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

接受癌症治疗的患者经历医源性免疫抑制，这使他们更容易感染严重的COVID，同时减弱了他们对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，这就提出了如何在接受积极癌症治疗的患者中最佳地接种疫苗和增强剂的关键问题。在我们的U54 SeroNet项目中，我们专注于积累正在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条件，但我们对接受B谱系消耗治疗、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，我们在研究中招募了826例癌症患者，其中738例（89%）接种了一次疫苗系列，543例（74%）接种了第一次加强疫苗，177例（33%）接种了第二次加强疫苗。我们的队列具有种族和民族多样性，其中20%为西班牙裔，9%为黑人，9%为亚洲人，6%为混合/其他种族，反映了居住在洛杉矶县的患者的多样性。在657例有血清学数据的癌症患者中，53.9%和38.1%的实体癌和血液学癌症患者在完成引物系列后达到高抗体水平（IgG(S-RBD) >590 BAU/ml），在增强后提高到76.8%和65.2%。在启动后无血清阳性的患者中，83.3%在加强免疫后血清转化（25.0%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，但仍有相当数量的患者血清学反应不理想。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是未知的

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