Preliminary study on predictive indicators of disease severity in patients with influenza A (H1N1)

Siran Lin, Yuzhen Xu, Wei Zhang, Qianqian Liu, Jing Wu, Bin Xu, Sheng-lei Yu, Sen Wang, Lei Zhou, Yuefeng Hu, Wenhong Zhang, L. Shao, Yan Gao
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Abstract

Objective To analyze the differences of peripheral blood transcriptome between mild and severe influenza A (H1N1) patients, and to find indicators for the assessment of disease severity. Methods A total of ten patients (five patients with mild disease and five patients with severe disease) diagnosed with H1N1 infection from January to May 2018 at Huashan Hospital, Fudan University in Shanghai were enrolled, and five healthy people were also enrolled as controls. The peripheral blood of patients was collected for transcriptome sequencing at the time when they were first diagnosed. Measurement data were compared using t test or Mann-Whitney U test. The count data were compared using Fisher exact test when appropriate. Data analysis of transcriptome predictions was performed using bioinformatics methods. Results The platelet counts were significantly different between mild and severe groups ((163.4±21.5 )×109/L vs (255.6±52.5)×109/L, t=3.636, P=0.007). There were no differences between the two groups in gender, age, white blood cell counts, neutrophil percentage, lymphocyte percentage and hemoglobin levels (all P>0.05). However, the average expression levels of matrix metalloproteinase (MMP) 8 and MMP9 in severe group (18.41 and 174.00, respectively) were both higher than those in mild group (2.33 and 22.91, respectively) and healthy control (1.43 and 34.65, respectively; all P<0.01). Conclusion MMP8 and MMP9 could be expected to serve as the molecular biological markers for predicting the disease severity in patients with influenza A (H1N1) infection. Key words: Influenza A virus, H1N1; Matrix metalloproteinase 8; Matrix metalloproteinase 9; RNA sequencing
甲型H1N1流感患者病情严重程度预测指标的初步研究
目的分析甲型H1N1流感轻、重度患者外周血转录组的差异,寻找疾病严重程度的评价指标。方法选取2018年1 - 5月在上海复旦大学华山医院确诊的H1N1感染患者10例(轻症患者5例,重症患者5例),同时选取健康人群5例作为对照。在患者首次诊断时收集患者外周血进行转录组测序。计量资料比较采用t检验或Mann-Whitney U检验。适当时采用Fisher精确检验比较计数数据。使用生物信息学方法对转录组预测进行数据分析。结果轻度组与重度组血小板计数差异有统计学意义((163.4±21.5)×109/L vs(255.6±52.5)×109/L, t=3.636, P=0.007)。两组患者性别、年龄、白细胞计数、中性粒细胞百分比、淋巴细胞百分比、血红蛋白水平差异无统计学意义(P < 0.05)。重度组基质金属蛋白酶(MMP) 8、MMP9的平均表达量(分别为18.41、174.00)均高于轻度组(分别为2.33、22.91)和健康对照组(分别为1.43、34.65);所有P < 0.01)。结论MMP8和MMP9可作为预测甲型H1N1流感患者病情严重程度的分子生物学标志物。关键词:甲型流感病毒,H1N1;基质金属蛋白酶8;基质金属蛋白酶9;RNA序列
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