Cancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes. Plasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in silico positional cloning approach was used to identify the presence of miRNAs at COVID-19 risk-associated genomic regions: CORSAIRs (COvid-19 RiSk AssocIated genomic Regions). The miRNA levels were measured by RT-qPCR. We found that miRNAs were enriched in CORSAIR. Low plasma levels of hsa-miR-150-5p and hsa-miR-93-5p were associated with higher COVID-19-related death. The levels of hsa-miR-92b-3p were associated with SARS-CoV-2 test positivity. Peripheral blood mononuclear cells (PBMC) increased secretion of hsa-miR-150-5p, hsa-miR-93-5p, and hsa-miR-92b-3p after in vitro TLR7/8- and T cell receptor (TCR)-mediated activation. Increased levels of these three miRNAs were measured in the serum samples of healthy individuals between one and nine months after the second dose of the Pfizer-BioNTech COVID-19 vaccine. SARS-CoV-2 infection of human airway epithelial cells influenced the miRNA levels inside their secreted extracellular vesicles. MiRNAs are enriched at CORSAIR. Plasma miRNA levels can represent a potential blood biomarker for predicting COVID-19-related death in cancer patients.

中文翻译：

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MicroRNA 在 COVID-19 基因组风险区域富集，其血液水平与感染 SARS-CoV-2 的癌症患者的 COVID-19 预后相关


癌症患者更容易受到 COVID-19 侵袭性病程的影响。开发识别 COVID-19 相关死亡高风险癌症患者的生物标志物可能有助于确定谁需要早期临床干预。位于与侵袭性 COVID-19 风险相关的基因组区域中的 miRNA 可能代表临床结果的潜在生物标志物。在德克萨斯大学 MD 安德森癌症中心从受 COVID-19 影响的癌症患者 （N = 128） 收集血浆样本。从罗马尼亚蒂米什瓦拉市临床急诊教学医院接种疫苗的健康个体 （n = 23） 中收集血清样本。使用计算机位置克隆方法鉴定 COVID-19 风险相关基因组区域是否存在 miRNA：CORSAIRs（COvid-19 RiSk 关联基因组区域）。通过 RT-qPCR 测量 miRNA 水平。我们发现 miRNA 在 CORSAIR 中富集。低血浆 hsa-miR-150-5p 和 hsa-miR-93-5p 水平与较高的 COVID-19 相关死亡率相关。hsa-miR-92b-3p 水平与 SARS-CoV-2 检测阳性相关。外周血单核细胞 （PBMC） 在体外 TLR7/8 和 T 细胞受体 （TCR） 介导的激活后增加了 hsa-miR-150-5p、hsa-miR-93-5p 和 hsa-miR-92b-3p 的分泌。在接种第二剂辉瑞-BioNTech COVID-19 疫苗后 1 至 9 个月期间，在健康个体的血清样本中测量了这三种 miRNA 水平的增加。人气道上皮细胞的 SARS-CoV-2 感染影响了其分泌的细胞外囊泡内的 miRNA 水平。MiRNA 在 CORSAIR 中富集。血浆 miRNA 水平可以代表预测癌症患者 COVID-19 相关死亡的潜在血液生物标志物。