Diversity and Determinants of the Immune-Inflammatory Response to SARS-CoV-2

SARS-CoV-2 免疫炎症反应的多样性和决定因素

• 批准号: 10706735
• 负责人: Jane C. Figueiredo
• 金额: $ 44万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706735
• 关键词: 2019-nCoV; Address; Affect; Area; Autoimmune Diseases; Basic Science; COVID-19; COVID-19 risk; COVID-19 susceptibility; COVID-19 treatment; California; Caring; Characteristics; Chronic Disease; Clinical; Clinical Sciences; Cohort Studies; Collaborations; Communities; Coronavirus; Data; Data Analyses; Data Collection; Disease; Enrollment; Ensure; Epidemiologist; Evaluation; Evaluation Studies; Exposure to; Foundations; Funding; Goals; Health; Health Personnel; Health system; Healthcare Systems; Home; Immune; Immunity; Immunologist; Individual; Infection; Inflammatory Response; Infrastructure; Institution; Knowledge; Los Angeles; Malignant Neoplasms; Metabolic Diseases; Minority; Molecular Profiling; Natural History; Nature; Outcome; Patients; Pattern; Persons; Population Heterogeneity; Population Sciences; Populations at Risk; Predisposition; Public Health; Publishing; Recovery; Recovery of Function; Reporting; Request for Applications; Research; Research Personnel; Research Project Grants; Resources; Risk; SARS-CoV-2 antibody; SARS-CoV-2 exposure; Scientific Advances and Accomplishments; Scientist; Seeds; Seroprevalences; Signal Transduction; Structure; Subgroup; Techniques; Therapeutic; Translational Research; Viral; Virus; Vulnerable Populations; World Health Organization; base; biobank; clinical phenotype; disorder risk; experience; immune function; immune reconstitution; innate immune function; insight; novel; operation; pandemic disease; programs; racial and ethnic; recruit; response; severe COVID-19; trait; translational scientist

Patients receiving cancer therapy experience iatrogenic immunosuppression which makes them more susceptible to severe COVID and simultaneously blunts their response to vaccines against SARS-CoV-2. Treatment related immunosuppression is often transient and/or cyclical which raises critical questions about how to optimally time vaccines and boosters in patients who are undergoing active cancer therapy. In our U54 SeroNet project, we have focused on accruing cancer patients undergoing active treatment. While patients with any cancer type were eligible, we oversampled patients either receiving B lineage depleting treatments, bone marrow transplant, and PD-1/PD-L1 immune check point inhibitors as we hypothesized these treatments were most likely to create immune altered states that would alter responses to SARS-CoV-2 vaccine or infection. As of July 8, 2022, we have enrolled 826 patients with cancer in our study, 738 (89%) of whom have received their primary vaccine series, 543 (74% of vaccinated) have received their first booster and 177 (33% of single boosted) have received their second booster. Our cohort is racially and ethnically diverse with 20% Hispanic, 9% Black, 9% Asian, and 6% mixed/other races, reflecting the diversity of patients who live in Los Angeles county. Among a subset of 657 cancer patients with serology data available, 53.9% and 38.1% of solid and hematologic cancer patients achieve high (IgG(S-RBD) >590 BAU/ml) antibody levels after completion of the primer series, which improves to 76.8% and 65.2% after boosting. Among patients with no seropositivity after priming, 83.3% seroconverted after a booster immunization (25.0% with high IgG-(S-RBD)). These data demonstrate that booster doses can improve serologic responses in patients immunosuppressed due to cancer therapy, however a substantial number of patients still have suboptimal serologic responses. Durability of the serological response, T cell/cellular immunity and resistance to breakthrough infection in this cohort are largely unknown

接受癌症治疗的患者会经历医源性免疫抑制，这使他们更容易感染严重的新冠病毒，同时削弱他们对 SARS-CoV-2 疫苗的反应。治疗相关的免疫抑制通常是短暂的和/或周期性的，这引发了关于如何为正在接受积极癌症治疗的患者提供最佳疫苗和加强疫苗接种时间的关键问题。在我们的 U54 SeroNet 项目中，我们专注于招募接受积极治疗的癌症患者。虽然任何癌症类型的患者都符合资格，但我们对接受 B 谱系耗竭治疗、骨髓移植和 PD-1/PD-L1 免疫检查点抑制剂的患者进行了过度采样，因为我们假设这些治疗最有可能产生免疫改变状态，从而改变对 SARS-CoV-2 疫苗或感染的反应。截至 2022 年 7 月 8 日，我们已在研究中招募了 826 名癌症患者，其中 738 名（89%）已接受初级疫苗系列，543 名（74% 已接种疫苗）已接受第一次加强疫苗接种，177 名（33% 已接种单次加强疫苗）已接受第二次加强疫苗接种。我们的队列在种族和民族上具有多样性，其中 20% 是西班牙裔，9% 是黑人，9% 是亚洲人，6% 是混血/其他种族，反映了居住在洛杉矶县的患者的多样性。在 657 名有血清学数据的癌症患者中，53.9% 和 38.1% 的实体癌和血液癌患者在完成引物系列后达到高抗体水平 (IgG(S-RBD) >590 BAU/ml)，在加强免疫后该比例提高至 76.8% 和 65.2%。在初免后无血清阳性的患者中，83.3% 的患者在加强免疫后出现血清转化（25.0% 具有高 IgG-(S-RBD)）。这些数据表明，加强剂量可以改善因癌症治疗而免疫抑制的患者的血清学反应，但仍有大量患者的血清学反应不佳。该队列中血清学反应的持久性、T 细胞/细胞免疫和对突破性感染的抵抗力在很大程度上尚不清楚