Dear Editor,Infection with the novel coronavirus(SARS-CoV-2,which is the virus responsible for the coronavirus disease 2019(COVID-19))was first reported in Wuhan,China on December 31,2019.The outbreak of COVID-19 rema...Dear Editor,Infection with the novel coronavirus(SARS-CoV-2,which is the virus responsible for the coronavirus disease 2019(COVID-19))was first reported in Wuhan,China on December 31,2019.The outbreak of COVID-19 remains ongoing and was linked to more than 80,000 infected patients and more than 3,000 deaths in China as of March 7,2020(Holshue et al.,2020).展开更多
The 2019 coronavirus disease(COVID-19)outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency.However,the virus'pathogenesis remains unclear,and there is no cure for the disease.We investigat...The 2019 coronavirus disease(COVID-19)outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency.However,the virus'pathogenesis remains unclear,and there is no cure for the disease.We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5'gene expression,T cell receptor(TCR),and B cell receptors(BCR)V(D)J transcriptome analysis at a single-cell resolution.We obtained single-cell mRNA sequencing(scRNA-seq)data of 341,420 peripheral blood mononuclear cells(PBMCs)and 185,430 donotypic T cells and 28,802 donotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies.In addition,we used three control samples.We found expansion of dendritic cells(DCs),CD14+monocytes,and megakaryocytes progenitor cells(MP)/platelets and a reduction of naive CD4+T lymphocytes in patients with COVID-19,along with a significant decrease of CD8+T lymphocytes,and natural killer cells(NKs)in patients in critical condition.The type I interferon(IFN-I),mitogen-activated protein kinase(MAPK),and ferroptosis pathways were activated while the disease was active,and recovered gradually after patient conditions improved.Consistent with this finding,the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls.The concentration of interferon-a(IFN-a)in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls,further suggesting the important role of the IFN-I pathway in the immune response of COVID-19.TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens.Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection,providing clues for therapeutic potentials in treating COVID-19.展开更多
基金supported by the grants from Sichuan Science and Technology Program(2020YFS0014 and 2020YFS0558)the Chinese Academy of Medical Sciences(2019-I2M-5032)Technology&Science&Technology Bureau of Chengdu(2020YF05-00060-SN and 2020-YF05-00075-SN)。
文摘Dear Editor,Infection with the novel coronavirus(SARS-CoV-2,which is the virus responsible for the coronavirus disease 2019(COVID-19))was first reported in Wuhan,China on December 31,2019.The outbreak of COVID-19 remains ongoing and was linked to more than 80,000 infected patients and more than 3,000 deaths in China as of March 7,2020(Holshue et al.,2020).
基金This work was supported by the Sichuan Science and Technology Program(2020YFS0014 and 2020YFS0558)the Chinese Academy of Medical Sciences(NO.2019-I2M-5-032)+1 种基金the National Key Research and Development Program of China(2016YFC20160905200)the National Natural Science Foundation of China(81790643,81970839 and 81670895).
文摘The 2019 coronavirus disease(COVID-19)outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency.However,the virus'pathogenesis remains unclear,and there is no cure for the disease.We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5'gene expression,T cell receptor(TCR),and B cell receptors(BCR)V(D)J transcriptome analysis at a single-cell resolution.We obtained single-cell mRNA sequencing(scRNA-seq)data of 341,420 peripheral blood mononuclear cells(PBMCs)and 185,430 donotypic T cells and 28,802 donotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies.In addition,we used three control samples.We found expansion of dendritic cells(DCs),CD14+monocytes,and megakaryocytes progenitor cells(MP)/platelets and a reduction of naive CD4+T lymphocytes in patients with COVID-19,along with a significant decrease of CD8+T lymphocytes,and natural killer cells(NKs)in patients in critical condition.The type I interferon(IFN-I),mitogen-activated protein kinase(MAPK),and ferroptosis pathways were activated while the disease was active,and recovered gradually after patient conditions improved.Consistent with this finding,the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls.The concentration of interferon-a(IFN-a)in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls,further suggesting the important role of the IFN-I pathway in the immune response of COVID-19.TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens.Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection,providing clues for therapeutic potentials in treating COVID-19.
