Alterations in T and B cell function persist in convalescent COVID-19 patients

Emerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these patients presently remains ill-defined. Here, we describe the phenotypic and functional char...

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Veröffentlicht in:Med (New York, N.Y. : Online) N.Y. : Online), 2021-06, Vol.2 (6), p.720-735.e4
Hauptverfasser: Shuwa, Halima A., Shaw, Tovah N., Knight, Sean B., Wemyss, Kelly, McClure, Flora A., Pearmain, Laurence, Prise, Ian, Jagger, Christopher, Morgan, David J., Khan, Saba, Brand, Oliver, Mann, Elizabeth R., Ustianowski, Andrew, Bakerly, Nawar Diar, Dark, Paul, Brightling, Christopher E., Brij, Seema, Ahmed, Rohan, Avery, Miriam, Birchall, Katharine, Charsley, Evelyn, Chenery, Alistair, Chew, Christine, Clark, Richard, Connolly, Emma, Connolly, Karen, Dawson, Simon, Durrans, Laura, Durrington, Hannah, Egan, Jasmine, Filbey, Kara, Fox, Claire, Francis, Helen, Franklin, Miriam, Glasgow, Susannah, Godfrey, Nicola, Gray, Kathryn J., Grundy, Seamus, Guerin, Jacinta, Hackney, Pamela, Hayes, Chantelle, Hardy, Emma, Harris, Jade, John, Anu, Jolly, Bethany, Kästele, Verena, Kerry, Gina, Lui, Sylvia, Lin, Lijing, Mathioudakis, Alex G., Mitchell, Joanne, Moizer, Clare, Moore, Katrina, Moss, Stuart, Baker, Syed Murtuza, Oliver, Rob, Padden, Grace, Parkinson, Christina, Phuycharoen, Michael, Saha, Ananya, Salcman, Barbora, Scott, Nicholas A., Sharma, Seema, Shaw, Jane, Shaw, Joanne, Shepley, Elizabeth, Smith, Lara, Stephan, Simon, Stephens, Ruth, Tavernier, Gael, Tudge, Rhys, Wareing, Louis, Warren, Roanna, Williams, Thomas, Willmore, Lisa, Younas, Mehwish, Felton, Timothy, Simpson, Angela, Grainger, John R., Hussell, Tracy, Konkel, Joanne E., Menon, Madhvi
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container_title Med (New York, N.Y. : Online)
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creator Shuwa, Halima A.
Shaw, Tovah N.
Knight, Sean B.
Wemyss, Kelly
McClure, Flora A.
Pearmain, Laurence
Prise, Ian
Jagger, Christopher
Morgan, David J.
Khan, Saba
Brand, Oliver
Mann, Elizabeth R.
Ustianowski, Andrew
Bakerly, Nawar Diar
Dark, Paul
Brightling, Christopher E.
Brij, Seema
Ahmed, Rohan
Avery, Miriam
Birchall, Katharine
Charsley, Evelyn
Chenery, Alistair
Chew, Christine
Clark, Richard
Connolly, Emma
Connolly, Karen
Dawson, Simon
Durrans, Laura
Durrington, Hannah
Egan, Jasmine
Filbey, Kara
Fox, Claire
Francis, Helen
Franklin, Miriam
Glasgow, Susannah
Godfrey, Nicola
Gray, Kathryn J.
Grundy, Seamus
Guerin, Jacinta
Hackney, Pamela
Hayes, Chantelle
Hardy, Emma
Harris, Jade
John, Anu
Jolly, Bethany
Kästele, Verena
Kerry, Gina
Lui, Sylvia
Lin, Lijing
Mathioudakis, Alex G.
Mitchell, Joanne
Moizer, Clare
Moore, Katrina
Moss, Stuart
Baker, Syed Murtuza
Oliver, Rob
Padden, Grace
Parkinson, Christina
Phuycharoen, Michael
Saha, Ananya
Salcman, Barbora
Scott, Nicholas A.
Sharma, Seema
Shaw, Jane
Shaw, Joanne
Shepley, Elizabeth
Smith, Lara
Stephan, Simon
Stephens, Ruth
Tavernier, Gael
Tudge, Rhys
Wareing, Louis
Warren, Roanna
Williams, Thomas
Willmore, Lisa
Younas, Mehwish
Felton, Timothy
Simpson, Angela
Grainger, John R.
Hussell, Tracy
Konkel, Joanne E.
Menon, Madhvi
description Emerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these patients presently remains ill-defined. Here, we describe the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3–6 months of convalescence. We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic program evident in CD8+ T cells as well as elevated production of type 1 cytokines and interleukin-17 (IL-17). Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to Toll-like receptor activation, skewed toward a pro-inflammatory phenotype. Whereas the frequency of IL-6+ B cells was restored in convalescent patients irrespective of clinical outcome, the recovery of IL-10+ B cells was associated with the resolution of lung pathology. Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with 1 subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalization with COVID-19 could affect longer-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients. Provided by UKRI, Lister Institute of Preventative Medicine, the Wellcome Trust, The Kennedy Trust for Rheumatology Research, and 3M Global Giving. [Display omitted] Lymphocytes were examined during COVID-19 and at up to 6 months of convalescenceB cell changes seen during acute COVID-19 were largely restored in convalescenceT cells from convalescent COVID-19 patients displayed persistent changesLymphocyte signatures defined 3 convalescent patient groups, one with poorer outcomes The coronavirus disease 2019 (COVID-19) pandemic, caused by a novel coronavirus strain, has resulted in >100 million infections worldwide. Emerging evidence suggests that some COVID-19 patients suffer persistent symptoms, including fatigue, fibrotic lung disease, and myalgia; however, the long-term immune response in these patients remains ill-defined. Here, we
doi_str_mv 10.1016/j.medj.2021.03.013
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Here, we describe the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3–6 months of convalescence. We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic program evident in CD8+ T cells as well as elevated production of type 1 cytokines and interleukin-17 (IL-17). Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to Toll-like receptor activation, skewed toward a pro-inflammatory phenotype. Whereas the frequency of IL-6+ B cells was restored in convalescent patients irrespective of clinical outcome, the recovery of IL-10+ B cells was associated with the resolution of lung pathology. Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with 1 subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalization with COVID-19 could affect longer-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients. Provided by UKRI, Lister Institute of Preventative Medicine, the Wellcome Trust, The Kennedy Trust for Rheumatology Research, and 3M Global Giving. [Display omitted] Lymphocytes were examined during COVID-19 and at up to 6 months of convalescenceB cell changes seen during acute COVID-19 were largely restored in convalescenceT cells from convalescent COVID-19 patients displayed persistent changesLymphocyte signatures defined 3 convalescent patient groups, one with poorer outcomes The coronavirus disease 2019 (COVID-19) pandemic, caused by a novel coronavirus strain, has resulted in &gt;100 million infections worldwide. Emerging evidence suggests that some COVID-19 patients suffer persistent symptoms, including fatigue, fibrotic lung disease, and myalgia; however, the long-term immune response in these patients remains ill-defined. Here, we conducted an observational study examining lymphocyte populations in COVID-19 patients during hospitalization and at up to 6 months of convalescence. We identified a number of lymphocyte alterations that persisted in convalescent patients. Moreover, the compilation of lymphocyte parameters in convalescent COVID-19 patients identified 3 distinct patient subgroups, with 1 subgroup associated with poorer clinical outcome. Our study outlines lymphocyte changes in convalescent COVID-19 patients associated with negative effects on subsequent health. Shuwa et al. examine lymphocyte characteristics in acute and convalescent COVID-19 patients, detailing persistent alterations in lymphocyte phenotype up to 6 months following hospital discharge. In this report, they identify 3 subgroups of convalescent patients based on distinct lymphocyte signatures, with 1 subgroup associated with poorer clinical outcomes.</description><identifier>ISSN: 2666-6340</identifier><identifier>ISSN: 2666-6359</identifier><identifier>EISSN: 2666-6340</identifier><identifier>DOI: 10.1016/j.medj.2021.03.013</identifier><identifier>PMID: 33821250</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>B cells ; CD8-Positive T-Lymphocytes ; Clinical and Translational Report ; convalescent patients ; COVID-19 ; Cytokines ; Humans ; Interleukin-10 ; Interleukin-6 ; long COVID ; SARS-CoV-2 ; T cells ; viral Infection</subject><ispartof>Med (New York, N.Y. : Online), 2021-06, Vol.2 (6), p.720-735.e4</ispartof><rights>2021 The Author(s)</rights><rights>2021 The Author(s).</rights><rights>2021 The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-afc725d3ece8d4364379fd19ec602540069103e6056f2c848367638c103ba22a3</citedby><cites>FETCH-LOGICAL-c455t-afc725d3ece8d4364379fd19ec602540069103e6056f2c848367638c103ba22a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33821250$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shuwa, Halima A.</creatorcontrib><creatorcontrib>Shaw, Tovah N.</creatorcontrib><creatorcontrib>Knight, Sean B.</creatorcontrib><creatorcontrib>Wemyss, Kelly</creatorcontrib><creatorcontrib>McClure, Flora A.</creatorcontrib><creatorcontrib>Pearmain, 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Gina</creatorcontrib><creatorcontrib>Lui, Sylvia</creatorcontrib><creatorcontrib>Lin, Lijing</creatorcontrib><creatorcontrib>Mathioudakis, Alex G.</creatorcontrib><creatorcontrib>Mitchell, Joanne</creatorcontrib><creatorcontrib>Moizer, Clare</creatorcontrib><creatorcontrib>Moore, Katrina</creatorcontrib><creatorcontrib>Moss, Stuart</creatorcontrib><creatorcontrib>Baker, Syed Murtuza</creatorcontrib><creatorcontrib>Oliver, Rob</creatorcontrib><creatorcontrib>Padden, Grace</creatorcontrib><creatorcontrib>Parkinson, Christina</creatorcontrib><creatorcontrib>Phuycharoen, Michael</creatorcontrib><creatorcontrib>Saha, Ananya</creatorcontrib><creatorcontrib>Salcman, Barbora</creatorcontrib><creatorcontrib>Scott, Nicholas A.</creatorcontrib><creatorcontrib>Sharma, Seema</creatorcontrib><creatorcontrib>Shaw, Jane</creatorcontrib><creatorcontrib>Shaw, Joanne</creatorcontrib><creatorcontrib>Shepley, Elizabeth</creatorcontrib><creatorcontrib>Smith, Lara</creatorcontrib><creatorcontrib>Stephan, Simon</creatorcontrib><creatorcontrib>Stephens, Ruth</creatorcontrib><creatorcontrib>Tavernier, Gael</creatorcontrib><creatorcontrib>Tudge, Rhys</creatorcontrib><creatorcontrib>Wareing, Louis</creatorcontrib><creatorcontrib>Warren, Roanna</creatorcontrib><creatorcontrib>Williams, Thomas</creatorcontrib><creatorcontrib>Willmore, Lisa</creatorcontrib><creatorcontrib>Younas, Mehwish</creatorcontrib><creatorcontrib>Felton, Timothy</creatorcontrib><creatorcontrib>Simpson, Angela</creatorcontrib><creatorcontrib>Grainger, John R.</creatorcontrib><creatorcontrib>Hussell, Tracy</creatorcontrib><creatorcontrib>Konkel, Joanne E.</creatorcontrib><creatorcontrib>Menon, Madhvi</creatorcontrib><creatorcontrib>CIRCO</creatorcontrib><title>Alterations in T and B cell function persist in convalescent COVID-19 patients</title><title>Med (New York, N.Y. : Online)</title><addtitle>Med (N Y)</addtitle><description>Emerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these patients presently remains ill-defined. Here, we describe the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3–6 months of convalescence. We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic program evident in CD8+ T cells as well as elevated production of type 1 cytokines and interleukin-17 (IL-17). Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to Toll-like receptor activation, skewed toward a pro-inflammatory phenotype. Whereas the frequency of IL-6+ B cells was restored in convalescent patients irrespective of clinical outcome, the recovery of IL-10+ B cells was associated with the resolution of lung pathology. Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with 1 subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalization with COVID-19 could affect longer-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients. Provided by UKRI, Lister Institute of Preventative Medicine, the Wellcome Trust, The Kennedy Trust for Rheumatology Research, and 3M Global Giving. [Display omitted] Lymphocytes were examined during COVID-19 and at up to 6 months of convalescenceB cell changes seen during acute COVID-19 were largely restored in convalescenceT cells from convalescent COVID-19 patients displayed persistent changesLymphocyte signatures defined 3 convalescent patient groups, one with poorer outcomes The coronavirus disease 2019 (COVID-19) pandemic, caused by a novel coronavirus strain, has resulted in &gt;100 million infections worldwide. Emerging evidence suggests that some COVID-19 patients suffer persistent symptoms, including fatigue, fibrotic lung disease, and myalgia; however, the long-term immune response in these patients remains ill-defined. Here, we conducted an observational study examining lymphocyte populations in COVID-19 patients during hospitalization and at up to 6 months of convalescence. We identified a number of lymphocyte alterations that persisted in convalescent patients. Moreover, the compilation of lymphocyte parameters in convalescent COVID-19 patients identified 3 distinct patient subgroups, with 1 subgroup associated with poorer clinical outcome. Our study outlines lymphocyte changes in convalescent COVID-19 patients associated with negative effects on subsequent health. Shuwa et al. examine lymphocyte characteristics in acute and convalescent COVID-19 patients, detailing persistent alterations in lymphocyte phenotype up to 6 months following hospital discharge. In this report, they identify 3 subgroups of convalescent patients based on distinct lymphocyte signatures, with 1 subgroup associated with poorer clinical outcomes.</description><subject>B cells</subject><subject>CD8-Positive T-Lymphocytes</subject><subject>Clinical and Translational Report</subject><subject>convalescent patients</subject><subject>COVID-19</subject><subject>Cytokines</subject><subject>Humans</subject><subject>Interleukin-10</subject><subject>Interleukin-6</subject><subject>long COVID</subject><subject>SARS-CoV-2</subject><subject>T cells</subject><subject>viral Infection</subject><issn>2666-6340</issn><issn>2666-6359</issn><issn>2666-6340</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1LxDAQDaKorP4BD5Kjl9ZJ0qYtiKDr14K4l9VriOlUU7rtmrQL_ntTVhe9eJph5s3Ly3uEnDCIGTB5XsdLLOuYA2cxiBiY2CGHXEoZSZHA7q_-gBx7XwMAT5lgBd8nB0LknPEUDsnTVdOj073tWk9tSxdUtyW9pgabhlZDa8YNXaHz1vcjwHTtWjfoDbY9nc5fZjcRK-gqMISBPyJ7lW48Hn_XCXm-u11MH6LH-f1sevUYmSRN-0hXJuNpKdBgXiZCJiIrqpIVaGRQmQDIgoFACamsuMmTXMhMityE4avmXIsJudzwrobX4MMoxulGrZxdavepOm3V301r39Vbt1Y5MCbzIhCcfRO47mNA36ul9eOndYvd4FUwp-AZ54kIUL6BGtd577DaPsNAjVmoWo1ZqDELBUKFLMLR6W-B25Mf5wPgYgPAYNPaolPeBAsNltah6VXZ2f_4vwDiQZlD</recordid><startdate>20210611</startdate><enddate>20210611</enddate><creator>Shuwa, Halima A.</creator><creator>Shaw, Tovah N.</creator><creator>Knight, Sean B.</creator><creator>Wemyss, Kelly</creator><creator>McClure, Flora A.</creator><creator>Pearmain, Laurence</creator><creator>Prise, 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Elizabeth</creator><creator>Smith, Lara</creator><creator>Stephan, Simon</creator><creator>Stephens, Ruth</creator><creator>Tavernier, Gael</creator><creator>Tudge, Rhys</creator><creator>Wareing, Louis</creator><creator>Warren, Roanna</creator><creator>Williams, Thomas</creator><creator>Willmore, Lisa</creator><creator>Younas, Mehwish</creator><creator>Felton, Timothy</creator><creator>Simpson, Angela</creator><creator>Grainger, John R.</creator><creator>Hussell, Tracy</creator><creator>Konkel, Joanne E.</creator><creator>Menon, Madhvi</creator><general>Elsevier Inc</general><general>Cell Press</general><scope>6I.</scope><scope>AAFTH</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>20210611</creationdate><title>Alterations in T and B cell function persist in convalescent COVID-19 patients</title><author>Shuwa, Halima A. ; Shaw, Tovah N. ; Knight, Sean B. ; Wemyss, Kelly ; McClure, Flora A. ; Pearmain, Laurence ; Prise, Ian ; Jagger, Christopher ; Morgan, David J. ; Khan, Saba ; Brand, Oliver ; Mann, Elizabeth R. ; Ustianowski, Andrew ; Bakerly, Nawar Diar ; Dark, Paul ; Brightling, Christopher E. ; Brij, Seema ; Ahmed, Rohan ; Avery, Miriam ; Birchall, Katharine ; Charsley, Evelyn ; Chenery, Alistair ; Chew, Christine ; Clark, Richard ; Connolly, Emma ; Connolly, Karen ; Dawson, Simon ; Durrans, Laura ; Durrington, Hannah ; Egan, Jasmine ; Filbey, Kara ; Fox, Claire ; Francis, Helen ; Franklin, Miriam ; Glasgow, Susannah ; Godfrey, Nicola ; Gray, Kathryn J. ; Grundy, Seamus ; Guerin, Jacinta ; Hackney, Pamela ; Hayes, Chantelle ; Hardy, Emma ; Harris, Jade ; John, Anu ; Jolly, Bethany ; Kästele, Verena ; Kerry, Gina ; Lui, Sylvia ; Lin, Lijing ; Mathioudakis, Alex G. ; Mitchell, Joanne ; Moizer, Clare ; Moore, Katrina ; Moss, Stuart ; Baker, Syed Murtuza ; Oliver, Rob ; Padden, Grace ; Parkinson, Christina ; Phuycharoen, Michael ; Saha, Ananya ; Salcman, Barbora ; Scott, Nicholas A. ; Sharma, Seema ; Shaw, Jane ; Shaw, Joanne ; Shepley, Elizabeth ; Smith, Lara ; Stephan, Simon ; Stephens, Ruth ; Tavernier, Gael ; Tudge, Rhys ; Wareing, Louis ; Warren, Roanna ; Williams, Thomas ; Willmore, Lisa ; Younas, Mehwish ; Felton, Timothy ; Simpson, Angela ; Grainger, John R. ; Hussell, Tracy ; Konkel, Joanne E. ; Menon, Madhvi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-afc725d3ece8d4364379fd19ec602540069103e6056f2c848367638c103ba22a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>B cells</topic><topic>CD8-Positive T-Lymphocytes</topic><topic>Clinical and Translational Report</topic><topic>convalescent patients</topic><topic>COVID-19</topic><topic>Cytokines</topic><topic>Humans</topic><topic>Interleukin-10</topic><topic>Interleukin-6</topic><topic>long COVID</topic><topic>SARS-CoV-2</topic><topic>T cells</topic><topic>viral Infection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shuwa, Halima A.</creatorcontrib><creatorcontrib>Shaw, Tovah N.</creatorcontrib><creatorcontrib>Knight, Sean B.</creatorcontrib><creatorcontrib>Wemyss, Kelly</creatorcontrib><creatorcontrib>McClure, Flora A.</creatorcontrib><creatorcontrib>Pearmain, Laurence</creatorcontrib><creatorcontrib>Prise, Ian</creatorcontrib><creatorcontrib>Jagger, Christopher</creatorcontrib><creatorcontrib>Morgan, David J.</creatorcontrib><creatorcontrib>Khan, Saba</creatorcontrib><creatorcontrib>Brand, Oliver</creatorcontrib><creatorcontrib>Mann, Elizabeth R.</creatorcontrib><creatorcontrib>Ustianowski, Andrew</creatorcontrib><creatorcontrib>Bakerly, Nawar Diar</creatorcontrib><creatorcontrib>Dark, Paul</creatorcontrib><creatorcontrib>Brightling, Christopher E.</creatorcontrib><creatorcontrib>Brij, Seema</creatorcontrib><creatorcontrib>Ahmed, Rohan</creatorcontrib><creatorcontrib>Avery, Miriam</creatorcontrib><creatorcontrib>Birchall, Katharine</creatorcontrib><creatorcontrib>Charsley, Evelyn</creatorcontrib><creatorcontrib>Chenery, Alistair</creatorcontrib><creatorcontrib>Chew, Christine</creatorcontrib><creatorcontrib>Clark, Richard</creatorcontrib><creatorcontrib>Connolly, Emma</creatorcontrib><creatorcontrib>Connolly, Karen</creatorcontrib><creatorcontrib>Dawson, Simon</creatorcontrib><creatorcontrib>Durrans, Laura</creatorcontrib><creatorcontrib>Durrington, Hannah</creatorcontrib><creatorcontrib>Egan, Jasmine</creatorcontrib><creatorcontrib>Filbey, Kara</creatorcontrib><creatorcontrib>Fox, Claire</creatorcontrib><creatorcontrib>Francis, Helen</creatorcontrib><creatorcontrib>Franklin, Miriam</creatorcontrib><creatorcontrib>Glasgow, Susannah</creatorcontrib><creatorcontrib>Godfrey, Nicola</creatorcontrib><creatorcontrib>Gray, Kathryn J.</creatorcontrib><creatorcontrib>Grundy, Seamus</creatorcontrib><creatorcontrib>Guerin, Jacinta</creatorcontrib><creatorcontrib>Hackney, Pamela</creatorcontrib><creatorcontrib>Hayes, Chantelle</creatorcontrib><creatorcontrib>Hardy, Emma</creatorcontrib><creatorcontrib>Harris, Jade</creatorcontrib><creatorcontrib>John, Anu</creatorcontrib><creatorcontrib>Jolly, Bethany</creatorcontrib><creatorcontrib>Kästele, Verena</creatorcontrib><creatorcontrib>Kerry, Gina</creatorcontrib><creatorcontrib>Lui, Sylvia</creatorcontrib><creatorcontrib>Lin, Lijing</creatorcontrib><creatorcontrib>Mathioudakis, Alex G.</creatorcontrib><creatorcontrib>Mitchell, Joanne</creatorcontrib><creatorcontrib>Moizer, Clare</creatorcontrib><creatorcontrib>Moore, Katrina</creatorcontrib><creatorcontrib>Moss, Stuart</creatorcontrib><creatorcontrib>Baker, Syed Murtuza</creatorcontrib><creatorcontrib>Oliver, Rob</creatorcontrib><creatorcontrib>Padden, Grace</creatorcontrib><creatorcontrib>Parkinson, Christina</creatorcontrib><creatorcontrib>Phuycharoen, Michael</creatorcontrib><creatorcontrib>Saha, Ananya</creatorcontrib><creatorcontrib>Salcman, Barbora</creatorcontrib><creatorcontrib>Scott, Nicholas A.</creatorcontrib><creatorcontrib>Sharma, Seema</creatorcontrib><creatorcontrib>Shaw, Jane</creatorcontrib><creatorcontrib>Shaw, Joanne</creatorcontrib><creatorcontrib>Shepley, Elizabeth</creatorcontrib><creatorcontrib>Smith, Lara</creatorcontrib><creatorcontrib>Stephan, Simon</creatorcontrib><creatorcontrib>Stephens, Ruth</creatorcontrib><creatorcontrib>Tavernier, Gael</creatorcontrib><creatorcontrib>Tudge, Rhys</creatorcontrib><creatorcontrib>Wareing, Louis</creatorcontrib><creatorcontrib>Warren, Roanna</creatorcontrib><creatorcontrib>Williams, Thomas</creatorcontrib><creatorcontrib>Willmore, Lisa</creatorcontrib><creatorcontrib>Younas, Mehwish</creatorcontrib><creatorcontrib>Felton, Timothy</creatorcontrib><creatorcontrib>Simpson, Angela</creatorcontrib><creatorcontrib>Grainger, John R.</creatorcontrib><creatorcontrib>Hussell, Tracy</creatorcontrib><creatorcontrib>Konkel, Joanne E.</creatorcontrib><creatorcontrib>Menon, Madhvi</creatorcontrib><creatorcontrib>CIRCO</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>Med (New York, N.Y. : Online)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shuwa, Halima A.</au><au>Shaw, Tovah N.</au><au>Knight, Sean B.</au><au>Wemyss, Kelly</au><au>McClure, Flora A.</au><au>Pearmain, Laurence</au><au>Prise, Ian</au><au>Jagger, Christopher</au><au>Morgan, David J.</au><au>Khan, Saba</au><au>Brand, Oliver</au><au>Mann, Elizabeth R.</au><au>Ustianowski, Andrew</au><au>Bakerly, Nawar Diar</au><au>Dark, Paul</au><au>Brightling, Christopher E.</au><au>Brij, Seema</au><au>Ahmed, Rohan</au><au>Avery, Miriam</au><au>Birchall, Katharine</au><au>Charsley, Evelyn</au><au>Chenery, Alistair</au><au>Chew, Christine</au><au>Clark, Richard</au><au>Connolly, Emma</au><au>Connolly, Karen</au><au>Dawson, Simon</au><au>Durrans, Laura</au><au>Durrington, Hannah</au><au>Egan, Jasmine</au><au>Filbey, Kara</au><au>Fox, Claire</au><au>Francis, Helen</au><au>Franklin, Miriam</au><au>Glasgow, Susannah</au><au>Godfrey, Nicola</au><au>Gray, Kathryn J.</au><au>Grundy, Seamus</au><au>Guerin, Jacinta</au><au>Hackney, Pamela</au><au>Hayes, Chantelle</au><au>Hardy, Emma</au><au>Harris, Jade</au><au>John, Anu</au><au>Jolly, Bethany</au><au>Kästele, Verena</au><au>Kerry, Gina</au><au>Lui, Sylvia</au><au>Lin, Lijing</au><au>Mathioudakis, Alex G.</au><au>Mitchell, Joanne</au><au>Moizer, Clare</au><au>Moore, Katrina</au><au>Moss, Stuart</au><au>Baker, Syed Murtuza</au><au>Oliver, Rob</au><au>Padden, Grace</au><au>Parkinson, Christina</au><au>Phuycharoen, Michael</au><au>Saha, Ananya</au><au>Salcman, Barbora</au><au>Scott, Nicholas A.</au><au>Sharma, Seema</au><au>Shaw, Jane</au><au>Shaw, Joanne</au><au>Shepley, Elizabeth</au><au>Smith, Lara</au><au>Stephan, Simon</au><au>Stephens, Ruth</au><au>Tavernier, Gael</au><au>Tudge, Rhys</au><au>Wareing, Louis</au><au>Warren, Roanna</au><au>Williams, Thomas</au><au>Willmore, Lisa</au><au>Younas, Mehwish</au><au>Felton, Timothy</au><au>Simpson, Angela</au><au>Grainger, John R.</au><au>Hussell, Tracy</au><au>Konkel, Joanne E.</au><au>Menon, Madhvi</au><aucorp>CIRCO</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alterations in T and B cell function persist in convalescent COVID-19 patients</atitle><jtitle>Med (New York, N.Y. : Online)</jtitle><addtitle>Med (N Y)</addtitle><date>2021-06-11</date><risdate>2021</risdate><volume>2</volume><issue>6</issue><spage>720</spage><epage>735.e4</epage><pages>720-735.e4</pages><issn>2666-6340</issn><issn>2666-6359</issn><eissn>2666-6340</eissn><abstract>Emerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these patients presently remains ill-defined. Here, we describe the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3–6 months of convalescence. We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic program evident in CD8+ T cells as well as elevated production of type 1 cytokines and interleukin-17 (IL-17). Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to Toll-like receptor activation, skewed toward a pro-inflammatory phenotype. Whereas the frequency of IL-6+ B cells was restored in convalescent patients irrespective of clinical outcome, the recovery of IL-10+ B cells was associated with the resolution of lung pathology. Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with 1 subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalization with COVID-19 could affect longer-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients. Provided by UKRI, Lister Institute of Preventative Medicine, the Wellcome Trust, The Kennedy Trust for Rheumatology Research, and 3M Global Giving. [Display omitted] Lymphocytes were examined during COVID-19 and at up to 6 months of convalescenceB cell changes seen during acute COVID-19 were largely restored in convalescenceT cells from convalescent COVID-19 patients displayed persistent changesLymphocyte signatures defined 3 convalescent patient groups, one with poorer outcomes The coronavirus disease 2019 (COVID-19) pandemic, caused by a novel coronavirus strain, has resulted in &gt;100 million infections worldwide. Emerging evidence suggests that some COVID-19 patients suffer persistent symptoms, including fatigue, fibrotic lung disease, and myalgia; however, the long-term immune response in these patients remains ill-defined. Here, we conducted an observational study examining lymphocyte populations in COVID-19 patients during hospitalization and at up to 6 months of convalescence. We identified a number of lymphocyte alterations that persisted in convalescent patients. Moreover, the compilation of lymphocyte parameters in convalescent COVID-19 patients identified 3 distinct patient subgroups, with 1 subgroup associated with poorer clinical outcome. Our study outlines lymphocyte changes in convalescent COVID-19 patients associated with negative effects on subsequent health. Shuwa et al. examine lymphocyte characteristics in acute and convalescent COVID-19 patients, detailing persistent alterations in lymphocyte phenotype up to 6 months following hospital discharge. In this report, they identify 3 subgroups of convalescent patients based on distinct lymphocyte signatures, with 1 subgroup associated with poorer clinical outcomes.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33821250</pmid><doi>10.1016/j.medj.2021.03.013</doi><oa>free_for_read</oa></addata></record>
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issn 2666-6340
2666-6359
2666-6340
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8011689
source MEDLINE; Alma/SFX Local Collection
subjects B cells
CD8-Positive T-Lymphocytes
Clinical and Translational Report
convalescent patients
COVID-19
Cytokines
Humans
Interleukin-10
Interleukin-6
long COVID
SARS-CoV-2
T cells
viral Infection
title Alterations in T and B cell function persist in convalescent COVID-19 patients
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