背景:大规模疫苗接种大大降低了严重COVID-19的发病率,大多数病例现在表现为自限性上呼吸道感染。然而,那些有合并症的人,老年人和免疫功能低下的人,以及未接种疫苗的人,仍然不成比例地容易受到严重的COVID-19及其后遗症的影响。此外,随着疫苗接种的有效性随着时间的推移而减弱,免疫逃逸SARS-CoV-2变体可能会导致严重的COVID-19。严重疾病的可靠预后生物标志物可作为严重COVID-19复发的早期指标,也可用于抗病毒治疗患者的分类。
方法:我们对7个公开数据集进行了系统回顾和重新分析,共分析140例严重和181例轻度COVID-19患者,确定重症COVID-19患者外周血中最一致的差异调节基因。此外,我们纳入了一个独立的队列,对COVID-19患者的血液转录组学进行了前瞻性和纵向监测,追踪这些基因表达变化发生在呼吸功能最低点之前的时间。然后使用来自公开可用数据集的外周血单核细胞的单细胞RNA测序来确定所涉及的免疫细胞亚群。
结果:在7个转录组学数据集中,重症COVID-19患者外周血中最一致的差异调节基因是MCEMP1、HLA-DRA和ETS1。此外,我们发现,早在呼吸功能最低点前四天,MCEMP1显著升高,HLA-DRA表达降低,MCEMP1和HLA-DRA的差异表达主要发生在CD14+细胞中。我们开发的在线平台可在https://kuanrongchan-covid19-severity-app-t7l38g上公开获得。streamlitapp.com/,供用户查询这些数据集中重度和轻度COVID-19患者之间的基因表达差异。
结论:疾病早期CD14+细胞中MCEMP1升高和HLA-DRA基因表达降低是严重COVID-19的预后因素。
背景:K.R.C由新加坡国家医学研究委员会(NMRC)根据开放基金个人研究资助(MOH-000610)资助。E.E.O.由NMRC高级临床科学家奖(MOH-000135-00)资助。J.G.H.L.由NMRC根据临床科学家奖(NMRC/CSAINV/013/2016-01)资助。S.K.由NMRC根据过渡奖资助。这项研究部分是由TheHourGlass的慷慨礼物赞助的。
BACKGROUND: Mass vaccination has dramatically reduced the incidence of severe COVID-19, with most cases now presenting as self-limiting upper respiratory tract infections. However, those with co-morbidities, the elderly and immunocompromised, as well as the unvaccinated, remain disproportionately vulnerable to severe COVID-19 and its sequelae. Furthermore, as the effectiveness of vaccination wanes with time, immune escape SARS-CoV-2 variants could emerge to cause severe COVID-19. Reliable prognostic biomarkers for severe disease could be used as early indicator of re-emergence of severe COVID-19 as well as for triaging of patients for antiviral therapy.
METHODS: We performed a systematic review and re-analysis of 7 publicly available datasets, analysing a total of 140 severe and 181 mild COVID-19 patients, to determine the most consistent differentially regulated genes in peripheral blood of severe COVID-19 patients. In addition, we included an independent cohort where blood transcriptomics of COVID-19 patients were prospectively and longitudinally monitored previously, to track the time in which these gene expression changes occur before nadir of respiratory function. Single cell RNA-sequencing of peripheral blood mononuclear cells from publicly available datasets was then used to determine the immune cell subsets involved.
RESULTS: The most consistent differentially regulated genes in peripheral blood of severe COVID-19 patients were MCEMP1, HLA-DRA and ETS1 across the 7 transcriptomics datasets. Moreover, we found significantly heightened MCEMP1 and reduced HLA-DRA expression as early as four days before the nadir of respiratory function, and the differential expression of MCEMP1 and HLA-DRA occurred predominantly in CD14+ cells. The online platform which we developed is publicly available at https://kuanrongchan-covid19-severity-app-t7l38g.streamlitapp.com/, for users to query gene expression differences between severe and mild COVID-19 patients in these datasets.
CONCLUSIONS: Elevated MCEMP1 and reduced HLA-DRA gene expression in CD14+ cells during the early phase of disease are prognostic of severe COVID-19.
BACKGROUND: K.R.C is funded by the National Medical Research Council (NMRC) of Singapore under the Open Fund Individual Research Grant (MOH-000610). E.E.O. is funded by the NMRC Senior Clinician-Scientist Award (MOH-000135-00). J.G.H.L. is funded by the NMRC under the Clinician-Scientist Award (NMRC/CSAINV/013/2016-01). S.K. is funded by the NMRC under the Transition Award. This study was sponsored in part by a generous gift from The Hour Glass.