我们对意大利佩斯卡拉省的总人口进行了队列研究，以评估SARS-CoV-2疫苗在疫苗接种活动开始后两年内对感染、严重或致命COVID-19的真实世界效果。我们包括了所有居民或居住在该地区的受试对象，并从2021年1月1日至2023年2月15日期间提取了官方的人口统计、疫苗、COVID-19、医院和报销免费等数据集。考虑到性别、年龄、糖尿病、高血压、慢性阻塞性肺病、重大心脏和脑血管事件、癌症以及肾脏疾病等因素，我们进行了Cox比例风险分析。在平均追踪时间（466天）内，有186,676名受试对象接种了大于等于三剂疫苗（ChAdOx1 nCoV-19、BNT162b2、mRNA-1273、NVX-CoV2373或JNJ-78436735），47,610名接种了两剂疫苗，11,452名接种了一剂疫苗，44,989名未接种。总体上，40.4%的受试对象感染了SARS-CoV-2，其中2.74%的人患有严重或致命（1.30%）COVID-19。与未接种疫苗的人相比，接种了大于等于一剂增强剂的个体患严重或致命COVID-19的风险降低了≥85%。疫苗在老年人中产生了巨大的影响：未接种疫苗的感染者中有22.0%死亡，而接种了大于等于三剂疫苗的人中只有不到3%的死亡。我们没有观察到对感染的保护作用，尽管这一结果当然受到了意大利控制疫情的限制政策的影响。值得注意的是，在Omicron主导时期，只有接种了至少一剂增强剂的人群的COVID-19相关死亡风险降低。

We carried out a cohort study on the overall population of the province of Pescara, Italy, to assess the real-world effectiveness of SARS-CoV-2 vaccination against infection, severe, or lethal COVID-19, two years after the start of the vaccination campaign. We included all the resident or domiciled subjects, and extracted the official demographic, vaccination, COVID-19, hospital and co-pay exemption datasets from 1 January 2021, up to 15 February 2023. Cox proportional hazards analyses were adjusted for gender, age, diabetes, hypertension, COPD, major cardio- and cerebrovascular events, cancer, and kidney diseases. Throughout the follow-up (466 days on average), 186,676 subjects received greater than or equal to three vaccine doses (of ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, NVX-CoV2373, or JNJ-78436735), 47,610 two doses, 11,452 one dose, and 44,989 none. Overall, 40.4% of subjects were infected with SARS-CoV-2. Of them, 2.74% had severe or lethal (1.30%) COVID-19. As compared to the unvaccinated, the individuals who received greater than or equal to one booster dose showed a ≥85% lower risk of severe or lethal COVID-19. A massive impact of vaccination was found among the elderly: 22.0% of the unvaccinated, infected individuals died, as opposed to less than 3% of those who received greater than or equal to three vaccine doses. No protection against infection was observed, although this finding was certainly influenced by the Italian restriction policies to control the pandemic. Importantly, during the Omicron predominance period, only the group who received at least a booster dose showed a reduced risk of COVID-19-related death.