{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T20:07:07Z","timestamp":1778962027431,"version":"3.51.4"},"reference-count":95,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"unspecified","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"crossref","award":["01KI20337"],"award-info":[{"award-number":["01KI20337"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,3,30]]},"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The SARS-CoV-2 pandemic remains a threat to public health. Soon after its outbreak, it became apparent that children are less severely affected. Indeed, opposing clinical manifestations between children and adults are observed for other infections. The SARS-CoV-2 outbreak provides the unique opportunity to study the underlying mechanisms. This protocol describes the methods of an observational study that aims to characterise age dependent differences in immune responses to primary respiratory infections using SARS-CoV-2 as a model virus and to assess age differences in clinical outcomes including lung function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>The study aims to recruit at least 120 children and 60 adults that are infected with SARS-CoV-2 and collect specimen for a multiomics analysis, including single cell RNA sequencing of nasal epithelial cells and peripheral blood mononuclear cells, mass cytometry of whole blood samples and nasal cells, mass spectrometry-based serum and plasma proteomics, nasal epithelial cultures with functional in vitro analyses, SARS-CoV-2 antibody testing, sequencing of the viral genome and lung function testing. Data obtained from this multiomics approach are correlated with medical history and clinical data. Recruitment started in October 2020 and is ongoing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>The study was reviewed and approved by the Ethics Committee of Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin (EA2\/066\/20). All collected specimens are stored in the central biobank of Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin and are made available to all participating researchers and on request.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>DRKS00025715, pre-results publication.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2022-065221","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T10:45:20Z","timestamp":1681728320000},"page":"e065221","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["RECAST: Study protocol for an observational study for the understanding of the increased REsilience of Children compared to Adults in SARS-CoV-2 infecTion"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-8997","authenticated-orcid":false,"given":"Sebastian","family":"Stricker","sequence":"first","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4195-8584","authenticated-orcid":false,"given":"Niklas","family":"Ziegahn","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Karsten","sequence":"additional","affiliation":[{"name":"Karsten, Rugo, Wagner, Paediatric Practice, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Boeckel","sequence":"additional","affiliation":[{"name":"Boeckel, Haverkaemper, Paediatric Practice and Practice for Paediatric Cardiology, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike","family":"Stich-Boeckel","sequence":"additional","affiliation":[{"name":"Stich-Boeckel, Paediatric Practice, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob","family":"Maske","sequence":"additional","affiliation":[{"name":"Maske, Pankok, Paediatric Practice, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyn","family":"Rugo","sequence":"additional","affiliation":[{"name":"Karsten, Rugo, Wagner, Paediatric Practice, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Balazs","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Millar B\u00fcchner","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantip","family":"Dang-Heine","sequence":"additional","affiliation":[{"name":"Clinical Study Center (CSC), Berlin Institute of Health at Charit\u00e9, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentin","family":"Schriever","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"},{"name":"Center for Chronically Sick Children (Sozialp\u00e4diatrisches Zentrum, SPZ), Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Eils","sequence":"additional","affiliation":[{"name":"Center for Digital Health, Berlin Institute of Health at Charit\u00e9, Berlin, Germany"},{"name":"Molecular Epidemiology Unit, Berlin Institute of Health at Charit\u00e9, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Center for Digital Health, Berlin Institute of Health at Charit\u00e9, Berlin, Germany"},{"name":"German Center for Lung Research, Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leif E","family":"Sander","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Respiratory Medicine, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Ralser","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"},{"name":"Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor M","family":"Corman","sequence":"additional","affiliation":[{"name":"Institute of Virology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus A","family":"Mall","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"},{"name":"German Center for Lung Research, Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"Sawitzki","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health, Berlin, Germany"},{"name":"Institute of Medical Immunology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1535-8852","authenticated-orcid":false,"given":"Jobst","family":"Roehmel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"},{"name":"Berlin Institute of Health, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"2025101812324050000_13.4.e065221.1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"Addendum: a pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"588","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"2025101812324050000_13.4.e065221.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001017"},{"key":"2025101812324050000_13.4.e065221.3","unstructured":"World Health Organization . WHO COVID-19 dashboard. 2020."},{"key":"2025101812324050000_13.4.e065221.4","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-020-03684-7"},{"key":"2025101812324050000_13.4.e065221.5","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1001\/jamapediatrics.2020.1467","article-title":"Severe acute respiratory syndrome coronavirus 2 (SARS-cov-2) infection in children and adolescents","volume":"174","author":"Castagnoli","year":"2020","journal-title":"JAMA Pediatr"},{"key":"2025101812324050000_13.4.e065221.6","doi-asserted-by":"publisher","DOI":"10.1016\/SO140-6736(20)30566-3"},{"key":"2025101812324050000_13.4.e065221.7","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2020-0702","article-title":"Epidemiology of COVID-19 among children in china","volume":"145","author":"Dong","year":"2020","journal-title":"Pediatrics"},{"key":"2025101812324050000_13.4.e065221.8","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1016\/S2352-4642(21)00066-3","article-title":"Children and young people remain at low risk of COVID-19 mortality","volume":"5","author":"Bhopal","year":"2021","journal-title":"The Lancet Child & Adolescent Health"},{"key":"2025101812324050000_13.4.e065221.9","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3390\/pediatric13030045","article-title":"Innate immunity in children and the role of ACE2 expression in SARS-cov-2 infection","volume":"13","author":"Dioguardi","year":"2021","journal-title":"Pediatr Rep"},{"key":"2025101812324050000_13.4.e065221.10","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd3871"},{"key":"2025101812324050000_13.4.e065221.11","doi-asserted-by":"crossref","DOI":"10.1126\/science.abd4250","article-title":"Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity","volume":"370","author":"Shrock","year":"2020","journal-title":"Science"},{"key":"2025101812324050000_13.4.e065221.12","doi-asserted-by":"crossref","DOI":"10.1126\/science.abh1823","article-title":"Cross-reactive cd4+ t cells enhance sars-cov-2 immune responses upon infection and vaccination","volume":"374","author":"Loyal","year":"2021","journal-title":"Science"},{"key":"2025101812324050000_13.4.e065221.13","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2598-9","article-title":"SARS-cov-2-reactive T cells in healthy donors and patients with COVID-19","volume":"587","author":"Braun","year":"2020","journal-title":"Nature"},{"key":"2025101812324050000_13.4.e065221.14","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1080\/22221751.2021.1905488","article-title":"Cross-Reactive antibody against human coronavirus OC43 spike protein correlates with disease severity in COVID-19 patients: a retrospective study","volume":"10","author":"Guo","year":"2021","journal-title":"Emerg Microbes Infect"},{"key":"2025101812324050000_13.4.e065221.15","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1001\/jamapediatrics.2015.1387","article-title":"Influenza A virus infection, innate immunity, and childhood","volume":"169","author":"Coates","year":"2015","journal-title":"JAMA Pediatr"},{"key":"2025101812324050000_13.4.e065221.16","doi-asserted-by":"publisher","DOI":"10.1038\/nri3277"},{"key":"2025101812324050000_13.4.e065221.17","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.l5021","article-title":"Respiratory syncytial virus infection in adults","volume":"366","author":"Nam","year":"2019","journal-title":"BMJ"},{"key":"2025101812324050000_13.4.e065221.18","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.cels.2021.05.005","article-title":"A time-resolved proteomic and prognostic map of COVID-19","volume":"12","author":"Demichev","year":"2021","journal-title":"Cell Syst"},{"key":"2025101812324050000_13.4.e065221.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.040"},{"key":"2025101812324050000_13.4.e065221.20","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1016\/j.cell.2020.08.001","article-title":"Severe COVID-19 is marked by a dysregulated myeloid cell compartment","volume":"182","author":"Schulte-Schrepping","year":"2020","journal-title":"Cell"},{"key":"2025101812324050000_13.4.e065221.21","doi-asserted-by":"crossref","unstructured":"Bal\u00e1zs A , Millar-B\u00fcchner P , M\u00fclleder M , et al . Age-Related differences in structure and function of nasal epithelial cultures from healthy children and elderly people. Front Immunol 2022;13. doi:10.3389\/fimmu.2022.822437","DOI":"10.3389\/fimmu.2022.822437"},{"key":"2025101812324050000_13.4.e065221.22","doi-asserted-by":"publisher","DOI":"10.1038\/nri3547"},{"key":"2025101812324050000_13.4.e065221.23","article-title":"Evolution of the immune system in humans from infancy to old age","volume":"282","author":"Simon","year":"2015","journal-title":"Proc Biol Sci"},{"key":"2025101812324050000_13.4.e065221.24","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-020-01464-x"},{"key":"2025101812324050000_13.4.e065221.25","doi-asserted-by":"publisher","DOI":"10.1055\/a-1551-9734"},{"key":"2025101812324050000_13.4.e065221.26","doi-asserted-by":"publisher","DOI":"10.1300\/J092v11n01_02"},{"key":"2025101812324050000_13.4.e065221.27","doi-asserted-by":"crossref","unstructured":"Kedor C , Freitag H , Meyer-Arndt L , et al . Chronic covid-19 syndrome and chronic fatigue syndrome (me\/cfs) following the first pandemic wave in germany \u2013 a first analysis of a prospective observational study. Infectious Diseases (except HIV\/AIDS) [Preprint] 2021. doi:10.1101\/2021.02.06.21249256","DOI":"10.1101\/2021.02.06.21249256"},{"key":"2025101812324050000_13.4.e065221.28","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3999(93)90081-P"},{"key":"2025101812324050000_13.4.e065221.29","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10428"},{"key":"2025101812324050000_13.4.e065221.30","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1002\/pbc.24706","article-title":"Fatigue in adolescents with cancer compared to healthy adolescents","volume":"60","author":"Daniel","year":"2013","journal-title":"Pediatr Blood Cancer"},{"key":"2025101812324050000_13.4.e065221.31","first-page":"2494","article-title":"The pedsql multidimensional fatigue scale in pediatric rheumatology: reliability and validity","volume":"31","author":"Varni","year":"2004","journal-title":"J Rheumatol"},{"key":"2025101812324050000_13.4.e065221.32","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-007-9282-5"},{"key":"2025101812324050000_13.4.e065221.33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5448.2008.00482.x"},{"key":"2025101812324050000_13.4.e065221.34","doi-asserted-by":"publisher","DOI":"10.3109\/17477160903111706"},{"key":"2025101812324050000_13.4.e065221.35","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1080\/02739615.2012.657068","article-title":"Assessment of Fatigue in Pediatric Patients With Short Stature Utilizing the PedsQL\u2122 Multidimensional Fatigue Scale","volume":"41","author":"Varni","year":"2012","journal-title":"Children\u2019s Health Care"},{"key":"2025101812324050000_13.4.e065221.36","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-013-0370-4"},{"key":"2025101812324050000_13.4.e065221.37","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24776"},{"key":"2025101812324050000_13.4.e065221.38","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jpeds.2018.03.011","article-title":"Development of an international odor identification test for children: the universal sniff test","volume":"198","author":"Schriever","year":"2018","journal-title":"J Pediatr"},{"key":"2025101812324050000_13.4.e065221.39","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ijporl.2019.01.009","article-title":"Normative data for olfactory threshold and odor identification in children and adolescents","volume":"123","author":"Gellrich","year":"2019","journal-title":"Int J Pediatr Otorhinolaryngol"},{"key":"2025101812324050000_13.4.e065221.40","doi-asserted-by":"publisher","DOI":"10.1016\/S0954-6111(06)80166-6"},{"key":"2025101812324050000_13.4.e065221.41","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1497.2001.016009606.x"},{"key":"2025101812324050000_13.4.e065221.42","doi-asserted-by":"publisher","DOI":"10.1002\/jts.22059"},{"key":"2025101812324050000_13.4.e065221.43","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008853819715"},{"key":"2025101812324050000_13.4.e065221.44","unstructured":"World Health Organization . n.d. COVID-19 clinical management: living guidance."},{"key":"2025101812324050000_13.4.e065221.45","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30483-7"},{"key":"2025101812324050000_13.4.e065221.46","doi-asserted-by":"crossref","unstructured":"Corman VM , Landt O , Kaiser M , et al . Detection of 2019 novel coronavirus (2019-ncov) by real-time RT-PCR. Euro Surveill 2020;25. doi:10.2807\/1560-7917.ES.2020.25.3.2000045","DOI":"10.2807\/1560-7917.ES.2020.25.3.2000045"},{"key":"2025101812324050000_13.4.e065221.47","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2196-x"},{"key":"2025101812324050000_13.4.e065221.48","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.174"},{"key":"2025101812324050000_13.4.e065221.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.10.036"},{"key":"2025101812324050000_13.4.e065221.50","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42297"},{"key":"2025101812324050000_13.4.e065221.51","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2016-0276ma"},{"key":"2025101812324050000_13.4.e065221.52","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1016\/j.jaci.2021.02.008","article-title":"Chronic rhinosinusitis with nasal polyps is associated with impaired TMEM16A-mediated epithelial chloride secretion","volume":"147","author":"Salomon","year":"2021","journal-title":"Journal of Allergy and Clinical Immunology"},{"key":"2025101812324050000_13.4.e065221.53","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1093\/infdis\/jiab523","article-title":"Analysis of severe acute respiratory syndrome 2 replication in explant cultures of the human upper respiratory tract reveals broad tissue tropism of wild-type and B.1.1.7 variant viruses","volume":"224","author":"Schulze","year":"2021","journal-title":"J Infect Dis"},{"key":"2025101812324050000_13.4.e065221.54","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-17952-4","article-title":"Conditionally reprogrammed primary airway epithelial cells maintain morphology, lineage and disease specific functional characteristics","volume":"7","author":"Martinovich","year":"2017","journal-title":"Sci Rep"},{"key":"2025101812324050000_13.4.e065221.55","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0071OC"},{"key":"2025101812324050000_13.4.e065221.56","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.151803"},{"key":"2025101812324050000_13.4.e065221.57","doi-asserted-by":"publisher","DOI":"10.1007\/S12250-020-00244-Z"},{"key":"2025101812324050000_13.4.e065221.58","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-15743-6","article-title":"Conditional deletion of nedd4-2 in lung epithelial cells causes progressive pulmonary fibrosis in adult mice","volume":"11","author":"Duerr","year":"2020","journal-title":"Nat Commun"},{"key":"2025101812324050000_13.4.e065221.59","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cels.2020.05.012","article-title":"Ultra-high-throughput clinical proteomics reveals classifiers of COVID-19 infection","volume":"11","author":"Messner","year":"2020","journal-title":"Cell Syst"},{"key":"2025101812324050000_13.4.e065221.60","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41592-019-0638-x","article-title":"DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput","volume":"17","author":"Demichev","year":"2020","journal-title":"Nat Methods"},{"key":"2025101812324050000_13.4.e065221.61","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0868-6"},{"key":"2025101812324050000_13.4.e065221.62","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0602-4"},{"key":"2025101812324050000_13.4.e065221.63","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2026131"},{"key":"2025101812324050000_13.4.e065221.64","first-page":"500","article-title":"The pathology of severe COVID-19-related lung damage","volume":"117","author":"Kommoss","year":"2020","journal-title":"Dtsch Arztebl Int"},{"key":"2025101812324050000_13.4.e065221.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.prrv.2020.06.004"},{"key":"2025101812324050000_13.4.e065221.66","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1159\/000357075","article-title":"Multiple breath washout is feasible in the clinical setting and detects abnormal lung function in infants and young children with cystic fibrosis","volume":"87","author":"Stahl","year":"2014","journal-title":"Respiration"},{"key":"2025101812324050000_13.4.e065221.67","doi-asserted-by":"crossref","DOI":"10.1183\/23120541.00408-2020","article-title":"Multicentre feasibility of multiple-breath washout in preschool children with cystic fibrosis and other lung diseases","volume":"6","author":"Stahl","year":"2020","journal-title":"ERJ Open Res"},{"key":"2025101812324050000_13.4.e065221.68","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200605-642ST"},{"key":"2025101812324050000_13.4.e065221.69","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.jcf.2019.11.006","article-title":"Integrating the multiple breath washout test into international multicentre trials","volume":"19","author":"Saunders","year":"2020","journal-title":"Journal of Cystic Fibrosis"},{"key":"2025101812324050000_13.4.e065221.70","doi-asserted-by":"crossref","DOI":"10.1038\/sdata.2016.18","article-title":"The fair guiding principles for scientific data management and stewardship","volume":"3","author":"Wilkinson","year":"2016","journal-title":"Sci Data"},{"key":"2025101812324050000_13.4.e065221.71","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000002660"},{"key":"2025101812324050000_13.4.e065221.72","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01329-2"},{"key":"2025101812324050000_13.4.e065221.73","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.immuni.2020.11.017","article-title":"Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells, and plasmablasts as hallmarks of severe COVID-19","volume":"53","author":"Bernardes","year":"2020","journal-title":"Immunity"},{"key":"2025101812324050000_13.4.e065221.74","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/s41587-020-00796-1","article-title":"Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19","volume":"39","author":"Trump","year":"2021","journal-title":"Nat Biotechnol"},{"key":"2025101812324050000_13.4.e065221.75","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03493-4"},{"key":"2025101812324050000_13.4.e065221.76","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41587-021-01037-9","article-title":"Pre-activated antiviral innate immunity in the upper airways controls early SARS-cov-2 infection in children","volume":"40","author":"Loske","year":"2022","journal-title":"Nat Biotechnol"},{"key":"2025101812324050000_13.4.e065221.77","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41586-021-04345-x","article-title":"Local and systemic responses to SARS-cov-2 infection in children and adults","volume":"602","author":"Yoshida","year":"2022","journal-title":"Nature"},{"key":"2025101812324050000_13.4.e065221.78","doi-asserted-by":"publisher","DOI":"10.7150\/thno.61832"},{"key":"2025101812324050000_13.4.e065221.79","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1126\/scitranslmed.abd5487","article-title":"Immune responses to SARS-cov-2 infection in hospitalized pediatric and adult patients","volume":"12","author":"Pierce","year":"2020","journal-title":"Sci Transl Med"},{"key":"2025101812324050000_13.4.e065221.80","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-24938-4","article-title":"SARS-cov-2 specific t cell responses are lower in children and increase with age and time after infection","volume":"12","author":"Cohen","year":"2021","journal-title":"Nat Commun"},{"key":"2025101812324050000_13.4.e065221.81","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1001\/jamapediatrics.2020.4573","article-title":"Susceptibility to SARS-cov-2 infection among children and adolescents compared with adults: A systematic review and meta-analysis","volume":"175","author":"Viner","year":"2021","journal-title":"JAMA Pediatr"},{"key":"2025101812324050000_13.4.e065221.82","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"2025101812324050000_13.4.e065221.83","doi-asserted-by":"crossref","first-page":"e4154","DOI":"10.1093\/cid\/ciaa1911","article-title":"Distinct disease severity between children and older adults with coronavirus disease 2019 (COVID-19): impacts of ACE2 expression, distribution, and lung progenitor cells","volume":"73","author":"Zhang","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2025101812324050000_13.4.e065221.84","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jpeds.2020.08.037","article-title":"Pediatric severe acute respiratory syndrome coronavirus 2 (SARS-cov-2): clinical presentation, infectivity, and immune responses","volume":"227","author":"Yonker","year":"2020","journal-title":"The Journal of Pediatrics"},{"key":"2025101812324050000_13.4.e065221.85","doi-asserted-by":"crossref","unstructured":"Koch CM , Prigge AD , Anekalla KR , et al . Immune response to SARS-cov-2 in the nasal mucosa in children and adults. Infectious Diseases (except HIV\/AIDS) [Preprint]. doi:10.1101\/2021.01.26.21250269","DOI":"10.1101\/2021.01.26.21250269"},{"key":"2025101812324050000_13.4.e065221.86","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2020.108588"},{"key":"2025101812324050000_13.4.e065221.87","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.579480"},{"key":"2025101812324050000_13.4.e065221.88","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41423-021-00700-0","article-title":"Cross-Reactive antibody immunity against SARS-cov-2 in children and adults","volume":"18","author":"Fraley","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"2025101812324050000_13.4.e065221.89","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.646894","article-title":"How children are protected from covid-19? a historical, clinical, and pathophysiological approach to address covid-19 susceptibility","volume":"12","author":"Massalska","year":"2021","journal-title":"Front Immunol"},{"key":"2025101812324050000_13.4.e065221.90","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.148694","article-title":"Natural mucosal barriers and COVID-19 in children","volume":"6","author":"Pierce","year":"2021","journal-title":"JCI Insight"},{"key":"2025101812324050000_13.4.e065221.91","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1002\/jmv.26683","article-title":"Predictive value of cytokine\/chemokine responses for the disease severity and management in children and adult cases with COVID-19","volume":"93","author":"Ozsurekci","year":"2021","journal-title":"J Med Virol"},{"key":"2025101812324050000_13.4.e065221.92","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1007\/s12250-020-00265-8","article-title":"Mild cytokine elevation, moderate CD4+\u2009T cell response and abundant antibody production in children with COVID-19","volume":"35","author":"Jia","year":"2020","journal-title":"Virol Sin"},{"key":"2025101812324050000_13.4.e065221.93","article-title":"Identifying risk factors that distinguish symptomatic severe acute respiratory syndrome coronavirus 2 infection from common upper respiratory infections in children","volume":"13","author":"Schneider","year":"2021","journal-title":"Cureus"},{"key":"2025101812324050000_13.4.e065221.94","doi-asserted-by":"crossref","unstructured":"Wu Q , Xing Y , Shi L , et al . Coinfection and other clinical characteristics of COVID-19 in children. Pediatrics 2020;146. doi:10.1542\/peds.2020-0961","DOI":"10.1542\/peds.2020-0961"},{"key":"2025101812324050000_13.4.e065221.95","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000024315","article-title":"Co-Infections of SARS-cov-2 with multiple common respiratory pathogens in infected children","volume":"100","author":"Li","year":"2021","journal-title":"Medicine (Baltimore)"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2022-065221","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T19:32:58Z","timestamp":1760815978000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2022-065221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":95,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4,17]]},"published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1136\/bmjopen-2022-065221"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2022-065221","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4]]}}}