Togami Yuki, Matsumoto Hisatake, Yoshimura Jumpei, Matsubara Tsunehiro, Ebihara Takeshi, Matsuura Hiroshi, Mitsuyama Yumi, Kojima Takashi, Ishikawa Masakazu, Sugihara Fuminori, Hirata Haruhiko, Okuzaki Daisuke, Ogura Hiroshi
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Osaka Prefectural Nakakawachi Emergency and Critical Care Center, Osaka 578-0947, Japan.
Mol Ther Nucleic Acids. 2022 Sep 13;29:343-353. doi: 10.1016/j.omtn.2022.07.005. Epub 2022 Jul 13.
We evaluated mRNA and miRNA in COVID-19 patients and elucidated the pathogenesis of COVID-19, including protein profiles, following mRNA and miRNA integration analysis. mRNA and miRNA sequencing was done on admission with whole blood of 5 and 16 healthy controls (HCs) and 10 and 31 critically ill COVID-19 patients (derivation and validation cohorts, respectively). Interferon (IFN)-α2, IFN-β, IFN-γ, interleukin-27, and IFN-λ1 were measured in COVID-19 patients on admission (day 1, 181 critical/22 non-critical patients) and days 6-8 (168 critical patients) and in 19 HCs. In the derivation cohort, 3,488 mRNA and 31 miRNA expressions were identified among differentially expressed RNA expressions in the patients versus those in HCs, and 2,945 mRNA and 32 miRNA expressions in the validation cohort. Canonical pathway analysis showed the IFN signaling pathway to be most activated. The IFN-β plasma level was elevated in line with increased severity compared with HCs, as were IFN-β downstream proteins, such as interleukin-27. IFN-λ1 was higher in non-critically ill patients versus HCs but lower in critical than non-critical patients. Integration of mRNA and miRNA analysis showed activated IFN signaling. Plasma IFN protein profile revealed that IFN-β (type I) and IFN-λ1 (type III) played important roles in COVID-19 disease progression.
我们对新冠肺炎患者的信使核糖核酸（mRNA）和微小核糖核酸（miRNA）进行了评估，并在mRNA与miRNA整合分析后，阐明了新冠肺炎的发病机制，包括蛋白质谱。对5名和16名健康对照者（HCs）以及10名和31名危重症新冠肺炎患者（分别为衍生队列和验证队列）入院时的全血进行了mRNA和miRNA测序。在新冠肺炎患者入院时（第1天，181名危重症/22名非危重症患者）、第6 - 8天（168名危重症患者）以及19名HCs中检测了干扰素（IFN）-α2、IFN-β、IFN-γ、白细胞介素-27和IFN-λ1。在衍生队列中，在患者与HCs的差异表达RNA中鉴定出3488种mRNA和31种miRNA表达，在验证队列中鉴定出2945种mRNA和32种miRNA表达。典型通路分析显示IFN信号通路激活程度最高。与HCs相比，IFN-β血浆水平随病情严重程度增加而升高，IFN-β下游蛋白如白细胞介素-27也是如此。与HCs相比，非危重症患者的IFN-λ1水平较高，但危重症患者低于非危重症患者。mRNA与miRNA分析的整合显示IFN信号被激活。血浆IFN蛋白质谱显示IFN-β（I型）和IFN-λ1（III型）在新冠肺炎疾病进展中起重要作用。
