{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:36:32Z","timestamp":1786534592145,"version":"build-2736575974"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The ongoing circulation of SARS-CoV-2 Omicron sublineages continues to threaten vulnerable populations such as individuals with diabetes mellitus. Diabetes is well documented to impair host immune function; however, the correlation between clinical manifestations and cross-variant neutralizing immunity against evolving Omicron strains remains poorly characterized in diabetic patients during large-scale Omicron outbreaks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cross-sectional study was conducted after the nationwide Omicron surge in China from April to June 2023.\u00a0A total of 200 diabetic patients and 200 age-comparable healthy controls (HCs) were enrolled. We systematically compared their clinical symptoms, serum anti-RBD IgG levels, and neutralizing antibody (NAb) geometric mean titers (GMTs) against Omicron BA.4\/5 and XBB.1.5 using a pseudovirus neutralization assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Clinically, diabetic patients exhibited a significantly lower prevalence of high-grade fever (\u226538\u00a0\u00b0C, 11.8% vs. 46.1%, P&amp;lt;0.001) and myalgia (1.5% vs. 37.0%, P&amp;lt;0.001) compared with HCs. Immunologically, anti-RBD IgG concentrations were markedly reduced in the diabetic group (P&amp;lt;0.01). While NAb titers against BA.4\/5 were comparable between the two cohorts (P&amp;gt;0.05), diabetic patients had drastically diminished neutralizing activity against the immune-evasive XBB.1.5 variant (GMT: 18.9 vs. 59.6 in HCs, P&amp;lt;0.001). Diabetic individuals also showed a far greater fold reduction in cross-variant neutralizing capacity from BA.4\/5 to XBB.1.5 than HCs (P&amp;lt;0.001). Gender stratification revealed higher BA.4\/5-specific NAb titers in female participants across both groups. Age was negatively associated with BA.4\/5-specific NAb titers in both diabetic patients and healthy controls, whereas XBB.1.5 neutralization was uniformly low irrespective of age, which may reflect an age-independent susceptibility of diabetic patients to immune-evasive variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Diabetic patients showed a distinct self-reported symptom profile, characterized by lower reported frequencies of high-grade fever and myalgia, but also exhibited reduced cross-variant neutralizing activity, particularly against the immune-evasive XBB.1.5 sublineage. The reduced XBB.1.5 neutralizing activity observed in diabetic patients highlights the need for targeted immunological monitoring and risk management during waves of immune-evasive SARS-CoV-2 variants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1909061","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:02:49Z","timestamp":1786532569000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical characteristics of Chinese diabetic patients and their antibody responses to Omicron subvariants"],"prefix":"10.3389","volume":"17","author":[{"given":"Lanxin","family":"Ma","sequence":"first","affiliation":[{"name":"School of Life Sciences and Agriculture and Forestry, Qiqihar University","place":["Qiqihar, China"]},{"name":"Department of Prevention and Control of Infectious Disease, Zhejiang Provincial Center for Disease Control and Prevention","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijing","family":"Bao","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Agriculture and Forestry, Qiqihar University","place":["Qiqihar, China"]},{"name":"Department of Prevention and Control of Infectious Disease, Zhejiang Provincial Center for Disease Control and Prevention","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Ruan","sequence":"additional","affiliation":[{"name":"Zhejiang Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Medical College","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nani","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Immunization Program, Xihu District Center for Disease Control and Prevention","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Zhejiang Provincial People\u2019s Hospital","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Prevention and Control of Infectious Disease, Zhejiang Provincial Center for Disease Control and Prevention","place":["Hangzhou, China"]},{"name":"Zhejiang Key Lab of Vaccines, Department of Prevention and Control of Infectious Disease, Zhejiang Provincial Center for Disease Control and Prevention","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichang","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Agriculture and Forestry, Qiqihar University","place":["Qiqihar, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Prevention and Control of Infectious Disease, Zhejiang Provincial Center for Disease Control and Prevention","place":["Hangzhou, China"]},{"name":"Zhejiang Key Lab of Vaccines, Department of Prevention and Control of Infectious Disease, Zhejiang Provincial Center for Disease Control and Prevention","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanwpc.2023.100945","article-title":"Antibody response assessment of immediate breakthrough infections after zero-COVID policy adjustment in China","volume":"40","author":"Li","year":"2023","journal-title":"Lancet Regional Health - Western Pacific"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1016\/j.chom.2022.09.002","article-title":"Antigenic characterization of the SARS-CoV-2 Omicron subvariant BA.2.75","volume":"30","author":"Wang","year":"2022","journal-title":"Cell Host Microbe"},{"key":"B3","doi-asserted-by":"publisher","first-page":"964525","DOI":"10.3389\/fimmu.2022.964525","article-title":"Breakthrough infections with the omicron and delta variants of SARS-CoV-2 result in similar re-activation of vaccine-induced immunity","volume":"13","author":"S\u00f8raas","year":"2022","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00213-1","article-title":"China\u2019s COVID-19 reopening measures\u2014warriors and weapons","volume":"401","author":"Huang","year":"2023","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(22)00017-4","article-title":"Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study","volume":"399","author":"Wolter","year":"2022","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04581-9","article-title":"Molecular basis of receptor binding and antibody neutralization of Omicron","volume":"604","author":"Hong","year":"2022","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-022-04396-2","article-title":"An insight into the mechanisms of COVID-19, SARS-CoV2 infection severity concerning \u03b2-cell survival and cardiovascular conditions in diabetic patients","volume":"477","author":"Srivastava","year":"2022","journal-title":"Mol Cell Biochem"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2024.116353","article-title":"Real-world effectiveness of molnupiravir, azvudine and paxlovid against mortality and viral clearance among hospitalized patients with COVID-19 infection during the omicron wave in China: A retrospective cohort study","volume":"109","author":"Chen","year":"2024","journal-title":"Diagn Microbiol Infect Dis"},{"key":"B9","doi-asserted-by":"publisher","first-page":"4757","DOI":"10.1038\/s41467-023-40489-2","article-title":"Safety and immunogenicity of Ad5-nCoV immunization after three-dose priming with inactivated SARS-CoV-2 vaccine in Chinese adults","volume":"14","author":"Zhang","year":"2023","journal-title":"Nat Commun"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104485","article-title":"COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses","volume":"89","author":"Chen","year":"2023","journal-title":"eBioMedicine"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/s2666-5247(23)00255-0","article-title":"Durability and cross-reactive immune memory to SARS-CoV-2 in individuals 2 years after recovery from COVID-19: a longitudinal cohort study","volume":"5","author":"Guo","year":"2024","journal-title":"Lancet Microbe"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanwpc.2023.100939","article-title":"Evaluation of cross-neutralizing antibodies in children infected with omicron sub-variants","volume":"40","author":"Peng","year":"2023","journal-title":"Lancet Regional Health - Western Pacific"},{"key":"B13","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.bbi.2021.12.020","article-title":"Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis","volume":"101","author":"Ceban","year":"2022","journal-title":"Brain Behavior Immun"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc2018688","article-title":"New-onset diabetes in covid-19","volume":"383","author":"Rubino","year":"2020","journal-title":"N Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.imj.2025.100211","article-title":"Immune dysregulation in type 2 diabetes mellitus: Implications for tuberculosis, COVID-19, and HIV\/AIDS","volume":"4","author":"Abbas","year":"2025","journal-title":"Infect Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v9.i24.6969","article-title":"Multiple immune function impairments in diabetic patients and their effects on COVID-19","volume":"9","author":"Lu","year":"2021","journal-title":"World J Clin cases"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v12.i7.1026","article-title":"Immunometabolic bases of type 2 diabetes in the severity of COVID-19","volume":"12","author":"Viurcos-Sanabria","year":"2021","journal-title":"World J Diabetes"},{"key":"B18","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/s41392-025-02319-3","article-title":"Dynamics of neutralizing antibodies against COVID-19 omicron subvariants following breakthrough infection in southwest China between december 2022 and april 2024","volume":"10","author":"He","year":"2025","journal-title":"Signal Transduction Targeted Ther"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1080\/20477724.2024.2369378","article-title":"JN.1 and the ongoing battle: unpacking the characteristics of a new dominant COVID-19 variant","volume":"118","author":"Eshraghi","year":"2024","journal-title":"Pathog Global Health"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-024-06102-x","article-title":"Diabetes and infection: Review of the epidemiology, mechanisms and principles of treatment","volume":"67","author":"Holt","year":"2024","journal-title":"Diabetologia"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.988004","article-title":"Association between immunosuppressants and poor antibody responses to SARS-CoV-2 vaccines in patients with autoimmune liver diseases","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1476186","article-title":"Clinical characteristics and antibody response to omicron variants among solid carcinoma patients in China on the 2022.12\u20132023.4 wave of the COVID-19 pandemic","volume":"15","author":"Dai","year":"2024","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9061211","article-title":"Type-2 diabetes as a risk factor for severe COVID-19 infection","volume":"9","author":"Norouzi","year":"2021","journal-title":"Microorganisms"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(24)00574-7","article-title":"Clinical profile analysis of SARS-CoV-2 community infections during periods with omicron BA.2, BA.4\/5, and XBB dominance in hong kong: A prospective cohort study","volume":"25","author":"Wang","year":"2025","journal-title":"Lancet Infect Dis"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2174\/18756417mtaxgodqqy","article-title":"Type 2 Diabetes and its Impact on the Immune System","volume":"16","author":"Berbudi","year":"2020","journal-title":"Curr Diabetes Rev"},{"key":"B26","doi-asserted-by":"crossref","DOI":"10.1101\/2020.03.22.20040774","volume-title":"Hypertension and diabetes delay the viral clearance in COVID-19 patients","author":"Chen","year":"2020"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2700-3","article-title":"Sex differences in immune responses that underlie COVID-19 disease outcomes","volume":"588","author":"Takahashi","year":"2020","journal-title":"Nature"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03739-1","article-title":"Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2","volume":"596","author":"Collier","year":"2021","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.cell.2022.12.018","article-title":"Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants","volume":"186","author":"Wang","year":"2023","journal-title":"Cell"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11071203","article-title":"Assessment of the immune response in patients with insulin resistance, obesity, and diabetes to COVID-19 vaccination","volume":"11","author":"Warpechowski","year":"2023","journal-title":"Vaccines"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1909061\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:02:51Z","timestamp":1786532571000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1909061\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":30,"alternative-id":["10.3389\/fimmu.2026.1909061"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1909061","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"article-number":"1909061"}}