Multi-platform omics analysis reveals molecular signature for COVID-19 pathogenesis,prognosis and drug target discovery

Disease progression prediction and therapeutic drug target discovery for Coronavirus disease 2019(COVID-19)are particularly important,as there is still no effective strategy for severe COVID-19 patient treatment.Herein,we performed multi-platform omics analysis of serial plasma and urine samples collected from patients during the course of COVID-19.Integrative analyses of these omics data revealed several potential therapeutic targets,such as ANXA1 and CLEC3B.Molecular changes in plasma indicated dysregulation of macrophage and suppression of T cell functions in severe patients compared to those in non-severe patients.Further,we chose 25 important molecular signatures as potential biomarkers for the prediction of disease severity.The prediction power was validated using corresponding urine samples and plasma samples from new COVID-19 patient cohort,with AUC reached to 0.904 and 0.988,respectively.In conclusion,our omics data proposed not only potential therapeutic targets,but also biomarkers for understanding the pathogenesis of severe COVID-19.

Genetic and pathogenicity diversity of dengue virus type 2 strains circulating in Guangdong,China

Dengue fever is a mosquito-borne viral disease spread in tropical and subtropical regions caused by the dengue virus(DENV).DENV causes a febrile illness,severe forms including hemorrhagic fevers and shock with fatalities in humans.DENV-2 is frequently associated with severe dengue infections and epidemics.DENV-2 strains from Guangdong,China,have not been characterized to compare the phylogenetics and pathogenicity of different DENV-2 subgenotype strains in both vitro and vivo.A total of 22 patients tested to be DENV-2 positive and were enrolled in this study,22 complete genomes were obtained by virus isolation and high-throughput sequencing.Phylogenetic and single amino polymorphism(SAP)analysis indicated that two major subgenotypes(A and C)of DENV-2 Cosmopolitan were prevalent in Guangdong in 2018.The apparent change of major subgenotypes of DENV-2 circulating in Guangdong indicated the diversity of DENV-2 strains,including endemic genotype and imported genotype.It alerted the risk of cross-border transmission of DENV.A significant difference in replication rate was observed in C6/36 between different DENV-2 strains,although growth kinetics comparison of different DENV-2 Cosmopolitan subgenotypes showed similar profiles.DENV-2 subgenotypes(A and C)replicated efficiently in IFNAR−/−C57BL/6 mice,and subgenotype A of Cosmopolitan infected mice showed increased weight loss and delayed viral clearance compared with the subgenotype C group.DENV-2 prevalent in Guangdong in 2018 showed apparent genetic and pathogenicity diversity in both vitro and vivo,indicating the necessity of molecular surveillance and exploration of the relationship between its pathogenicity and clinical characteristics.