{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:08:15Z","timestamp":1792714095890,"version":"4.5.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003032","name":"Association Nationale de la Recherche et de la Technologie","doi-asserted-by":"publisher","award":["CIFRE 2018\/1212"],"award-info":[{"award-number":["CIFRE 2018\/1212"]}],"id":[{"id":"10.13039\/501100003032","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["Research and Innovation Program under Marie Sklodowska-Curie Grant Agreement 812890, ArthritisHeal"],"award-info":[{"award-number":["Research and Innovation Program under Marie Sklodowska-Curie Grant Agreement 812890, ArthritisHeal"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A strong bias related to age is observed in COVID-19 patients with pediatric subjects developing a milder disease than adults. We hypothesized that a specific SARS-CoV-2 effect conjugated with preexisting differences in the immune systems may explain this. Using flow cytometry, we investigated basal immune differences in a cohort consisting of 16 non-infected young and 16 aged individuals and further leveraged an in vitro whole blood model of SARS-CoV-2 infection so that functional differences could be mined as well. In short, blood diluted in culture media was incubated 5 or 24\u00a0h with the trimeric spike protein or controls. Following unsupervised analysis, we first confirmed that the immune lymphoid and myeloid systems in adults are less efficient and prone to develop higher inflammation than those in children. We notably identified in adults a higher CD43 lymphocyte expression, known for its potentially inhibitory role. The spike protein induced different responses between adults and children, notably a higher increase of inflammatory markers together with lower monocyte and B cell activation in adults. Interestingly, CD169, a CD43 ligand overexpressed in COVID-19 patients, was confirmed to be strongly modulated by the spike protein. In conclusion, the spike protein exacerbated the preexisting lower immune responsiveness and higher inflammatory potential in adults. Altogether, some of the markers identified may explain the marked age bias and be predictive of severity.<\/jats:p>","DOI":"10.1038\/s41598-022-25259-2","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T10:29:11Z","timestamp":1669976951000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["SARS-CoV-2 spike protein induces a differential monocyte activation that may contribute to age bias in COVID-19 severity"],"prefix":"10.1038","volume":"12","author":[{"given":"Ines","family":"Ait-Belkacem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Cartagena Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Millet-Wallisky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Izquierdo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Loosveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Arnoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Emmanuel","family":"Morange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Galland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Malergue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Busnel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"25259_CR1","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1186\/s13054-020-03240-7","volume":"24","author":"SJ Tzotzos","year":"2020","unstructured":"Tzotzos, S. J., Fischer, B., Fischer, H. & Zeitlinger, M. Incidence of ARDS and outcomes in hospitalized patients with COVID-19: A global literature survey. Crit. Care 24, 516 (2020).","journal-title":"Crit. Care"},{"key":"25259_CR2","doi-asserted-by":"publisher","unstructured":"Machhi, J. et al. The natural history, pathobiology, and clinical manifestations of SARS-CoV-2 infections. J. Neuroimmune Pharmacol. 1\u201328. https:\/\/doi.org\/10.1007\/s11481-020-09944-5 (2020).","DOI":"10.1007\/s11481-020-09944-5"},{"key":"25259_CR3","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1038\/sj.emboj.7600640","volume":"24","author":"W Li","year":"2005","unstructured":"Li, W. et al. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J. 24, 1634\u20131643 (2005).","journal-title":"EMBO J."},{"key":"25259_CR4","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1002\/jmv.25685","volume":"92","author":"G Li","year":"2020","unstructured":"Li, G. et al. Coronavirus infections and immune responses. J. Med. Virol. 92, 424\u2013432 (2020).","journal-title":"J. Med. Virol."},{"key":"25259_CR5","doi-asserted-by":"publisher","unstructured":"Graf, M. et al. SIGLEC1 enables straightforward assessment of type I interferon activity in inflammatory myopathies. 2021.09.13.21263325. https:\/\/doi.org\/10.1101\/2021.09.13.21263325 (2021).","DOI":"10.1101\/2021.09.13.21263325"},{"key":"25259_CR6","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s10875-016-0359-1","volume":"37","author":"GI Rice","year":"2017","unstructured":"Rice, G. I. et al. Assessment of type I interferon signaling in pediatric inflammatory disease. J. Clin. Immunol. 37, 123\u2013132 (2017).","journal-title":"J. Clin. Immunol."},{"key":"25259_CR7","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/iid3.289","volume":"8","author":"P Bourgoin","year":"2020","unstructured":"Bourgoin, P., Bi\u00e9chel\u00e9, G., Ait Belkacem, I., Morange, P.-E. & Malergue, F. Role of the interferons in CD64 and CD169 expressions in whole blood: Relevance in the balance between viral- or bacterial-oriented immune responses. Immun. Inflamm. Dis. 8, 106\u2013123 (2020).","journal-title":"Immun. Inflamm. Dis."},{"key":"25259_CR8","doi-asserted-by":"publisher","first-page":"3810","DOI":"10.1038\/s41467-020-17665-9","volume":"11","author":"X Lei","year":"2020","unstructured":"Lei, X. et al. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat. Commun. 11, 3810 (2020).","journal-title":"Nat. Commun."},{"key":"25259_CR9","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/d41586-020-03070-1","volume":"587","author":"E Meffre","year":"2020","unstructured":"Meffre, E. & Iwasaki, A. Interferon deficiency can lead to severe COVID. Nature 587, 374\u2013376 (2020).","journal-title":"Nature"},{"key":"25259_CR10","unstructured":"Bastard, P. et al. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. Sci. Immunol. 6, eabl4340 (2021)."},{"key":"25259_CR11","doi-asserted-by":"publisher","unstructured":"Bedin, A.-S. et al. Monocyte CD169 expression as a biomarker in the early diagnosis of COVID-19. J. Infect. Dis. jiaa724. https:\/\/doi.org\/10.1093\/infdis\/jiaa724 (2020).","DOI":"10.1093\/infdis\/jiaa724"},{"key":"25259_CR12","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1002\/cyto.a.24314","volume":"99","author":"P Bourgoin","year":"2021","unstructured":"Bourgoin, P. et al. CD169 and CD64 could help differentiate bacterial from CoVID-19 or other viral infections in the emergency department. Cytometry A 99, 435\u2013445 (2021).","journal-title":"Cytometry A"},{"key":"25259_CR13","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1007\/s15010-021-01606-9","volume":"49","author":"J-M Doehn","year":"2021","unstructured":"Doehn, J.-M. et al. CD169\/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity. Infection 49, 757\u2013762 (2021).","journal-title":"Infection"},{"key":"25259_CR14","doi-asserted-by":"publisher","unstructured":"Minutolo, A. et al. High CD169 Monocyte\/lymphocyte ratio reflects the immunophenotyping disruption and predicts oxygen need in COVID-19 patients. https:\/\/doi.org\/10.20944\/preprints202105.0731.v1 (2021).","DOI":"10.20944\/preprints202105.0731.v1"},{"key":"25259_CR15","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1002\/cyto.a.24315","volume":"99","author":"M Ortillon","year":"2021","unstructured":"Ortillon, M. et al. Monocyte CD169 expression in COVID-19 patients upon intensive care unit admission. Cytometry A 99, 466\u2013471 (2021).","journal-title":"Cytometry A"},{"key":"25259_CR16","doi-asserted-by":"crossref","unstructured":"Roussel, M. et al. Comparative immune profiling of acute respiratory distress syndrome patients with or without SARS-CoV-2 infection. CR Med 2, (2021).","DOI":"10.1016\/j.xcrm.2021.100291"},{"key":"25259_CR17","doi-asserted-by":"crossref","unstructured":"Zaki, H. & Khan, S. SARS-CoV-2 spike protein induces inflammatory molecules through TLR2 in macrophages and monocytes. J. Immunol. 206, 62.07\u201362.07 (2021).","DOI":"10.4049\/jimmunol.206.Supp.62.07"},{"key":"25259_CR18","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1038\/s41422-021-00495-9","volume":"31","author":"Y Zhao","year":"2021","unstructured":"Zhao, Y. et al. SARS-CoV-2 spike protein interacts with and activates TLR41. Cell Res. 31, 818\u2013820 (2021).","journal-title":"Cell Res."},{"key":"25259_CR19","doi-asserted-by":"crossref","unstructured":"Kuri-Cervantes, L. et al. Comprehensive mapping of immune perturbations associated with severe COVID-19. Sci. Immunol. 5, eabd7114 (2020).","DOI":"10.1126\/sciimmunol.abd7114"},{"key":"25259_CR20","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1038\/s41591-020-1038-6","volume":"26","author":"AG Laing","year":"2020","unstructured":"Laing, A. G. et al. A dynamic COVID-19 immune signature includes associations with poor prognosis. Nat. Med. 26, 1623\u20131635 (2020).","journal-title":"Nat. Med."},{"key":"25259_CR21","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1093\/cid\/ciaa248","volume":"71","author":"C Qin","year":"2020","unstructured":"Qin, C. et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan China. Clin. Infect. Dis. 71, 762\u2013768 (2020).","journal-title":"Clin. Infect. Dis."},{"key":"25259_CR22","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1056\/NEJMc2005073","volume":"382","author":"X Lu","year":"2020","unstructured":"Lu, X. et al. SARS-CoV-2 infection in children. N. Engl. J. Med. 382, 1663\u20131665 (2020).","journal-title":"N. Engl. J. Med."},{"key":"25259_CR23","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1111\/apa.15270","volume":"109","author":"JF Ludvigsson","year":"2020","unstructured":"Ludvigsson, J. F. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr. 109, 1088\u20131095 (2020).","journal-title":"Acta Paediatr."},{"key":"25259_CR24","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1186\/s12879-021-06536-3","volume":"21","author":"ZG Dessie","year":"2021","unstructured":"Dessie, Z. G. & Zewotir, T. Mortality-related risk factors of COVID-19: A systematic review and meta-analysis of 42 studies and 423,117 patients. BMC Infect. Dis. 21, 855 (2021).","journal-title":"BMC Infect. Dis."},{"key":"25259_CR25","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.3389\/fimmu.2020.01748","volume":"11","author":"LL Cunha","year":"2020","unstructured":"Cunha, L. L., Perazzio, S. F., Azzi, J., Cravedi, P. & Riella, L. V. Remodeling of the immune response with aging: Immunosenescence and its potential impact on COVID-19 immune response. Front. Immunol. 11, 1748 (2020).","journal-title":"Front. Immunol."},{"key":"25259_CR26","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1007\/s11357-020-00213-0","volume":"42","author":"BD Pence","year":"2020","unstructured":"Pence, B. D. Severe COVID-19 and aging: Are monocytes the key?. Geroscience 42, 1051\u20131061 (2020).","journal-title":"Geroscience"},{"key":"25259_CR27","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/s41577-020-0331-4","volume":"20","author":"M Merad","year":"2020","unstructured":"Merad, M. & Martin, J. C. Pathological inflammation in patients with COVID-19: A key role for monocytes and macrophages. Nat. Rev. Immunol. 20, 355\u2013362 (2020).","journal-title":"Nat. Rev. Immunol."},{"key":"25259_CR28","unstructured":"France COVID - Coronavirus Statistics - Worldometer. https:\/\/www.worldometers.info\/coronavirus\/country\/france\/."},{"key":"25259_CR29","doi-asserted-by":"crossref","unstructured":"Ait Belkacem, I., Bourgoin, P., Busnel, J. M., Galland, F. & Malergue, F. One-step white blood cell extracellular staining method for flow cytometry. Bio-protocol 11, e4135\u2013e4135 (2021).","DOI":"10.21769\/BioProtoc.4135"},{"key":"25259_CR30","first-page":"204993612110340","volume":"8","author":"M Karawajczyk","year":"2021","unstructured":"Karawajczyk, M. et al. High expression of neutrophil and monocyte CD64 with simultaneous lack of upregulation of adhesion receptors CD11b, CD162, CD15, CD65 on neutrophils in severe COVID-19. Ther. Adv. Infect. Dis. 8, 20499361211034064 (2021).","journal-title":"Ther. Adv. Infect. Dis."},{"key":"25259_CR31","doi-asserted-by":"crossref","unstructured":"Lacaille, V. & Miloud, T. Development of a dried pre-formulated antibody panel (7 colors\/17antibodies) for the identification of human innate lymphoid cells by flow cytometry. J. Immunol. 206, 27.28\u201327.28 (2021).","DOI":"10.4049\/jimmunol.206.Supp.27.28"},{"key":"25259_CR32","doi-asserted-by":"crossref","unstructured":"Villani, A.-C. et al. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science 356, eaah4573 (2017).","DOI":"10.1126\/science.aah4573"},{"key":"25259_CR33","unstructured":"See, P. et al. Mapping the human DC lineage through the integration of high-dimensional techniques. Science 356, eaag3009 (2017)."},{"key":"25259_CR34","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1111\/j.1432-2277.2009.00927.x","volume":"22","author":"D Weiskopf","year":"2009","unstructured":"Weiskopf, D., Weinberger, B. & Grubeck-Loebenstein, B. The aging of the immune system. Transpl. Int. 22, 1041\u20131050 (2009).","journal-title":"Transpl. Int."},{"key":"25259_CR35","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.3389\/fimmu.2017.01960","volume":"8","author":"T Fulop","year":"2017","unstructured":"Fulop, T. et al. Immunosenescence and inflamm-aging as two sides of the same coin: Friends or foes?. Front. Immunol. 8, 1960 (2017).","journal-title":"Front. Immunol."},{"key":"25259_CR36","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1002\/eji.201747161","volume":"48","author":"J Jans","year":"2018","unstructured":"Jans, J. et al. Siglec-1 inhibits RSV-induced interferon gamma production by adult T cells in contrast to newborn T cells. Eur. J. Immunol. 48, 621\u2013631 (2018).","journal-title":"Eur. J. Immunol."},{"key":"25259_CR37","first-page":"449","volume":"58","author":"AD Yalcin","year":"2012","unstructured":"Yalcin, A. D., Gorczynski, R. M., Kahraman, M. S., Demirel, M. U. & Terzioglu, E. CD40, CD45 CTLA-4 levels are elevated in healthy older adults. Clin. Lab. 58, 449\u2013456 (2012).","journal-title":"Clin. Lab."},{"key":"25259_CR38","doi-asserted-by":"crossref","unstructured":"Courtney, A. H. et al. CD45 functions as a signaling gatekeeper in T cells. Sci. Signal. 12, eaaw8151 (2019).","DOI":"10.1126\/scisignal.aaw8151"},{"key":"25259_CR39","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/377535a0","volume":"377","author":"N Manjunath","year":"1995","unstructured":"Manjunath, N., Correa, M., Ardman, M. & Ardman, B. Negative regulation of T-cell adhesion and activation by CD43. Nature 377, 535\u2013538 (1995).","journal-title":"Nature"},{"key":"25259_CR40","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/BF02786465","volume":"20","author":"Y Rosenstein","year":"1999","unstructured":"Rosenstein, Y., Santana, A. & Pedraza-Alva, G. CD43, a molecule with multiple functions. Immunol. Res. 20, 89\u201399 (1999).","journal-title":"Immunol. Res."},{"key":"25259_CR41","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1093\/intimm\/dxp012","volume":"21","author":"A Klinger","year":"2009","unstructured":"Klinger, A. et al. Cyclical expression of L-selectin (CD62L) by recirculating T cells. Int. Immunol. 21, 443\u2013455 (2009).","journal-title":"Int. Immunol."},{"key":"25259_CR42","doi-asserted-by":"publisher","first-page":"3173","DOI":"10.1002\/eji.200526004","volume":"35","author":"AW Bingaman","year":"2005","unstructured":"Bingaman, A. W. et al. Novel phenotypes and migratory properties distinguish memory CD4 T cell subsets in lymphoid and lung tissue. Eur. J. Immunol. 35, 3173\u20133186 (2005).","journal-title":"Eur. J. Immunol."},{"key":"25259_CR43","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3389\/fmed.2018.00052","volume":"5","author":"SQ Khan","year":"2018","unstructured":"Khan, S. Q., Khan, I. & Gupta, V. CD11b activity modulates pathogenesis of lupus nephritis. Front. Med. 5, 52 (2018).","journal-title":"Front. Med."},{"key":"25259_CR44","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1172\/JCI57990","volume":"122","author":"J Pillay","year":"2012","unstructured":"Pillay, J. et al. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1. J. Clin. Invest. 122, 327\u2013336 (2012).","journal-title":"J. Clin. Invest."},{"key":"25259_CR45","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1093\/infdis\/jiaa591","volume":"222","author":"J Vitte","year":"2020","unstructured":"Vitte, J. et al. A granulocytic signature identifies COVID-19 and its severity. J. Infect. Dis. 222, 1985\u20131996 (2020).","journal-title":"J. Infect. Dis."},{"key":"25259_CR46","doi-asserted-by":"publisher","unstructured":"Beyerstedt, S., Casaro, E. B. & Rangel, \u00c9. B. COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. Eur. J. Clin. Microbiol. Infect. Dis. 1\u201315. https:\/\/doi.org\/10.1007\/s10096-020-04138-6 (2021).","DOI":"10.1007\/s10096-020-04138-6"},{"key":"25259_CR47","first-page":"287","volume":"32","author":"B Trojanowicz","year":"2017","unstructured":"Trojanowicz, B. et al. Monocytic angiotensin-converting enzyme 2 relates to atherosclerosis in patients with chronic kidney disease. Nephrol. Dial. Transplant 32, 287\u2013298 (2017).","journal-title":"Nephrol. Dial. Transplant"},{"key":"25259_CR48","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa724","author":"A-S Bedin","year":"2020","unstructured":"Bedin, A.-S. et al. Monocyte CD169 expression as a biomarker in the early diagnosis of coronavirus disease 2019. J. Infect. Dis. https:\/\/doi.org\/10.1093\/infdis\/jiaa724 (2020).","journal-title":"J. Infect. Dis."},{"key":"25259_CR49","doi-asserted-by":"publisher","first-page":"3637","DOI":"10.4049\/jimmunol.166.6.3637","volume":"166","author":"TK van den Berg","year":"2001","unstructured":"van den Berg, T. K. et al. Cutting edge: CD43 functions as a T cell counterreceptor for the macrophage adhesion receptor sialoadhesin (Siglec-1). J. Immunol. 166, 3637\u20133640 (2001).","journal-title":"J. Immunol."},{"key":"25259_CR50","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1084\/jem.20021602","volume":"199","author":"J Tong","year":"2004","unstructured":"Tong, J. et al. CD43 Regulation of T cell activation is not through steric inhibition of T Cell\u2013APC interactions but through an intracellular mechanism. J. Exp. Med. 199, 1277\u20131283 (2004).","journal-title":"J. Exp. Med."},{"key":"25259_CR51","doi-asserted-by":"publisher","first-page":"2676","DOI":"10.1038\/s41423-021-00794-6","volume":"18","author":"D Perez-Zsolt","year":"2021","unstructured":"Perez-Zsolt, D. et al. SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells. Cell. Mol. Immunol. 18, 2676\u20132678 (2021).","journal-title":"Cell. Mol. Immunol."},{"key":"25259_CR52","doi-asserted-by":"publisher","first-page":"1914","DOI":"10.1177\/0961203320965699","volume":"29","author":"SL von Stuckrad","year":"2020","unstructured":"von Stuckrad, S. L. et al. SIGLEC1 (CD169) is a sensitive biomarker for the deterioration of the clinical course in childhood systemic lupus erythematosus. Lupus 29, 1914\u20131925 (2020).","journal-title":"Lupus"},{"key":"25259_CR53","first-page":"79","volume":"3","author":"L de Oliviera Nascimento","year":"2012","unstructured":"de Oliviera Nascimento, L., Massari, P. & Wetzler, L. The role of TLR2 in infection and immunity. Front. Immunol. 3, 79 (2012).","journal-title":"Front. Immunol."},{"key":"25259_CR54","doi-asserted-by":"crossref","unstructured":"Kuzmich, N. N. et al. TLR4 Signaling Pathway Modulators as Potential Therapeutics in Inflammation and Sepsis. Vaccines (Basel) 5, 34 (2017).","DOI":"10.3390\/vaccines5040034"},{"key":"25259_CR55","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1126\/science.282.5396.2085","volume":"282","author":"A Poltorak","year":"1998","unstructured":"Poltorak, A. et al. Defective LPS signaling in C3H\/HeJ and C57BL\/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085\u20132088 (1998).","journal-title":"Science"},{"key":"25259_CR56","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.jinf.2010.02.013","volume":"60","author":"J Cid","year":"2010","unstructured":"Cid, J., Aguinaco, R., S\u00e1nchez, R., Garc\u00eda-Pardo, G. & Llorente, A. Neutrophil CD64 expression as marker of bacterial infection: A systematic review and meta-analysis. J. Infect. 60, 313\u2013319 (2010).","journal-title":"J. Infect."},{"key":"25259_CR57","unstructured":"An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies - PubMed. https:\/\/pubmed.ncbi.nlm.nih.gov\/34139176\/."},{"key":"25259_CR58","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0000000000000868","author":"I Rudan","year":"2022","unstructured":"Rudan, I., Adeloye, D. & Sheikh, A. COVID 19: vaccines, efficacy and effects on variants. Curr. Opin. Pulm. Med. https:\/\/doi.org\/10.1097\/MCP.0000000000000868 (2022).","journal-title":"Curr. Opin. Pulm. Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-25259-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-25259-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-25259-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T05:06:34Z","timestamp":1678856794000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-25259-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,2]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["25259"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-25259-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,2]]},"assertion":[{"value":"12 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"I.A.B., C.C.G., E.W., N.I., F.M., and J.M.B. are Beckman Coulter Life Sciences employees. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20824"}}