Institute of Neuroimmune Pharmacology, Seton Hall University, South Orange, NJ, USA.
Department of Biological Sciences, Seton Hall University, South Orange, NJ, USA.
Alcohol Clin Exp Res. 2021 Apr;45(4):675-688. doi: 10.1111/acer.14573. Epub 2021 Mar 20.
The coronavirus disease 2019 (COVID-19) pandemic is a worldwide crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many COVID-19 patients present with fever in the early phase, with some progressing to a hyperinflammatory phase. Ethanol (EtOH) exposure may lead to systemic inflammation. Network meta-analysis was conducted to examine possible relationships between EtOH consumption and COVID-19 pathologies.
Molecules affected by EtOH exposure were identified by analysis with QIAGEN Knowledge Base. Molecules affected by COVID-19 were identified from studies in MEDLINE, bioRxiv, and medRxiv reporting gene expression profiles in COVID-19 patients, QIAGEN Coronavirus Network Explorer, and analysis of the RNA-sequencing data of autopsied lungs of COVID-19 patients retrieved from the GEO database. Network meta-analysis was then conducted on these molecules using QIAGEN Ingenuity Pathway Analysis (IPA).
Twenty-eight studies reporting significant gene expression changes in COVID-19 patients were identified. One RNA-sequencing dataset on autopsied lungs of COVID-19 patients was retrieved from GEO. Our network meta-analysis suggests that EtOH exposure may augment the effects of SARS-CoV-2 infection on hepatic fibrosis signaling pathway, cellular metabolism and homeostasis, inflammation, and neuroinflammation. EtOH may also enhance the activity of key mediators including cytokines, such as IL-1β, IL-6, and TNF, and transcription factors, such as JUN and STAT, while inhibiting the activity of anti-inflammatory mediators including glucocorticoid receptor. Furthermore, IL-1β, IL-6, TNF, JUN, and STAT were mapped to 10 pathways predicted to associate with SARS-CoV-2 proteins, including HMGB1, IL-1, and IL-6 signaling pathways.
Our meta-analyses demonstrate that EtOH exposure may augment SARS-CoV-2-induced inflammation by altering the activity of key inflammatory mediators. Our findings suggest that it is important for clinicians to caution patients about the risk of alcohol consumption, which has increased during the COVID-19 pandemic. The findings also call for further investigation into how alcohol exposure affects viral infections.
由严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起的 2019 年冠状病毒病（COVID-19）大流行是一场全球性危机。许多 COVID-19 患者在早期表现出发热，有些患者进展为高炎症期。乙醇（EtOH）暴露可能导致全身炎症。网络荟萃分析旨在研究 EtOH 消耗与 COVID-19 病理之间可能存在的关系。
通过对 QIAGEN Knowledge Base 的分析，确定受 EtOH 暴露影响的分子。从 MEDLINE、bioRxiv 和 medRxiv 中报告 COVID-19 患者基因表达谱的研究、QIAGEN 冠状病毒网络浏览器以及从 GEO 数据库检索的 COVID-19 患者尸检肺的 RNA 测序数据中确定受 COVID-19 影响的分子。然后使用 QIAGEN Ingenuity Pathway Analysis（IPA）对这些分子进行网络荟萃分析。
确定了 28 项报告 COVID-19 患者显著基因表达变化的研究。从 GEO 数据库中检索到一个关于 COVID-19 患者尸检肺的 RNA 测序数据集。我们的网络荟萃分析表明，EtOH 暴露可能增强 SARS-CoV-2 感染对肝纤维化信号通路、细胞代谢和稳态、炎症和神经炎症的影响。EtOH 还可能增强细胞因子（如 IL-1β、IL-6 和 TNF）和转录因子（如 JUN 和 STAT）等关键介质的活性，同时抑制糖皮质激素受体等抗炎介质的活性。此外，IL-1β、IL-6、TNF、JUN 和 STAT 被映射到 10 条与 SARS-CoV-2 蛋白相关的途径，包括 HMGB1、IL-1 和 IL-6 信号通路。
我们的荟萃分析表明，EtOH 暴露可能通过改变关键炎症介质的活性来增强 SARS-CoV-2 诱导的炎症。我们的研究结果表明，临床医生告诫患者饮酒风险很重要，因为在 COVID-19 大流行期间，饮酒量有所增加。这一发现还呼吁进一步研究酒精暴露如何影响病毒感染。
