{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:00:22Z","timestamp":1791388822413,"version":"4.3.3"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"German Federal Ministry of Education and Research (BMBF) Network of University Medicine 2.0","award":["01KX2121"],"award-info":[{"award-number":["01KX2121"]}]},{"name":"German Federal Ministry of Education and Research (BMBF) Network of University Medicine 2.0","award":["01KX2121"],"award-info":[{"award-number":["01KX2121"]}]},{"name":"German Federal Ministry of Education and Research (BMBF) Network of University Medicine 2.0","award":["01KX2121"],"award-info":[{"award-number":["01KX2121"]}]},{"DOI":"10.13039\/501100006254","name":"Ruhr-Universit\u00e4t Bochum","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006254","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Infection"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>A lot of research has been done, mainly on tuberculosis (TB), on the extent to which cellular immune protection as measured by interferon-\u03b3 release assays (IGRA) is age-dependent. In a previous study we showed that following an Omicron infection, adolescents with a hybrid immunity had a higher probability of having a reactive SARS-CoV-2-specific IGRA than children. Therefore, we examined in a large group of minors and adults whether age influences cellular immunity as measured by IGRA in TB and SARS-CoV-2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants were recruited at 13 German study sites between September and December 2022. Cellular immunity was analyzed using SARS-CoV-2 and Tb-specific IGRA and humoral immunity against SARS-CoV-2 by measuring antibodies against spike (S) and nucleocapsid protein. Analysis was done depending on natural (convalescent, not vaccinated) or hybrid immunity (convalescent and vaccinated).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 1401 adults and 392 minors were included. The amount of interferon-\u03b3 released by T cells, as well as the probability of a positive SARS-CoV-2 IGRA (OR 1.022) and a positive Tb IGRA (OR 1.047) were age dependent. Sensitivity of SARS-CoV-2 IGRA in natural immunity was lower in minors (0.45), especially in those less than 5\u00a0years (0.29) as compared to adults (0.66).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The interferon-\u03b3 response to SARS-CoV-2 infections and\/or vaccinations and to Tb infections as measured by IGRA is in quality and quantity dependent on age. The sensitivity of commercially available tests in young children seems to be suboptimal, limiting their use as a diagnostic or research tool in this age group.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s15010-025-02613-w","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T17:32:47Z","timestamp":1753896767000},"page":"2669-2680","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Performance of whole blood interferon-\u03b3 release assays in SARS-CoV-2 and tuberculosis is age dependent"],"prefix":"10.1007","volume":"53","author":[{"given":"Tobias","family":"Rothoeft","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Teresa","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Denz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Kobbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Friedrichs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg M. N.","family":"Behrens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Behrens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Berner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amke","family":"Caliebe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia M.","family":"Denkinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Giesbrecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonhard","family":"Hojenski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Hovardovska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Dopfer-Jablonka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Iatseniuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim J.","family":"Kaasch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Kraus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lazar","family":"Mitrov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Nauck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana Nunes","family":"de Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarete","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Schmiedel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Stahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Timmesfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Toepfner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne","family":"Vehreschild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter A.","family":"Wohlgemuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Petersmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J. G. T.","family":"Vehreschild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folke","family":"Brinkmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The NU(M)KRAINE Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"2613_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1128\/CMR.00034-13","volume":"27","author":"M Pai","year":"2014","unstructured":"Pai M, Denkinger CM, Kik SV, Rangaka MX, Zwerling A, Oxlade O, et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev. 2014;27:3\u201320.","journal-title":"Clin Microbiol Rev"},{"key":"2613_CR2","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1016\/j.cmi.2021.07.005","volume":"27","author":"D Goletti","year":"2021","unstructured":"Goletti D, Petrone L, Manissero D, Bertoletti A, Rao S, Ndunda N, et al. The potential clinical utility of measuring severe acute respiratory syndrome coronavirus 2-specific T-cell responses. Clin Microbiol Infect. 2021;27:1784\u20139.","journal-title":"Clin Microbiol Infect"},{"key":"2613_CR3","doi-asserted-by":"publisher","first-page":"1370859","DOI":"10.3389\/fcimb.2024.1370859","volume":"14","author":"E Culebras","year":"2024","unstructured":"Culebras E, Mart\u00ednez M, Novella C, Le\u00f3n JM, Marcos E, Delgado-Iribarren A, et al. Cell immunity to SARS-CoV-2 after natural infection and\/or different vaccination regimens. Front Cell Infect Microbiol. 2024;14:1370859.","journal-title":"Front Cell Infect Microbiol"},{"key":"2613_CR4","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.jinf.2021.02.023","volume":"82","author":"L Petrone","year":"2021","unstructured":"Petrone L, Petruccioli E, Alonzi T, Vanini V, Cuzzi G, Najafi Fard S, et al. In-vitro evaluation of the immunomodulatory effects of Baricitinib: implication for COVID-19 therapy. J Infect. 2021;82:58\u201366.","journal-title":"J Infect"},{"key":"2613_CR5","doi-asserted-by":"publisher","first-page":"286.e7","DOI":"10.1016\/j.cmi.2020.09.051","volume":"27","author":"L Petrone","year":"2021","unstructured":"Petrone L, Petruccioli E, Vanini V, Cuzzi G, Najafi Fard S, Alonzi T, et al. A whole blood test to measure SARS-CoV-2-specific response in COVID-19 participants. Clin Microbiol Infect. 2021;27:286.e7-286.e13.","journal-title":"Clin Microbiol Infect"},{"key":"2613_CR6","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-024-02225-w","author":"T Rothoeft","year":"2024","unstructured":"Rothoeft T, Maier C, Talarico A, Hoffmann A, Schlegtendal A, Lange B, et al. Natural and hybrid immunity after SARS-CoV-2 infection in children and adolescents. Infection. 2024. https:\/\/doi.org\/10.1007\/s15010-024-02225-w.","journal-title":"Infection"},{"key":"2613_CR7","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1097\/INF.0b013e3181c4822f","volume":"29","author":"TG Connell","year":"2010","unstructured":"Connell TG, Tebruegge M, Ritz N, Bryant PA, Leslie D, Curtis N. Indeterminate interferon-\u03b3 release assay results in children. Pediatr Infect Dis J. 2010;29:285\u20136.","journal-title":"Pediatr Infect Dis J"},{"key":"2613_CR8","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1097\/INF.0b013e3181a16394","volume":"28","author":"T Haustein","year":"2009","unstructured":"Haustein T, Ridout DA, Hartley JC, Thaker U, Shingadia D, Klein NJ, et al. The likelihood of an indeterminate test result from a whole-blood interferon-\u03b3 release assay for the diagnosis of Mycobacterium tuberculosis infection in children correlates with age and immune status. Pediatr Infect Dis J. 2009;28:669\u201373.","journal-title":"Pediatr Infect Dis J"},{"key":"2613_CR9","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1136\/thorax-2022-218929","volume":"78","author":"D Buonsenso","year":"2023","unstructured":"Buonsenso D, Noguera-Julian A, Moroni R, Hern\u00e1ndez-Bartolom\u00e9 A, Fritschi N, Lancella L, et al. Performance of quantiferon-TB gold plus assays in paediatric tuberculosis: a multicentre PTBNET study. Thorax. 2023;78:288\u201396.","journal-title":"Thorax"},{"key":"2613_CR10","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1007\/s00431-024-05847-2","volume":"184","author":"AT Hoffmann","year":"2024","unstructured":"Hoffmann AT, Kobbe R, Denz R, Maier C, Toepfner N, Timmesfeld N, et al. Health and socio-demographic background of Ukrainian minors and their families in Germany - challenges for refugee medicine: a cross-sectional study from the German network university medicine (NUM). Eur J Pediatr. 2024;184:64.","journal-title":"Eur J Pediatr"},{"key":"2613_CR11","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/j.jiph.2024.02.003","volume":"17","author":"F Brinkmann","year":"2024","unstructured":"Brinkmann F, Friedrichs A, Behrens GM, Behrens P, Berner R, Caliebe A, et al. Prevalence of infectious diseases, immunity to vaccine-preventable diseases and chronic medical conditions among Ukrainian refugees in Germany \u2013 a cross sectional study from the German network university medicine (NUM). J Infect Public Health. 2024;17:642\u20139.","journal-title":"J Infect Public Health"},{"key":"2613_CR12","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1016\/j.jmii.2022.09.004","volume":"55","author":"K Widyasari","year":"2022","unstructured":"Widyasari K, Jang J, Lee S, Kang T, Kim S. Evaluation of the T cell and B cell response following the administration of COVID-19 vaccines in Korea. J Microbiol Immunol Infect. 2022;55:1013\u201324.","journal-title":"J Microbiol Immunol Infect"},{"key":"2613_CR13","doi-asserted-by":"publisher","first-page":"844","DOI":"10.3390\/v15040844","volume":"15","author":"JYL Fu","year":"2023","unstructured":"Fu JYL, Pukhari MH, Bador MK, Sam I-C, Chan YF. Humoral and T cell immune responses against SARS-CoV-2 after primary and homologous or heterologous booster vaccinations and breakthrough infection: a longitudinal cohort study in Malaysia. Viruses. 2023;15:844.","journal-title":"Viruses"},{"key":"2613_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2022.105098","volume":"148","author":"D Huzly","year":"2022","unstructured":"Huzly D, Panning M, Smely F, Enders M, Komp J, Falcone V, et al. Accuracy and real life performance of a novel interferon-\u03b3 release assay for the detection of SARS-CoV2 specific T cell response. J Clin Virol. 2022;148:105098.","journal-title":"J Clin Virol"},{"key":"2613_CR15","doi-asserted-by":"publisher","first-page":"e02199","DOI":"10.1128\/jcm.02199-21","volume":"60","author":"P Barreiro","year":"2022","unstructured":"Barreiro P, Sanz JC, San Rom\u00e1n J, P\u00e9rez-Abeledo M, Carretero M, Meg\u00edas G, et al. A pilot study for the evaluation of an interferon gamma release assay (IGRA) to measure T-cell immune responses after SARS-CoV-2 infection or vaccination in a unique cloistered cohort. J Clin Microbiol. 2022;60:e02199.","journal-title":"J Clin Microbiol"},{"key":"2613_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2023.115948","volume":"106","author":"M-M Dourdouna","year":"2023","unstructured":"Dourdouna M-M, Tatsi E-B, Syriopoulou V, Michos A. Evaluation of T cell responses with the QuantiFERON SARS-CoV-2 assay in individuals with 3 doses of BNT162b2 vaccine, SARS-CoV-2 infection, or hybrid immunity. Diagn Microbiol Infect Dis. 2023;106:115948.","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2613_CR17","doi-asserted-by":"publisher","first-page":"1242380","DOI":"10.3389\/fimmu.2023.1242380","volume":"14","author":"A No\u00e9","year":"2023","unstructured":"No\u00e9 A, Dang TD, Axelrad C, Burrell E, Germano S, Elia S, et al. BNT162b2 COVID-19 vaccination in children alters cytokine responses to heterologous pathogens and toll-like receptor agonists. Front Immunol. 2023;14:1242380.","journal-title":"Front Immunol"},{"key":"2613_CR18","doi-asserted-by":"publisher","first-page":"2206360","DOI":"10.1080\/21645515.2023.2206360","volume":"19","author":"K Tawinprai","year":"2023","unstructured":"Tawinprai K, Jungsomsri P, Pinijnai O, Tavonvunchai F, Lievjaroen A, Suwannaroj P, et al. Immunogenicity and reactogenicity of heterologous prime-boost vaccination with inactivated COVID-19 and ChAdOx1 nCoV-19 (AZD1222) vaccines, a quasi-experimental study. Hum Vaccin Immunother. 2023;19:2206360.","journal-title":"Hum Vaccin Immunother"},{"key":"2613_CR19","doi-asserted-by":"publisher","first-page":"E1483","DOI":"10.1503\/cmaj.210053","volume":"193","author":"O Drouin","year":"2021","unstructured":"Drouin O, Hepburn CM, Farrar DS, Baerg K, Chan K, Cyr C, et al. Characteristics of children admitted to hospital with acute SARS-CoV-2 infection in Canada in 2020. CMAJ. 2021;193:E1483\u201393.","journal-title":"CMAJ"},{"key":"2613_CR20","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1097\/INF.0000000000002660","volume":"39","author":"P Zimmermann","year":"2020","unstructured":"Zimmermann P, Curtis N. Coronavirus infections in children including COVID-19: an overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children. Pediatr Infect Dis J. 2020;39:355\u201368.","journal-title":"Pediatr Infect Dis J"},{"key":"2613_CR21","first-page":"100433","volume":"24","author":"A Hoang","year":"2020","unstructured":"Hoang A, Chorath K, Moreira A, Evans M, Burmeister-Morton F, Burmeister F, et al. COVID-19 in 7780 pediatric participants: a systematic review. eClin Med. 2020;24:100433.","journal-title":"eClin Med"},{"key":"2613_CR22","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2021-052273","volume":"148","author":"DW McCormick","year":"2021","unstructured":"McCormick DW, Richardson LC, Young PR, Viens LJ, Gould CV, Kimball A, et al. Deaths in children and adolescents associated with COVID-19 and MIS-C in the United States. Pediatrics. 2021;148: e2021052273.","journal-title":"Pediatrics"},{"key":"2613_CR23","doi-asserted-by":"publisher","first-page":"2694","DOI":"10.1128\/JCM.00814-14","volume":"52","author":"M Tebruegge","year":"2014","unstructured":"Tebruegge M, De Graaf H, Sukhtankar P, Elkington P, Marshall B, Schuster H, et al. Extremes of age are associated with indeterminate QuantiFERON-TB gold assay results. J Clin Microbiol. 2014;52:2694.","journal-title":"J Clin Microbiol"},{"key":"2613_CR24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038556","volume":"7","author":"S Banfield","year":"2012","unstructured":"Banfield S, Pascoe E, Thambiran A, Siafarikas A, Burgner D. Factors associated with the performance of a blood-based interferon-\u03b3 release assay in diagnosing tuberculosis. PLoS ONE. 2012;7: e38556.","journal-title":"PLoS ONE"},{"key":"2613_CR25","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy184","volume":"5","author":"JC Sharninghausen","year":"2018","unstructured":"Sharninghausen JC, Shapiro AE, Koelle DM, Kim HN. Risk factors for indeterminate outcome on interferon gamma release assay in non-US-born persons screened for latent tuberculosis infection. Open Forum Infect Dis. 2018;5: ofy184.","journal-title":"Open Forum Infect Dis"},{"key":"2613_CR26","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1136\/thx.2005.048033","volume":"61","author":"TG Connell","year":"2006","unstructured":"Connell TG. Performance of a whole blood interferon gamma assay for detecting latent infection with Mycobacterium tuberculosis in children. Thorax. 2006;61:616\u201320.","journal-title":"Thorax"},{"key":"2613_CR27","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1164\/rccm.200212-1483OC","volume":"168","author":"C Lienhardt","year":"2003","unstructured":"Lienhardt C, Fielding K, Sillah J, Tunkara A, Donkor S, Manneh K, et al. Risk factors for tuberculosis infection in sub-Saharan Africa: a contact study in the Gambia. Am J Respir Crit Care Med. 2003;168:448\u201355.","journal-title":"Am J Respir Crit Care Med"},{"key":"2613_CR28","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1186\/s12879-016-1989-x","volume":"16","author":"JR Ncayiyana","year":"2016","unstructured":"Ncayiyana JR, Bassett J, West N, Westreich D, Musenge E, Emch M, et al. Prevalence of latent tuberculosis infection and predictive factors in an urban informal settlement in Johannesburg, South Africa: a cross-sectional study. BMC Infect Dis. 2016;16:661.","journal-title":"BMC Infect Dis"},{"key":"2613_CR29","doi-asserted-by":"publisher","first-page":"8456","DOI":"10.4049\/jimmunol.177.12.8456","volume":"177","author":"DO Co","year":"2006","unstructured":"Co DO, Hogan LH, Karman J, Heninger E, Vang S, Wells K, et al. Interactions between T cells responding to concurrent mycobacterial and influenza infections. J Immunol. 2006;177:8456\u201365.","journal-title":"J Immunol"},{"key":"2613_CR30","doi-asserted-by":"crossref","unstructured":"Jerbi A, Feki S, Chtourou L, Hachicha H, Fourati H, Ben Amor F, et al. Study of the results of tuberculosis interferon-gamma release assays before and after the SARS CoV-2 pandemic. Indian J Tuberc. 2024;S0019570724000829.","DOI":"10.1016\/j.ijtb.2024.05.007"},{"key":"2613_CR31","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.ijid.2022.06.044","volume":"122","author":"N-Y Chen","year":"2022","unstructured":"Chen N-Y, Liu Z-H, Kao S-W, Lin H-S, Lee I-K, Zheng J-Y, et al. Changes in interferon-\u03b3 release assay readout after COVID-19 vaccination: a prospective cohort study. Int J Infect Dis. 2022;122:537\u201342.","journal-title":"Int J Infect Dis"},{"key":"2613_CR32","doi-asserted-by":"publisher","first-page":"e70008","DOI":"10.1002\/cti2.70008","volume":"13","author":"ZQ Toh","year":"2024","unstructured":"Toh ZQ, Anderson J, Mazarakis N, Quah L, Nguyen J, Higgins RA, et al. Humoral and cellular immune responses in vaccinated and unvaccinated children following SARS-CoV-2 omicron infection. Clin Trans Immunol. 2024;13:e70008.","journal-title":"Clin Trans Immunol"},{"key":"2613_CR33","doi-asserted-by":"publisher","first-page":"5487","DOI":"10.1126\/scitranslmed.abd5487","volume":"12","author":"CA Pierce","year":"2020","unstructured":"Pierce CA, Preston-Hurlburt P, Dai Y, Aschner CB, Cheshenko N, Galen B, et al. Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult participants. Sci Transl Med. 2020;12:5487.","journal-title":"Sci Transl Med"},{"key":"2613_CR34","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1020865","volume":"11","author":"A Seidel","year":"2023","unstructured":"Seidel A, Jacobsen E-M, Fabricius D, Class M, Zernickel M, Blum C, et al. Serum neutralizing capacity and T-cell response against the omicron BA.1 variant in seropositive children and their parents one year after SARS-CoV-2 infection. Front Pediatr. 2023;11: 1020865.","journal-title":"Front Pediatr"},{"key":"2613_CR35","doi-asserted-by":"publisher","first-page":"4678","DOI":"10.1038\/s41467-021-24938-4","volume":"12","author":"CA Cohen","year":"2021","unstructured":"Cohen CA, Li APY, Hachim A, Hui DSC, Kwan MYW, Tsang OTY, et al. SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection. Nat Commun. 2021;12:4678.","journal-title":"Nat Commun"},{"key":"2613_CR36","doi-asserted-by":"publisher","first-page":"7315","DOI":"10.1038\/s41467-022-35055-1","volume":"13","author":"E-M Jacobsen","year":"2022","unstructured":"Jacobsen E-M, Fabricius D, Class M, Topfstedt F, Lorenzetti R, Janowska I, et al. High antibody levels and reduced cellular response in children up to one year after SARS-CoV-2 infection. Nat Commun. 2022;13:7315.","journal-title":"Nat Commun"},{"key":"2613_CR37","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adl1997","volume":"16","author":"B Manfroi","year":"2024","unstructured":"Manfroi B, Cuc BT, Sokal A, Vandenberghe A, Temmam S, Attia M, et al. Preschool-age children maintain a distinct memory CD4+ T cell and memory B cell response after SARS-CoV-2 infection. Sci Transl Med. 2024;16:eadl1997.","journal-title":"Sci Transl Med"},{"key":"2613_CR38","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1038\/s12276-020-00486-7","volume":"52","author":"H-G Lee","year":"2020","unstructured":"Lee H-G, Cho M-J, Choi J-M. Bystander CD4+ T cells: crossroads between innate and adaptive immunity. Exp Mol Med. 2020;52:1255\u201363.","journal-title":"Exp Mol Med"},{"key":"2613_CR39","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/s41467-019-08482-w","volume":"10","author":"H-G Lee","year":"2019","unstructured":"Lee H-G, Lee J-U, Kim D-H, Lim S, Kang I, Choi J-M. Pathogenic function of bystander-activated memory-like CD4+ T cells in autoimmune encephalomyelitis. Nat Commun. 2019;10:709.","journal-title":"Nat Commun"},{"key":"2613_CR40","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1126\/science.272.5270.1947","volume":"272","author":"DF Tough","year":"1996","unstructured":"Tough DF, Borrow P, Sprent J. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science. 1996;272:1947\u201350.","journal-title":"Science"},{"key":"2613_CR41","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s12979-024-00454-z","volume":"21","author":"Z Gerelkhuu","year":"2024","unstructured":"Gerelkhuu Z, Park S, Lee KH, Kim YC, Kwon SJ, Song K-H, et al. Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling. Immun Ageing. 2024;21:51.","journal-title":"Immun Ageing"},{"key":"2613_CR42","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1111\/j.1600-0609.2008.01052.x","volume":"80","author":"S Huenecke","year":"2008","unstructured":"Huenecke S, Behl M, Fadler C, Zimmermann SY, Bochennek K, Tramsen L, et al. Age-matched lymphocyte subpopulation reference values in childhood and adolescence: application of exponential regression analysis. Eur J Haematol. 2008;80:532\u20139.","journal-title":"Eur J Haematol"},{"key":"2613_CR43","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1111\/j.1365-2249.2007.03497.x","volume":"150","author":"T Rothoeft","year":"2007","unstructured":"Rothoeft T, Fischer K, Zawatzki S, Schulz V, Schauer U, K\u00f6rner Rettberg C. Differential response of human naive and memory\/effector T cells to dendritic cells infected by respiratory syncytial virus. Clin Exp Immunol. 2007;150:263\u201373.","journal-title":"Clin Exp Immunol"},{"key":"2613_CR44","doi-asserted-by":"publisher","first-page":"2976","DOI":"10.1073\/pnas.96.6.2976","volume":"96","author":"BK Cho","year":"1999","unstructured":"Cho BK, Wang C, Sugawa S, Eisen HN, Chen J. Functional differences between memory and naive CD8 T cells. Proc Natl Acad Sci USA. 1999;96:2976\u201381.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"2613_CR45","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1136\/thorax-2022-218929","volume":"78","author":"D Buonsenso","year":"2023","unstructured":"Buonsenso D, Noguera-Julian A, Moroni R, Hern\u00e1ndez-Bartolom\u00e9 A, et al. Performance of quantiferon-TB gold plus assays in paediatric tuberculosis: a multicentre PTBNET study. Thorax. 2023;78(3):288\u201396. https:\/\/doi.org\/10.1136\/thorax-2022-218929.","journal-title":"Thorax"}],"container-title":["Infection"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s15010-025-02613-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s15010-025-02613-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s15010-025-02613-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T10:03:21Z","timestamp":1764756201000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s15010-025-02613-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,30]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["2613"],"URL":"https:\/\/doi.org\/10.1007\/s15010-025-02613-w","relation":{},"ISSN":["0300-8126","1439-0973"],"issn-type":[{"value":"0300-8126","type":"print"},{"value":"1439-0973","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,30]]},"assertion":[{"value":"22 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Two different leading ethics committees evaluated the study protocol, the committee of the Goethe University in Frankfurt for adult participants (reference number 2022-831) and the committee of the Ruhr University in Bochum for the paediatric cohort (registration number 22-7623). Subsequently, the study was approved by all local ethic committees of participating study centres. The study was conducted in accordance with the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All study participants received informed consent. Informed consent was obtained from all subjects and\/or their legal guardian(s).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}