Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Catalonia, Spain.
Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain.
EBioMedicine. 2021 Apr;66:103339. doi: 10.1016/j.ebiom.2021.103339. Epub 2021 Apr 15.
Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities.
Peripheral blood samples were obtained from 407 confirmed COVID-19 patients ≤ 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support. The set of cases was divided into discovery (n = 207) and validation (n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients.
The DNA methylation status of 44 CpG sites was associated with the clinical severity of COVID-19. Of these loci, 23 (52.3%) were located in 20 annotated coding genes. These genes, such as the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C) candidates, were mainly involved in the response of interferon to viral infection. We used the EWAS-identified sites to establish a DNA methylation signature (EPICOVID) that is associated with the severity of the disease.
We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2.
The Unstoppable campaign of the Josep Carreras Leukaemia Foundation, the Cellex Foundation and the CERCA Programme/Generalitat de Catalunya.
导致 2019 年冠状病毒病（COVID-19）的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染患者表现出广泛的疾病行为。由于 DNA 甲基化已被牵连到病毒感染和免疫系统的调节中，我们进行了全基因组关联研究（EWAS），以鉴定受这种表观遗传标记调节的候选基因座，这些基因座可能与无合并症的 COVID-19 患者的发病有关。
从 407 名年龄≤61 岁且无合并症的确诊 COVID-19 患者中采集外周血样本，其中 194 名（47.7%）患者症状较轻，无需住院治疗，213 名（52.3%）患者病情严重，需要呼吸支持。该病例组分为发现（n=207）和验证（n=200）队列，在个体的年龄和性别上平衡。我们分析了这些患者 850000 个 CpG 位点的 DNA 甲基化状态。
COVID-19 临床严重程度与 44 个 CpG 位点的 DNA 甲基化状态相关。这些基因座中，23 个（52.3%）位于 20 个注释编码基因中。这些基因，如炎症小体成分 Absent in Melanoma 2（AIM2）和主要组织相容性复合体，I 类 C（HLA-C）候选基因，主要参与干扰素对病毒感染的反应。我们使用 EWAS 鉴定的位点建立了与疾病严重程度相关的 DNA 甲基化特征（EPICOVID）。
我们发现 DNA 甲基化位点是 COVID-19 患者呼吸衰竭的表观遗传易感性基因座。这些候选生物标志物，结合其他临床、细胞和遗传因素，可能有助于 SARS-CoV-2 感染患者的临床分层和管理。
Josep Carreras 白血病基金会的“Unstoppable”运动、Cellex 基金会和 CERCA 计划/加泰罗尼亚政府。
