Longitudinal analysis of humoral and cellular immunity in SARS-CoV-2 exposed families

Abstract Identification of previous SARS-CoV-2 infection typically relies on serology, yet T-cells play a key role in the adaptive immune response against SARS-CoV-2. Here, we investigated in parallel the SARS-CoV-2-specific as well as endemic human coronavirus-specific humoral and cross-reactive ce...

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Main Authors: Alex Dulovic, Armin Rabsteyn, Jonathan Remppis, Irene K. E. Gentzcke, Julia Mueller, Nadja Tuecks, Matthias Becker, Daniel Junker, Philipp D. Kaiser, Bjoern Traenkle, Ulrich Rothbauer, Juliane S. Walz, Andreas Peter, Sebastian Hörber, Tina Ganzenmueller, Thomas Iftner, Maximilian Stich, Burkhard Tönshoff, Philipp Henneke, Roland Elling, Klaus-Michael Debatin, Ales Janda, Nicole Schneiderhan-Marra, Axel R. Franz, Peter Lang, Hanna Renk
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-07739-3
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author Alex Dulovic
Armin Rabsteyn
Jonathan Remppis
Irene K. E. Gentzcke
Julia Mueller
Nadja Tuecks
Matthias Becker
Daniel Junker
Philipp D. Kaiser
Bjoern Traenkle
Ulrich Rothbauer
Juliane S. Walz
Andreas Peter
Sebastian Hörber
Tina Ganzenmueller
Thomas Iftner
Maximilian Stich
Burkhard Tönshoff
Philipp Henneke
Roland Elling
Klaus-Michael Debatin
Ales Janda
Nicole Schneiderhan-Marra
Axel R. Franz
Peter Lang
Hanna Renk
author_facet Alex Dulovic
Armin Rabsteyn
Jonathan Remppis
Irene K. E. Gentzcke
Julia Mueller
Nadja Tuecks
Matthias Becker
Daniel Junker
Philipp D. Kaiser
Bjoern Traenkle
Ulrich Rothbauer
Juliane S. Walz
Andreas Peter
Sebastian Hörber
Tina Ganzenmueller
Thomas Iftner
Maximilian Stich
Burkhard Tönshoff
Philipp Henneke
Roland Elling
Klaus-Michael Debatin
Ales Janda
Nicole Schneiderhan-Marra
Axel R. Franz
Peter Lang
Hanna Renk
author_sort Alex Dulovic
collection DOAJ
description Abstract Identification of previous SARS-CoV-2 infection typically relies on serology, yet T-cells play a key role in the adaptive immune response against SARS-CoV-2. Here, we investigated in parallel the SARS-CoV-2-specific as well as endemic human coronavirus-specific humoral and cross-reactive cellular responses in children and adults. We analyzed clinical data and blood samples from a family cohort of 96 children and 144 adults at 3–4 and 11–12 months after their first contact with SARS-CoV-2. Humoral response was assessed by a multiplex immunoassay with high sensitivity and specificity (MULTICOV-AB). Cellular responses were analyzed by IFN-γ ELISPOT using four different established epitope compositions (ECs) to discriminate between SARS-CoV-2 specific and HCoV cross-reactive T-cell responses. While the majority of adults had a combined serological and T-cell response, relatively more children had a T-cell response alone rather than a combined response. The magnitude of the T-cell response correlated with symptoms and the humoral response. In addition, SARS-CoV-2 infection significantly boosted the endemic coronavirus-specific cellular response. Overall, our data suggest discordant humoral and cellular responses, reflecting either abortive infection, cellular sensitization with rapid viral clearance or rapid antibody waning or a combination of these phenomena. Restricting epidemiologic analysis to SARS-CoV-2 serological data may underestimate rates of infection with or at least exposure to SARS-CoV-2 in children.
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spelling doaj-art-8d2f8abb7f9e480d8368e169beab1df42025-08-20T03:05:23ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-07739-3Longitudinal analysis of humoral and cellular immunity in SARS-CoV-2 exposed familiesAlex Dulovic0Armin Rabsteyn1Jonathan Remppis2Irene K. E. Gentzcke3Julia Mueller4Nadja Tuecks5Matthias Becker6Daniel Junker7Philipp D. Kaiser8Bjoern Traenkle9Ulrich Rothbauer10Juliane S. Walz11Andreas Peter12Sebastian Hörber13Tina Ganzenmueller14Thomas Iftner15Maximilian Stich16Burkhard Tönshoff17Philipp Henneke18Roland Elling19Klaus-Michael Debatin20Ales Janda21Nicole Schneiderhan-Marra22Axel R. Franz23Peter Lang24Hanna Renk25NMI Natural and Medical Sciences Institute at the University of TübingenGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site TübingenDepartment of Pediatric Oncology and Hematology, University Children’s Hospital TübingenDepartment of Neuropediatrics, General Pediatrics, Diabetology, Endocrinology and Social Pediatrics, University Children’s Hospital TübingenDepartment of Neuropediatrics, General Pediatrics, Diabetology, Endocrinology and Social Pediatrics, University Children’s Hospital TübingenDepartment of Neuropediatrics, General Pediatrics, Diabetology, Endocrinology and Social Pediatrics, University Children’s Hospital TübingenNMI Natural and Medical Sciences Institute at the University of TübingenNMI Natural and Medical Sciences Institute at the University of TübingenNMI Natural and Medical Sciences Institute at the University of TübingenNMI Natural and Medical Sciences Institute at the University of TübingenPharmaceutical Biotechnology, University of TübingenGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site TübingenInstitute for Clinical Chemistry and Pathobiochemistry, University Hospital TübingenInstitute for Clinical Chemistry and Pathobiochemistry, University Hospital TübingenInstitute for Medical Virology and Epidemiology of Viral Diseases, University Hospital TübingenInstitute for Medical Virology and Epidemiology of Viral Diseases, University Hospital TübingenHeidelberg University, Medical Faculty, Departement of Pediatrics I, , University Children‘s Hospital HeidelbergHeidelberg University, Medical Faculty, Departement of Pediatrics I, , University Children‘s Hospital HeidelbergCenter for Pediatrics and Adolescent Medicine, Faculty of Medicine, Medical Center Freiburg, University of FreiburgCenter for Pediatrics and Adolescent Medicine, Faculty of Medicine, Medical Center Freiburg, University of FreiburgDepartment of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm UniversityDepartment of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm UniversityNMI Natural and Medical Sciences Institute at the University of TübingenCenter for Pediatric Clinical Studies, University Hospital TübingenGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site TübingenDepartment of Pediatric Oncology and Hematology, University Children’s Hospital TübingenAbstract Identification of previous SARS-CoV-2 infection typically relies on serology, yet T-cells play a key role in the adaptive immune response against SARS-CoV-2. Here, we investigated in parallel the SARS-CoV-2-specific as well as endemic human coronavirus-specific humoral and cross-reactive cellular responses in children and adults. We analyzed clinical data and blood samples from a family cohort of 96 children and 144 adults at 3–4 and 11–12 months after their first contact with SARS-CoV-2. Humoral response was assessed by a multiplex immunoassay with high sensitivity and specificity (MULTICOV-AB). Cellular responses were analyzed by IFN-γ ELISPOT using four different established epitope compositions (ECs) to discriminate between SARS-CoV-2 specific and HCoV cross-reactive T-cell responses. While the majority of adults had a combined serological and T-cell response, relatively more children had a T-cell response alone rather than a combined response. The magnitude of the T-cell response correlated with symptoms and the humoral response. In addition, SARS-CoV-2 infection significantly boosted the endemic coronavirus-specific cellular response. Overall, our data suggest discordant humoral and cellular responses, reflecting either abortive infection, cellular sensitization with rapid viral clearance or rapid antibody waning or a combination of these phenomena. Restricting epidemiologic analysis to SARS-CoV-2 serological data may underestimate rates of infection with or at least exposure to SARS-CoV-2 in children.https://doi.org/10.1038/s41598-025-07739-3
spellingShingle Alex Dulovic
Armin Rabsteyn
Jonathan Remppis
Irene K. E. Gentzcke
Julia Mueller
Nadja Tuecks
Matthias Becker
Daniel Junker
Philipp D. Kaiser
Bjoern Traenkle
Ulrich Rothbauer
Juliane S. Walz
Andreas Peter
Sebastian Hörber
Tina Ganzenmueller
Thomas Iftner
Maximilian Stich
Burkhard Tönshoff
Philipp Henneke
Roland Elling
Klaus-Michael Debatin
Ales Janda
Nicole Schneiderhan-Marra
Axel R. Franz
Peter Lang
Hanna Renk
Longitudinal analysis of humoral and cellular immunity in SARS-CoV-2 exposed families
Scientific Reports
title Longitudinal analysis of humoral and cellular immunity in SARS-CoV-2 exposed families
title_full Longitudinal analysis of humoral and cellular immunity in SARS-CoV-2 exposed families
title_fullStr Longitudinal analysis of humoral and cellular immunity in SARS-CoV-2 exposed families
title_full_unstemmed Longitudinal analysis of humoral and cellular immunity in SARS-CoV-2 exposed families
title_short Longitudinal analysis of humoral and cellular immunity in SARS-CoV-2 exposed families
title_sort longitudinal analysis of humoral and cellular immunity in sars cov 2 exposed families
url https://doi.org/10.1038/s41598-025-07739-3
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