Mousavi Seyyed R, Lotfi Hajie, Salmanizadeh Sharareh, Feizbakhshan Sara, Khosravian Farinaz, Sajjadi Maryam S, Komachali Sajad R, Beni Faeze A, Torkan Banafshe, Kazemi Mohammad, Sami Ramin, Salehi Mansoor
Cellular, Molecular and Genetics Research Center Isfahan University of Medical Sciences Isfahan Iran.
Medical Genetics Research Center of Genome Isfahan University of Medical Sciences Isfahan Iran.
Health Sci Rep. 2022 Mar 7;5(2):e548. doi: 10.1002/hsr2.548. eCollection 2022 Mar.
All components of the immune system are involved in alleviating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further research is required to provide detailed insights into COVID-19-related immune compartments and pathways. In addition, a significant percentage of hospitalized COVID-19 patients suspect bacterial infections and antimicrobial resistance occurs following antibiotics treatment. The aim of this study was to evaluate the possible effects of antibiotics on the response of neutrophil-related genes in SARS-CoV-2 patients by an experimental in silico study.
The two data sets GSE1739 and GSE21802 including 10 SARS positive patients and 35 influenza A (H1N1) patients were analyzed, respectively. Differentially expressed genes (DEGs) between these two data sets were determined by GEO2R analysis and the Venn diagram online tool. After determining the hub genes involved in immune responses, the expression of these genes in 30 COVID-19 patients and 30 healthy individuals was analyzed by real-time polymerase chain reaction (PCR). All patients received antibiotics, including levofloxacin, colistin, meropenem, and ceftazidime.
GEO2R analysis detected 240 and 120 DEGs in GSE21802 and GSE1739, respectively. Twenty DEGs were considered as enriched hub genes involved in immune processes such as neutrophil degranulation, neutrophil activation, and antimicrobial humoral response. The central nodes were attributed to the genes of neutrophil elastase (ELANE), arginase 1 (ARG-1), lipocalin 2 (LCN2), and defensin 4 (DEFA4). Compared to the healthy subjects, the expression of LCN2 and DEFA4 were significantly reduced in COVID-19 patients. However, no significant differences were observed in the ELANE and AGR-1 levels between COVID-19 subjects and the control group.
Activation and degranulation of neutrophils were observed mainly in SARS, and H1N1 infection processes and antibiotics administration could affect neutrophil activity during viral infection. It can be suggested that antibiotics can decrease inflammation by restoring the expression of neutrophil-related genes in COVID-19 patients.
免疫系统的所有组成部分都参与减轻严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染。需要进一步研究以深入了解与2019冠状病毒病（COVID-19）相关的免疫区室和途径。此外，相当一部分住院的COVID-19患者怀疑有细菌感染，并且抗生素治疗后会出现抗菌药物耐药性。本研究的目的是通过一项计算机模拟实验研究评估抗生素对SARS-CoV-2患者中性粒细胞相关基因反应的可能影响。
分别分析了两个数据集GSE1739和GSE21802，其中包括10例SARS阳性患者和35例甲型流感（H1N1）患者。通过GEO2R分析和在线维恩图工具确定这两个数据集之间的差异表达基因（DEG）。在确定参与免疫反应的关键基因后，通过实时聚合酶链反应（PCR）分析这些基因在30例COVID-19患者和30例健康个体中的表达。所有患者均接受了抗生素治疗，包括左氧氟沙星、黏菌素、美罗培南和头孢他啶。
GEO2R分析在GSE21802和GSE1739中分别检测到240个和120个DEG。20个DEG被认为是参与免疫过程的富集关键基因，如中性粒细胞脱颗粒、中性粒细胞活化和抗微生物体液反应。中心节点归因于中性粒细胞弹性蛋白酶（ELANE）、精氨酸酶1（ARG-1）、脂质运载蛋白2（LCN2）和防御素4（DEFA4）的基因。与健康受试者相比，COVID-19患者中LCN2和DEFA4的表达显著降低。然而，COVID-19受试者与对照组之间的ELANE和AGR-1水平未观察到显著差异。
主要在SARS和H1N1感染过程中观察到中性粒细胞的活化和脱颗粒，抗生素给药可能会影响病毒感染期间的中性粒细胞活性。可以认为抗生素可通过恢复COVID-19患者中性粒细胞相关基因的表达来减轻炎症。
