PMC:7200337 / 39807-43902 JSON TXT

Annnotations TAB JSON ListView MergeView

2_test

{"project":"2_test","denotations":[{"id":"32505227-32284614-46575327","span":{"begin":462,"end":466},"obj":"32284614"},{"id":"32505227-32284614-46575329","span":{"begin":656,"end":660},"obj":"32284614"},{"id":"32505227-18832706-46575330","span":{"begin":774,"end":778},"obj":"18832706"},{"id":"32505227-29654146-46575331","span":{"begin":1171,"end":1175},"obj":"29654146"},{"id":"32505227-18832706-46575337","span":{"begin":2845,"end":2849},"obj":"18832706"},{"id":"32505227-32284614-46575338","span":{"begin":3813,"end":3817},"obj":"32284614"},{"id":"T4570","span":{"begin":462,"end":466},"obj":"32284614"},{"id":"T63291","span":{"begin":656,"end":660},"obj":"32284614"},{"id":"T22882","span":{"begin":774,"end":778},"obj":"18832706"},{"id":"T81493","span":{"begin":1171,"end":1175},"obj":"29654146"},{"id":"T22604","span":{"begin":2845,"end":2849},"obj":"18832706"},{"id":"T87043","span":{"begin":3813,"end":3817},"obj":"32284614"}],"text":"Phenotype and Function of T Cell Subsets in COVID-19\nCurrently, little is known about specific phenotypical and/or functional T cell changes associated with COVID-19. In the majority of preprints and peer-reviewed studies, there are reports of increased presence of activated T cells (Figure 3) characterized by expression of HLA-DR, CD38, CD69, CD25, CD44, and Ki-67 (Braun et al., 2020, Ni et al., 2020, Guo et al., 2020, Liao et al., 2020, Thevarajan et al., 2020, Yang et al., 2020a, Zheng et al., 2020a). Generally, independent of COVID-19 disease severity, CD8 T cells seem to be more activated than CD4 T cells (Qin et al., 2020, Thevarajan et al., 2020, Yang et al., 2020a), a finding that echoes stronger CD8 than CD4 T cell responses during SARS-CoV-1 (Li et al., 2008). Furthermore, in a case study of 10 COVID-19 patients, Diao et al. showed that levels of PD-1 increased from prodromal to symptomatic stages of the disease (Diao et al., 2020). PD-1 expression is commonly associated with T cell exhaustion, but it is important to emphasize that PD-1 is primarily induced by TCR signaling; it is thus also expressed by activated effector T cells (Ahn et al., 2018).\nIn addition, several studies reported higher expression of various co-stimulatory and inhibitory molecules such as OX-40 and CD137 (Zhou et al., 2020c), CTLA-4 and TIGIT (Zheng et al., 2020a), and NKG2a (Zheng et al., 2020b). Reduced numbers of CD28+ CD8 T cells (Qin et al., 2020) as well as larger frequencies of PD-1+ TIM3+ CD8 T cells in ICU patients were also reported (Zhou et al., 2020c). Expression of most of these markers was found to be higher in CD8 than in CD4 T cells, and levels tended to increase in severe versus non-severe cases, which may be due to differences in viral load. Cellular functionality was shown to be impaired in CD4 and CD8 T cells of critically ill patients, with reduced frequencies of polyfunctional T cells (producing more than one cytokine) as well as generally lower IFN-γ and TNF-α production following restimulation with phorbol myristate acetate (PMA) and ionomycin (Chen et al., 2020c, Zheng et al., 2020a, Zheng et al., 2020b). Similarly, Zheng et al. reported that CD8 T cells in severe COVID-19 appear less cytotoxic and effector-like with reduced CD107a degranulation and granzyme B (GzmB) production (Zheng et al., 2020b). In contrast, a different study found that both GzmB and perforin were increased in CD8 T cells of severely sick patients (Zheng et al., 2020a). In accordance with the latter observation, when compared to a moderate disease group, convalescent patients with resolved severe SARS-CoV-1 infection had significantly higher frequencies of polyfunctional T cells, with CD4 T cells producing more IFN-γ, TNF-α, and IL-2 and CD8 T cells producing more IFN-γ, TNF-α, and CD107a, respectively (Li et al., 2008). However, given the vigorous dynamics of acute T cell responses and potential differences in sample timing throughout disease course, these observations are not necessarily mutually exclusive. Accordingly, RNA sequencing (RNA-seq) data by Liao et al. showed that CD8 T cells in the BAL fluid of severe COVID-19 patients express cytotoxic genes such as GZMA, GZMB, and GZMK at higher levels, while KLRC1 and XCL1 are enriched in mild cases (Liao et al., 2020).\nIn summary, T cells in severe COVID-19 seem to be more activated and may exhibit a trend toward exhaustion based on continuous expression of inhibitory markers such as PD-1 and TIM-3 as well as overall reduced polyfunctionality and cytotoxicity. Conversely, recovering patients were shown to have an increase in follicular helper CD4 T cells (TFH) as well as decreasing levels of inhibitory markers along with enhanced levels of effector molecules such as Gzm A, GzmB, and perforin (Thevarajan et al., 2020, Yang et al., 2020a, Zheng et al., 2020b). Collectively, these studies provide a first glimpse into T cell dynamics in acute SARS-CoV-2 infection, but any conclusions have to be tempered at this stage on account of significant limitations in many of the current investigations."}

LitCovid-PD-FMA-UBERON

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T138","span":{"begin":1091,"end":1100},"obj":"http://purl.obolibrary.org/obo/GO_0023052"}],"text":"Phenotype and Function of T Cell Subsets in COVID-19\nCurrently, little is known about specific phenotypical and/or functional T cell changes associated with COVID-19. In the majority of preprints and peer-reviewed studies, there are reports of increased presence of activated T cells (Figure 3) characterized by expression of HLA-DR, CD38, CD69, CD25, CD44, and Ki-67 (Braun et al., 2020, Ni et al., 2020, Guo et al., 2020, Liao et al., 2020, Thevarajan et al., 2020, Yang et al., 2020a, Zheng et al., 2020a). Generally, independent of COVID-19 disease severity, CD8 T cells seem to be more activated than CD4 T cells (Qin et al., 2020, Thevarajan et al., 2020, Yang et al., 2020a), a finding that echoes stronger CD8 than CD4 T cell responses during SARS-CoV-1 (Li et al., 2008). Furthermore, in a case study of 10 COVID-19 patients, Diao et al. showed that levels of PD-1 increased from prodromal to symptomatic stages of the disease (Diao et al., 2020). PD-1 expression is commonly associated with T cell exhaustion, but it is important to emphasize that PD-1 is primarily induced by TCR signaling; it is thus also expressed by activated effector T cells (Ahn et al., 2018).\nIn addition, several studies reported higher expression of various co-stimulatory and inhibitory molecules such as OX-40 and CD137 (Zhou et al., 2020c), CTLA-4 and TIGIT (Zheng et al., 2020a), and NKG2a (Zheng et al., 2020b). Reduced numbers of CD28+ CD8 T cells (Qin et al., 2020) as well as larger frequencies of PD-1+ TIM3+ CD8 T cells in ICU patients were also reported (Zhou et al., 2020c). Expression of most of these markers was found to be higher in CD8 than in CD4 T cells, and levels tended to increase in severe versus non-severe cases, which may be due to differences in viral load. Cellular functionality was shown to be impaired in CD4 and CD8 T cells of critically ill patients, with reduced frequencies of polyfunctional T cells (producing more than one cytokine) as well as generally lower IFN-γ and TNF-α production following restimulation with phorbol myristate acetate (PMA) and ionomycin (Chen et al., 2020c, Zheng et al., 2020a, Zheng et al., 2020b). Similarly, Zheng et al. reported that CD8 T cells in severe COVID-19 appear less cytotoxic and effector-like with reduced CD107a degranulation and granzyme B (GzmB) production (Zheng et al., 2020b). In contrast, a different study found that both GzmB and perforin were increased in CD8 T cells of severely sick patients (Zheng et al., 2020a). In accordance with the latter observation, when compared to a moderate disease group, convalescent patients with resolved severe SARS-CoV-1 infection had significantly higher frequencies of polyfunctional T cells, with CD4 T cells producing more IFN-γ, TNF-α, and IL-2 and CD8 T cells producing more IFN-γ, TNF-α, and CD107a, respectively (Li et al., 2008). However, given the vigorous dynamics of acute T cell responses and potential differences in sample timing throughout disease course, these observations are not necessarily mutually exclusive. Accordingly, RNA sequencing (RNA-seq) data by Liao et al. showed that CD8 T cells in the BAL fluid of severe COVID-19 patients express cytotoxic genes such as GZMA, GZMB, and GZMK at higher levels, while KLRC1 and XCL1 are enriched in mild cases (Liao et al., 2020).\nIn summary, T cells in severe COVID-19 seem to be more activated and may exhibit a trend toward exhaustion based on continuous expression of inhibitory markers such as PD-1 and TIM-3 as well as overall reduced polyfunctionality and cytotoxicity. Conversely, recovering patients were shown to have an increase in follicular helper CD4 T cells (TFH) as well as decreasing levels of inhibitory markers along with enhanced levels of effector molecules such as Gzm A, GzmB, and perforin (Thevarajan et al., 2020, Yang et al., 2020a, Zheng et al., 2020b). Collectively, these studies provide a first glimpse into T cell dynamics in acute SARS-CoV-2 infection, but any conclusions have to be tempered at this stage on account of significant limitations in many of the current investigations."}

LitCovid-PubTator

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T216","span":{"begin":0,"end":52},"obj":"Sentence"},{"id":"T217","span":{"begin":53,"end":166},"obj":"Sentence"},{"id":"T218","span":{"begin":167,"end":509},"obj":"Sentence"},{"id":"T219","span":{"begin":510,"end":780},"obj":"Sentence"},{"id":"T220","span":{"begin":781,"end":956},"obj":"Sentence"},{"id":"T221","span":{"begin":957,"end":1177},"obj":"Sentence"},{"id":"T222","span":{"begin":1178,"end":1403},"obj":"Sentence"},{"id":"T223","span":{"begin":1404,"end":1573},"obj":"Sentence"},{"id":"T224","span":{"begin":1574,"end":1772},"obj":"Sentence"},{"id":"T225","span":{"begin":1773,"end":2150},"obj":"Sentence"},{"id":"T226","span":{"begin":2151,"end":2349},"obj":"Sentence"},{"id":"T227","span":{"begin":2350,"end":2493},"obj":"Sentence"},{"id":"T228","span":{"begin":2494,"end":2851},"obj":"Sentence"},{"id":"T229","span":{"begin":2852,"end":3043},"obj":"Sentence"},{"id":"T230","span":{"begin":3044,"end":3310},"obj":"Sentence"},{"id":"T231","span":{"begin":3311,"end":3556},"obj":"Sentence"},{"id":"T232","span":{"begin":3557,"end":3860},"obj":"Sentence"},{"id":"T233","span":{"begin":3861,"end":4095},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Phenotype and Function of T Cell Subsets in COVID-19\nCurrently, little is known about specific phenotypical and/or functional T cell changes associated with COVID-19. In the majority of preprints and peer-reviewed studies, there are reports of increased presence of activated T cells (Figure 3) characterized by expression of HLA-DR, CD38, CD69, CD25, CD44, and Ki-67 (Braun et al., 2020, Ni et al., 2020, Guo et al., 2020, Liao et al., 2020, Thevarajan et al., 2020, Yang et al., 2020a, Zheng et al., 2020a). Generally, independent of COVID-19 disease severity, CD8 T cells seem to be more activated than CD4 T cells (Qin et al., 2020, Thevarajan et al., 2020, Yang et al., 2020a), a finding that echoes stronger CD8 than CD4 T cell responses during SARS-CoV-1 (Li et al., 2008). Furthermore, in a case study of 10 COVID-19 patients, Diao et al. showed that levels of PD-1 increased from prodromal to symptomatic stages of the disease (Diao et al., 2020). PD-1 expression is commonly associated with T cell exhaustion, but it is important to emphasize that PD-1 is primarily induced by TCR signaling; it is thus also expressed by activated effector T cells (Ahn et al., 2018).\nIn addition, several studies reported higher expression of various co-stimulatory and inhibitory molecules such as OX-40 and CD137 (Zhou et al., 2020c), CTLA-4 and TIGIT (Zheng et al., 2020a), and NKG2a (Zheng et al., 2020b). Reduced numbers of CD28+ CD8 T cells (Qin et al., 2020) as well as larger frequencies of PD-1+ TIM3+ CD8 T cells in ICU patients were also reported (Zhou et al., 2020c). Expression of most of these markers was found to be higher in CD8 than in CD4 T cells, and levels tended to increase in severe versus non-severe cases, which may be due to differences in viral load. Cellular functionality was shown to be impaired in CD4 and CD8 T cells of critically ill patients, with reduced frequencies of polyfunctional T cells (producing more than one cytokine) as well as generally lower IFN-γ and TNF-α production following restimulation with phorbol myristate acetate (PMA) and ionomycin (Chen et al., 2020c, Zheng et al., 2020a, Zheng et al., 2020b). Similarly, Zheng et al. reported that CD8 T cells in severe COVID-19 appear less cytotoxic and effector-like with reduced CD107a degranulation and granzyme B (GzmB) production (Zheng et al., 2020b). In contrast, a different study found that both GzmB and perforin were increased in CD8 T cells of severely sick patients (Zheng et al., 2020a). In accordance with the latter observation, when compared to a moderate disease group, convalescent patients with resolved severe SARS-CoV-1 infection had significantly higher frequencies of polyfunctional T cells, with CD4 T cells producing more IFN-γ, TNF-α, and IL-2 and CD8 T cells producing more IFN-γ, TNF-α, and CD107a, respectively (Li et al., 2008). However, given the vigorous dynamics of acute T cell responses and potential differences in sample timing throughout disease course, these observations are not necessarily mutually exclusive. Accordingly, RNA sequencing (RNA-seq) data by Liao et al. showed that CD8 T cells in the BAL fluid of severe COVID-19 patients express cytotoxic genes such as GZMA, GZMB, and GZMK at higher levels, while KLRC1 and XCL1 are enriched in mild cases (Liao et al., 2020).\nIn summary, T cells in severe COVID-19 seem to be more activated and may exhibit a trend toward exhaustion based on continuous expression of inhibitory markers such as PD-1 and TIM-3 as well as overall reduced polyfunctionality and cytotoxicity. Conversely, recovering patients were shown to have an increase in follicular helper CD4 T cells (TFH) as well as decreasing levels of inhibitory markers along with enhanced levels of effector molecules such as Gzm A, GzmB, and perforin (Thevarajan et al., 2020, Yang et al., 2020a, Zheng et al., 2020b). Collectively, these studies provide a first glimpse into T cell dynamics in acute SARS-CoV-2 infection, but any conclusions have to be tempered at this stage on account of significant limitations in many of the current investigations."}

PMC:7200337 / 39807-43902 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7200337 / 39807-43902 JSON TXT