Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases. In severe COVID-19, CD177 a neutrophil marker, was upregulated while interferon stimulated genes (ISGs) were downregulated. Asymptomatic COVID-19 cases displayed upregulation of ISGs and humoral response genes with downregulation of ICAM3 and TLR8. Compared across the COVID-19 disease spectrum, we found type I interferon (IFN) responses to be significantly upregulated (IFNAR2, IRF2BP1, IRF4, MAVS, SAMHD1, TRIM1), or downregulated (SOCS3, IRF2BP2, IRF2BPL) in Asymptomatic as compared with mild and severe COVID-19, with the dysregulation of an increasing number of ISGs associated with progressive disease. These data suggest that initial early responses against SARS-CoV-2 may be effectively controlled by ISGs. Therefore, we hypothesize that treatment with type I interferons in the early stage of COVID-19 may limit disease progression by limiting SARS-CoV-2 in the host.
【저자키워드】 immunology, Microbiology, Computational biology and bioinformatics, 【초록키워드】 COVID-19, Treatment, Transcriptome, SARS-CoV-2, Biomarker, Biomarkers, severe COVID-19, SARS-COV-2 infection, neutrophil, interferons, interferon, type I interferon, COVID-19 disease, Disease progression, Viral, Asymptomatic, severity of COVID-19, response, pathway, Asymptomatic cases, understanding, Mild, IFN, type I interferons, Antigen presentation, SAMHD1, disease, early stage, ISGs, ISG, mRNA translation, marker, IFNAR2, Inflammatory, MAVS, Pathways, humoral, Asymptomatic COVID-19, dysregulation, protective mechanisms, protective mechanism, suppression, These data, COVID-19 case, TLR8, help, upregulation, SOCS3, ICAM3, downregulation, progressive disease, symptomatic disease, early response, CD177, IRF2BP1, IRF2BP2, IRF2BPL, IRF4, Host, uninfected, approach, limit, blood transcriptome, initial, IMPROVE, stimulated, significantly, upregulated, downregulated, effectively controlled, 【제목키워드】 Infection, type I interferon, Clinical outcome, response,