{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T11:16:51Z","timestamp":1760267811159,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006687","name":"Claude Bernard University Lyon 1","doi-asserted-by":"publisher","award":["Anti-CoV-2"],"award-info":[{"award-number":["Anti-CoV-2"]}],"id":[{"id":"10.13039\/501100006687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006451","name":"Hospices Civils de Lyon","doi-asserted-by":"publisher","award":["Anti-CoV-2"],"award-info":[{"award-number":["Anti-CoV-2"]}],"id":[{"id":"10.13039\/501100006451","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Individuals with pre-existing chronic systemic low-grade inflammation are prone to develop severe COVID-19 and stronger anti-SARS-CoV-2 antibody responses. Whether this phenomenon reflects a differential expansion of antiviral B cells or a failure to regulate antibody synthesis remains unknown. Here, we compared the antiviral B cell repertoire of convalescent healthcare personnel to that of hospitalized patients with pre-existing comorbidities. Out of 277,500 immortalized B cell clones, antiviral B cell frequencies were determined by indirect immunofluorescence screening on SARS-CoV-2 infected cells. Surprisingly, frequencies of SARS-CoV-2 specific clones from the two groups were not statistically different, despite higher antibody levels in hospitalized patients. Moreover, functional analyses revealed that several B cell clones from healthcare personnel with low antibody levels had neutralizing properties. This study reveals for the first time a key qualitative defect of antibody synthesis in severe patients and calls for caution regarding estimated protective immunity based only on circulating antiviral antibodies.<\/jats:p>","DOI":"10.3390\/ijms222011095","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T22:42:18Z","timestamp":1634251338000},"page":"11095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of Host Immune Status on Discordant Anti-SARS-CoV-2 Circulating B Cell Frequencies and Antibody Levels"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2485-5284","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Coutant","sequence":"first","affiliation":[{"name":"Immunogenomics and Inflammation Research Team, University of Lyon, Edouard Herriot Hospital, 69003 Lyon, France"},{"name":"Immunology Department, Lyon-Sud Hospital, Hospices Civils of Lyon, 69310 Pierre-B\u00e9nite, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Jacques","family":"Pin","sequence":"additional","affiliation":[{"name":"Dendritics-Edouard Herriot Hospital, 69003 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florence","family":"Morfin-Sherpa","sequence":"additional","affiliation":[{"name":"Virology Department, Infective Agents Institute, National Reference Center for Respiratory Viruses, North Hospital Network, 69004 Lyon, France"},{"name":"Virpath Team, CIRI, INSERM U1111, CNRS UMR5308, ENS Lyon, University Claude Bernard Lyon 1, 69100 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tristan","family":"Ferry","sequence":"additional","affiliation":[{"name":"Department of Infectious and Tropical Diseases, Hospices Civils of Lyon-Croix-Rousse Hospital, 69004 Lyon, France"},{"name":"Stapath Team, CIRI, INSERM U1111, CNRS, UMR5308, ENS Lyon, University Claude Bernard Lyon 1, 69100 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8830-4273","authenticated-orcid":false,"given":"St\u00e9phane","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Immunology, University Hospital of Saint-Etienne, 42055 Saint-Etienne, France"},{"name":"GIMAP Team, CIRI, INSERM U1111, CNRS, UMR530, University Claude Bernard Lyon 1, CIC 1408 Vaccinology, 42023 Saint-Etienne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Pozzetto","sequence":"additional","affiliation":[{"name":"GIMAP Team, CIRI, INSERM U1111, CNRS, UMR530, University Claude Bernard Lyon 1, CIC 1408 Vaccinology, 42023 Saint-Etienne, France"},{"name":"Department of Infectious Agents and Hygiene, University Hospital of Saint-Etienne, 42055 Saint-Etienne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myriam","family":"Normand","sequence":"additional","affiliation":[{"name":"SAINBIOSE, INSERM, U1059, University of Lyon, 42270 Saint-Etienne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Miossec","sequence":"additional","affiliation":[{"name":"Immunogenomics and Inflammation Research Team, University of Lyon, Edouard Herriot Hospital, 69003 Lyon, France"},{"name":"Department of Immunology and Rheumatology, Edouard Herriot Hospital, 69003 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1016\/j.cell.2021.02.029","article-title":"COVID-19 and the Human Innate Immune System","volume":"184","author":"Schultze","year":"2021","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41577-020-0402-6","article-title":"T Cell Responses in Patients with COVID-19","volume":"20","author":"Chen","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.medj.2021.03.013","article-title":"Alterations in T and B Cell Function Persist in Convalescent COVID-19 Patients","volume":"2","author":"Shuwa","year":"2021","journal-title":"Med"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yu, K.K., Fischinger, S., Smith, M.T., Atyeo, C., Cizmeci, D., Wolf, C.R., Layton, E.D., Logue, J.K., Aguilar, M.S., and Shuey, K. (2021). Comorbid Illnesses Are Associated with Altered Adaptive Immune Responses to SARS-CoV-2. JCI Insight, 6.","DOI":"10.1172\/jci.insight.146242"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.cell.2020.09.038","article-title":"Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity","volume":"183","author":"Ramirez","year":"2020","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mathew, D., Giles, J.R., Baxter, A.E., Greenplate, A.R., Wu, J.E., Alanio, C., Oldridge, D.A., Kuri-Cervantes, L., Pampena, M.B., and D\u2019Andrea, K. (2020). Deep Immune Profiling of COVID-19 Patients Reveals Patient Heterogeneity and Distinct Immunotypes with Implications for Therapeutic Interventions. bioRxiv.","DOI":"10.1126\/science.abc8511"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1002\/eji.202048908","article-title":"Divergent SARS-CoV-2-Specific T- and B-Cell Responses in Severe but Not Mild COVID-19 Patients","volume":"50","author":"Oja","year":"2020","journal-title":"Eur. J. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Terpos, E., Politou, M., Sergentanis, T.N., Mentis, A., Rosati, M., Stellas, D., Bear, J., Hu, X., Felber, B.K., and Pappa, V. (2020). Anti-SARS-CoV-2 Antibody Responses in Convalescent Plasma Donors Are Increased in Hospitalized Patients; Subanalyses of a Phase 2 Clinical Study. Microorganisms, 8.","DOI":"10.3390\/microorganisms8121885"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Andrade, F.B., Gualberto, A., Rezende, C., Percegoni, N., Gameiro, J., and Hottz, E.D. (2021). The Weight of Obesity in Immunity from Influenza to COVID-19. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.638852"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1002\/oby.22918","article-title":"Obesity and COVID-19: An Italian Snapshot","volume":"28","author":"Busetto","year":"2020","journal-title":"Obesity"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.orcp.2020.07.007","article-title":"Coronavirus (SARS-CoV-2) and the Risk of Obesity for Critically Illness and ICU Admitted: Meta-Analysis of the Epidemiological Evidence","volume":"14","author":"Bonato","year":"2020","journal-title":"Obes. Res. Clin. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/s43587-021-00114-7","article-title":"SARS-CoV-2, COVID-19 and the Aging Immune System","volume":"1","author":"Bartleson","year":"2021","journal-title":"Nat. Aging"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bajaj, V., Gadi, N., Spihlman, A.P., Wu, S.C., Choi, C.H., and Moulton, V.R. (2021). Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections?. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.571416"},{"key":"ref_14","first-page":"402","article-title":"High Oligoclonality of Immunoglobulins in SARS-CoV2 Positive Patients","volume":"80","author":"Miossec","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41586-021-03631-y","article-title":"Diverse Functional Autoantibodies in Patients with COVID-19","volume":"595","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1038\/s41366-020-0597-4","article-title":"COVID-19 and the Role of Chronic Inflammation in Patients with Obesity","volume":"44","author":"Chiappetta","year":"2020","journal-title":"Int. J. Obes."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E736","DOI":"10.1152\/ajpendo.00124.2020","article-title":"COVID-19 Pandemic, Coronaviruses, and Diabetes Mellitus","volume":"318","author":"Muniyappa","year":"2020","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Galarza, J., Pr\u00f3cel, C., Ca\u00f1adas, C., Aguirre, D., Pibaque, R., Bed\u00f3n, R., Semp\u00e9rtegui, F., Drexhage, H., and Balde\u00f3n, L. (2021). Immune Response to SARS-CoV-2 Infection in Obesity and T2D: Literature Review. Vaccines, 9.","DOI":"10.3390\/vaccines9020102"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1002\/oby.22843","article-title":"Is Adipose Tissue a Reservoir for Viral Spread, Immune Activation, and Cytokine Amplification in Coronavirus Disease 2019?","volume":"28","author":"Ryan","year":"2020","journal-title":"Obesity"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Banchereau, J. (2015). Generation of Human B-Cell Lines Dependent on CD40-Ligation and Interleukin-4. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00055"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1126\/science.1702555","article-title":"Long-Term Human B Cell Lines Dependent on Interleukin-4 and Antibody to CD40","volume":"251","author":"Banchereau","year":"1991","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Weidner, L., G\u00e4nsdorfer, S., Unterweger, S., Weseslindtner, L., Drexler, C., Farcet, M., Witt, V., Schistal, E., Schlenke, P., and Kreil, T.R. (2020). Quantification of SARS-CoV-2 Antibodies with Eight Commercially Available Immunoassays. J. Clin. Virol., 129.","DOI":"10.1016\/j.jcv.2020.104540"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Li, K., Huang, B., Wu, M., Zhong, A., Li, L., Cai, Y., Wang, Z., Wu, L., Zhu, M., and Li, J. (2020). Dynamic Changes in Anti-SARS-CoV-2 Antibodies during SARS-CoV-2 Infection and Recovery from COVID-19. Nat. Commun., 11.","DOI":"10.1038\/s41467-020-19943-y"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hartley, G.E., Edwards, E.S.J., Aui, P.M., Varese, N., Stojanovic, S., McMahon, J., Peleg, A.Y., Boo, I., Drummer, H.E., and Hogarth, P.M. (2020). Rapid Generation of Durable B Cell Memory to SARS-CoV-2 Spike and Nucleocapsid Proteins in COVID-19 and Convalescence. Sci. Immunol., 5.","DOI":"10.1126\/sciimmunol.abf8891"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41586-020-2456-9","article-title":"Convergent Antibody Responses to SARS-CoV-2 in Convalescent Individuals","volume":"584","author":"Robbiani","year":"2020","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Callender, L.A., Curran, M., Bates, S.M., Mairesse, M., Weigandt, J., and Betts, C.J. (2020). The Impact of Pre-Existing Comorbidities and Therapeutic Interventions on COVID-19. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01991"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1002\/art.41458","article-title":"Synergy Between Cytokines and Risk Factors in the Cytokine Storm of COVID-19: Does Ongoing Use of Cytokine Inhibitors Have a Protective Effect?","volume":"72","author":"Miossec","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9959","DOI":"10.18632\/aging.103344","article-title":"Why Does COVID-19 Disproportionately Affect Older People?","volume":"12","author":"Mueller","year":"2020","journal-title":"Aging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s00592-020-01636-z","article-title":"The Triumvirate: Why Hypertension, Obesity, and Diabetes Are Risk Factors for Adverse Effects in Patients with COVID-19","volume":"58","author":"Shah","year":"2021","journal-title":"Acta Diabetol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wang, M., Fan, Y., Chai, Y., Cheng, W., Wang, K., Cao, J., and Hu, X. (2021). Association of Clinical and Immunological Characteristics With Disease Severity and Outcomes in 211 Patients With COVID-19 in Wuhan, China. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.667487"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Diao, B., Wang, C., Tan, Y., Chen, X., Liu, Y., Ning, L., Chen, L., Li, M., Liu, Y., and Wang, G. (2020). Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00827"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1111\/all.14866","article-title":"Profound Dysregulation of T Cell Homeostasis and Function in Patients with Severe COVID-19","volume":"76","author":"Adamo","year":"2021","journal-title":"Allergy"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Schub, D., Klemis, V., Schneitler, S., Mihm, J., Lepper, P.M., Wilkens, H., Bals, R., Eichler, H., G\u00e4rtner, B.C., and Becker, S.L. (2020). High Levels of SARS-CoV-2-Specific T Cells with Restricted Functionality in Severe Courses of COVID-19. JCI Insight, 5.","DOI":"10.1172\/jci.insight.142167"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mann, E.R., Menon, M., Knight, S.B., Konkel, J.E., Jagger, C., Shaw, T.N., Krishnan, S., Rattray, M., Ustianowski, A., and Bakerly, N.D. (2020). Longitudinal Immune Profiling Reveals Key Myeloid Signatures Associated with COVID-19. Sci. Immunol., 5.","DOI":"10.1126\/sciimmunol.abd6197"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kuri-Cervantes, L., Pampena, M.B., Meng, W., Rosenfeld, A.M., Ittner, C.A.G., Weisman, A.R., Agyekum, R.S., Mathew, D., Baxter, A.E., and Vella, L.A. (2020). Comprehensive Mapping of Immune Perturbations Associated with Severe COVID-19. Sci. Immunol., 5.","DOI":"10.1126\/sciimmunol.abd7114"},{"key":"ref_36","unstructured":"Woodruff, M., Ramonell, R., Cashman, K., Nguyen, D., Ley, A., Kyu, S., Saini, A., Haddad, N., Chen, W., and Howell, J.C. (2020). Critically Ill SARS-CoV-2 Patients Display Lupus-like Hallmarks of Extrafollicular B Cell Activation. medRxiv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1038\/s41590-020-00822-z","article-title":"Overlapping B Cell Pathways in Severe COVID-19 and Lupus","volume":"21","author":"Farris","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/(SICI)1521-4141(199802)28:02<508::AID-IMMU508>3.0.CO;2-I","article-title":"IL-10 Interrupts Memory B Cell Expansion in the Germinal Center by Inducing Differentiation into Plasma Cells","volume":"28","author":"Choe","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.it.2020.10.012","article-title":"A Potential Role of Interleukin 10 in COVID-19 Pathogenesis","volume":"42","author":"Lu","year":"2021","journal-title":"Trends Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.immuni.2020.07.020","article-title":"Distinct Early Serological Signatures Track with SARS-CoV-2 Survival","volume":"53","author":"Atyeo","year":"2020","journal-title":"Immunity"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/s41423-020-00588-2","article-title":"A Longitudinal Study of SARS-CoV-2-Infected Patients Reveals a High Correlation between Neutralizing Antibodies and COVID-19 Severity","volume":"18","author":"Legros","year":"2021","journal-title":"Cell. Mol. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/20\/11095\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:14:49Z","timestamp":1760166889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/20\/11095"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,14]]},"references-count":41,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms222011095"],"URL":"https:\/\/doi.org\/10.3390\/ijms222011095","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,10,14]]}}}