Neutralizing immunity across SARS-CoV-2 variants in kidney disease: broad deficits and sex-related heterogeneity after China’s Omicron wave

Background Variant-specific SARS-CoV-2 neutralizing responses in kidney disease (KD) remain incompletely characterized after China’s 2022–2023 Omicron wave. We compared these responses and their heterogeneity between participants with KD and healthy controls (HC) sampled in the same region. Methods This cross-sectional study included 380 participants: 197 HC and 183 participants with KD, sampled in Zhejiang Province from March to early April 2023. Pseudovirus assays measured neutralization against the prototype strain (PT), BA.4/5, and XBB.1.5. KD/HC geometric mean ratios (GMRs) and 95% confidence intervals (CIs) were calculated. Group differences and interactions with sex, age, and vaccination-dose category were assessed using log 10 -transformed titers. Disease categories and confirmed infection before sampling were examined in exploratory analyses. Results KD participants had significantly lower titers against PT, BA.4/5, and XBB.1.5, with KD/HC GMRs of 0.167 (95% CI, 0.110–0.255), 0.491 (0.359–0.672), and 0.626 (0.489–0.802), respectively. Group-by-sex interactions were significant for all three viruses (interaction P = 0.0006, 0.0163, and 0.0067, respectively), with larger relative HC–KD differences among women. Receipt of ≥3 doses, compared with 0–2 doses, was associated with higher PT titers in both groups, whereas no significant overall dose associations were detected for BA.4/5 or XBB.1.5. No significant group interactions with age or vaccination-dose category were detected. Exploratory analyses showed lower PT and BA.4/5 titers in glomerular/immune-mediated than in metabolic/vascular kidney disease. In the questionnaire subgroup, confirmed infection before sampling was associated with higher BA.4/5 titers without a significant group-by-infection interaction. Conclusions KD was associated with lower neutralization across all three viruses, with consistently larger relative HC–KD differences among women. These findings highlight sex-related heterogeneity in post-wave neutralizing immunity and support prospective studies integrating renal phenotype, treatment, vaccination history, and clinical outcomes.