School of Medical Sciences, State University of Campinas, Campinas 13083-887, Brazil.
Bone Metabolism Laboratory, Rheumatology Division, School of Medical Sciences, University of Sao Paulo, Sao Paulo 01246903, Brazil.
Exp Biol Med (Maywood). 2023 Jun;248(12):1024-1033. doi: 10.1177/15353702231175412. Epub 2023 Jul 4.
Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The uncontrolled systemic inflammatory response, resulting from the release of large amounts of pro-inflammatory cytokines, is the main mechanism behind severe acute respiratory syndrome and multiple organ failure, the two main causes of death in COVID-19. Epigenetic mechanisms, such as gene expression regulation by microRNAs (miRs), may be at the basis of the immunological changes associated with COVID-19. Therefore, the main objective of the study was to evaluate whether the expression of miRNAs upon hospital admission could predict the risk of fatal COVID-19. To evaluate the level of circulating miRNAs, we used serum samples of COVID-19 patients collected upon hospital admission. Screening of differentially expressed miRNAs in fatal COVID-19 was performed by miRNA-Seq and the validation of miRNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The Mann-Whitney test and receiver operating characteristic (ROC) curve were used to validate the miRNAs, whose potential signaling pathways and biological processes were identified through an approach. A cohort of 100 COVID-19 patients was included in this study. By comparing the circulating levels of miRs between survivors and patients who died due to complications of the infection, we found that the expression of was increased in those who died during hospitalization, and the expression of both (area under the curve [AUC] = 0.62, 95% confidence interval [CI] = 0.5-0.7, = 0.03) and (AUC = 0.62, 95% CI = 0.5-0.7, = 0.03) was increased in those who lately evolved to severe forms of the disease (AUC = 0.70, 95% CI = 0.6-0.8, = 0.002)."In silico" analysis revealed that has the potential to enhance the activation of NLPR3 inflammasome and to inhibit vascular endothelial growth factor (VEGF) pathways. Impaired innate immune response against SARS-CoV-2 may be explained by epigenetic mechanisms, which could form early biomarkers of adverse outcomes.
新型冠状病毒病（COVID-19）是由严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起的急性呼吸道感染。大量促炎细胞因子的释放引起的失控的全身炎症反应是导致严重急性呼吸综合征和多器官衰竭的主要机制，这也是 COVID-19 死亡的两个主要原因。表观遗传机制，如微小 RNA（miRs）对基因表达的调控，可能是 COVID-19 相关免疫变化的基础。因此，本研究的主要目的是评估入院时 miRNA 的表达是否可以预测 COVID-19 致死的风险。为了评估循环 miRNA 的水平，我们使用了入院时采集的 COVID-19 患者的血清样本。通过 miRNA-Seq 筛选致死性 COVID-19 中的差异表达 miRNA，并通过逆转录定量聚合酶链反应（RT-qPCR）进行 miRNA 验证。采用 Mann-Whitney 检验和受试者工作特征（ROC）曲线对 miRNA 进行验证，并通过 方法鉴定其潜在的信号通路和生物学过程。本研究纳入了 100 例 COVID-19 患者。通过比较幸存者和因感染并发症死亡患者的循环 miR 水平，我们发现住院期间死亡患者的表达增加，而 和 （曲线下面积 [AUC] = 0.62，95%置信区间 [CI] = 0.5-0.7， = 0.03）和 （AUC = 0.62，95% CI = 0.5-0.7， = 0.03）的表达也增加，而那些最近发展为严重疾病形式的患者（AUC = 0.70，95% CI = 0.6-0.8， = 0.002）。“ 分析显示， 有可能增强 NLPR3 炎性小体的激活，并抑制血管内皮生长因子（VEGF）途径。对 SARS-CoV-2 的先天免疫反应受损可以用表观遗传机制来解释，这些机制可能成为不良预后的早期生物标志物。
