SCHWARTZBERG, PAMELA · 2021 to 2025
$1.3M
Immunologic Studies Associated with COVID-19 ZIAAI001325 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MOIR, SUSAN · 2020 to 2025
$1.3M
Clinical and Molecular Features of Coronavirus Disease 2019ZIACL090070 · CLC · CLINICAL CENTER · PI CHERTOW, DANIEL S · 2020 to 2025
$0k
Intramural NIH HHS Z99 AI999999Intramural NIH HHS ZIA AI001345NIAID NIH HHS R01 AI104739
6 · The paper itself

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.

Indexed as

COVID-19SARS-CoV-2Adaptive ImmunityAntibodies, ViralChildHumansPalatine TonsilPandemicsAntibodies, Viral

Identifiers

PMID36536106
PMCPMC10777159
OpenAlexW4312019644

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.