Influenza is a common respiratory infectious disease that poses a serious threat to the health of the elderly population. Vaccination against influenza is an important measure to prevent infection and reduce disease burden among the elderly. However, individuals who have been vaccinated against influenza may still contract the disease, resulting in breakthrough cases, and there is currently limited research on breakthrough cases of influenza vaccination among the elderly.

To investigate risk factors for breakthrough influenza cases among individuals aged 70 years and older, construct a predictive model to facilitate early identification and prevention of influenza infection among the elderly.

A nested case-control study was conducted among individuals aged 70 years and older in Xiaoshan and Linping Districts of Hangzhou who received influenza vaccination between September 1, 2023, and March 31, 2024. The survey includes demographic information (gender, age, living arrangements, and residential area) , information on influenza vaccination in the past year, a history of chronic illnesses (such as hypertension, diabetes, hyperlipidaemia, stroke, coronary heart disease, chronic obstructive pulmonary disease, asthma, etc.) , and details of personal lifestyle (average sleep duration in the past week, and engagement in moderate or higher intensity physical activity) . Individuals who developed influenza infection during the 2023-2024 influenza season were classified as breakthrough cases, while those who remained uninfected served as controls. Multivariate Logistic regression analysis with backward stepwise was used to identify significant risk factors. A nomogram-based risk predictive model was constructed using these factors, the model was evaluated using the Hosmer-Lemeshow goodness-of-fit test, receiver operating characteristic (ROC) curve analysis, Calibration curve.

Among 99 735 vaccinated individuals aged 70 years and older, 4 689 breakthrough cases were identified during the follow-up period, yielding a breakthrough infection rate of 4.70%. A stratified random sample of 4 853 individuals was selected as the control group. Statistically significant differences (P<0.05) between cases and controls were observed in age, sex, living arrangement, residential area, history of hypertension, diabetes, stroke, coronary heart disease, chronic obstructive pulmonary disease (COPD) , asthma, prior-season influenza vaccination, and engagement in moderate or vigorous physical activity. Multivariate Logistic regression analysis identified all these variables as independent influence factors (P<0.05) . The predictive model incorporating these variables demonstrated good fit (Hosmer-Lemeshow P=0.762) , strong discrimination (AUC=0.806, 95%CI=0.786-0.834) , and good calibration, indicating close agreement between predicted and observed outcomes.

Breakthrough influenza infections can still occur in older adults aged 70 years and older after influenza vaccination, and their occurrence is associated with age, gender, living arrangement, residential area, multiple chronic conditions, influenza vaccination status in the previous year, and moderate-to-vigorous physical activity. The risk prediction model developed in this study demonstrates good predictive performance and can provide a reference for identifying older adults at high risk of breakthrough influenza infections.

流行性感冒（以下简称流感）作为常见的呼吸道传染病，对老年人健康构成严重威胁，接种流感疫苗成为预防流感病毒、降低老年人流感疾病负担的重要手段，然而在实际应用中，接种了流感疫苗仍可能感染流感病毒，即突破病例，目前对老年人流感疫苗突破病例发生的相关研究较少。

探究70岁及以上老年人流感疫苗突破病例的危险因素，并构建风险预测模型，为早期识别老年人流感病毒感染和预防提供科学依据。

将2023-09-01—2024-03-31杭州市萧山区、临平区70岁及以上且期间接种流感疫苗的老年人作为研究对象并纳入研究队列，调查资料包括人口统计学资料（性别、年龄、居住方式、居住地区）、上年度流感疫苗接种情况、慢性病史（高血压、糖尿病、高脂血症、脑卒中、冠心病、慢性阻塞性肺疾病、哮喘等），个人生活情况（近一周平均睡眠时长、中等强度及以上锻炼情况），采用巢式病例对照研究，其中再感染流感病毒的老年人作为突破病例组，未感染的老年人作为对照组，采用多因素Logistic回归分析（向后逐步法）探索流感疫苗突破病例发生的影响因素，构建风险预测模型并绘制列线图，同时进行Hosmer-Lemeshow拟合优度检验，绘制受试者工作特征（ROC）曲线和校准曲线对模型进行预测效能评价。

70岁及以上老年人流感疫苗接种99 735人，2023—2024年流感流行季期间共观察随访到突破病例4 689人，疫苗突破率为4.70%，分层随机抽取对照组共4 853人，对照组和突破病例组的年龄、性别、居住方式、居住地区、高血压史、糖尿病史、脑卒中史、冠心病史、慢性阻塞性肺疾病史、哮喘史、上年度流感疫苗接种情况、中等强度及以上锻炼情况比较，差异有统计学意义（P<0.05），依据赤池信息准则，多因素Logistic回归分析向后逐步法显示，年龄、性别、居住方式、居住地区、高血压史、糖尿病史、脑卒中史、冠心病史、慢性阻塞性肺疾病史、哮喘史、上年度流感疫苗接种、中等强度及以上锻炼是70岁及以上老年人流感疫苗突破病例发生的影响因素（P<0.05），采用上述变量构建风险预测模型，Hosmer-Lemeshow拟合优度检验P值为0.762；ROC曲线下面积（AUC）为0.806（95%CI=0.786~0.834）；校准曲线显示预测模型的预测值和实际值一致性较好。

70岁及以上老年人接种流感疫苗后仍可发生突破感染，其发生与年龄、性别、居住方式、居住地区、多种慢性病史、上年度流感疫苗接种情况及中等强度及以上锻炼情况有关。本研究构建的风险预测模型具有较好的预测效能，可为识别流感疫苗突破感染高风险老年人提供参考。