新泽西州是COVID-19大流行最早波及的州之一，全国死亡率较高。然而，关于新泽西州的研究报告相对较少。本文我们报告了泽西州最大的医疗网络中，对已接种和未接种实验室确认的SARS-CoV-2感染个体的分子学、临床学和流行病学观察。我们从2020年12月至2022年6月，对来自九家医院收集的SARS-CoV-2阳性鼻咽拭子进行分子监测，采用整个基因组测序（WGS）和实时RT-PCR筛查法，针对我们所在地区的关注变异体（VOCs）中发现的刺突蛋白突变进行检测。我们回顾性获取了去识别的临床数据，包括人口统计学资料、COVID-19疫苗接种情况、重症监护病房入院、呼吸机支持、死亡和病史。进行了统计分析，以确定SARS-CoV-2变异体、疫苗接种情况、临床结果和医学危险因素之间的关联。成功筛查和/或测序了5007份SARS-CoV-2阳性鼻咽拭子。变异体筛查鉴定了三个主要的VOCs，包括Alpha（n = 714）、Delta（n = 1877）和Omicron（n = 1802）。Omicron分离物进一步分型为BA.1（n = 899）、BA.2（n = 853）或BA.4/BA.5（n = 50）；其余614个孤立物被归类为“其他”。约31.5%（1577/5007）的样品与疫苗突破感染有关，在Delta和Omicron出现后频率增加。严重的临床结果包括重症监护病房入院（336/5007 = 6.7%）、呼吸机支持（236/5007 = 4.7%）和死亡（430/5007 = 8.6%），其中年龄增长是每个临床结果中最重要的因素（p < 0.001）。未接种疫苗的个体占重症监护病房入院的79.7%（268/336），占呼吸机病例的78.3%（185/236），占死亡的74.4%（320/430）。心血管疾病、高血压、癌症、糖尿病和高血脂症，在未接种和接种疫苗的个体中，与死亡率的显著增加（p < 0.001）有关，但与肥胖症、甲状腺疾病或呼吸系统疾病无关。不同的SARS-CoV-2变异体，包括Delta、Omicron BA.1和Omicron BA.2之间也存在显着差异（p < 0.001）。尽管与免疫衰减、抗原变异性或两者都有关联，但本研究表明疫苗与临床结果有显着改善。潜在的共病因素对接种和未接种的个体的死亡率有明显的贡献，风险增加与共病因素的总数相关。基于实时RT-PCR的筛查法，使用较少数量的刺突蛋白突变，与WGS相比，具有更快的周转时间和更低的成本，有助于及时识别主要变异体。SARS-CoV-2变异的持续演变可能需要持续监测新的VOCs，并实时评估其临床影响。

New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations, from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOCs) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOCs, including Alpha (n = 714), Delta (n = 1877), and Omicron (n = 1802). Omicron isolates were further sub-typed as BA.1 (n = 899), BA.2 (n = 853), or BA.4/BA.5 (n = 50); the remaining 614 isolates were classified as "Other". Approximately 31.5% (1577/5007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p < 0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p < 0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p < 0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.