Clinical characteristics of Chinese diabetic patients and their antibody responses to Omicron subvariants

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Background: 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. Methods: A cross-sectional study was conducted after the nationwide Omicron surge in China from April to June 2023. A 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. Results: Clinically, diabetic patients exhibited a significantly lower prevalence of high-grade fever (≥38 °C, 11.8% vs. 46.1%, P<0.001) and myalgia (1.5% vs. 37.0%, P<0.001) compared with HCs. Immunologically, anti-RBD IgG concentrations were markedly reduced in the diabetic group (P<0.01). While NAb titers against BA.4/5 were comparable between the two cohorts (P>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<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<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. Conclusions: 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.

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