Downregulated Gene Expression Spectrum and Immune Responses Changed During the Disease Progression in Patients With COVID-19

Abstract Background The World Health Organization characterizes novel coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a pandemic. Here, we investigated the clinical, cytokine levels; T-cell proportion; and related gene expressi...

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Veröffentlicht in:Clinical infectious diseases 2020-11, Vol.71 (16), p.2052-2060
Hauptverfasser: Ouyang, Yabo, Yin, Jiming, Wang, Wenjing, Shi, Hongbo, Shi, Ying, Xu, Bin, Qiao, Luxin, Feng, Yingmei, Pang, Lijun, Wei, Feili, Guo, Xianghua, Jin, Ronghua, Chen, Dexi
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container_end_page 2060
container_issue 16
container_start_page 2052
container_title Clinical infectious diseases
container_volume 71
creator Ouyang, Yabo
Yin, Jiming
Wang, Wenjing
Shi, Hongbo
Shi, Ying
Xu, Bin
Qiao, Luxin
Feng, Yingmei
Pang, Lijun
Wei, Feili
Guo, Xianghua
Jin, Ronghua
Chen, Dexi
description Abstract Background The World Health Organization characterizes novel coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a pandemic. Here, we investigated the clinical, cytokine levels; T-cell proportion; and related gene expression occurring in patients with COVID-19 on admission and after initial treatment. Methods Eleven patients diagnosed with COVID-19 with similar initial treatment regimens were enrolled in the hospital. Plasma cytokine, peripheral T cell proportions, and microfluidic quantitative polymerase chain reaction analyses for gene expression were conducted. Results Five patients with mild and 6 with severe disease were included. Cough and fever were the primary symptoms in the 11 COVID-19 cases. Older age, higher neutrophil count, and higher C-reactive protein levels were found in severe cases. IL-10 level significantly varied with disease progression and treatment. Decreased T-cell proportions were observed in patients with COVID-19, especially in severe cases, and all were returned to normal in patients with mild disease after initial treatment, but only CD4+ T cells returned to normal in severe cases. The number of differentially expressed genes (DEGs) increased with the disease progression, and decreased after initial treatment. All downregulated DEGs in severe cases mainly involved Th17-cell differentiation, cytokine-mediated signaling pathways, and T-cell activation. After initial treatment in severe cases, MAP2K7 and SOS1 were upregulated relative to that on admission. Conclusions Our findings show that a decreased T-cell proportion with downregulated gene expression related to T-cell activation and differentiation occurred in patients with severe COVID-19, which may help to provide effective treatment strategies for COVID-19. Suppressed T-cell immune response and decreased T cells occurred in patients with COVID-19 related to downregulated gene expression involved in T-cell activation and differentiation, especially in severe disease, against SARS-CoV-2 infection and at the early period of treatment.
doi_str_mv 10.1093/cid/ciaa462
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Here, we investigated the clinical, cytokine levels; T-cell proportion; and related gene expression occurring in patients with COVID-19 on admission and after initial treatment. Methods Eleven patients diagnosed with COVID-19 with similar initial treatment regimens were enrolled in the hospital. Plasma cytokine, peripheral T cell proportions, and microfluidic quantitative polymerase chain reaction analyses for gene expression were conducted. Results Five patients with mild and 6 with severe disease were included. Cough and fever were the primary symptoms in the 11 COVID-19 cases. Older age, higher neutrophil count, and higher C-reactive protein levels were found in severe cases. IL-10 level significantly varied with disease progression and treatment. Decreased T-cell proportions were observed in patients with COVID-19, especially in severe cases, and all were returned to normal in patients with mild disease after initial treatment, but only CD4+ T cells returned to normal in severe cases. The number of differentially expressed genes (DEGs) increased with the disease progression, and decreased after initial treatment. All downregulated DEGs in severe cases mainly involved Th17-cell differentiation, cytokine-mediated signaling pathways, and T-cell activation. After initial treatment in severe cases, MAP2K7 and SOS1 were upregulated relative to that on admission. Conclusions Our findings show that a decreased T-cell proportion with downregulated gene expression related to T-cell activation and differentiation occurred in patients with severe COVID-19, which may help to provide effective treatment strategies for COVID-19. Suppressed T-cell immune response and decreased T cells occurred in patients with COVID-19 related to downregulated gene expression involved in T-cell activation and differentiation, especially in severe disease, against SARS-CoV-2 infection and at the early period of treatment.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/ciaa462</identifier><identifier>PMID: 32307550</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Aged ; and Commentaries ; CD4-Positive T-Lymphocytes - metabolism ; Cell Differentiation - physiology ; Computational Biology ; COVID-19 - immunology ; COVID-19 - pathology ; COVID-19 - virology ; Female ; Humans ; Interleukin-10 - metabolism ; Male ; MAP Kinase Kinase 7 - metabolism ; Microfluidics ; Middle Aged ; Signal Transduction - physiology ; SOS1 Protein - metabolism ; Th17 Cells - metabolism</subject><ispartof>Clinical infectious diseases, 2020-11, Vol.71 (16), p.2052-2060</ispartof><rights>The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-5f77478dc0003852a653ea08f1b81dad56c7b4acd4806d8943f155d8e3bdb2343</citedby><cites>FETCH-LOGICAL-c412t-5f77478dc0003852a653ea08f1b81dad56c7b4acd4806d8943f155d8e3bdb2343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32307550$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ouyang, Yabo</creatorcontrib><creatorcontrib>Yin, Jiming</creatorcontrib><creatorcontrib>Wang, Wenjing</creatorcontrib><creatorcontrib>Shi, Hongbo</creatorcontrib><creatorcontrib>Shi, Ying</creatorcontrib><creatorcontrib>Xu, Bin</creatorcontrib><creatorcontrib>Qiao, Luxin</creatorcontrib><creatorcontrib>Feng, Yingmei</creatorcontrib><creatorcontrib>Pang, Lijun</creatorcontrib><creatorcontrib>Wei, Feili</creatorcontrib><creatorcontrib>Guo, Xianghua</creatorcontrib><creatorcontrib>Jin, Ronghua</creatorcontrib><creatorcontrib>Chen, Dexi</creatorcontrib><title>Downregulated Gene Expression Spectrum and Immune Responses Changed During the Disease Progression in Patients With COVID-19</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Abstract Background The World Health Organization characterizes novel coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a pandemic. Here, we investigated the clinical, cytokine levels; T-cell proportion; and related gene expression occurring in patients with COVID-19 on admission and after initial treatment. Methods Eleven patients diagnosed with COVID-19 with similar initial treatment regimens were enrolled in the hospital. Plasma cytokine, peripheral T cell proportions, and microfluidic quantitative polymerase chain reaction analyses for gene expression were conducted. Results Five patients with mild and 6 with severe disease were included. Cough and fever were the primary symptoms in the 11 COVID-19 cases. Older age, higher neutrophil count, and higher C-reactive protein levels were found in severe cases. IL-10 level significantly varied with disease progression and treatment. Decreased T-cell proportions were observed in patients with COVID-19, especially in severe cases, and all were returned to normal in patients with mild disease after initial treatment, but only CD4+ T cells returned to normal in severe cases. The number of differentially expressed genes (DEGs) increased with the disease progression, and decreased after initial treatment. All downregulated DEGs in severe cases mainly involved Th17-cell differentiation, cytokine-mediated signaling pathways, and T-cell activation. After initial treatment in severe cases, MAP2K7 and SOS1 were upregulated relative to that on admission. Conclusions Our findings show that a decreased T-cell proportion with downregulated gene expression related to T-cell activation and differentiation occurred in patients with severe COVID-19, which may help to provide effective treatment strategies for COVID-19. Suppressed T-cell immune response and decreased T cells occurred in patients with COVID-19 related to downregulated gene expression involved in T-cell activation and differentiation, especially in severe disease, against SARS-CoV-2 infection and at the early period of treatment.</description><subject>Aged</subject><subject>and Commentaries</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Cell Differentiation - physiology</subject><subject>Computational Biology</subject><subject>COVID-19 - immunology</subject><subject>COVID-19 - pathology</subject><subject>COVID-19 - virology</subject><subject>Female</subject><subject>Humans</subject><subject>Interleukin-10 - metabolism</subject><subject>Male</subject><subject>MAP Kinase Kinase 7 - metabolism</subject><subject>Microfluidics</subject><subject>Middle Aged</subject><subject>Signal Transduction - physiology</subject><subject>SOS1 Protein - metabolism</subject><subject>Th17 Cells - metabolism</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kctr3DAQh0VpadK0p96LTqVQ3EiWZMuXQtnNYyGQ0OdRyNLYq2JLjmT3Afnjo7Cb0Fx6EBLMp2-G-SH0mpIPlDTs2Dibj9a8Kp-gQypYXVSioU_zmwhZcMnkAXqR0k9CKJVEPEcHrGSkFoIcopt1-O0j9MugZ7D4DDzgkz9ThJRc8PjLBGaOy4i1t3gzjksuf4Y0BZ8g4dVW-z7_Wi_R-R7PW8Brl0AnwFcx9PcS5_GVnh34OeEfbt7i1eX3zbqgzUv0rNNDglf7-wh9Oz35ujovLi7PNqtPF4XhtJwL0dU1r6U1hBAmRakrwUAT2dFWUqutqEzdcm0sl6SysuGso0JYCay1bck4O0Ifd95paUewJk8S9aCm6EYd_6qgnXpc8W6r-vBL1VRKKu8E7_aCGK4XSLMaXTIwDNpDWJIqWVPyvE9WZfT9DjUxpBShe2hDibrLS-W81D6vTL_5d7IH9j6gDLzdAWGZ_mu6BbfboLU</recordid><startdate>20201119</startdate><enddate>20201119</enddate><creator>Ouyang, Yabo</creator><creator>Yin, Jiming</creator><creator>Wang, Wenjing</creator><creator>Shi, Hongbo</creator><creator>Shi, Ying</creator><creator>Xu, Bin</creator><creator>Qiao, Luxin</creator><creator>Feng, Yingmei</creator><creator>Pang, Lijun</creator><creator>Wei, Feili</creator><creator>Guo, Xianghua</creator><creator>Jin, Ronghua</creator><creator>Chen, Dexi</creator><general>Oxford University Press</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20201119</creationdate><title>Downregulated Gene Expression Spectrum and Immune Responses Changed During the Disease Progression in Patients With COVID-19</title><author>Ouyang, Yabo ; Yin, Jiming ; Wang, Wenjing ; Shi, Hongbo ; Shi, Ying ; Xu, Bin ; Qiao, Luxin ; Feng, Yingmei ; Pang, Lijun ; Wei, Feili ; Guo, Xianghua ; Jin, Ronghua ; Chen, Dexi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-5f77478dc0003852a653ea08f1b81dad56c7b4acd4806d8943f155d8e3bdb2343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>and Commentaries</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Cell Differentiation - physiology</topic><topic>Computational Biology</topic><topic>COVID-19 - immunology</topic><topic>COVID-19 - pathology</topic><topic>COVID-19 - virology</topic><topic>Female</topic><topic>Humans</topic><topic>Interleukin-10 - metabolism</topic><topic>Male</topic><topic>MAP Kinase Kinase 7 - metabolism</topic><topic>Microfluidics</topic><topic>Middle Aged</topic><topic>Signal Transduction - physiology</topic><topic>SOS1 Protein - metabolism</topic><topic>Th17 Cells - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ouyang, Yabo</creatorcontrib><creatorcontrib>Yin, Jiming</creatorcontrib><creatorcontrib>Wang, Wenjing</creatorcontrib><creatorcontrib>Shi, Hongbo</creatorcontrib><creatorcontrib>Shi, Ying</creatorcontrib><creatorcontrib>Xu, Bin</creatorcontrib><creatorcontrib>Qiao, Luxin</creatorcontrib><creatorcontrib>Feng, Yingmei</creatorcontrib><creatorcontrib>Pang, Lijun</creatorcontrib><creatorcontrib>Wei, Feili</creatorcontrib><creatorcontrib>Guo, Xianghua</creatorcontrib><creatorcontrib>Jin, Ronghua</creatorcontrib><creatorcontrib>Chen, Dexi</creatorcontrib><collection>Access via Oxford University Press (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ouyang, Yabo</au><au>Yin, Jiming</au><au>Wang, Wenjing</au><au>Shi, Hongbo</au><au>Shi, Ying</au><au>Xu, Bin</au><au>Qiao, Luxin</au><au>Feng, Yingmei</au><au>Pang, Lijun</au><au>Wei, Feili</au><au>Guo, Xianghua</au><au>Jin, Ronghua</au><au>Chen, Dexi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Downregulated Gene Expression Spectrum and Immune Responses Changed During the Disease Progression in Patients With COVID-19</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2020-11-19</date><risdate>2020</risdate><volume>71</volume><issue>16</issue><spage>2052</spage><epage>2060</epage><pages>2052-2060</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><abstract>Abstract Background The World Health Organization characterizes novel coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a pandemic. Here, we investigated the clinical, cytokine levels; T-cell proportion; and related gene expression occurring in patients with COVID-19 on admission and after initial treatment. Methods Eleven patients diagnosed with COVID-19 with similar initial treatment regimens were enrolled in the hospital. Plasma cytokine, peripheral T cell proportions, and microfluidic quantitative polymerase chain reaction analyses for gene expression were conducted. Results Five patients with mild and 6 with severe disease were included. Cough and fever were the primary symptoms in the 11 COVID-19 cases. Older age, higher neutrophil count, and higher C-reactive protein levels were found in severe cases. IL-10 level significantly varied with disease progression and treatment. Decreased T-cell proportions were observed in patients with COVID-19, especially in severe cases, and all were returned to normal in patients with mild disease after initial treatment, but only CD4+ T cells returned to normal in severe cases. The number of differentially expressed genes (DEGs) increased with the disease progression, and decreased after initial treatment. All downregulated DEGs in severe cases mainly involved Th17-cell differentiation, cytokine-mediated signaling pathways, and T-cell activation. After initial treatment in severe cases, MAP2K7 and SOS1 were upregulated relative to that on admission. Conclusions Our findings show that a decreased T-cell proportion with downregulated gene expression related to T-cell activation and differentiation occurred in patients with severe COVID-19, which may help to provide effective treatment strategies for COVID-19. Suppressed T-cell immune response and decreased T cells occurred in patients with COVID-19 related to downregulated gene expression involved in T-cell activation and differentiation, especially in severe disease, against SARS-CoV-2 infection and at the early period of treatment.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>32307550</pmid><doi>10.1093/cid/ciaa462</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Aged
and Commentaries
CD4-Positive T-Lymphocytes - metabolism
Cell Differentiation - physiology
Computational Biology
COVID-19 - immunology
COVID-19 - pathology
COVID-19 - virology
Female
Humans
Interleukin-10 - metabolism
Male
MAP Kinase Kinase 7 - metabolism
Microfluidics
Middle Aged
Signal Transduction - physiology
SOS1 Protein - metabolism
Th17 Cells - metabolism
title Downregulated Gene Expression Spectrum and Immune Responses Changed During the Disease Progression in Patients With COVID-19
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